CAP Profiles

Bio

Clinical Focus

  • Neurology

Academic Appointments

Administrative Appointments

  • Director, Stanford Stroke Center, Stanford Medical Center (1992 - Present)
  • Coyote Foundation Professor, Neurology and Neurological Sciences (2007 - Present)

Professional Education

  • Internship: Stanford University Internal Medicine Residency (1985) CA
  • Residency: Stanford University Neurology Residency (1988) CA
  • Medical Education: University of California San Diego School of Medicine Registrar (1984) CA
  • Board Certification: Vascular Neurology, American Board of Psychiatry and Neurology (2008)
  • Board Certification: Neurology, American Board of Psychiatry and Neurology (1990)

Contact

    • Tel: (650) 723-4448
  • Evelyn Ray Administrative Associate
    • Tel: 650 498-6164
  • Stanford Neuroscience Health Center 213 Quarry Rd Rm 2851 MC 5957 Palo Alto, CA 94304
    • Tel: (650) 723-6469
    Fax: (650) 725-0390

Links

Research & Scholarship

Current Research and Scholarly Interests

Our group’'s research focus is the acute treatment and prevention of cerebrovascular disorders. Our primary interest is the use of advanced imaging techniques to expand the treatment window for ischemic stroke. We are also conducting clinical studies of both neuroprotective and thrombolytic strategies for the treatment of acute stroke and investigating new antithrombotic strategies for stroke prevention.

Clinical Trials

  • Diagnostic Utility of MRI in Intracerebral Hemorrhage Recruiting

    The overall aim of this project is to prospectively determine whether MRI can improve the conventional neuroradiological evaluation (CT with or without cerebral angiography) of patients with a spontaneous ICH or IVH. The study design will also allow us to identify the added benefit of specific MR sequences and repeat MRI in the chronic stage, thereby allowing us to prospectively determine their value in a consecutive series of patients. This information should have a major impact on the management of these patients by providing data on the diagnostic yield of routine MRI in patients presenting with a wide variety of causes for ICH or IVH. These data will help guide the diagnostic evaluation and the management of brain hemorrhage patients in the future.

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  • Glyburide Advantage in Malignant Edema and Stroke - Remedy Pharmaceuticals Recruiting

    This is a randomized, multi-center, prospective, double blind study. The primary objective is to demonstrate the efficacy of RP-1127 compared to placebo in subjects with a severe anterior circulation ischemic stroke who are likely to develop malignant edema. This objective will be addressed by comparing the proportion of RP-1127 treated patients and placebo treated patients with a Day 90 modified Rankin Scale (mRS) ≤ 4 without decompressive craniectomy (DC).

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  • Tenecteplase in Stroke Patients Between 4.5 and 24 Hours Recruiting

    This study will evaluate the efficacy and safety of tenecteplase compared with placebo in patients with acute ischemic stroke (AIS). All patients will receive standard-of-care therapy according to American Heart Association / American Stroke Association clinical guidelines (2018). To determine eligibility for randomization, all patients will undergo multimodal CT or MRI at baseline. Only patients with a vessel occlusion (ICA or MCA) and penumbral tissue will be randomized. The primary analysis is to compare the efficacy of tenecteplase versus placebo in all patients at Day 90.

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  • Blood Pressure Lowering in Acute Stroke Trial Not Recruiting

    The investigators hope to show that valsartan can be used safely in the setting of acute stroke to lower elevated blood pressure. There are novel properties of this class of drug (an angiotensive-receptor blocker or ARB), and promising human and animal data, that would suggest this drug can be safely used to lower blood pressure in the setting of acute stroke without compromising brain blood flow (i.e. cerebral perfusion). If this is proved to be the case, this compound could potentially be used routinely in this setting, with the hope of improving outcome. This pilot study may pave the way for a larger randomized trial looking at outcome measures in stroke patients. Further, a positive result in the this pilot study will serve as proof of concept that ARBs maintain cerebral perfusion while decreasing blood pressure, an overall favorable property.

    Stanford is currently not accepting patients for this trial.

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  • Blood Pressure Lowering in Acute Stroke Trial (BLAST) Not Recruiting

    Patients who are suffering from a stroke often present to the hospital with elevated blood pressure. Elevated blood pressure in the setting of stroke increases the risk of brain swelling or bleeding into the brain. Even so, there has been concern about lowering the blood pressure with medications because the newly injured parts of the brain may not get the blood flow they need, thereby worsening the damage from the initial stroke. We hope to demonstrate that the drug valsartan can be used safely and modestly to lower blood pressure in acute stroke patients, without having a detrimental effect on brain blood flow or neurologic status. Novel MRI techniques to measure brain blood flow will be used in conjunction with clinical scales to demonstrate safety.

    Stanford is currently not accepting patients for this trial.

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  • Clot Lysis: Evaluating Accelerated Resolution of Intraventricular Hemorrhage Phase III Not Recruiting

    The overall objective of this Phase III clinical trial is to obtain information from a population of 500 ICH subjects with intraventricular hemorrhage (IVH), representative of current clinical practice and national demographics of ICH regarding the benefit (or lack thereof) of IVH clot removal on subject function as measured by modified Rankin Scale (mRS). This application requests funding for five years to initiate a Phase III randomized clinical trial (RCT) testing the benefit of clot removal for intraventricular hemorrhage. The investigators propose to compare extraventricular drainage (EVD) use plus recombinant tissue plasminogen activator (rt-PA; Alteplase; Genentech, Inc., San Francisco, CA) with EVD+ placebo in the management and treatment of subjects with small intracerebral hemorrhage (ICH) and large intraventricular hemorrhage (IVH defined as ICH < 30 cc and obstruction of the 3rd or 4th ventricles by intraventricular blood clot).

    Stanford is currently not accepting patients for this trial. For more information, please contact Christine Wijman, (650) 723 - 4448.

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  • Computed Tomography Perfusion (CTP) to Predict Response to Recanalization in Ischemic Stroke Project (CRISP) Not Recruiting

    The overall goal of the CTP to predict Response to recanalization in Ischemic Stroke Project (CRISP) is to develop a practical tool to identify acute stroke patients who are likely to benefit from endovascular therapy. The project has two main parts. During the first part, the investigators propose to develop a fully automated system (RAPID) for processing of CT Perfusion (CTP) images that will generate brain maps of the ischemic core and penumbra. There will be no patient enrollment in part one of this project. During the second part, the investigators aim to demonstrate that physicians in the emergency setting, with the aid of a fully automated CTP analysis program (RAPID), can accurately predict response to recanalization in stroke patients undergoing revascularization. To achieve this aim the investigators will conduct a prospective cohort study of 240 consecutive stroke patients who will undergo a CTP scan prior to endovascular therapy. The study will be conducted at four sites (Stanford University, St Luke's Hospital, University of Pittsburgh Medical Center, and Emory University/Grady Hospital). Patients will have an early follow-up MRI scan within 12+/-6 hours to assess reperfusion and a late follow-up MRI scan at day 5 to determine the final infarct.

    Stanford is currently not accepting patients for this trial. For more information, please contact Stephanie M Kemp, BS, 650-723-4481.

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  • Diffusion Weighted Imaging Evaluation for Understanding Stroke Evolution Study-2 (DEFUSE-2) Not Recruiting

    Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution Study 2 (DEFUSE 2) is a multi-center pilot study to determine if cerebral perfusion imaging can help identify which patients, who are ineligible for intravenous tissue plasminogen activator (iv tPA) therapy or have failed iv tPA therapy, are most likely to benefit from an endovascular clot removal procedure.

    Stanford is currently not accepting patients for this trial.

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  • Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke 3 Not Recruiting

    This is a study to evaluate the hypothesis that FDA cleared thrombectomy devices plus medical management leads to superior clinical outcomes in acute ischemic stroke patients at 90 days when compared to medical management alone in appropriately selected subjects with the Target mismatch profile and an MCA (M1 segment) or ICA occlusion who can be randomized and have endovascular treatment initiated between 6-16 hours after last seen well.

    Stanford is currently not accepting patients for this trial.

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  • Imaging Collaterals in Acute Stroke (iCAS) Not Recruiting

    Stroke is caused by a sudden blockage of a blood vessel that delivers blood to the brain. Unblocking the blood vessel with a blood clot removal device restores blood flow and if done quickly may prevent the disability that can be caused by a stroke. However, not all stroke patients benefit from having their blood vessel unblocked. The aim of this study is to determine if special brain imaging, called MRI, can be used to identify which stroke patients are most likely to benefit from attempts to unblock their blood vessel with a special blood clot removal device. In particular, we will assess in this trial whether a noncontrast MR imaging sequence, arterial spin labeling (ASL), can demonstrate the presence of collateral blood flow (compared with a gold standard of the angiogram) and whether it is useful to predict who will benefit from treatment.

    Stanford is currently not accepting patients for this trial. For more information, please contact Gregory Zaharchuk, MD, 650-723-4448.

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  • Insulin Resistance Intervention After Stroke Trial Not Recruiting

    The purpose of this study is to determine if pioglitazone is effective in preventing future strokes or heart attacks among non-diabetic persons who have had a recent ischemic stroke.

    Stanford is currently not accepting patients for this trial. For more information, please contact Madelleine Garcia, (650) 725 - 2326.

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  • Transient Ischemic Attack (TIA) Triage and Evaluation of Stroke Risk Not Recruiting

    Transient ischemic attack (TIA) is a transient neurological deficit (speech disturbance, weakness…), caused by temporary occlusion of a brain vessel by a blood clot that leaves no lasting effect. TIA diagnosis can be challenging and an expert stroke evaluation combined with magnetic resonance imaging (MRI) could improve the diagnosis accuracy. The risk of a debilitating stroke can be as high as 5% during the first 72 hrs after TIA. TIA characteristics (duration, type of symptoms, age of the patient), the presence of a significant narrowing of the neck vessels responsible for the patient's symptoms (symptomatic stenosis), and an abnormal MRI are associated with an increased risk of stroke. An emergent evaluation and treatment of TIA patients by a stroke specialist could reduce the risk of stroke to 2%. Stanford has implemented an expedited triage pathway for TIA patients combining a clinical evaluation by a stroke neurologist, an acute MRI of the brain and the vessels and a sampling of biomarkers (Lp-PLA2). The investigators are investigating the yield of this unique approach to improve TIA diagnosis, prognosis and secondary stroke prevention. The objective of this prospective cohort study is to determine which factors will help the physician to confirm the diagnosis of TIA and to define the risk of stroke after a TIA.

    Stanford is currently not accepting patients for this trial. For more information, please contact Stephanie Kemp, BS, 650-723-4481.

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Teaching

2019-20 Courses

Stanford Advisees

Publications

All Publications

  • Collateral status contributes to differences between observed and predicted 24-h infarct volumes in DEFUSE 3. Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism Rao, V. L., Mlynash, M., Christensen, S., Yennu, A., Kemp, S., Zaharchuk, G., Heit, J. J., Marks, M. P., Lansberg, M. G., Albers, G. W. 2020: 271678X20918816

    Abstract

    We previously demonstrated that in the DEFUSE 3 trial, the union of the baseline core and the 24-h Tmax>6s perfusion lesion predicts the infarct volume at 24h. Presently, we assessed if collateral robustness measured by the hypoperfusion intensity ratio (HIR) and cerebral blood volume (CBV) index accounts for the variance in these predictions. DEFUSE 3 patients underwent MRI/CT perfusion imaging at baseline and 24h post-randomization. We compared baseline and follow-up HIR and CBV index across subgroups stratified by differences between predicted and observed 24-h infarct volumes. Of 123 eligible patients, 34 with 24-h infarcts larger than predicted had less favorable collaterals at baseline (HIR 0.43 vs. 0.32, p=0.006; CBV Index 0.78 vs. 0.85, p=0.001) and 24h (HIR 0.56 vs. 0.07, p=0.004; CBV Index 0.47 vs. 0.73, p=0.006) compared to 71 patients with more accurate infarct volume prediction. Eighteen patients with 24-h infarcts smaller than predicted had similar baseline collateral scores but more favorable 24-h CBV indices (0.81 vs. 0.73, p=0.040). Overall, patients with 24-h infarcts larger than predicted had evidence of less favorable baseline collaterals that fail within 24h, while patients with 24-h infarcts smaller than predicted typically had favorable collaterals that persisted for 24h.

    View details for DOI 10.1177/0271678X20918816

    View details for PubMedID 32423329

  • Thrombolysis before Thrombectomy - To Be or DIRECT-MT? The New England journal of medicine Albers, G. W. 2020

    View details for DOI 10.1056/NEJMe2004550

    View details for PubMedID 32374954

  • Prognostic value of diffusion-weighted MRI for post-cardiac arrest coma. Neurology Hirsch, K. G., Fischbein, N., Mlynash, M., Kemp, S., Bammer, R., Eyngorn, I., Tong, J., Moseley, M., Venkatasubramanian, C., Caulfield, A. F., Albers, G. 2020

    Abstract

    OBJECTIVE: To validate quantitative diffusion-weighted imaging (DWI) MRI thresholds that correlate with poor outcome in comatose cardiac arrest survivors, we conducted a clinician-blinded study and prospectively obtained MRIs from comatose patients after cardiac arrest.METHODS: Consecutive comatose post-cardiac arrest adult patients were prospectively enrolled. MRIs obtained within 7 days after arrest were evaluated. The clinical team was blinded to the DWI MRI results and followed a prescribed prognostication algorithm. Apparent diffusion coefficient (ADC) values and thresholds differentiating good and poor outcome were analyzed. Poor outcome was defined as a Glasgow Outcome Scale score of ≤2 at 6 months after arrest.RESULTS: Ninety-seven patients were included, and 75 patients (77%) had MRIs. In 51 patients with MRI completed by postarrest day 7, the prespecified threshold of >10% of brain tissue with an ADC <650 *10-6 mm2/s was highly predictive for poor outcome with a sensitivity of 0.63 (95% confidence interval [CI] 0.42-0.80), a specificity of 0.96 (95% CI 0.77-0.998), and a positive predictive value (PPV) of 0.94 (95% CI 0.71-0.997). The mean whole-brain ADC was higher among patients with good outcomes. Receiver operating characteristic curve analysis showed that ADC <650 *10-6 mm2/s had an area under the curve of 0.79 (95% CI 0.65-0.93, p < 0.001). Quantitative DWI MRI data improved prognostication of both good and poor outcomes.CONCLUSIONS: This prospective, clinician-blinded study validates previous research showing that an ADC <650 *10-6 mm2/s in >10% of brain tissue in an MRI obtained by postarrest day 7 is highly specific for poor outcome in comatose patients after cardiac arrest.

    View details for DOI 10.1212/WNL.0000000000009289

    View details for PubMedID 32269116

  • CT perfusion core and ASPECT score prediction of outcomes in DEFUSE 3. International journal of stroke : official journal of the International Stroke Society Kim-Tenser, M., Mlynash, M., Lansberg, M. G., Tenser, M., Bulic, S., Jagadeesan, B., Christensen, S., Simpkins, A., Albers, G. W., Marks, M. P. 2020: 1747493020915141

    Abstract

    BACKGROUND: The role of Alberta Stroke Program Early CT Score (ASPECTS) for thrombectomy patient selection and prognostication in late time windows is unknown.AIMS: We compared baseline ASPECTS and core infarction determined by CT perfusion (CTP) as predictors of clinical outcome in the Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke 3 (DEFUSE) 3 trial.METHODS: We included all DEFUSE 3 patients with baseline non-contrast CT and CTP imaging. ASPECTS and core infarction were determined by the DEFUSE 3 core laboratory. Primary outcome was functional independence (modified Rankin Scale (mRS) ≤2). Secondary outcomes included ordinal mRS shift at 90 days and final core infarction volume.RESULTS: Of the 142 patients, 85 patients (60%) had ASPECTS 8-10 and 57 (40%) had ASPECTS 5-7. Thirty-one patients (36%) with ASPECTS 8-10 and 11 patients (19%) with ASPECTS 5-7 were functionally independent at 90 days (p=0.03). In the primary and secondary logistic regression analysis, there was no difference in ordinal mRS shift (p=0.98) or functional independence (mRS≤2; p=0.36) at 90 days between ASPECTS 8-10 and ASPECTS 5-7 patients. Similarly, primary and secondary logistic regression analyses found no difference in ordinal mRS shift (p=1.0) or functional independence (mRS≤2; p=0.87) at 90 days between patients with baseline small core (<50ml) versus medium core (50-70ml).CONCLUSIONS: Higher ASPECTS (8-10) correlated with functional independence at 90 days in the DEFUSE trial. ASPECTS and core infarction volume did not modify the thrombectomy treatment effect, which indicates that patients with a target mismatch profile on perfusion imaging should undergo thrombectomy regardless of ASPECTS or core infarction volume in late time windows.

    View details for DOI 10.1177/1747493020915141

    View details for PubMedID 32233746

  • Hypoperfusion Intensity Ratio Correlates With Angiographic Collaterals In Acute Ischemic Stroke With M1 Occlusion. European journal of neurology Guenego, A., Fahed, R., Albers, G. W., Kuraitis, G., Sussman, E. S., Martin, B. W., Marcellus, D. G., Olivot, J., Marks, M. P., Lansberg, M. G., Wintermark, M., Heit, J. J. 2020

    Abstract

    PURPOSE: Among patients with an acute ischemic stroke (AIS) secondary to large-vessel-occlusion, the hypoperfusion-intensity-ratio (HIR, TMax>10 volume / TMax>6 volume) is a strong predictor of infarct growth. We studied the correlation between HIR and collaterals assessed with digital-subtraction-angiography (DSA) before thrombectomy.METHODS: Between January 2014 and March 2018, consecutive patients with an AIS and a M1 middle-cerebral-artery occlusion who underwent perfusion imaging and endovascular treatment at our center were screened. Ischemic core (mL), HIR and perfusion mismatch (TMax>6sec minus core volume) were assessed through MRI or CT perfusion. Collaterals were assessed on pre-intervention DSA using the American-Society of Interventional and Therapeutic-Neuroradiology/Society of Interventional-Radiology (ASITN/SIR) scale. Baseline clinical and perfusion characteristics were compared between patients with good (ASITN/SIR 3-4) and those with poor (ASITN/SIR 0-2) DSA collaterals. Correlation between HIR and ASITN/SIR was evaluated using Pearson's correlation. ROC analysis was performed to determine the optimal HIR threshold for the prediction of good DSA collaterals.RESULTS: Ninety-eight patients were included. 49% (48/98) had good DSA collaterals, those patients had significantly smaller hypoperfusion volumes (TMax >6sec 89mL versus 125mL; p=0.007) and perfusion mismatch volumes (72mL versus 89mL; p=0.016). HIR was significantly correlated with DSA collaterals (-0.327 [IC 95%: -0.494 to -0.138; p=0.01]). A HIR cut-off of <0.4 best predicted good DSA collaterals with an odds ratio of 4.3 (1.8-10.1) (Sensitivity=0.792, Specificity=0.560, AUC=0.708).CONCLUSION: HIR is a robust indicator of angiographic collaterals and might be used as a surrogate of collateral assessment in patients undergoing MRI. HIR<0.4 best predicted good DSA collaterals.

    View details for DOI 10.1111/ene.14181

    View details for PubMedID 32068938

  • Optimizing Patient Selection for Endovascular Treatment in Acute Ischemic Stroke (SELECT): A Prospective Multicenter Cohort Study of Imaging Selection. Annals of neurology Sarraj, A., Hassan, A. E., Grotta, J., Sitton, C., Cutter, G., Cai, C., Chen, P. R., Imam, B., Pujara, D., Arora, A., Reddy, S., Parsha, K., Riascos, R. F., Vora, N., Abraham, M., Edgell, R., Hellinger, F., Haussen, D. C., Blackburn, S., Kamal, H., Barreto, A. D., Martin-Schild, S., Lansberg, M., Gupta, R., Savitz, S., Albers, G. W. 2020

    Abstract

    OBJECTIVE: The primary imaging modalities used to select patients for endovascular thrombectomy (EVT) are non-contrast CT(CT) and CT-perfusion(CTP). However, their relative utility is uncertain. We prospectively assessed CT and CTP concordance/discordance and correlated the imaging profiles on both with EVT treatment decisions and clinical outcomes.METHODS: A phase-II multicenter, prospective-cohort study of large vessel occlusions who presented up-to-24hours from last-known-well was conducted. Patients received a unified pre-specified imaging evaluation(CT, CT-angiography, and CTP with RAPID software mismatch-determination). The treatment decision, EVT vs Medical Management, was non-randomized and at the treating physicians' discretion. An independent blinded neuroimaging-corelab adjudicated favorable profiles based on pre-defined criteria(CT:ASPECTS≥6, CTP:rCBF(<30%)<70cc with mismatch-ratio≥1.2 and mismatch-volume≥10cc.RESULTS: Of 4722 screened from January/2016-to-February/2018, 361 patients were included. 285(79%) received EVT, of whom, 87.0% had favorable-CTs; 91% favorable-CTPs; 81% both favorable profiles , 16% discordant and 3% both unfavorable. Favorable profiles on the two modalities correlated similarly with 90-day functional independence rates(favorable-CT=56% vs favorable-CTP=57%,aOR=1.91,95%CI=0.40-9.01, p=0.41). Having a favorable profile on both modalities significantly increased the odds of receiving thrombectomy as compared to discordant profiles (aOR:3.97,95% CI=1.97-8.01,p<0.001). 58% of the patients with favorable profiles on both modalities achieved functional independence as compared to 38% in discordant profiles and 0% when both were unfavorable(P<0.001 for trend). In favorable-CT/unfavorable-CTP profiles, EVT was associated with high sICH(24%) and mortality(53%) rates.INTERPRETATION: Patients with favorable imaging profiles on both modalities had higher odds of receiving EVT and high functional independence rates. Patients with discordant profiles achieved reasonable functional independence rates but those with an unfavorable-CTP had higher adverse outcomes. Clinical-Trial-Registration: NCT02446587.https://clinicaltrials.gov/ct2/show/NCT02446587 This article is protected by copyright. All rights reserved.

    View details for DOI 10.1002/ana.25669

    View details for PubMedID 31916270

  • Collateral Effect of Covid-19 on Stroke Evaluation in the United States. The New England journal of medicine Kansagra, A. P., Goyal, M. S., Hamilton, S., Albers, G. W. 2020

    View details for DOI 10.1056/NEJMc2014816

    View details for PubMedID 32383831

  • Use of Deep Learning to Predict Final Ischemic Stroke Lesions From Initial Magnetic Resonance Imaging. JAMA network open Yu, Y., Xie, Y., Thamm, T., Gong, E., Ouyang, J., Huang, C., Christensen, S., Marks, M. P., Lansberg, M. G., Albers, G. W., Zaharchuk, G. 2020; 3 (3): e200772

    Abstract

    Predicting infarct size and location is important for decision-making and prognosis in patients with acute stroke.To determine whether a deep learning model can predict final infarct lesions using magnetic resonance images (MRIs) acquired at initial presentation (baseline) and to compare the model with current clinical prediction methods.In this multicenter prognostic study, a specific type of neural network for image segmentation (U-net) was trained, validated, and tested using patients from the Imaging Collaterals in Acute Stroke (iCAS) study from April 14, 2014, to April 15, 2018, and the Diffusion Weighted Imaging Evaluation for Understanding Stroke Evolution Study-2 (DEFUSE-2) study from July 14, 2008, to September 17, 2011 (reported in October 2012). Patients underwent baseline perfusion-weighted and diffusion-weighted imaging and MRI at 3 to 7 days after baseline. Patients were grouped into unknown, minimal, partial, and major reperfusion status based on 24-hour imaging results. Baseline images acquired at presentation were inputs, and the final true infarct lesion at 3 to 7 days was considered the ground truth for the model. The model calculated the probability of infarction for every voxel, which can be thresholded to produce a prediction. Data were analyzed from July 1, 2018, to March 7, 2019.Area under the curve, Dice score coefficient (DSC) (a metric from 0-1 indicating the extent of overlap between the prediction and the ground truth; a DSC of ≥0.5 represents significant overlap), and volume error. Current clinical methods were compared with model performance in subgroups of patients with minimal or major reperfusion.Among the 182 patients included in the model (97 women [53.3%]; mean [SD] age, 65 [16] years), the deep learning model achieved a median area under the curve of 0.92 (interquartile range [IQR], 0.87-0.96), DSC of 0.53 (IQR, 0.31-0.68), and volume error of 9 (IQR, -14 to 29) mL. In subgroups with minimal (DSC, 0.58 [IQR, 0.31-0.67] vs 0.55 [IQR, 0.40-0.65]; P = .37) or major (DSC, 0.48 [IQR, 0.29-0.65] vs 0.45 [IQR, 0.15-0.54]; P = .002) reperfusion for which comparison with existing clinical methods was possible, the deep learning model had comparable or better performance.The deep learning model appears to have successfully predicted infarct lesions from baseline imaging without reperfusion information and achieved comparable performance to existing clinical methods. Predicting the subacute infarct lesion may help clinicians prepare for decompression treatment and aid in patient selection for neuroprotective clinical trials.

    View details for DOI 10.1001/jamanetworkopen.2020.0772

    View details for PubMedID 32163165

  • Response by Dula et al to Letter Regarding Article, "Neuroimaging in Ischemic Stroke Is Different Between Men and Women in the DEFUSE 3 Cohort". Stroke Dula, A. N., Mlynash, M., Albers, G. W., Warach, S. J. 2020: STROKEAHA120029168

    View details for DOI 10.1161/STROKEAHA.120.029168

    View details for PubMedID 32212895

  • Tilt-Corrected Region Boundaries May Enhance the Alberta Stroke Program Early Computed Tomography Score for Less Experienced Raters. Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association Culbertson, C. J., Christensen, S., Mlynash, M., Heit, J. J., Federau, C., Sells, C. M., Legault, C., McCaslin, A. F., Werbaneth, K., Albers, G. W., Lansberg, M. G. 2020: 104820

    Abstract

    The Alberta Stroke Program Early Computed Tomography Score (ASPECTS) is widely used to quantify early ischemic changes in the anterior circulation but has limited inter-rater reliability.We investigated whether application of 3-dimensional boundaries outlining the ASPECTS regions improves inter-rater reliability and accuracy.We included all patients from our DEFUSE 2 database who had a pretreatment noncontrast computed tomography scan (NCCT) of acceptable quality. Six raters (2 neuroradiologists, 2 vascular neurologists, and 2 neurology residents) scored ASPECTS of each NCCT without ("CT-native") and with the superimposed boundary template ("CT-template"). Gold-standard ASPECTS were generated by the 2 neuroradiologists through joint adjudication. Inter-rater reliability and accuracy were assessed using the intraclass correlation coefficient (ICC) for full-scale agreements and Gwet's AC1 for dichotomized (ASPECTS 0-6 vs 7-10) agreements.Eighty-two patients were included. Inter-rater reliability improved with higher training level for both CT-native (ICC = .15, .31, .54 for residents, neurologists, and radiologists, respectively) and CT-template (ICC = .18, .33, .56). Use of the boundary template improved correlation with the gold-standard for one resident on full-scale agreement (ICC increased from .01 to .31, P = .01) and another resident on dichotomized agreement (AC1 increased from .36 to .64, P = .01), but resulted in no difference for other raters. The template did not improve ICC between raters of the same training level.Inter-rater reliability of ASPECTS improves with physician training level. Standardized display of ASPECTS region boundaries on NCCT does not improve inter-rater reliability but may improve accuracy for some less experienced raters.

    View details for DOI 10.1016/j.jstrokecerebrovasdis.2020.104820

    View details for PubMedID 32307316

  • Estimated treatment effect of ticagrelor versus aspirin by investigator-assessed events compared with judgement by an independent event adjudication committee in the SOCRATES trial INTERNATIONAL JOURNAL OF STROKE Easton, J., Denison, H., Evans, S. R., Knutsson, M., Amarenco, P., Albers, G. W., Ladenvall, P., Minematsu, K., Molina, C. A., Wang, Y., Wong, K., Johnston, S., SOCRATES Steering Comm 2019; 14 (9): 908–14

    View details for DOI 10.1177/1747493019851282

    View details for Web of Science ID 000502477300016

  • Benefits of Magnetic Resonance Imaging for Patients Presenting With Low-risk Transient or Persistent Minor Neurologic Deficits. JAMA neurology McCullough-Hicks, M. E., Albers, G. W. 2019

    View details for DOI 10.1001/jamaneurol.2019.2963

    View details for PubMedID 31545348

  • Automated Calculation of Alberta Stroke Program Early CT Score. Stroke Albers, G. W., Wald, M. J., Mlynash, M., Endres, J., Bammer, R., Straka, M., Maier, A., Hinson, H. E., Sheth, K. N., Taylor Kimberly, W., Molyneaux, B. J. 2019: STROKEAHA119026430

    Abstract

    Background and Purpose- We compared the Alberta Stroke Program Early CT Score (ASPECTS), calculated using a machine learning-based automatic software tool, RAPID ASPECTS, as well as the median score from 4 experienced readers, with the diffusion-weighted imaging (DWI) ASPECTS obtained following the baseline computed tomography (CT) in patients with large hemispheric infarcts. Methods- CT and magnetic resonance imaging scans from the GAMES-RP study, which enrolled patients with large hemispheric infarctions (82-300 mL) documented on DWI-magnetic resonance imaging, were evaluated by blinded experienced readers to determine both CT and DWI ASPECTS. The CT scans were also evaluated by an automated software program (RAPID ASPECTS). Using the DWI ASPECTS as a reference standard, the median CT ASPECTS of the clinicians and the automated score were compared using the interclass correlation coefficient. Results- The median CT ASPECTS for the clinicians was 5 (interquartile range, 4-7), for RAPID ASPECTS 3 (interquartile range, 1-6), and for DWI ASPECTS 3 (2-4). Median error for RAPID ASPECTS was 1 (interquartile range, -1 to 3) versus 3 (interquartile range, 1-4) for clinicians (P<0.001). The automated score had a higher level of agreement with the median of the DWI ASPECTS, both for the full scale and when dichotomized at <6 versus 6 or more (difference in intraclass correlation coefficient, P=0.001). Conclusions- RAPID ASPECTS was more accurate than experienced clinicians in identifying early evidence of brain ischemia as documented by DWI.

    View details for DOI 10.1161/STROKEAHA.119.026430

    View details for PubMedID 31500555

  • Neuroimaging selection for thrombectomy in pediatric stroke: a single-center experience JOURNAL OF NEUROINTERVENTIONAL SURGERY Lee, S., Heit, J., Albers, G. W., Wintermark, M., Jiang, B., Bernier, E., Fischbein, N. J., Mlynash, M., Marks, M. P., Do, H. M., Dodd, R. L. 2019; 11 (9): 940–46

    View details for DOI 10.1136/neurintsurg-2019-014862

    View details for Web of Science ID 000490293400019

  • Endovascular versus medical therapy for large-vessel anterior occlusive stroke presenting with mild symptoms. International journal of stroke : official journal of the International Stroke Society Wolman, D. N., Marcellus, D. G., Lansberg, M. G., Albers, G., Guenego, A., Marks, M. P., Dodd, R. L., Do, H. M., Wintermark, M., Martin, B. W., Heit, J. J. 2019: 1747493019873510

    Abstract

    BACKGROUND: Acute ischemic stroke patients with a large-vessel occlusion but mild symptoms (NIHSS≤6) pose a treatment dilemma between medical management and endovascular thrombectomy.AIMS: To evaluate the differences in clinical outcomes of endovascular thrombectomy-eligible patients with target-mismatch perfusion profiles who undergo either medical management or endovascular thrombectomy.METHODS: Forty-seven patients with acute ischemic stroke due to large-vessel occlusion, NIHSS≤6, and a target-mismatch perfusion imaging profile were included. Patients underwent medical management or endovascular thrombectomy following treating neurointerventionalist and neurologist consensus. The primary outcome measure was NIHSS shift. Secondary outcome measures were symptomatic intracranial hemorrhage, in-hospital mortality, and 90-day mRS scores. The primary intention-to-treat and as-treated analyses were compared to determine the impact of crossover patient allocation on study outcome measures.RESULTS: Forty-seven patients were included. Thirty underwent medical management (64%) and 17 underwent endovascular thrombectomy (36%). Three medical management patients underwent endovascular thrombectomy due to early clinical deterioration. Presentation NIHSS (P=0.82), NIHSS shift (P=0.62), and 90-day functional independence (mRS 0-2; P=0.25) were similar between groups. Endovascular thrombectomy patients demonstrated an increased overall rate of intracranial hemorrhage (35.3% vs. 10.0%; P=0.04), but symptomatic intracranial hemorrhage was similar between groups (P=0.25). In-hospital mortality was similar between groups (P=0.46), though all two deaths in the medical management group occurred among crossover patients. Endovascular thrombectomy patients demonstrated a longer length of stay (7.6±7.2 vs. 4.3±3.9 days; P=0.04) and a higher frequency of unfavorable discharge to a skilled-nursing facility (P=0.03) rather than home (P=0.05).CONCLUSIONS: Endovascular thrombectomy may pose an unfavorable risk-benefit profile over medical management for endovascular thrombectomy-eligible acute ischemic stroke patients with mild symptoms, which warrants a randomized trial in this subpopulation.

    View details for DOI 10.1177/1747493019873510

    View details for PubMedID 31474193

  • Cerebral Blood Flow Predicts the Infarct Core. Stroke Amukotuwa, S., Straka, M., Aksoy, D., Fischbein, N., Desmond, P., Albers, G., Bammer, R. 2019: STROKEAHA119026640

    Abstract

    Background and Purpose- The aim of this study is to determine the spatial and volumetric accuracy of infarct core estimates from relative cerebral blood flow (rCBF) by comparison with near-contemporaneous diffusion-weighted imaging (DWI), and evaluate whether it is sufficient for patient triage to reperfusion therapies. Methods- One hundred ninety-three patients enrolled in the DEFUSE 2 (Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution) and SENSE 3 (Sensitivity Encoding) stroke studies were screened, and 119 who underwent acute magnetic resonance imaging with DWI and perfusion imaging within 24 hours of onset were included. Infarct core was estimated using reduced rCBF at 12 thresholds (<0.20-<0.44) and compared against DWI (apparent diffusion coefficient <620 10-6mm2/s). For each threshold, volumetric agreement between the rCBF and DWI core estimates was assessed using Bland-Altman, correlation, and linear regression analyses; spatial agreement was assessed using receiver operating characteristic analysis. Results- An rCBF threshold of 0.32 yielded the smallest mean absolute volume difference (14.7 mL), best linear regression fit (R2=0.84), and best spatial agreement (Youden index, 0.38; 95% CI, 0.34-0.41) between rCBF and DWI, with high correlation (r=0.91, P<0.05), a small mean volume difference (1.3 mL) and no fixed bias (P<0.05). At this threshold, 110 of 119 (92.4%) patients were correctly triaged when applying 70 mL as the volume limit for thrombectomy. Spatial agreement was better for prediction of large infarcts (>70 mL) than small infarcts (≤70 mL), with Youden indices of 0.53 (95% CI, 0.49-0.56) and 0.34 (95% CI, 0.30-0.37), respectively. Conclusions- Strong correlation and agreement with near-contemporaneous DWI indicate that infarct core estimates obtained using rCBF are sufficiently accurate for patient triage to reperfusion therapies. The identified optimal rCBF threshold of 0.32 closely approximates the threshold currently used in clinical practice.

    View details for DOI 10.1161/STROKEAHA.119.026640

    View details for PubMedID 31462191

  • Outcomes of Endovascular Thrombectomy vs Medical Management Alone in Patients With Large Ischemic Cores: A Secondary Analysis of the Optimizing Patient's Selection for Endovascular Treatment in Acute Ischemic Stroke (SELECT) Study. JAMA neurology Sarraj, A., Hassan, A. E., Savitz, S., Sitton, C., Grotta, J., Chen, P., Cai, C., Cutter, G., Imam, B., Reddy, S., Parsha, K., Pujara, D., Riascos, R., Vora, N., Abraham, M., Kamal, H., Haussen, D. C., Barreto, A. D., Lansberg, M., Gupta, R., Albers, G. W. 2019

    Abstract

    Importance: The efficacy and safety of endovascular thrombectomy (EVT) in patients with large ischemic cores remains unknown, to our knowledge.Objective: To compare outcomes in patients with large ischemic cores treated with EVT and medical management vs medical management alone.Design, Setting, and Participants: This prespecified analysis of the Optimizing Patient's Selection for Endovascular Treatment in Acute Ischemic Stroke (SELECT) trial, a prospective cohort study of imaging selection that was conducted in 9 US comprehensive stroke centers, enrolled patients between January 2016 and February 2018, and followed them up for 90 days. Patients with moderate to severe stroke and anterior circulation large-vessel occlusion presenting up to 24 hours from the time they were last known to be well were eligible for the cohort. Of these, patients with large ischemic cores on computed tomography (CT) (Alberta Stroke Program Early CT Score <6) or CT perfusion scanning (a volume with a relative cerebral blood flow <30% of ≥50 cm3) were included in analyses.Exposures: Endovascular thrombectomy with medical management (MM) or MM only.Main Outcomes and Measures: Functional outcomes at 90 days per modified Rankin scale; safety outcomes (mortality, symptomatic intracerebral hemorrhage, and neurological worsening).Results: A total of 105 patients with large ischemic cores on either CT or CT perfusion images were included: 71 with Alberta Stroke Program Early CT Scores of 5 or less (EVT, 37; MM, 34), 74 with cores of 50 cm3 or greater on CT perfusion images (EVT, 39; MM, 35), and 40 who had large cores on both CT and CT perfusion images (EVT, 14; MM, 26). The median (interquartile range) age was 66 (60-75) years; 45 patients (43%) were female. Nineteen of 62 patients (31%) who were treated with EVT achieved functional independence (modified Rankin Scale scores, 0-2) vs 6 of 43 patients (14%) treated with MM only (odds ratio [OR], 3.27 [95% CI, 1.11-9.62]; P=.03). Also, EVT was associated with better functional outcomes (common OR, 2.12 [95% CI, 1.05-4.31]; P=.04), less infarct growth (44 vs 98 mL; P=.006), and smaller final infarct volume (97 vs 190 mL; P=.001) than MM. In the odds of functional independence, there was a 42% reduction per 10-cm3 increase in core volume (adjusted OR, 0.58 [95% CI, 0.39-0.87]; P=.007) and a 40% reduction per hour of treatment delay (adjusted OR, 0.60 [95% CI, 0.36-0.99]; P=.045). Of 10 patients who had EVT with core volumes greater than 100 cm3, none had a favorable outcome.Conclusions and Relevance: Although the odds of good outcomes for patients with large cores who receive EVT markedly decline with increasing core size and time to treatment, these data suggest potential benefits. Randomized clinical trials are needed.

    View details for DOI 10.1001/jamaneurol.2019.2109

    View details for PubMedID 31355873

  • Thrombectomy Results in Reduced Hospital Stay, More Home-Time, and More Favorable Living Situations in DEFUSE 3. Stroke Tate, W. J., Polding, L. C., Kemp, S., Mlynash, M., Heit, J. J., Marks, M. P., Albers, G. W., Lansberg, M. G. 2019: STROKEAHA119025165

    Abstract

    Background and Purpose- The DEFUSE 3 trial (Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke) demonstrated that endovascular thrombectomy in the 6- to 16-hour time window improves functional outcomes of patients with evidence of salvageable tissue on baseline computed tomography or magnetic resonance imaging. The purpose of this study is to assess the effect of endovascular therapy on length of hospital stay, home-time during the first 3 months poststroke, and living situation poststroke in DEFUSE 3. Methods- Duration of hospital stay and home-time (number of days during the 90-day poststroke period that the patient resides in their own home or in that of a relative) were compared between treatment groups using the Wilcoxon rank-sum test. Patient living situation was assessed at discharge, 30 days, and 90 days on an ordinal 4-point scale (home, acute rehabilitation unit, institutionalized care, or hospice/death) and differences between groups were analyzed using the Cochran-Armitage trend test. Results- Median length of hospital stay was 9.1 (interquartile range, 6.2-15.0) days in the medical group versus 6.5 (interquartile range, 3.7-9.3) days in the endovascular group ( P<0.001). Median home-time during the first 90 days after stroke was 0 (interquartile range, 0-53) days in the medical group versus 55 (interquartile range, 0-83) days in the endovascular group ( P<0.001). The endovascular group had more favorable living situations at time of discharge ( P<0.001), 30 days ( P<0.001), and 90 days ( P<0.001) poststroke. Conclusions- Endovascular thrombectomy resulted in reduced hospital stay, more home-time, and more desirable living situations in the 90 days after stroke. These results provide evidence that endovascular therapy in the delayed time window can improve quality of life for stroke patients and reduce healthcare costs. Clinical Trial Registration- URL: https://www.clinicaltrials.gov . Unique identifier: NCT02586415.

    View details for DOI 10.1161/STROKEAHA.119.025165

    View details for PubMedID 31288666

  • The feasibility of deep learning to predict final stroke lesion using baseline diffusion-weighted imaging only in non-recanalized acute ischemic stroke patients Yu, Y., Xie, Y., Thamm, T., Gong, E., Christensen, S., Lansberg, M. G., Albers, G. W., Zaharchuk, G. SAGE PUBLICATIONS INC. 2019: 231–32

    View details for Web of Science ID 000473954100265

  • Deep learning-based penumbra estimation using DWI and ASL for acute ischemic stroke patients Xie, Y., Yu, Y., Thamm, T., Gong, E., Ouyang, J., Huang, C., Christensen, S., Albers, G., Zaharchuk, G. SAGE PUBLICATIONS INC. 2019: 622

    View details for Web of Science ID 000473954100806

  • Clinical validation of penumbra and ischemic core prediction from deep learning algorithm using baseline multimodal MRI in acute ischemic stroke patients: A multi-center study Yu, Y., Xie, Y., Thamm, T., Gong, E., Huang, C., Christensen, S., Lansberg, M. G., Albers, G. W., Zaharchuk, G. SAGE PUBLICATIONS INC. 2019: 10–11

    View details for Web of Science ID 000473954100011

  • Time Course for Benefit and Risk of Clopidogrel and Aspirin after Acute Transient Ischemic Attack and Minor Ischemic Stroke: A Secondary Analysis from the POINT Randomized Trial. Circulation Johnston, S. C., Elm, J. J., Easton, J. D., Farrant, M., Barsan, W. G., Kim, A. S., Lindblad, A. S., Palesch, Y. Y., Zurita, K. G., Albers, G. W., Cucchiara, B. L., Kleindorfer, D. O., Lutsep, H. L., Pearson, C., Sethi, P., Vora, N., POINT and Neurological Emergencies Treatment Trials Network Investigators 2019

    Abstract

    BACKGROUND: In patients with acute minor ischemic stroke or high-risk transient ischemic attack enrolled in the POINT trial, the combination of clopidogrel and aspirin for 90 days reduced major ischemic events but increased major hemorrhage compared to aspirin alone.METHODS: In a secondary analysis of POINT (N=4,881), we assessed the time course for benefit and risk from the combination of clopidogrel and aspirin. The primary efficacy outcome was a composite of ischemic stroke, myocardial infarction, or ischemic vascular death. The primary safety outcome was major hemorrhage. Risks and benefits were estimated for delayed times of treatment initiation using left-truncated models.RESULTS: Through 90 days, the rate of major ischemic events was initially high then decreased markedly, while the rate of major hemorrhage remained low but relatively constant throughout. Using a model-based approach, the optimal change-point for major ischemic events was 21 days (0-21 days HR 0.65 for clopidogrel-aspirin vs. aspirin, 95% CI 0.50-0.85, p=0.0015, compared to 22-90 days HR 1.38, 95% CI 0.81-2.35, p=0.24). Models showed benefits of clopidogrel-aspirin for treatment delayed as long as 3 days after symptom onset.CONCLUSIONS: The benefit of clopidogrel-aspirin occurs predominantly within the first 21 days, and outweighs the low, but ongoing risk of major hemorrhage. When considered with the results of CHANCE, a similar trial treating with clopidogrel-aspirin for 21 days and showing no increase in major hemorrhage, these results suggest limiting clopidogrel-aspirin use to 21 days may maximize benefit and reduce risk after high-risk TIA or minor ischemic stroke.CLINICAL TRIAL REGISTRATION: URL: https://clinicaltrials.gov Unique Identifier: NCT00991029.

    View details for DOI 10.1161/CIRCULATIONAHA.119.040713

    View details for PubMedID 31238700

  • Advanced Brain Imaging in Late-Arriving Drip and Ship Patients With Known Large Vessel Occlusion. Stroke Albers, G. W., Molina, C. A., Selim, M. H., Jovin, T. G. 2019: STROKEAHA118020574

    View details for DOI 10.1161/STROKEAHA.118.020574

    View details for PubMedID 31216963

  • Outcomes of Thrombectomy in Transferred Patients With Ischemic Stroke in the Late Window: A Subanalysis From the DEFUSE 3 Trial JAMA NEUROLOGY Sarraj, A., Mlynash, M., Savitz, S. I., Heit, J. J., Lansberg, M. G., Marks, M. P., Albers, G. W. 2019; 76 (6): 682–89

    View details for DOI 10.1001/jamaneurol.2019.0118

    View details for Web of Science ID 000474834200011

  • Thrombectomy with Conscious Sedation Compared with General Anesthesia: A DEFUSE 3 Analysis AMERICAN JOURNAL OF NEURORADIOLOGY Powers, C. J., Dornbos, D., Mlynash, M., Gulati, D., Torbey, M., Nimjee, S. M., Lansberg, M. G., Albers, G. W., Marks, M. P. 2019; 40 (6): 1001–5

    View details for DOI 10.3174/ajnr.A6059

    View details for Web of Science ID 000476574200012

  • Artificial Neural Network Computer Tomography Perfusion Prediction of Ischemic Core STROKE Kasasbeh, A. S., Christensen, S., Parsons, M. W., Campbell, B., Albers, G. W., Lansberg, M. G. 2019; 50 (6): 1578–81

    View details for DOI 10.1161/STROKEAHA.118.022649

    View details for Web of Science ID 000470074200063

  • Response by de Havenon et al to Letter Regarding Article, "Results From DEFUSE 3: Good Collaterals Are Associated With Reduced Ischemic Core Growth but Not Neurologic Outcome" STROKE de Havenon, A., Albers, G. W., Heit, J. J. 2019; 50 (6): E166

    View details for DOI 10.1161/STROKEAHA.119.025713

    View details for Web of Science ID 000470074200014

  • Collateral blood flow measurement with intravoxel incoherent motion perfusion imaging in hyperacute brain stroke NEUROLOGY Federau, C., Wintermark, M., Christensen, S., Mlynash, M., Marcellus, D. G., Zhu, G., Martin, B. W., Lansberg, M. G., Albers, G. W., Heit, J. J. 2019; 92 (21): E2462–E2471

    View details for DOI 10.1212/WNL.0000000000007538

    View details for Web of Science ID 000480767200007

  • Rapid Neurologic Improvement Predicts Favorable Outcome 90 Days After Thrombectomy in the DEFUSE 3 Study STROKE Heit, J. J., Mlynash, M., Kemp, S. M., Lansberg, M. G., Christensen, S., Marks, M. P., Ortega-Gutierrez, S., Albers, G. W. 2019; 50 (5): 1172–77

    View details for DOI 10.1161/STROKEAHA.119.024928

    View details for Web of Science ID 000469350000042

  • Collateral blood flow measurement with intravoxel incoherent motion perfusion imaging in hyperacute brain stroke. Neurology Federau, C., Wintermark, M., Christensen, S., Mlynash, M., Marcellus, D. G., Zhu, G., Martin, B. W., Lansberg, M. G., Albers, G. W., Heit, J. J. 2019

    Abstract

    OBJECTIVE: To determine if intravoxel incoherent motion (IVIM) magnetic resonance perfusion can measure the quality of the collateral blood flow in the penumbra in hyperacute stroke.METHODS: A 6 b values IVIM MRI sequence was acquired in stroke patients with large vessel occlusion imaged <16 hours of last seen well. IVIM perfusion measures were evaluated in regions of interest drawn in the infarct core (D < 600 mm2/s), in the corresponding region in the contralateral hemisphere, and in the dynamic susceptibility contrast penumbra. In patients with a penumbra >15 mL, images were reviewed for the presence of a penumbra perfusion lesion on the IVIM f map, which was correlated with infarct size metrics. Statistical significance was tested using Student t test, Mann-Whitney U test, and Fisher exact test.RESULTS: A total of 34 patients were included. In the stroke core, IVIM f was significantly lower (4.6 ± 3.3%) compared to the healthy contralateral region (6.3 ± 2.2%, p < 0.001). In the 25 patients with a penumbra >15 mL, 9 patients had an IVIM penumbra perfusion lesion (56 ± 76 mL), and 16 did not. Patients with an IVIM penumbra perfusion lesion had a larger infarct core (82 ± 84 mL) at baseline, a larger infarct growth (68 ± 40 mL), and a larger final infarct size (126 ± 81 mL) on follow-up images compared to the patients without (resp. 20 ± 17 mL, p < 0.05; 13 ± 19 mL, p < 0.01; 29 ± 24 mL, p < 0.05). All IVIM penumbra perfusion lesions progressed to infarction despite thrombectomy treatment.CONCLUSIONS: IVIM is a promising tool to assess the quality of the collateral blood flow in hyperacute stroke. IVIM penumbra perfusion lesion may be a marker of nonsalvageable tissue despite treatment with thrombectomy, suggesting that the IVIM penumbra perfusion lesion might be counted to the stroke core, together with the DWI lesion.

    View details for PubMedID 31019105

  • STAIR X. Stroke Demchuk, A. M., Albers, G. W., Nogueira, R. G., STAIR X Consortium *, STAIR X (Stroke Treatment Academic Industry Roundtable) writing contributors, Alexandrov, A. V., Arbe-Barnes, S., Baron, J., Boltze, J., Broderick, J. P., Broschat, K., Campbell, B. C., Derdeyn, C. P., Elkind, M. S., Emberson, J. R., En'Wezoh, D., Furlan, A. J., Gorelick, P. B., Hancock, A. M., Hill, M. D., Holt, B., Khatri, P., Kim, W., Kjos, D., Kleindorfer, D., Lansberg, M. G., Liberman, M., Liebeskind, D. S., Luby, M., Lyden, P., Lynch, J. K., Mocco, J., Palesch, Y. Y., Pereira, V. M., Sanossian, N., Savitz, S. I., Schwamm, L. H., Selim, M., Sheth, K. N., Simpkins, A. N., Singhal, A., Solberg, Y., Steinberg, G. K., Tymianski, M., Warach, S., Wechsler, L. R., Wright, C., Yoo, A. J., Zaidat, O. O. 2019: STROKEAHA119024337

    View details for DOI 10.1161/STROKEAHA.119.024337

    View details for PubMedID 31112484

  • Baseline Perfusion Imaging Collateral Scores Predict Infarct Growth in DEFUSE 3 MacLellan, A., Mlynash, M., Heit, J., Marks, M., Lansberg, M., Albers, G. LIPPINCOTT WILLIAMS & WILKINS. 2019

    View details for Web of Science ID 000475965907014

  • Design of a Phase III Study of Intravenous Glibenclamide (BIIB093) for Large Hemispheric Infarction: the CHARM Study Sheth, K. N., Kimberley, W., Albers, G. W., Hinson, H. E., Molyneaux, B. J., Nogueira, R., Saver, J., Steiner, T., Toyoda, K., Wintermark, M., Elkins, J., Deykin, A., Wald, M., Landen, J. LIPPINCOTT WILLIAMS & WILKINS. 2019

    View details for Web of Science ID 000475965901294

  • Association of Thrombectomy With Stroke Outcomes Among Patient Subgroups Secondary Analyses of the DEFUSE 3 Randomized Clinical Trial JAMA NEUROLOGY Lansberg, M. G., Mlynash, M., Hamilton, S., Yeatts, S. D., Christensen, S., Kemp, S., Lavori, P. W., Ortega-Gutierrez, S., Broderick, J., Heit, J., Marks, M. P., Albers, G. W., Ortega-Gutierrez, S., Leira, E., McTaggart, R., Yaghi, S., Torbey, M., Powers, C. J., Kim-Tenser, M., Tenser, M., Lansberg, M., Marks, M., Leslie-Mazwi, T., Hurst, R., Kasner, S., Sarraj, A., Spiegel, G., Ansari, S. A., Prabhakaran, S., Altschul, D., de Havenon, A., Park, M., Fifi, J., Tuhrim, S., Hoesch, R., Blatter, D., Kayan, Y., Young, M., Stephens, R., Finch, I., Afshinnik, A., Ryan, R., Chaudhary, N., Brown, D., Feske, S., Aziz-Sultan, A., Smith, W., Cooke, D., Warach, S., Miley, J., Ahmed, A., Bradbury, E., Bozorgchami, H., Priest, R., Gropen, T., Harrigan, M., Kalafut, M., Ammirati, G., Meyer, B., Khalessi, A., Schlaug, G., Sen, S., Moftakhar, R., Streib, C., Jagadeesan, B. D., Toth, G., Uchino, K., Hsia, A., Liu, A., Jagadeesan, B. D., Streib, C., Vagal, A., Ringer, A. J., Willey, J. Z., Meyers, P. M., Zaidat, O. O., Froehler, M., Leifer, D., Patsalides, A., Lowenkopf, T., Deshmukh, V., Tirschwell, D., Hallam, D., DEFUSE 3 Investigators 2019; 76 (4): 447–53

    View details for DOI 10.1001/jamaneurol.2018.4587

    View details for Web of Science ID 000463873600013

  • Rapid Neurologic Improvement Predicts Favorable Outcome 90 Days After Thrombectomy in the DEFUSE 3 Study. Stroke Heit, J. J., Mlynash, M., Kemp, S. M., Lansberg, M. G., Christensen, S., Marks, M. P., Ortega-Gutierrez, S., Albers, G. W. 2019: STROKEAHA119024928

    Abstract

    Background and Purpose- Thrombectomy in late time windows leads to improved outcomes in patients with ischemic stroke due to large vessel occlusion. We determined whether patients with rapid neurological improvement (RNI) 24 hours after thrombectomy were more likely to have a favorable clinical outcome in the DEFUSE 3 study (Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke 3). Methods- All patients who underwent thrombectomy in DEFUSE 3 were included. RNI was defined as a reduction of ≥8 on the National Institutes of Health Stroke Scale or National Institutes of Health Stroke Scale zero to one 24 hours after thrombectomy. Clinical outcomes were assessed by an ordinal analysis modified Rankin Scale score and a dichotomous analysis for 90-day independence (modified Rankin Scale score, 0-2). Results- Ninety-one patients in DEFUSE 3 underwent thrombectomy with follow-up data; 31 patients (34%) experienced RNI (RNI+) after thrombectomy and 60 patients (66%) did not (RNI-). Patient demographics and stroke presentation and imaging details were similar between RNI+ and RNI- patients. Reperfusion (Thrombolysis in Cerebral Infarction 2b-3) after thrombectomy was achieved in 26 (84%) RNI+ and 43 (72%) RNI- ( P=0.2). Symptomatic intracranial hemorrhage occurred in no RNI+ and 8% of RNI- patients ( P=0.2). RNI was associated with a favorable modified Rankin Scale shift at day 90 (odds ratio, 3.8; CI, 1.7-8.6; P=0.001) and higher rates of modified Rankin Scale zero to 2 (61% versus 37%; odds ratio, 2.7; CI, 1.1-6.7; P=0.03). Mortality was 3% in RNI+ versus 18% in RNI- ( P=0.05). RNI+ patients had lower median 24-hour National Institutes of Health Stroke Scale (5 [interquartile range (IQR), 1-7] versus 13 [IQR, 7.5-21]; P<0.001), smaller 24-hour infarction volume (21 [IQR, 5-32] versus 65 [IQR, 27-145] mL; P<0.001), and less 24-hour infarct growth (8 [IQR, 1-18] versus 37 [IQR, 16-105] mL; P<0.001) compared with RNI- patients. Hospital stay was shorter in RNI+ (3.7 [IQR, 2.9-7.1] versus 7.4 [IQR, 5.2-12.1] days in RNI-; P<0.001). Conclusions- RNI following thrombectomy correlates with favorable clinical and radiographic outcomes and reduced hospital length of stay. RNI was a favorable prognostic sign following late-window thrombectomy in DEFUSE 3. Clinical Trial Registration- URL: https://www.clinicaltrials.gov . Unique identifier: NCT02586415.

    View details for PubMedID 30932783

  • Hypoperfusion Intensity Ratio Is Correlated With Patient Eligibility for Thrombectomy STROKE Guenego, A., Marcellus, D. G., Martin, B. W., Christensen, S., Albers, G. W., Lansberg, M. G., Marks, M. P., Wintermark, M., Heit, J. J. 2019; 50 (4): 917–22

    View details for DOI 10.1161/STROKEAHA.118.024134

    View details for Web of Science ID 000469347900033

  • Validation and iteration of CT perfusion defined malignant profile thresholds for acute ischemic stroke. International journal of stroke : official journal of the International Stroke Society Keenan, K. J., Christensen, S., Inoue, M., Mlynash, M., Albers, G. W., Smith, W. S. 2019: 1747493019832987

    Abstract

    BACKGROUND: Malignant profile computed tomography perfusion (CTP) lesions are associated with poor outcomes after administration of intravenous tissue-plasminogen activator (IV-tPA) for ischemic stroke.AIMS: To determine whether published CTP-based lesion thresholds predictive of poor outcomes in a predominantly 8cm of CTP anatomic coverage cohort would predict poor outcomes in an independent 4cm of CTP anatomic coverage cohort and to generate optimized 4cm CTP thresholds.METHODS: Ischemic stroke patients with baseline CTP imaging with 4cm of anatomic coverage before receiving IV-tPA at a single institution were retrospectively studied. Perfusion lesion time to maximum of tissue residue function (Tmax) and cerebral blood flow (CBF) volumes were determined using RAPID automated software. Fisher's exact tests assessed associations between lesion thresholds and outcomes. Receiver operating characteristic (ROC) curves generated optimized thresholds for 4cm of CTP coverage.RESULTS: Sixty-three patients were included. Poor outcomes were associated with published thresholds of Tmax >6s>103mL, Tmax>8s>86mL, and Tmax>10s>78mL but not CBF core >53mL. Thresholds optimized for 4cm of CTP coverage and associated with poor outcomes were Tmax>6s>100mL, Tmax>8s>65mL, Tmax>10s>46mL, and CBF core >39mL.CONCLUSIONS: We validated the ability of published CTP Tmax lesion volume thresholds to predict poor outcomes despite IV-tPA in an independent cohort using only 4cm of CTP anatomical coverage. A CBF>39mL threshold, rather than the predominantly 8cm CTP coverage derived CBF threshold of >53mL, was associated with poor outcomes in this 4cm CTP coverage cohort.

    View details for DOI 10.1177/1747493019832987

    View details for PubMedID 30794104

  • Time to Loading Dose and Risk of Recurrent Events in the SOCRATES Trial. Stroke Molina, C. A., Johnston, S. C., Ladenvall, P., Amarenco, P., Albers, G. W., Denison, H., Easton, J. D., Evans, S. R., Held, P., Knutsson, M., Minematsu, K., Rother, J., Wang, Y., Wong, K. S., SOCRATES Steering Committee and Investigators 2019: STROKEAHA118022675

    Abstract

    Background and Purpose- Recurrent ischemia risk is high in the acute period after cerebral ischemic events. Effects of antiplatelet agents may vary by time to loading dose (TLD). We explored the risk of recurrent events and safety and efficacy of ticagrelor versus aspirin in relation to TLD. Methods- We randomized 13 199 patients with noncardioembolic, nonsevere ischemic stroke, or high-risk transient ischemic attack to 90-day ticagrelor or aspirin treatment within 24 hours of symptom onset. For this analysis, 13 126 patients were categorized by TLD as <12 hours or ≥12 hours from start of index event. The primary end point was the composite of stroke, myocardial infarction, or death within 90 days. Major bleeding was the primary safety end point. Results- TLD was <12 hours in 4403 (33.5%) and ≥12 hours in 8723 (66.5%). The Kaplan-Meier% for the primary end point for all patients with TLD<12 hours was 7.5% versus 6.9% in TLD≥12 hours. Among patients with TLD<12 hours, the primary end point occurred in 147/2196 (6.8%) randomized to ticagrelor and in 184/2207 (8.3%) randomized to aspirin (hazard ratio, 0.79; 95% CI, 0.64-0.98; P=0.036). Among patients with TLD≥12 hours, the primary end point occurred in 6.7% patients randomized to ticagrelor versus 7.0% to aspirin (hazard ratio, 0.95; 95% CI, 0.81-1.12; P=0.55). There was no significant treatment-by-TLD interaction. Major bleeding rates were comparable on ticagrelor and aspirin, regardless of TLD. Conclusions- The event rate for the primary end point was higher in patients treated early (<12 hours) versus later (≥12 hours). In this exploratory analysis, a larger numerical difference in the primary end point was observed among patients on ticagrelor than on aspirin when TLD was <12 hours compared with ≥12 hours, although the interaction terms for treatment-by-TLD were not significant. For major bleeding, no relation to TLD was observed. Clinical Trial Registration- URL: https://www.clinicaltrials.gov . Unique identifier: NCT01994720.

    View details for PubMedID 30776996

  • Persistent Target Mismatch Profile >24 Hours After Stroke Onset in DEFUSE 3. Stroke Christensen, S., Mlynash, M., Kemp, S., Yennu, A., Heit, J. J., Marks, M. P., Lansberg, M. G., Albers, G. W. 2019: STROKEAHA118023392

    Abstract

    Background and Purpose- Efficacy of endovascular thrombectomy has been demonstrated up to 24 hours after stroke onset in patients selected with perfusion imaging. We hypothesized that a persistent favorable perfusion profile exists in some patients beyond 24 hours from the onset and can be predicted by a lower baseline hypoperfusion intensity ratio, which indicates favorable collaterals. Methods- We identified control arm patients from the DEFUSE 3 trial (The Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke) with a diffusion weighted imaging and perfusion magnetic resonance imaging performed 24 hours following randomization and compared imaging and clinical variables between patients with persistent mismatch versus patients who no longer had a mismatch 24 hours after randomization. Results- Eighteen percent of the control arm patients had a persistent favorable profile >38 hours after last known well time. These patients had similar baseline diffusion weighted imaging and Tmax >6 seconds volumes as patients whose initially favorable perfusion profile became unfavorable (diffusion weighted imaging lesion 7 versus 17 mL; P=0.17, Tmax >6 seconds 98 versus 100 mL; P=0.48) yet experienced less infarct growth (15 versus 59 mL; P<0.001) and had 3-fold smaller infarct volumes (15 versus 59 mL; P<0.001) 24 hours after randomization. Patients with a persistent favorable perfusion profile had a significantly lower hypoperfusion intensity ratio on baseline imaging (0.2 versus 0.4; P<0.01). Favorable clinical outcome at 90 days occurred in only 10% of the persistent mismatch patients. Conclusions- About 20% of patients with a middle cerebral artery or internal carotid artery occlusion who present in an extended time window and are not treated with thrombectomy have a persistent mismatch for at least an additional 24 hours. These patients have a favorable hypoperfusion intensity ratio at presentation, may experience delayed infarct expansion, and have poor clinical outcomes. Clinical trials are needed to determine if patients with a favorable perfusion profile benefit from reperfusion beyond 24 hours. Clinical Trial Registration- URL: https://www.clinicaltrials.gov . Unique identifier: NCT02586415.

    View details for PubMedID 30735466

  • Outcomes of Thrombectomy in Transferred Patients With Ischemic Stroke in the Late Window: A Subanalysis From the DEFUSE 3 Trial. JAMA neurology Sarraj, A., Mlynash, M., Savitz, S. I., Heit, J. J., Lansberg, M. G., Marks, M. P., Albers, G. W. 2019

    Abstract

    Importance: Although thrombectomy benefit was maintained in transfer patients with ischemic stroke in early-window trials, overall functional independence rates were lower in thrombectomy and medical management-only groups.Objective: To evaluate whether the imaging-based selection criteria used in the Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke 3 (DEFUSE 3) trial would lead to comparable outcome rates and treatment benefits in transfer vs direct-admission patients.Design, Setting, and Participants: Subgroup analysis of DEFUSE 3, a prospective, randomized, multicenter, blinded-end point trial. Patients were enrolled between May 2016 and May 2017 and were followed up for 90 days. The trial comprised 38 stroke centers in the United States and 182 patients with stroke with a large-vessel anterior circulation occlusion and initial infarct volume of less than 70 mL, mismatch ratio of at least 1.8, and mismatch volume of at least 15 mL, treated within 6 to 16 hours from last known well. Patients were stratified based on whether they presented directly to the study site or were transferred from a primary center. Data were analyzed between July 2018 and October 2018.Interventions or Exposures: Endovascular thrombectomy plus standard medical therapy vs standard medical therapy alone.Main Outcomes and Measures: The primary outcome was the distribution of 90-day modified Rankin Scale scores.Results: Of the 296 patients who consented, 182 patients were randomized (66% were transfer patients and 34% directly presented to a study site). Median age was 71 years (interquartile range [IQR], 60-79 years) vs 70 years (IQR, 59-80 years); 69 transfer patients were women (57%) and 23 of the direct group were women (37%). Transfer patients had longer median times from last known well to study site arrival (9.43 vs 9 hours) and more favorable collateral profiles (based on hypoperfusion intensity ratio): median for transfer, 0.35 (IQR, 0.18-0.47) vs 0.42 (IQR, 0.25-0.56) for direct (P=.05). The primary outcome (90-day modified Rankin Scale score shift) did not differ in the direct vs transfer groups (direct OR, 2.9; 95% CI, 1.2-7.2; P=.01; transfer OR, 2.6; 95% CI, 1.3-4.8; P=.009). The overall functional independence rate (90-day modified Rankin Scale score 0-2) in the thrombectomy group did not differ (direct 44% vs transfer 45%) nor did the treatment effect (direct OR, 2.0; 95% CI, 0.9-4.4 vs transfer OR, 3.1; 95% CI, 1.6-6.1). Thrombectomy reperfusion rates, mortality, and symptomatic intracranial hemorrhage rates did not differ.Conclusions and Relevance: In late-window patients selected by penumbral mismatch criteria, both the favorable outcome rate and treatment effect did not decline in transfer patients. These results have health care implications indicating transferring potential candidates for late-window thrombectomy is associated with substantial clinical benefits and should be encouraged.Trial Registration: ClinicalTrials.gov identifier: NCT02586415.

    View details for PubMedID 30734042

  • Ischemic Core and Hypoperfusion Volumes Correlate With Infarct Size 24 Hours After Randomization in DEFUSE 3. Stroke Rao, V., Christensen, S., Yennu, A., Mlynash, M., Zaharchuk, G., Heit, J., Marks, M. P., Lansberg, M. G., Albers, G. W. 2019: STROKEAHA118023177

    Abstract

    Background and Purpose- Accurate prediction of the subsequent infarct volume early after stroke onset helps determine appropriate interventions and prognosis. In the DEFUSE 3 trial (Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke), we evaluated the accuracy of baseline ischemic core and hypoperfusion volumes for predicting infarct volume 24 hours after randomization to endovascular thrombectomy versus medical management. We also assessed if the union of baseline ischemic core and the volume of persistent hypoperfusion at 24 hours after randomization predicts infarct volume. Methods- Patients in DEFUSE 3 with computed tomography perfusion imaging or magnetic resonance diffusion weighted imaging/perfusion imaging acquired at baseline and at 24 hours after randomization were included. Ischemic core and Tmax >6s hypoperfusion volumes at baseline and follow-up were calculated using RAPID software and compared with the infarct volumes obtained 24 hours after randomization. Patients were stratified by reperfusion status for analyses. Results- Of 125 eligible patients, 59 patients with >90% reperfusion had a strong correlation between baseline ischemic core volume and infarct volume 24 hours postrandomization ( r=0.83; P<0.0001), and 14 patients with <10% reperfusion had a strong correlation between baseline Tmax >6s volume and infarct volume 24 hours postrandomization ( r=0.77; P<0.001). In the 52 patients with 10% to 90% reperfusion, as well as in all 125 patients, the union of the baseline ischemic core and the follow-up Tmax >6s perfusion volume was highly correlated with infarct volume 24 hours postrandomization (for N=125; r=0.83; P<0.0001), with a median absolute difference of 21.3 mL between observed and predicted infarct volumes. Conclusions- The union of the irreversibly injured ischemic core and persistently hypoperfused tissue volumes, as identified by computed tomography perfusion or magnetic resonance diffusion weighted imaging/perfusion, predicted infarct volume at 24 hours after randomization in DEFUSE 3 patients. Clinical Trial Registration- URL: http://www.clinicaltrials.gov . Unique identifier: NCT02586415.

    View details for PubMedID 30727840

  • DEFUSE 3 Non-DAWN Patients. Stroke Leslie-Mazwi, T. M., Hamilton, S., Mlynash, M., Patel, A. B., Schwamm, L. H., Lansberg, M. G., Marks, M., Hirsch, J. A., Albers, G. W. 2019: STROKEAHA118023310

    Abstract

    Background and Purpose- DAWN (Clinical Mismatch in the Triage of Wake Up and Late Presenting Strokes Undergoing Neurointervention With Trevo) and DEFUSE 3 (Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke) established thrombectomy for patients with emergent large vessel occlusions presenting 6 to 24 hours after symptom onset. Given the greater inclusivity of DEFUSE 3, we evaluated the effect of thrombectomy in DEFUSE 3 patients who would have been excluded from DAWN. Methods- Eligibility criteria of the DAWN trial were applied to DEFUSE 3 patient data to identify DEFUSE 3 patients not meeting DAWN criteria (DEFUSE 3 non-DAWN). Reasons for DAWN exclusion in DEFUSE 3 were infarct core too large, National Institutes of Health Stroke Scale (NIHSS) score 6 to 9, and modified Rankin Scale score of 2. Subgroups were compared with the DEFUSE 3 non-DAWN and entire DEFUSE 3 cohorts. Results- There were 71 DEFUSE 3 non-DAWN patients; 31 patients with NIHSS 6 to 9, 33 with core too large, and 13 with premorbid modified Rankin Scale score of 2 (some patients met multiple criteria). For core-too-large patients, median 24-hour infarct volume was 119 mL (interquartile range, 74.6-180) versus 31.5 mL (interquartile range, 17.6-64.3) for core-not-too-large patients ( P<0.001). Complications and functional outcomes were similar between the groups. Thrombectomy in core-too-large patients compared with the remaining DEFUSE 3 non-DAWN patients conveyed benefit for functional outcome (odds ratio, 20.9; CI, 1.3-337.8). Comparing the NIHSS 6 to 9 group with the NIHSS ≥10 patients, modified Rankin Scale score 0 to 2 outcomes were achieved in 74% versus 22% ( P<0.001), with mortality in 6% versus 23% ( P=0.024), respectively. For patients with NIHSS 6 to 9 compared with the remaining DEFUSE 3 non-DAWN patients, thrombectomy trended toward a better chance of functional outcome (odds ratio, 1.86; CI, 0.36-9.529). Conclusions- Patients with pretreatment core infarct volumes <70 mL but too large for inclusion by DAWN criteria demonstrate benefit from endovascular therapy. More permissive pretreatment core thresholds in core-clinical mismatch selection paradigms may be appropriate. In contrast to data supporting a beneficial treatment effect across the full range of NIHSS scores in the entire DEFUSE 3 population, only a trend toward benefit of thrombectomy in patients with NIHSS 6 to 9 was found in this small subgroup.

    View details for PubMedID 30727856

  • Results From DEFUSE 3. Stroke de Havenon, A., Mlynash, M., Kim-Tenser, M. A., Lansberg, M. G., Leslie-Mazwi, T., Christensen, S., McTaggart, R. A., Alexander, M., Albers, G., Broderick, J., Marks, M. P., Heit, J. J., DEFUSE 3 Investigators 2019: STROKEAHA118023407

    Abstract

    Background and Purpose- The effect of leptomeningeal collaterals for acute ischemic stroke patients with large vessel occlusion in the late window (>6 hours from last known normal) remains unknown. We sought to determine if collateral status on baseline computed tomography angiography impacted neurological outcome, ischemic core growth, and moderated the effect of endovascular thrombectomy in the late window. Methods- This is a prespecified analysis of DEFUSE 3 (Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke). We included patients with computed tomography angiography as their baseline imaging and rated collateral status using the validated scales described by Tan and Maas. The primary outcome is functional independence (modified Rankin scale score of ≤2). Additional outcomes include the full range of the modified Rankin scale, baseline ischemic core volume, change from baseline in the ischemic core volume at 24 hours, and death at 90 days. Results- Of the 130 patients in our cohort, 33 (25%) had poor collaterals and 97 (75%) had good collaterals. There was no difference in the rate of functional independence with good versus poor collaterals in unadjusted analysis (30% versus 39%; P=0.3) or after adjustment for treatment arm (odds ratio [95% CI], 0.61 [0.26-1.45]). Good collaterals were associated with significantly smaller ischemic core volume and less ischemic core growth. The difference in the treatment effect of endovascular thrombectomy was not significant ( P=0.8). Collateral status also did not affect the rate of stroke-related death (n [%], good versus poor collaterals, 18/97 [19%] versus 8/33 [24%], P=0.5]. Conclusions- In DEFUSE 3 patients, good leptomeningeal collaterals on single phase computed tomography angiography were not predictive of functional independence or death and did not impact the treatment effect of endovascular thrombectomy. These unexpected findings require further study to confirm their validity and to better understand the role of collaterals for stroke patients with anterior circulation large vessel occlusion in the late therapeutic window. Clinical Trial Registration- URL: https://www.clinicaltrials.gov . Unique identifier: NCT02586415.

    View details for PubMedID 30726184

  • Union of Ischemic Core and Hypoperfusion Volume Correlates With 24-hour Infarct Size in DEFUSE 3 Rao, V., Christensen, S., Yennu, A., Mylnash, M., Zaharchuk, G., Heit, J., Marks, M. P., Lansberg, M. G., Albers, G. W. LIPPINCOTT WILLIAMS & WILKINS. 2019

    View details for Web of Science ID 000478733402495

  • Comparison of Predicted vs. Actual Enrollment Into the NIH StrokeNet DEFUSE 3 Trial: Effectiveness of a Population-Based Epidemiology Feasibility Assessment in Improving Enrollment Into Clinical Trials. Kleindorfer, D. O., Moomaw, C. J., Mlynash, M., Broderick, J. P., Khatri, P., Saver, J. L., Alwell, K., Kemp, S., Janis, S., Moy, C., Woo, D., Flaherty, M. L., Ferioli, S., Adeoye, O., Kissela, B. M., Lansberg, M., Albers, G. LIPPINCOTT WILLIAMS & WILKINS. 2019

    View details for Web of Science ID 000478733401331

  • Ischemic Core Volume Modifies the Association Between ASPECT Score and Clinical Outcome. Sarraj, A., Hassan, A., Grotta, J., Sitton, C., Chen, P. R., Cai Chunyan, Cutter, G., Pujara, D., Imam, B., Reddy, S., Kamal, H., Abraham, M., McCullough, L., Lansberg, M., Savitz, S., Albers, G., Gupta, R. LIPPINCOTT WILLIAMS & WILKINS. 2019

    View details for Web of Science ID 000478733403006

  • Early Infarct Growth Correlates With Both Collateral Status and Clinical Outcomes After Thrombecomy Sarraj, A., Savitz, S., Sitton, C., Hassan, A., Cai Chunyuan, Pujara, D., Grotta, J., Imam, B., Chen, P. R., Cutter, G., Reddy, S., Kamal, H., Abraham, M., McCullough, L., Lansberg, M., Gupta, R., Albers, G. LIPPINCOTT WILLIAMS & WILKINS. 2019

    View details for Web of Science ID 000478733400160

  • Baseline Perfusion Imaging Collateral Scores Predict Infarct Growth in DEFUSE 3 MacLellan, A., Heit, J. J., Marks, M. P., Lansberg, M. G., Michael, M., Albers, G. W. LIPPINCOTT WILLIAMS & WILKINS. 2019

    View details for Web of Science ID 000478733400155

  • Deep Learning Based Prediction of Tissue Status From Native CT Perfusion Images. Robben, D., Christensen, S., Boers, A. M., Marquering, H. A., Majoie, C. B., van Oostenbrugge, R. J., Roos, Y. B., Dippel, D. W., van Zwam, W. H., van der Lugt, A., Lansberg, M. G., Albers, G. W., Suetens, P., Lemmens, R. LIPPINCOTT WILLIAMS & WILKINS. 2019

    View details for Web of Science ID 000478733401351

  • Endovascular Thrombectomy May Be Safe and Effective in Patients With Large Core Lesions on Either Simple CT or Perfusion Images Sarraj, A., Hassan, A., Grotta, J., Sitton, C., Chen, P. R., Vora, N., Cai Chuyan, Cutter, G., Pujara, D., Imam, B., Reddy, S., Kamal, H., Abraham, M., McCullough, L., Lansberg, M., Savitz, S., Gupta, R., Albers, G. LIPPINCOTT WILLIAMS & WILKINS. 2019

    View details for Web of Science ID 000478733400005

  • Evaluating the Generalizability of the Common Odds Ratio: A Demonstration using Two Trials of Endovascular Therapy. Yeatts, S. D., Mlynash, M., Lavori, P. W., Albers, G. W., Lansberg, M. G., Broderick, J. P., Palesch, Y. Y., Hamilton, S. LIPPINCOTT WILLIAMS & WILKINS. 2019

    View details for Web of Science ID 000478733401165

  • Endovascular Thrombectomy May Be Safe and Effective in Patients With Large Core and Early Presentation Sarraj, A., Hassan, A., Sitton, C., Chen, P. R., Cai Chunyan, Cutter, G., Pujara, D., Imam, B., Reddy, S., Kamal, H., Gutierrez, O., Abraham, M., Edgell, R., McCullough, L., Savitz, S., Albers, G., Gupta, R., Grotta, J. LIPPINCOTT WILLIAMS & WILKINS. 2019

    View details for Web of Science ID 000478733400110

  • Optimizing CT Perfusion Thresholds for Identification of Ischemic Core in Hyperacute Stroke. Legault, C., Lansberg, M., Heit, J., Albers, G. LIPPINCOTT WILLIAMS & WILKINS. 2019

    View details for Web of Science ID 000478733401337

  • Later Imaging More Accurately Captures Infarct Growth in DEFUSE 3 Tate, W. J., Polding, L. C., Christensen, S., Mlynash, M., Heit, J. J., Marks, M. M., Albers, G. W., Lansberg, M. G. LIPPINCOTT WILLIAMS & WILKINS. 2019

    View details for Web of Science ID 000478733402494

  • Improved Quality of Life With Endovascular Therapy in the DEFUSE 3 Trial Polding, L. C., Tate, W. J., Mlynash, M., Marks, M. P., Heit, J. J., Kemp, S., Albers, G. W., Lansberg, M. G. LIPPINCOTT WILLIAMS & WILKINS. 2019

    View details for Web of Science ID 000478733400006

  • Thrombectomy Results in Reduced Hospital Stay, More Time at Home, and More Favorable Living Situations for Patients in the DEFUSE 3 Trial. Tate, W. J., Polding, L. C., Kemp, S., Mlynash, M., Heit, J. J., Marks, M. P., Albers, G. W., Lansberg, M. G. LIPPINCOTT WILLIAMS & WILKINS. 2019

    View details for Web of Science ID 000478733400173

  • Combination of Tmax and Relative CBV Perfusion Parameters More Accurately Predicts CTA Collaterals Than a Single Perfusion Parameter in DEFUSE 3. Mlynash, M., Lansberg, M. G., Kemp, S., Christensen, S., Yennu, A., Heit, J. J., Marks, M. P., Albers, G. W. LIPPINCOTT WILLIAMS & WILKINS. 2019

    View details for Web of Science ID 000478733403010

  • Early Dramatic Improvement on the National Institutes of Health Stroke Scale Predicts Favorable Outcome 90 Days After Thrombectomy in the DEFUSE 3 Study. Heit, J. J., Mlynash, M., Kemp, S., Lansberg, M. G., Christiansen, S., Marks, M. P., Albers, G. W. LIPPINCOTT WILLIAMS & WILKINS. 2019

    View details for Web of Science ID 000478733402332

  • Results From the DEFUSE 3 Trial: Good Leptomeningeal Collaterals Are Associated With Reduced Core Infarct Size but Not Improved Neurologic Outcome de Havenon, A., Mlynash, M., Kim-Tenser, M. A., Lansberg, M., Leslie-Mazwi, T., Christensen, S., McTaggart, R., Alexander, M., Albers, G., Broderick, J., Marks, M. P., Heit, J., DEFUSE 3 Investigators LIPPINCOTT WILLIAMS & WILKINS. 2019

    View details for Web of Science ID 000478733400007

  • DEFUSE 3 Trial Outcomes not Affected by the Enrollment Rates of the Participating Centers. Mlynash, M., Lansberg, M. G., Kemp, S., Christensen, S., Heit, J. J., Marks, M. P., Albers, G. W. LIPPINCOTT WILLIAMS & WILKINS. 2019

    View details for Web of Science ID 000478733402235

  • Late Window Transfer Patients had Favorable Outcomes Following Thrombectomy in DEFUSE 3 Sarraj, A., Mlynash, M., Heit, J., Marks, M., Lansberg, M., Albers, G. LIPPINCOTT WILLIAMS & WILKINS. 2019

    View details for Web of Science ID 000478733400112

  • Selection Criteria for Thrombectomy in Pediatric Stroke: A Single-Center Series Lee, S., Heit, J. J., Albers, G. W., Wintermark, M., Elbers, J., Bernier, E., Jiang, B., Marks, M. P., Do Huy, M., Dodd, R. LIPPINCOTT WILLIAMS & WILKINS. 2019

    View details for Web of Science ID 000478733401386

  • A Closer Look at Late Window Thrombectomy Selection Lesile-Mazwi, T. M., Hamilton, S., Mlynash, M., Patel, A. B., Schwamm, L. H., Lansberg, M. G., Marks, M. P., Hirsch, J. A., Albers, G. W. LIPPINCOTT WILLIAMS & WILKINS. 2019

    View details for Web of Science ID 000478733401369

  • CT Perfusion Collateral Score Predicts Which Patients Will Maintain a Penumbral Profile on MRI for Greater than 24 Hours Christensen, S., Mlynash, M., Kemp, S., Yennu, A., Heit, J. J., Marks, M. P., Lansberg, M. G., Albers, G., DEFUSE 3 Investigators LIPPINCOTT WILLIAMS & WILKINS. 2019

    View details for Web of Science ID 000478733400161

  • Correlation between Modified Rankin Scale and Quality of Life in DEFUSE 3 Polding, L. C., Tate, W. J., Mlynash, M., Marks, M. P., Heit, J. J., Kemp, S., Albers, G. W., Lansberg, M. G. LIPPINCOTT WILLIAMS & WILKINS. 2019

    View details for Web of Science ID 000478733400174

  • Association of Thrombectomy With Stroke Outcomes Among Patient Subgroups: Secondary Analyses of the DEFUSE 3 Randomized Clinical Trial. JAMA neurology Lansberg, M. G., Mlynash, M., Hamilton, S., Yeatts, S. D., Christensen, S., Kemp, S., Lavori, P. W., Gutierrez, S. O., Broderick, J., Heit, J., Marks, M. P., Albers, G. W., DEFUSE 3 Investigators 2019

    Abstract

    Importance: The DEFUSE 3 randomized clinical trial previously demonstrated benefit of endovascular thrombectomy for acute ischemic stroke in the 6- to 16-hour time window. For treatment recommendations, it is important to know if the treatment benefit was universal.Objective: To determine the outcomes among patients who may have a reduced effect of thrombectomy, including those who are older, have milder symptoms, or present late.Design, Setting, and Participants: DEFUSE 3 was a randomized, open-label, blinded end point trial conducted from May 2016 to May 2017. This multicenter study included 38 sites in the United States. Of 296 patients who were enrolled in DEFUSE 3, 182 patients met all inclusion criteria and were randomized and included in the intention-to-treat analysis, which was conducted in August 2017. These patients had acute ischemic strokes due to an occlusion of the internal carotid artery or middle cerebral artery and evidence of salvageable tissue on perfusion computed tomography or magnetic resonance imaging. The study was stopped early for efficacy.Interventions: Endovascular thrombectomy plus medical management vs medical management alone.Main Outcomes and Measures: Functional outcome at day 90, assessed on the modified Rankin Scale. Multivariate ordinal logistic regression was used to calculate the adjusted proportional association between endovascular treatment and clinical outcome (shift in the distribution of modified Rankin Scale scores expressed as a common odds ratio) among patients of different ages, baseline stroke severities, onset-to-treatment times, locations of the arterial occlusion, and imaging modalities used to document the presence of salvageable tissue (computed tomography vs magnetic resonance imaging).Results: This study included 182 patients (median [interquartile range] age, 70 [59-80] years; median [interquartile range] National Institutes of Health Stroke Scale score, 16 [11-21], and 92 women [51%]). In the overall cohort, independent predictors of better functional outcome were younger age, lower baseline National Institutes of Health Stroke Scale score, and lower serum glucose level. The common odds ratio for improved functional outcome with endovascular therapy, adjusted for these variables, was 3.1 (95% CI, 1.8-5.4). There was no significant interaction between this treatment effect and age (P=.93), National Institutes of Health Stroke Scale score (P=.87), time to randomization (P=.56), imaging modality (P=.49), or location of the arterial occlusion (P=.54).Conclusions and Relevance: Endovascular thrombectomy, initiated up to 16 hours after last known well time in patients with salvageable tissue on perfusion imaging, benefits patients with a broad range of clinical features. Owing to the small sample size of this study, a pooled analysis of late time window endovascular stroke trials is needed to confirm these results.Trial Registration: ClinicalTrials.gov identifier: NCT02586415.

    View details for PubMedID 30688974

  • Mediation of the Relationship Between Endovascular Therapy and Functional Outcome by Follow-up Infarct Volume in Patients With Acute Ischemic Stroke. JAMA neurology Boers, A. M., Jansen, I. G., Brown, S., Lingsma, H. F., Beenen, L. F., Devlin, T. G., Roman, L. S., Heo, J., Ribo, M., Almekhlafi, M. A., Liebeskind, D. S., Teitelbaum, J., Cuadras, P., du Mesnil de Rochemont, R., Beaumont, M., Brown, M. M., Yoo, A. J., Donnan, G. A., Mas, J. L., Oppenheim, C., Dowling, R. J., Moulin, T., Agrinier, N., Lopes, D. K., Aja Rodriguez, L., Compagne, K. C., Al-Ajlan, F. S., Madigan, J., Albers, G. W., Soize, S., Blasco, J., Davis, S. M., Nogueira, R. G., Davalos, A., Menon, B. K., van der Lugt, A., Muir, K. W., Roos, Y. B., White, P., Mitchell, P. J., Demchuk, A. M., van Zwam, W. H., Jovin, T. G., van Oostenbrugge, R. J., Dippel, D. W., Campbell, B. C., Guillemin, F., Bracard, S., Hill, M. D., Goyal, M., Marquering, H. A., Majoie, C. B. 2019

    Abstract

    Importance: The positive treatment effect of endovascular therapy (EVT) is assumed to be caused by the preservation of brain tissue. It remains unclear to what extent the treatment-related reduction in follow-up infarct volume (FIV) explains the improved functional outcome after EVT in patients with acute ischemic stroke.Objective: To study whether FIV mediates the relationship between EVT and functional outcome in patients with acute ischemic stroke.Design, Setting, and Participants: Patient data from 7 randomized multicenter trials were pooled. These trials were conducted between December 2010 and April 2015 and included 1764 patients randomly assigned to receive either EVT or standard care (control). Follow-up infarct volume was assessed on computed tomography or magnetic resonance imaging after stroke onset. Mediation analysis was performed to examine the potential causal chain in which FIV may mediate the relationship between EVT and functional outcome. A total of 1690 patients met the inclusion criteria. Twenty-five additional patients were excluded, resulting in a total of 1665 patients, including 821 (49.3%) in the EVT group and 844 (50.7%) in the control group. Data were analyzed from January to June 2017.Main Outcome and Measure: The 90-day functional outcome via the modified Rankin Scale (mRS).Results: Among 1665 patients, the median (interquartile range [IQR]) age was 68 (57-76) years, and 781 (46.9%) were female. The median (IQR) time to FIV measurement was 30 (24-237) hours. The median (IQR) FIV was 41 (14-120) mL. Patients in the EVT group had significantly smaller FIVs compared with patients in the control group (median [IQR] FIV, 33 [11-99] vs 51 [18-134] mL; P=.007) and lower mRS scores at 90 days (median [IQR] score, 3 [1-4] vs 4 [2-5]). Follow-up infarct volume was a predictor of functional outcome (adjusted common odds ratio, 0.46; 95% CI, 0.39-0.54; P<.001). Follow-up infarct volume partially mediated the relationship between treatment type with mRS score, as EVT was still significantly associated with functional outcome after adjustment for FIV (adjusted common odds ratio, 2.22; 95% CI, 1.52-3.21; P<.001). Treatment-reduced FIV explained 12% (95% CI, 1-19) of the relationship between EVT and functional outcome.Conclusions and Relevance: In this analysis, follow-up infarct volume predicted functional outcome; however, a reduced infarct volume after treatment with EVT only explained 12% of the treatment benefit. Follow-up infarct volume as measured on computed tomography and magnetic resonance imaging is not a valid proxy for estimating treatment effect in phase II and III trials of acute ischemic stroke.

    View details for PubMedID 30615038

  • Thrombectomy with Conscious Sedation Compared with General Anesthesia: A DEFUSE 3 Analysis. AJNR. American journal of neuroradiology Powers, C. J., Dornbos, D., Mlynash, M., Gulati, D., Torbey, M., Nimjee, S. M., Lansberg, M. G., Albers, G. W., Marks, M. P. 2019

    Abstract

    The optimal patient sedation during mechanical thrombectomy for ischemic stroke in the extended time window is unknown. The purpose of this study was to assess the impact of patient sedation on outcome in patients undergoing thrombectomy 6-16 hours from stroke onset.Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke 3 (DEFUSE 3) was a multicenter, randomized, open-label trial of thrombectomy for ICA and M1 occlusions in patients 6-16 hours from stroke onset. Subjects underwent thrombectomy with either general anesthesia or conscious sedation at the discretion of the treating institution.Of the 92 patients who were randomized to intervention, 26 (28%) underwent thrombectomy with general anesthesia and 66 (72%) underwent thrombectomy with conscious sedation. Baseline clinical and imaging characteristics were similar among all groups. Functional independence at 90 days was 23% for general anesthesia, 53% for conscious sedation, and 17% for medical management (P = .009 for general anesthesia versus conscious sedation). Conscious sedation was associated with a shorter time from arrival in the angiosuite to femoral puncture (median, 14 versus 18 minutes; P = 0.05) and a shorter time from femoral puncture to reperfusion (median, 36 versus 48 minutes; P = .004). Sixty-six patients were treated at sites that exclusively used general anesthesia (n = 14) or conscious sedation (n = 52). For these patients, functional independence at 90 days was significantly higher in the conscious sedation subgroup (58%) compared with the general anesthesia subgroup (21%) (P = .03).Patients who underwent thrombectomy with conscious sedation in the extended time window experienced a higher likelihood of functional independence at 90 days, a lower NIHSS score at 24 hours, and a shorter time from femoral puncture to reperfusion compared with those who had general anesthesia. This effect remained robust in institutions that only treated patients with a single anesthesia technique.

    View details for PubMedID 31072970

  • Neuroimaging in Ischemic Stroke Is Different Between Men and Women in the DEFUSE 3 Cohort. Stroke Dula, A. N., Mlynash, M., Zuck, N. D., Albers, G. W., Warach, S. J. 2019: STROKEAHA119028205

    Abstract

    Background and Purpose- Clinical deficits from ischemic stroke are more severe in women, but the pathophysiological basis of this sex difference is unknown. Sex differences in core and penumbral volumes and their relation to outcome were assessed in this substudy of the DEFUSE 3 clinical trial (Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke). Methods- DEFUSE 3 randomized patients to thrombectomy or medical management who presented 6 to 16 hours from last known well with proximal middle cerebral artery or internal carotid artery occlusion and had target core and perfusion mismatch volumes on computed tomography or magnetic resonance imaging. Using univariate and adjusted regression models, the effect of sex was assessed on prerandomization measures of core, perfusion, and mismatch volumes and hypoperfusion intensity ratio, and on core volume growth using 24-hour scans. Results- All patients were included in the analysis (n=182) with 90 men and 92 women. There was no sex difference in the site of baseline arterial occlusion. Adjusted by age, baseline National Institutes of Health Stroke Scale, baseline modified Rankin Scale score, time to randomization, and imaging modality, women had smaller core, hypoperfusion, and penumbral volumes than men. Median (interquartile range) volumes for core were 8.0 mL (1.9-18.4) in women versus 12.6 mL (2.7-29.6) in men, for Tmax>6 seconds 89.0 mL (63.8-131.7) versus 133.9 mL (87.0-175.4), and for mismatch 82.1mL (53.8-112.8) versus 108.2 (64.1-149.2). The hypoperfusion intensity ratio was lower in women, 0.31 (0.15-0.46) versus 0.39 (0.26-0.57), P=0.006, indicating better collateral circulation, which was consistent with the observed slower ischemic core growth than men within the medical group (P=0.003). Conclusions- In the large vessel ischemic stroke cohort selected for DEFUSE 3, women had imaging evidence of better collateral circulation, smaller baseline core volumes, and slower ischemic core growth. These observations suggest sex differences in hemodynamic and temporal features of anterior circulation large artery occlusions. Clinical Trial Registration- URL: https://www.clinicaltrials.gov. Unique identifier: NCT02586415.

    View details for DOI 10.1161/STROKEAHA.119.028205

    View details for PubMedID 31826731

  • Factors that may contribute to poor outcome despite good reperfusion after acute endovascular stroke therapy INTERNATIONAL JOURNAL OF STROKE Rabinstein, A. A., Albers, G. W., Brinjikji, W., Koch, S. 2019; 14 (1): 23–31

    Abstract

    Endovascular therapy with mechanical thrombectomy is a formidable treatment for severe acute ischemic stroke caused by occlusion of a proximal intracranial artery. Its strong beneficial effect is explained by the high rates of very good and excellent reperfusion achieved with current endovascular techniques. However, there is a sizable proportion of patients who do not experience clinical improvement despite successful recanalization of the occluded artery and reperfusion of the ischemic territory. Factors such as baseline reserve, collateral flow, anesthesia and systemic factors have been identified as potential culprits for lack of improvement in the setting of timely and successful revascularization. Older age, baseline disability and perhaps radiological markers of chronic brain injury can affect the prognosis of patients treated with endovascular therapy. Collateral flow is a major determinant of outcome after endovascular therapy and it is manifested by the size of the core in relation to the volume of the salvageable tissue. Parenchymal and vascular imaging can help assess the quality of collateral flow, but the optimal radiological strategy for daily practice (i.e. the optimal combination of rapid availability and diagnostic precision) has not been established. A sizable body of observational evidence indicates that acute hypertension, hyperglycemia and fever are associated with worse outcomes after a stroke even after optimal reperfusion with endovascular therapy. Lastly, current randomized controlled trials in anesthesia for stroke demonstrate similar rates of good functional outcome between general anesthesia and conscious sedation suggesting equipoise exists.

    View details for PubMedID 30188259

  • Estimated treatment effect of ticagrelor versus aspirin by investigator-assessed events compared with judgement by an independent event adjudication committee in the SOCRATES trial. International journal of stroke : official journal of the International Stroke Society Easton, J. D., Denison, H., Evans, S. R., Knutsson, M., Amarenco, P., Albers, G. W., Ladenvall, P., Minematsu, K., Molina, C. A., Wang, Y., Wong, K. L., Johnston, S. C. 2019: 1747493019851282

    Abstract

    Adjudication of endpoints is a standard procedure in cardiovascular clinical trials. However, several studies indicate that the benefit of adjudication in estimating treatment effect may be limited.This post hoc analysis of SOCRATES (NCT01994720) compared the treatment effects and investigated the agreement of clinical event assessment by site investigators and independent adjudicators.SOCRATES compared ticagrelor and aspirin in 13,199 patients with acute minor stroke or high-risk transient ischemic attack. The primary endpoint was stroke, myocardial infarction, or death. Stroke was the major component of the primary endpoint and a secondary endpoint. The endpoints were adjudicated by a blinded independent committee. We compared the treatment effect on the primary endpoint and stroke alone based on the investigators' and adjudicators' assessments, and investigated the agreement rate on the stroke endpoint and major hemorrhages.The hazard ratios (95% confidence interval) for ticagrelor versus aspirin therapy for the primary endpoint were 0.89 (0.78-1.01) when calculated on adjudicator-assessed events and 0.88 (0.78-1.00) for investigator-assessed events. The hazard ratios (95% confidence intervals) for stroke were 0.86 (0.75-0.99) based on the adjudicators' diagnoses and 0.85 (0.75-0.97) based on the investigators' diagnoses. The overall agreement between adjudicator- and investigator-diagnosed stroke was 91%, and for major hemorrhages was 88%.In SOCRATES, there was no clinically meaningful difference in the estimated treatment effect, on either the primary endpoint or stroke, by using investigator- or adjudicator-assessed events. Double-blind treatment outcome studies with stroke endpoints may not benefit from adjudication.ClinicalTrials.gov Identifier: NCT01994720.

    View details for PubMedID 31092152

  • Artificial Neural Network Computer Tomography Perfusion Prediction of Ischemic Core. Stroke Kasasbeh, A. S., Christensen, S., Parsons, M. W., Campbell, B., Albers, G. W., Lansberg, M. G. 2019: STROKEAHA118022649

    Abstract

    Background and Purpose- Computed tomography perfusion (CTP) is a useful tool in the evaluation of acute ischemic stroke, where it can provide an estimate of the ischemic core and the ischemic penumbra. The optimal CTP parameters to identify the ischemic core remain undetermined. Methods- We used artificial neural networks (ANNs) to optimally predict the ischemic core in acute stroke patients, using diffusion-weighted imaging as the gold standard. We first designed an ANN based on CTP data alone and next designed an ANN based on clinical and CTP data. Results- The ANN based on CTP data predicted the ischemic core with a mean absolute error of 13.8 mL (SD, 13.6 mL) compared with diffusion-weighted imaging. The area under the receiver operator characteristic curve was 0.85. At the optimal threshold, the sensitivity for predicting the ischemic core was 0.90 and the specificity was 0.62. Combining CTP data with clinical data available at time of presentation resulted in the same mean absolute error (13.8 mL) but lower SD (12.4 mL). The area under the curve, sensitivity, and specificity were 0.87, 0.91, and 0.65, respectively. The maximal Dice coefficient was 0.48 in the ANN based on CTP data exclusively. Conclusions- An ANN that integrates clinical and CTP data predicts the ischemic core with accuracy.

    View details for PubMedID 31092162

  • Neuroimaging selection for thrombectomy in pediatric stroke: a single-center experience. Journal of neurointerventional surgery Lee, S., Heit, J. J., Albers, G. W., Wintermark, M., Jiang, B., Bernier, E., Fischbein, N. J., Mlynash, M., Marks, M. P., Do, H. M., Dodd, R. L. 2019

    Abstract

    The extended time window for endovascular therapy in adult stroke represents an opportunity for stroke treatment in children for whom diagnosis may be delayed. However, selection criteria for pediatric thrombectomy has not been defined.We performed a retrospective cohort study of patients aged <18 years presenting within 24 hours of acute large vessel occlusion. Patient consent was waived by our institutional IRB. Patient data derived from our institutional stroke database was compared between patients with good and poor outcome using Fisher's exact test, t-test, or Mann-Whitney U-test.Twelve children were included: 8/12 (66.7%) were female, mean age 9.7±5.0 years, median National Institutes of Health Stroke Scale (NIHSS) 11.5 (IQR 10-14). Stroke etiology was cardioembolic in 75%, dissection in 16.7%, and cryptogenic in 8.3%. For 2/5 with perfusion imaging, Tmax >4 s appeared to better correlate with NIHSS. Nine patients (75%) were treated: seven underwent thrombectomy alone; one received IV alteplase and thrombectomy, and one received IV alteplase alone. Favorable outcome was achieved in 78% of treated patients versus 0% of untreated patients (P=0.018). All untreated patients had poor outcome, with death (n=2) or severe disability (n=1) at follow-up. Among treated patients, older children (12.8±2.9 vs 4.2±5.0 years, P=0.014) and children presenting as outpatient (100% vs 0%, P=0.028) appeared to have better outcomes.Perfusion imaging is feasible in pediatric stroke and may help identify salvageable tissue in extended time windows, though penumbral thresholds may differ from adult values. Further studies are needed to define criteria for thrombectomy in this unique population.

    View details for PubMedID 31097548

  • Comparison of T2*GRE and DSC-PWI for hemorrhage detection in acute ischemic stroke patients: Pooled analysis of the EPITHET, DEFUSE 2, and SENSE 3 stroke studies. International journal of stroke : official journal of the International Stroke Society Amukotuwa, S. A., Fischbein, N. J., Albers, G. W., Davis, S., Donnan, G. A., Andre, J. B., Bammer, R. 2019: 1747493019858781

    Abstract

    The objective of this study was to compare the diagnostic performance of the baseline pre-contrast images of dynamic susceptibility contrast perfusion-weighted imaging (DSC-PWI) with conventional T2*gradient recalled echo (GRE) imaging for detection of hemorrhage in acute ischemic stroke patients.T2*GRE and DSC-PWI from 393 magnetic resonance imaging scans from 221 patients enrolled in three prospective stroke studies were independently evaluated by two readers blinded to clinical and other imaging data. Agreement between T2*GRE and DSC-PWI for the presence of hemorrhage, and acute hemorrhagic transformation, was assessed using the kappa statistic. Inter-reader agreement was also assessed using the kappa statistic.Agreement between the baseline images of DSC-PWI and T2*GRE regarding the presence of hemorrhage was almost perfect (kreader 1 : 0.90, 95% confidence interval 0.86-0.95 and kreader 2 : 0.91, 95% confidence interval 0.87-0.96). Agreement between the sequences was still higher for detection of acute hemorrhagic transformation (kreader 1 : 0.94, 95% confidence interval 0.91-0.98 and kreader 2 : 0.95, 95% confidence interval 0.92-0.98). Inter-reader agreement for detection of hemorrhage was also almost perfect for both T2*GRE (k: 0.95, 95% confidence interval 0.91-0.98) and DSC-PWI (k: 0.96, 95% confidence interval 0.93-0.99). Acute hemorrhagic transformation detected on T2*GRE was missed on DSC-PWI by one or both readers in 5/393 (1.3%) scans.The almost perfect statistical agreement between DSC-PWI and conventional T2*GRE suggests that DSC-PWI is sufficient for hemorrhage screening prior to thrombolysis in stroke patients. T2*GRE can therefore be omitted when DSC-PWI is included, thereby shortening the acute ischemic stroke magnetic resonance imaging protocol and expediting treatment. Trial registration: ClinicalTrials.gov Identifier: NCT02586415.

    View details for DOI 10.1177/1747493019858781

    View details for PubMedID 31291850

  • Thrombectomy for acute ischemic stroke in nonagenarians compared with octogenarians. Journal of neurointerventional surgery Sussman, E. S., Martin, B., Mlynash, M., Marks, M. P., Marcellus, D., Albers, G., Lansberg, M., Dodd, R., Do, H. M., Heit, J. J. 2019

    Abstract

    Multiple randomized trials have shown that endovascular thrombectomy (EVT) leads to improved outcomes in acute ischemic stroke (AIS) due to large vessel occlusion (LVO). Elderly patients were poorly represented in these trials, and the efficacy of EVT in nonagenarian patients remains uncertain.We performed a retrospective cohort study at a single center. Inclusion criteria were: age 80-99, LVO, core infarct <70 mL, and salvageable penumbra. Patients were stratified into octogenarian (80-89) and nonagenarian (90-99) cohorts. The primary outcome was the ordinal score on the modified Rankin Scale (mRS) at 90 days. Secondary outcomes included dichotomized functional outcome (mRS ≤2 vs mRS ≥3), successful revascularization, symptomatic intracranial hemorrhage (ICH), and mortality.108 patients met the inclusion criteria, including 79 octogenarians (73%) and 29 nonagenarians (27%). Nonagenarians were more likely to be female (86% vs 58%; p<0.01); there were no other differences between groups in terms of demographics, medical comorbidities, or treatment characteristics. Successful revascularization (TICI 2b-3) was achieved in 79% in both cohorts. Median mRS at 90 days was 5 in octogenarians and 6 in nonagenarians (p=0.09). Functional independence (mRS ≤2) at 90 days was achieved in 12.5% and 19.7% of nonagenarians and octogenarians, respectively (p=0.54). Symptomatic ICH occurred in 21.4% and 6.4% (p=0.03), and 90-day mortality rate was 63% and 40.9% (p=0.07) in nonagenarians and octogenarians, respectively.Nonagenarians may be at higher risk of symptomatic ICH than octogenarians, despite similar stroke- and treatment-related factors. While there was a trend towards higher mortality and worse functional outcomes in nonagenarians, the difference was not statistically significant in this relatively small retrospective study.

    View details for DOI 10.1136/neurintsurg-2019-015147

    View details for PubMedID 31350369

  • Contralateral Hemispheric Cerebral Blood Flow Measured With Arterial Spin Labeling Can Predict Outcome in Acute Stroke. Stroke Thamm, T., Guo, J., Rosenberg, J., Liang, T., Marks, M. P., Christensen, S., Do, H. M., Kemp, S. M., Adair, E., Eyngorn, I., Mlynash, M., Jovin, T. G., Keogh, B. P., Chen, H. J., Lansberg, M. G., Albers, G. W., Zaharchuk, G. 2019: STROKEAHA119026499

    Abstract

    Background and Purpose- Imaging is frequently used to select acute stroke patients for intra-arterial therapy. Quantitative cerebral blood flow can be measured noninvasively with arterial spin labeling magnetic resonance imaging. Cerebral blood flow levels in the contralateral (unaffected) hemisphere may affect capacity for collateral flow and patient outcome. The goal of this study was to determine whether higher contralateral cerebral blood flow (cCBF) in acute stroke identifies patients with better 90-day functional outcome. Methods- Patients were part of the prospective, multicenter iCAS study (Imaging Collaterals in Acute Stroke) between 2013 and 2017. Consecutive patients were enrolled after being diagnosed with anterior circulation acute ischemic stroke. Inclusion criteria were ischemic anterior circulation stroke, baseline National Institutes of Health Stroke Scale score ≥1, prestroke modified Rankin Scale score ≤2, onset-to-imaging time <24 hours, with imaging including diffusion-weighted imaging and arterial spin labeling. Patients were dichotomized into high and low cCBF groups based on median cCBF. Outcomes were assessed by day-1 and day-5 National Institutes of Health Stroke Scale; and day-30 and day-90 modified Rankin Scale. Multivariable logistic regression was used to test whether cCBF predicted good neurological outcome (modified Rankin Scale score, 0-2) at 90 days. Results- Seventy-seven patients (41 women) met the inclusion criteria with median (interquartile range) age of 66 (55-76) yrs, onset-to-imaging time of 4.8 (3.6-7.7) hours, and baseline National Institutes of Health Stroke Scale score of 13 (9-20). Median cCBF was 38.9 (31.2-44.5) mL per 100 g/min. Higher cCBF predicted good outcome at day 90 (odds ratio, 4.6 [95% CI, 1.4-14.7]; P=0.01), after controlling for baseline National Institutes of Health Stroke Scale, diffusion-weighted imaging lesion volume, and intra-arterial therapy. Conclusions- Higher quantitative cCBF at baseline is a significant predictor of good neurological outcome at day 90. cCBF levels may inform decisions regarding stroke triage, treatment of acute stroke, and general outcome prognosis. Clinical Trial Registration- URL: https://www.clinicaltrials.gov. Unique identifier: NCT02225730.

    View details for DOI 10.1161/STROKEAHA.119.026499

    View details for PubMedID 31619150

  • Response to letter by Samuels et al. International journal of stroke : official journal of the International Stroke Society Brinjikji, W., Albers, G. W., Koch, S., Rabinstein, A. A. 2019: 1747493019840929

    View details for PubMedID 30935348

  • Association of follow-up infarct volume with functional outcome in acute ischemic stroke: a pooled analysis of seven randomized trials JOURNAL OF NEUROINTERVENTIONAL SURGERY Boers, A. M., Jansen, I. H., Beenen, L. M., Devlin, T. G., San Roman, L., Heo, J., Ribo, M., Brown, S., Almekhlafi, M. A., Liebeskind, D. S., Teitelbaum, J., Lingsma, H. F., van Zwam, W. H., Cuadras, P., de Rochemont, R., Beaumont, M., Brown, M. M., Yoo, A. J., van Oostenbrugge, R. J., Menon, B. K., Donnan, G. A., Mas, J., Roos, Y. M., Oppenheim, C., van der Lugt, A., Dowling, R. J., Hill, M. D., Davalos, A., Moulin, T., Agrinier, N., Demchuk, A. M., Lopes, D. K., Aja Rodriguez, L., Dippel, D. J., Campbell, B. V., Mitchell, P. J., Al-Ajlan, F. S., Jovin, T. G., Madigan, J., Albers, G. W., Soize, S., Guillemin, F., Reddy, V. K., Bracard, S., Blasco, J., Muir, K. W., Nogueira, R. G., White, P. M., Goyal, M., Davis, S. M., Marquering, H. A., Majoie, C. M. 2018; 10 (12): 1137–42

    Abstract

    Follow-up infarct volume (FIV) has been recommended as an early indicator of treatment efficacy in patients with acute ischemic stroke. Questions remain about the optimal imaging approach for FIV measurement.To examine the association of FIV with 90-day modified Rankin Scale (mRS) score and investigate its dependency on acquisition time and modality.Data of seven trials were pooled. FIV was assessed on follow-up (12 hours to 2 weeks) CT or MRI. Infarct location was defined as laterality and involvement of the Alberta Stroke Program Early CT Score regions. Relative quality and strength of multivariable regression models of the association between FIV and functional outcome were assessed. Dependency of imaging modality and acquisition time (≤48 hours vs >48 hours) was evaluated.Of 1665 included patients, 83% were imaged with CT. Median FIV was 41 mL (IQR 14-120). A large FIV was associated with worse functional outcome (OR=0.88(95% CI 0.87 to 0.89) per 10 mL) in adjusted analysis. A model including FIV, location, and hemorrhage type best predicted mRS score. FIV of ≥133 mL was highly specific for unfavorable outcome. FIV was equally strongly associated with mRS score for assessment on CT and MRI, even though large differences in volume were present (48 mL (IQR 15-131) vs 22 mL (IQR 8-71), respectively). Associations of both early and late FIV assessments with outcome were similar in strength (ρ=0.60(95% CI 0.56 to 0.64) and ρ=0.55(95% CI 0.50 to 0.60), respectively).In patients with an acute ischemic stroke due to a proximal intracranial occlusion of the anterior circulation, FIV is a strong independent predictor of functional outcome and can be assessed before 48 hours, oneither CT or MRI.

    View details for PubMedID 29627794

  • Response by Demeestere et al to Letter Regarding Article, "Alberta Stroke Program Early CT Score Versus Computed Tomographic Perfusion to Predict Functional Outcome After Successful Reperfusion in Acute Ischemic Stroke". Stroke Demeestere, J., Albers, G. W., Lansberg, M., Lemmens, R. 2018: STROKEAHA118023955

    View details for PubMedID 30580744

  • Penumbral imaging and functional outcome in patients with anterior circulation ischaemic stroke treated with endovascular thrombectomy versus medical therapy: a meta-analysis of individual patient-level data. The Lancet. Neurology Campbell, B. C., Majoie, C. B., Albers, G. W., Menon, B. K., Yassi, N., Sharma, G., van Zwam, W. H., van Oostenbrugge, R. J., Demchuk, A. M., Guillemin, F., White, P., Davalos, A., van der Lugt, A., Butcher, K. S., Cherifi, A., Marquering, H. A., Cloud, G., Macho Fernandez, J. M., Madigan, J., Oppenheim, C., Donnan, G. A., Roos, Y. B., Shankar, J., Lingsma, H., Bonafe, A., Raoult, H., Hernandez-Perez, M., Bharatha, A., Jahan, R., Jansen, O., Richard, S., Levy, E. I., Berkhemer, O. A., Soudant, M., Aja, L., Davis, S. M., Krings, T., Tisserand, M., San Roman, L., Tomasello, A., Beumer, D., Brown, S., Liebeskind, D. S., Bracard, S., Muir, K. W., Dippel, D. W., Goyal, M., Saver, J. L., Jovin, T. G., Hill, M. D., Mitchell, P. J., HERMES collaborators, Berkhemer, O. A., Fransen, P. S., Beumer, D., van den Berg, L. A., Lingsma, H. F., Yoo, A. J., Schonewille, W. J., Vos, J. A., Nederkoorn, P. J., Wermer, M. J., van Walderveen, M. A., Staals, J., Hofmeijer, J., van Oostayen, J. A., Lycklama A Nijeholt, G. J., Boiten, J., Brouwer, P. A., Emmer, B. J., de Bruijn, S. F., van Dijk, L. C., Kappelle, J., Lo, R. H., van Dijk, E. J., de Vries, J., de Kort, P. L., van Rooij, W. J., van den Berg, J. S., van Hasselt, B. A., Aerden, L. A., Dallinga, R. J., Visser, M. C., Bot, J. C., Vroomen, P. C., Eshghi, O., Schreuder, T. H., Heijboer, R. J., Keizer, K., Tielbeek, A. V., den Hertog, H. M., Gerrits, D. G., van den Berg-Vos, R. M., Karas, G. B., Steyerberg, E. W., Flach, Z., Marquering, H. A., Sprengers, M. E., Jenniskens, S. F., Beenen, L. F., van den Berg, R., Koudstaal, P. J., van Zwam, W. H., Roos, Y. B., van der Lugt, A., van Oostenbrugge, R. J., Majoie, C. B., Dippel, D. W., Brown, M. M., Liebig, T., Stijnen, T., Andersson, T., Mattle, H., Wahlgren, N., van der Heijden, E., Ghannouti, N., Fleitour, N., Hooijenga, I., Puppels, C., Pellikaan, W., Geerling, A., Lindl-Velema, A., van Vemde, G., de Ridder, A., Greebe, P., de Bont-Stikkelbroeck, J., de Meris, J., Janssen, K., Struijk, W., Licher, S., Boodt, N., Ros, A., Venema, E., Slokkers, I., Ganpat, R., Mulder, M., Saiedie, N., Heshmatollah, A., Schipperen, S., Vinken, S., van Boxtel, T., Koets, J., Boers, M., Santos, E., Borst, J., Jansen, I., Kappelhof, M., Lucas, M., Geuskens, R., Barros, R. S., Dobbe, R., Csizmadia, M., Hill, M. D., Goyal, M., Demchuk, A. M., Menon, B. K., Eesa, M., Ryckborst, K. J., Wright, M. R., Kamal, N. R., Andersen, L., Randhawa, P. A., Stewart, T., Patil, S., Minhas, P., Almekhlafi, M., Mishra, S., Clement, F., Sajobi, T., Shuaib, A., Montanera, W. J., Roy, D., Silver, F. L., Jovin, T. G., Frei, D. F., Sapkota, B., Rempel, J. L., Thornton, J., Williams, D., Tampieri, D., Poppe, A. Y., Dowlatshahi, D., Wong, J. H., Mitha, A. P., Subramaniam, S., Hull, G., Lowerison, M. W., Sajobi, T., Salluzzi, M., Wright, M. R., Maxwell, M., Lacusta, S., Drupals, E., Armitage, K., Barber, P. A., Smith, E. E., Morrish, W. F., Coutts, S. B., Derdeyn, C., Demaerschalk, B., Yavagal, D., Martin, R., Brant, R., Yu, Y., Willinsky, R. A., Montanera, W. J., Weill, A., Kenney, C., Aram, H., Stewart, T., Stys, P. K., Watson, T. W., Klein, G., Pearson, D., Couillard, P., Trivedi, A., Singh, D., Klourfeld, E., Imoukhuede, O., Nikneshan, D., Blayney, S., Reddy, R., Choi, P., Horton, M., Musuka, T., Dubuc, V., Field, T. S., Desai, J., Adatia, S., Alseraya, A., Nambiar, V., van Dijk, R., Wong, J. H., Mitha, A. P., Morrish, W. F., Eesa, M., Newcommon, N. J., Shuaib, A., Schwindt, B., Butcher, K. S., Jeerakathil, T., Buck, B., Khan, K., Naik, S. S., Emery, D. J., Owen, R. J., Kotylak, T. B., Ashforth, R. A., Yeo, T. 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    Abstract

    BACKGROUND: CT perfusion (CTP) and diffusion or perfusion MRI might assist patient selection for endovascular thrombectomy. We aimed to establish whether imaging assessments of irreversibly injured ischaemic core and potentially salvageable penumbra volumes were associated with functional outcome and whether they interacted with the treatment effect of endovascular thrombectomy on functional outcome.METHODS: In this systematic review and meta-analysis, the HERMES collaboration pooled patient-level data from all randomised controlled trials that compared endovascular thrombectomy (predominantly using stent retrievers) with standard medical therapy in patients with anterior circulation ischaemic stroke, published in PubMed from Jan 1, 2010, to May 31, 2017. The primary endpoint was functional outcome, assessed by the modified Rankin Scale (mRS) at 90 days after stroke. Ischaemic core was estimated, before treatment with either endovascular thrombectomy or standard medical therapy, by CTP as relative cerebral blood flow less than 30% of normal brain blood flow or by MRI as an apparent diffusion coefficient less than 620 mum2/s. Critically hypoperfused tissue was estimated as the volume of tissue with a CTP time to maximum longer than 6 s. Mismatch volume (ie, the estimated penumbral volume) was calculated as critically hypoperfused tissue volume minus ischaemic core volume. The association of ischaemic core and penumbral volumes with 90-day mRS score was analysed with multivariable logistic regression (functional independence, defined as mRS score 0-2) and ordinal logistic regression (functional improvement by at least one mRS category) in all patients and in a subset of those with more than 50% endovascular reperfusion, adjusted for baseline prognostic variables. The meta-analysis was prospectively designed by the HERMES executive committee, but not registered.FINDINGS: We identified seven studies with 1764 patients, all of which were included in the meta-analysis. CTP was available and assessable for 591 (34%) patients and diffusion MRI for 309 (18%) patients. Functional independence was worse in patients who had CTP versus those who had diffusion MRI, after adjustment for ischaemic core volume (odds ratio [OR] 0·47 [95% CI 0·30-0·72], p=0·0007), so the imaging modalities were not pooled. Increasing ischaemic core volume was associated with reduced likelihood of functional independence (CTP OR 0·77 [0·69-0·86] per 10 mL, pinteraction=0·29; diffusion MRI OR 0·87 [0·81-0·94] per 10 mL, pinteraction=0·94). Mismatch volume, examined only in the CTP group because of the small numbers of patients who had perfusion MRI, was not associated with either functional independence or functional improvement. In patients with CTP with more than 50% endovascular reperfusion (n=186), age, ischaemic core volume, and imaging-to-reperfusion time were independently associated with functional improvement. Risk of bias between studies was generally low.INTERPRETATION: Estimated ischaemic core volume was independently associated with functional independence and functional improvement but did not modify the treatment benefit of endovascular thrombectomy over standard medical therapy for improved functional outcome. Combining ischaemic core volume with age and expected imaging-to-reperfusion time will improve assessment of prognosis and might inform endovascular thrombectomy treatment decisions.FUNDING: Medtronic.

    View details for PubMedID 30413385

  • Alberta Stroke Program Early CT Score Versus Computed Tomographic Perfusion to Predict Functional Outcome After Successful Reperfusion in Acute Ischemic Stroke. Stroke Demeestere, J., Scheldeman, L., Cornelissen, S. A., Heye, S., Wouters, A., Dupont, P., Christensen, S., Mlynash, M., Albers, G. W., Lansberg, M., Lemmens, R. 2018; 49 (10): 2361–67

    Abstract

    Background and Purpose- We aimed to compare the ability of conventional Alberta Stroke Program Early CT Score (ASPECTS), automated ASPECTS, and ischemic core volume on computed tomographic perfusion to predict clinical outcome in ischemic stroke because of large vessel occlusion ≤18 hours after symptom onset. Methods- We selected patients with acute ischemic stroke from the CRISP study (Computed Tomographic Perfusion to Predict Response to Recanalization in Ischemic Stroke Project) with successful reperfusion (modified treatment in cerebral ischemia score 2b or 3). We used e-ASPECTS software to calculate automated ASPECTS and RAPID software to estimate ischemic core volumes. We studied associations between these imaging characteristics and good outcome (modified Rankin Scale score, 0-2) or poor outcome (modified Rankin Scale score, 4-6) in univariable and multivariable analysis, after adjustment for relevant clinical confounders. Results- We included 156 patients. Conventional and automated ASPECTS was not associated with good or poor outcome in univariable analysis ( P=nonsignificant for all). Automated ASPECTS was associated with good outcome in multivariable analysis ( P=0.02) but not with poor outcome. Ischemic core volume was associated with good ( P<0.01) and poor outcome ( P=0.04) in univariable and multivariable analysis ( P=0.03 and P=0.02, respectively). Computed tomographic perfusion predicted good outcome with an area under the curve of 0.62 (95% CI, 0.53-0.71) and optimal cutoff core volume of 15 mL. Conclusions- Ischemic core volume assessed on computed tomographic perfusion is a predictor of clinical outcome among patients in whom endovascular reperfusion is achieved ≤18 hours after symptom onset. In this population, conventional or automated ASPECTS did not predict outcome.

    View details for PubMedID 30355098

  • Endovascular thrombectomy in patients with large infarctions: reasons for restraint. The Lancet. Neurology Albers, G. W. 2018; 17 (10): 836–37

    View details for PubMedID 30264719

  • KEY SUBGROUP ANALYSES FROM THE SELECT STUDY Sarraj, A., Grotta, J., Hassan, A., Abraham, M., Haussen, D., Vora, N., Hellinger, F., Edgell, R., Gupta, R., Albers, G. SAGE PUBLICATIONS LTD. 2018: 228

    View details for Web of Science ID 000448113303244

  • Relative cerebral blood volume is associated with collateral status and infarct growth in stroke patients in SWIFT PRIME JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM Arenillas, J. F., Cortijo, E., Garcia-Bermejo, P., Levy, E. I., Jahan, R., Liebeskind, D., Goyal, M., Saver, J. L., Albers, G. W. 2018; 38 (10): 1839–47

    Abstract

    We aimed to evaluate how predefined candidate cerebral perfusion parameters correlate with collateral circulation status and to assess their capacity to predict infarct growth in patients with acute ischemic stroke (AIS) eligible for endovascular therapy. Patients enrolled in the SWIFT PRIME trial with baseline computed tomography perfusion (CTP) scans were included. RAPID software was used to calculate mean relative cerebral blood volume (rCBV) in hypoperfused regions, and hypoperfusion index ratio (HIR). Blind assessments of collaterals were performed using CT angiography in the whole sample and cerebral angiogram in the endovascular group. Reperfusion was assessed on 27-h CTP; infarct volume was assessed on 27-h magnetic resonance imaging/CT scans. Logistic and rank linear regression models were conducted. We included 158 patients. High rCBV ( p = 0.03) and low HIR ( p = 0.03) were associated with good collaterals. A positive association was found between rCBV and better collateral grades on cerebral angiography ( p = 0.01). Baseline and 27-h follow-up CTP were available for 115 patients, of whom 74 (64%) achieved successful reperfusion. Lower rCBV predicted a higher infarct growth in successfully reperfused patients ( p = 0.038) and in the endovascular treatment group ( p = 0.049). Finally, rCBV and HIR may serve as markers of collateral circulation in AIS patients prior to endovascular therapy.Unique identifier: NCT0165746.

    View details for PubMedID 29135347

    View details for PubMedCentralID PMC6168913

  • Volumetric and Spatial Accuracy of Computed Tomography Perfusion Estimated Ischemic Core Volume in Patients With Acute Ischemic Stroke. Stroke Hoving, J. W., Marquering, H. A., Majoie, C. B., Yassi, N., Sharma, G., Liebeskind, D. S., van der Lugt, A., Roos, Y. B., van Zwam, W., van Oostenbrugge, R. J., Goyal, M., Saver, J. L., Jovin, T. G., Albers, G. W., Davalos, A., Hill, M. D., Demchuk, A. M., Bracard, S., Guillemin, F., Muir, K. W., White, P., Mitchell, P. J., Donnan, G. A., Davis, S. M., Campbell, B. C. 2018; 49 (10): 2368–75

    Abstract

    Background and Purpose- The volume of estimated ischemic core using computed tomography perfusion (CTP) imaging can identify ischemic stroke patients who are likely to benefit from reperfusion, particularly beyond standard time windows. We assessed the accuracy of pretreatment CTP estimated ischemic core in patients with successful endovascular reperfusion. Methods- Patients from the HERMES (Highly Effective Reperfusion Evaluated in Multiple Endovascular Stroke Trials) and EXTEND-IA TNK (Tenecteplase Versus Alteplase Before Endovascular Therapy for Ischemic Stroke) databases who had pretreatment CTP, >50% angiographic reperfusion, and follow-up magnetic resonance imaging at 24 hours were included. Ischemic core volume on baseline CTP data was estimated using relative cerebral blood flow <30% (RAPID, iSchemaView). Follow-up diffusion magnetic resonance imaging was registered to CTP, and the diffusion lesion was outlined using a semiautomated algorithm. Volumetric and spatial agreement (using Dice similarity coefficient, average Hausdorff distance, and precision) was assessed, and expert visual assessment of quality was performed. Results- In 120 patients, median CTP estimated ischemic core volume was 7.8 mL (IQR, 1.8-19.9 mL), and median diffusion lesion volume at 24 hours was 30.8 mL (IQR, 14.9-67.6 mL). Median volumetric difference was 4.4 mL (IQR, 1.2-12.0 mL). Dice similarity coefficient was low (median, 0.24; IQR, 0.15-0.37). The median precision (positive predictive value) of 0.68 (IQR, 0.40-0.88) and average Hausdorff distance (median, 3.1; IQR, 1.8-5.7 mm) indicated reasonable spatial agreement for regions estimated as ischemic core at baseline. Overestimation of total ischemic core volume by CTP was uncommon. Expert visual review revealed overestimation predominantly in white matter regions. Conclusions- CTP estimated ischemic core volumes were substantially smaller than follow-up diffusion-weighted imaging lesions at 24 hours despite endovascular reperfusion within 2 hours of imaging. This may be partly because of infarct growth. Volumetric CTP core overestimation was uncommon and not related to imaging-to-reperfusion time. Core overestimation in white matter should be a focus of future efforts to improve CTP accuracy.

    View details for PubMedID 30355095

  • Rivaroxaban for Thromboprophylaxis after Hospitalization for Medical Illness NEW ENGLAND JOURNAL OF MEDICINE Spyropoulos, A. C., Ageno, W., Albers, G. W., Elliott, C., Halperin, J. L., Hiatt, W. R., Maynard, G. A., Steg, P., Weitz, J. I., Suh, E., Spiro, T. E., Barnathan, E. S., Raskob, G. E., Jure, H., Alvarisqueta, A., Cartasegna, L., Hominal, M., Cursack, G., Alzogaray, M., Maillo, M., Parody, M., Caccavo, A., Dran, R., Muntaner, J., Casas, M., Schmidberg, J., Sarjanovich, R., Gabito, A., Garrido, M., Amuchastegui, M., Fernandez, A., Loureyro, J., Giumelli, C., Heazlewood, V., Karrasch, J., Colquhoun, D., White, H., Sabet, A., Bowler, S., Carroll, P., Khalafallah, A., Baker, R., Hedger, S., Simpson, F., Jackson, D., Chong Beng, Eichinger-Hasenauer, S., Siostrzonek, P., Gary, T., Hoppe, U., Dosta, N., Krivenchuk, V., Prystrom, A., Gorokhovsky, S., Yanushko, V., Skrahin, A., Kulik, A., Maslianski, B., Yakubtsevich, R., Timkin, I., Moguchaya, O., Tanaskovic, N., Miljkovic, S., Stojkovic, S., Kovacevic-Preradovic, T., Jovic, D., Basagic, E., Radjen, M., Mutapcic, M., Rizvanovic-Vojic, E., Galic, K., Terzic, I., Pojskic, B., Stevanovic, D., Cehajic, M., Trbojevic, S., Rech, R., Annichino-Bizzacchi, J., Stelmach, R., Blanco, D., Castro, I., Backes, L., Saraiva, J., Ramacciotti, E., de Barros e Silva, P., Reis, G., Vieira, M., Leaes, P., Zimmermann, S., Van Bellen, B., Precoma, D., Silvestrini, L., Hernandes, M., Kyoleyan, M., Kalinova, T., Tiholov, R., Petrov, I., Mihov, A., Chompalova, B., Velikov, C., Pencheva, G., Atanasov, P., Raev, D., Kinova, E., Peltegov, V., Marchev, S., Mincheva, V., Siulemezova, S., Ayryanova, I., Grigorov, M., Naydenova, I., Koteva, N., Dimov, B., Runev, N., Getov, D., Metev, H., Donchev, K., Taseva, M., Hadzhieva, A., Benov, H., Stoyanov, M., Tisheva-Gospodinova, S., Mihaylova, N., Abadzhiev, S., Atzev, B., Georgiev, R., Mollov, M., Stoikov, A., Mazhdrakov, G., Karastanev, K., Dube, F., Roth, S., Mansour, S., Carrier, M., Wu, C., Dolan, S., Pesant, Y., Pietrangelo, M., Dresser, G., Kahn, S., Kruisselbrink, R., Cadena Bonfanti, A., Botero, R., Quintero Ossa, A., Poveda, C., Cedano, J., Gomez Isaza, L., Villaquiran Torres, C., MARINER Investigators 2018; 379 (12): 1118–27

    View details for DOI 10.1056/NEJMoa1805090

    View details for Web of Science ID 000445020900006

  • Hypoperfusion Ratio predicts infarct growth during transfer for thrombectomy. Annals of neurology Guenego, A., Mlynash, M., Christensen, S., Kemp, S., Heit, J. J., Lansberg, M. G., Albers, G. W. 2018

    Abstract

    We hypothesized that automated assessment of collaterals on computed-tomography (CT) perfusion can predict the rate of infarct growth during transfer from a primary to a comprehensive stroke center for endovascular stroke treatment. We identified consecutive patients (N=28) and assessed their collaterals based on the hypoperfusion intensity ratio (HIR) prior to transfer. Infarct growth rate was strongly correlated with HIR (r= 0.78, p<0.001). ROC analysis identified an HIR of ≥0.5 as optimal for predicting infarct growth. Patients with HIR ≥ 0.5 had a median infarct growth rate of 10.1 mL/h (IQR: 6.4-18.4) compared with 0.9 mL/h (IQR: 0-2.8), p< 0.001) in patients with a HIR < 0.5. Patients with an HIR above ≥ 0.5 had an 83% probability of significant core growth, whereas patients with HIR <0.5 had an 88% probability of core stability. These preliminary data have the potential to guide decision making regarding whether repeat brain imaging should be performed after transfer to a comprehensive stroke center. This article is protected by copyright. All rights reserved.

    View details for PubMedID 30168180

  • Rivaroxaban for Thromboprophylaxis after Hospitalization for Medical Illness. The New England journal of medicine Spyropoulos, A. C., Ageno, W., Albers, G. W., Elliott, C. G., Halperin, J. L., Hiatt, W. R., Maynard, G. A., Steg, P. G., Weitz, J. I., Suh, E., Spiro, T. E., Barnathan, E. S., Raskob, G. E., MARINER Investigators 2018

    Abstract

    Background Patients who are hospitalized for medical illness remain at risk for venous thromboembolism after discharge, but the role of extended thromboprophylaxis in the treatment of such patients is a subject of controversy. Methods In this randomized, double-blind trial, medically ill patients who were at increased risk for venous thromboembolism on the basis of a modified International Medical Prevention Registry on Venous Thromboembolism (IMPROVE) score of 4 or higher (scores range from 0 to 10, with higher scores indicating a higher risk of venous thromboembolism) or a score of 2 or 3 plus a plasma d-dimer level of more than twice the upper limit of the normal range (defined according to local laboratory criteria) were assigned at hospital discharge to either once-daily rivaroxaban at a dose of 10 mg (with the dose adjusted for renal insufficiency) or placebo for 45 days. The primary efficacy outcome was a composite of symptomatic venous thromboembolism or death due to venous thromboembolism. The principal safety outcome was major bleeding. Results Of the 12,024 patients who underwent randomization, 12,019 were included in the intention-to-treat analysis. The primary efficacy outcome occurred in 50 of 6007 patients (0.83%) who were given rivaroxaban and in 66 of 6012 patients (1.10%) who were given placebo (hazard ratio, 0.76; 95% confidence interval [CI], 0.52 to 1.09; P=0.14). The prespecified secondary outcome of symptomatic nonfatal venous thromboembolism occurred in 0.18% of patients in the rivaroxaban group and 0.42% of patients in the placebo group (hazard ratio, 0.44; 95% CI, 0.22 to 0.89). Major bleeding occurred in 17 of 5982 patients (0.28%) in the rivaroxaban group and in 9 of 5980 patients (0.15%) in the placebo group (hazard ratio, 1.88; 95% CI, 0.84 to 4.23). Conclusions Rivaroxaban, given to medical patients for 45 days after hospital discharge, was not associated with a significantly lower risk of symptomatic venous thromboembolism and death due to venous thromboembolism than placebo. The incidence of major bleeding was low. (Funded by Janssen Research and Development; MARINER ClinicalTrials.gov number, NCT02111564 .).

    View details for PubMedID 30145946

  • Endovascular Treatment in the DEFUSE 3 Study. Stroke Marks, M. P., Heit, J. J., Lansberg, M. G., Kemp, S., Christensen, S., Derdeyn, C. P., Rasmussen, P. A., Zaidat, O. O., Broderick, J. P., Yeatts, S. D., Hamilton, S., Mlynash, M., Albers, G. W. 2018

    Abstract

    BACKGROUND AND PURPOSE: Endovascular therapy in an extended time window has been shown to be beneficial in selected patients. This study correlated angiographic outcomes of patients randomized to endovascular therapy with clinical and imaging outcomes in the DEFUSE 3 study (Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke 3).METHODS: Angiograms were assessed for the primary arterial occlusive lesion and the modified Thrombolysis in Cerebral Infarction (TICI) score at baseline and the final modified TICI score. Clinical outcomes were assessed using an ordinal analysis of 90-day modified Rankin Scale and a dichotomous analysis for functional independence (modified Rankin Scale score of 0-2). TICI scores were correlated with outcome, types of device used for thrombectomy, and 24-hour follow-up imaging.RESULTS: TICI 2B-3 reperfusion was achieved in 70 of 92 patients (76%). TICI 2B-3 reperfusion showed a more favorable distribution of Rankin scores compared with TICI 0-2A; odds ratio, 2.77; 95% confidence interval, 1.17-6.56; P=0.019. Good functional outcome (90-day modified Rankin Scale score of 0-2) increased with better TICI scores (P=0.0028). There was less disability comparing TICI 3 patients to TICI 2B patients (P=0.037). Successful reperfusion (TICI 2B-3) was independent of the device used, the site of occlusion (internal carotid artery or M1) or adjunctive use of carotid angioplasty and stenting. Significantly less infarct growth at 24 hours was seen in TICI 3 patients compared with TICI 0-2A (P=0.0015) and TICI 2B (P=0.0002) patients.CONCLUSIONS: Thrombectomy in an extended time window demonstrates similar rates of TICI 2B-3 reperfusion to earlier time window studies. Successful reperfusion was independent of the device used, the site of occlusion or adjunctive use of carotid angioplasty and stenting. TICI 3 reperfusion was more likely to result in low rates of infarct growth at 24 hours and good functional outcome at 90 days.CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02586415.

    View details for DOI 10.1161/STROKEAHA.118.022147

    View details for PubMedID 29986935

  • Efficacy and Safety of Ticagrelor in Relation to Aspirin Use Within the Week Before Randomization in the SOCRATES Trial STROKE Wong, K., Amarenco, P., Albers, G. W., Denison, H., Easton, J., Evans, S. R., Held, P., Himmelmann, A., Kasner, S. E., Knutsson, M., Ladenvall, P., Minematsu, K., Molina, C. A., Wang, Y., Johnston, S., SOCRATES Steering Comm 2018; 49 (7): 1678–85

    Abstract

    SOCRATES (Acute Stroke or Transient Ischemic Attack Treated With Aspirin or Ticagrelor and Patient Outcomes), comparing ticagrelor with aspirin in patients with acute cerebral ischemia, found a nonsignificant 11% relative risk reduction for stroke, myocardial infarction, or death (P=0.07). Aspirin intake before randomization could enhance the effect of ticagrelor by conferring dual antiplatelet effect during a high-risk period for subsequent stroke. Therefore, we explored the efficacy and safety of ticagrelor versus aspirin in the patients who received any aspirin the week before randomization.A prespecified subgroup analysis in SOCRATES (n=13 199), randomizing patients with acute ischemic stroke (National Institutes of Health Stroke Scale score of ≤5) or transient ischemic attack (ABCD2 score of ≥4) to 90-day treatment with ticagrelor or aspirin. Patients in the prior-aspirin group had received any aspirin within the week before randomization. Primary end point was time to stroke, myocardial infarction, or death. Safety end point was PLATO (Study of Platelet Inhibition and Patient Outcomes) major bleeding.The 4232 patients in the prior-aspirin group were older, had more vascular risk factors, and vascular disease than the other patients. In the prior-aspirin group, the primary end point occurred in 138/2130 (6.5%) of patients on ticagrelor and in 177/2102 (8.3%) on aspirin (hazard ratio, 0.76; 95% confidence interval, 0.61-0.95; P=0.02); in patients with no prior-aspirin usage an event occurred in 304/4459 (6.9%) and 320/4508 (7.1%) on ticagrelor and aspirin, respectively (hazard ratio, 0.96; 95% confidence interval, 0.82-1.12; P=0.59). The treatment-by-prior-aspirin interaction was not statistically significant (P=0.10). In the prior-aspirin group, major bleeding occurred in 0.7% and 0.4% of patients on ticagrelor and aspirin, respectively (hazard ratio, 1.58; 95% confidence interval, 0.68-3.65; P=0.28).In this secondary analysis from SOCRATES, fewer primary end points occurred on ticagrelor treatment than on aspirin in patients receiving aspirin before randomization, but there was no significant treatment-by-prior-aspirin interaction. A new study will investigate the benefit-risk of combining ticagrelor and aspirin in patients with acute cerebral ischemia (URL: https://www.clinicaltrials.gov. Unique identifier: NCT03354429).URL: https://www.clinicaltrials.gov. Unique identifier: NCT01994720.

    View details for PubMedID 29915123

    View details for PubMedCentralID PMC6019568

  • Multimodal magnetic resonance imaging to identify stroke onset within 6 h in patients with large vessel occlusions EUROPEAN STROKE JOURNAL Wouters, A., Dupont, P., Christensen, S., Norrving, B., Laage, R., Thomalla, G., Kemp, S., Lansberg, M., Thijs, V., Albers, G. W., Lemmens, R. 2018; 3 (2): 185–92

    View details for DOI 10.1177/2396987317753486

    View details for Web of Science ID 000432064200011

  • Five-Year Risk of Stroke after TIA or Minor Ischemic Stroke. The New England journal of medicine Amarenco, P., Lavallee, P. C., Monteiro Tavares, L., Labreuche, J., Albers, G. W., Abboud, H., Anticoli, S., Audebert, H., Bornstein, N. M., Caplan, L. R., Correia, M., Donnan, G. A., Ferro, J. M., Gongora-Rivera, F., Heide, W., Hennerici, M. G., Kelly, P. J., Kral, M., Lin, H., Molina, C., Park, J. M., Purroy, F., Rothwell, P. M., Segura, T., Skoloudik, D., Steg, P. G., Touboul, P., Uchiyama, S., Vicaut, E., Wang, Y., Wong, L. K., TIAregistry.org Investigators,, 2018

    Abstract

    Background After a transient ischemic attack (TIA) or minor stroke, the long-term risk of stroke and other vascular events is not well known. In this follow-up to a report on 1-year outcomes from a registry of TIA clinics in 21 countries that enrolled 4789 patients with a TIA or minor ischemic stroke from 2009 through 2011, we examined the 5-year risk of stroke and vascular events. Methods We evaluated patients who had had a TIA or minor stroke within 7 days before enrollment in the registry. Among 61 sites that participated in the 1-year outcome study, we selected 42 sites that had follow-up data on more than 50% of their enrolled patients at 5 years. The primary outcome was a composite of stroke, acute coronary syndrome, or death from cardiovascular causes (whichever occurred first), with an emphasis on events that occurred in the second through fifth years. In calculating the cumulative incidence of the primary outcome and secondary outcomes (except death from any cause), we treated death as a competing risk. Results A total of 3847 patients were included in the 5-year follow-up study; the median percentage of patients with 5-year follow-up data per center was 92.3% (interquartile range, 83.4 to 97.8). The composite primary outcome occurred in 469 patients (estimated cumulative rate, 12.9%; 95% confidence interval [CI], 11.8 to 14.1), with 235 events (50.1%) occurring in the second through fifth years. At 5 years, strokes had occurred in 345 patients (estimated cumulative rate, 9.5%; 95% CI, 8.5 to 10.5), with 149 of these patients (43.2%) having had a stroke during the second through fifth years. Rates of death from any cause, death from cardiovascular causes, intracranial hemorrhage, and major bleeding were 10.6%, 2.7%, 1.1%, and 1.5%, respectively, at 5 years. In multivariable analyses, ipsilateral large-artery atherosclerosis, cardioembolism, and a baseline ABCD2 score for the risk of stroke (range, 0 to 7, with higher scores indicating greater risk) of 4 or more were each associated with an increased risk of subsequent stroke. Conclusions In a follow-up to a 1-year study involving patients who had a TIA or minor stroke, the rate of cardiovascular events including stroke in a selected cohort was 6.4% in the first year and 6.4% in the second through fifth years. (Funded by AstraZeneca and others.).

    View details for PubMedID 29766771

  • Thrombectomy for Stroke with Selection by Perfusion Imaging REPLY NEW ENGLAND JOURNAL OF MEDICINE Albers, G. W., Marks, M. P., Lansberg, M. G. 2018; 378 (19): 1849–50

    View details for Web of Science ID 000431774400020

  • Automated DWI analysis can identify patients within the thrombolysis time window of 4.5 hours. Neurology Wouters, A., Cheng, B., Christensen, S., Dupont, P., Robben, D., Norrving, B., Laage, R., Thijs, V. N., Albers, G. W., Thomalla, G., Lemmens, R. 2018; 90 (18): e1570–e1577

    Abstract

    OBJECTIVE: To develop an automated model based on diffusion-weighted imaging (DWI) to detect patients within 4.5 hours after stroke onset and compare this method to the visual DWI-FLAIR (fluid-attenuated inversion recovery) mismatch.METHODS: We performed a subanalysis of the "DWI-FLAIR mismatch for the identification of patients with acute ischemic stroke within 4.5 hours of symptom onset" (PRE-FLAIR) and the "AX200 for ischemic stroke" (AXIS 2) trials. We developed a prediction model with data from the PRE-FLAIR study by backward logistic regression with the 4.5-hour time window as dependent variable and the following explanatory variables: age and median relative DWI (rDWI) signal intensity, interquartile range (IQR) rDWI signal intensity, and volume of the core. We obtained the accuracy of the model to predict the 4.5-hour time window and validated our findings in an independent cohort from the AXIS 2 trial. We compared the receiver operating characteristic curve to the visual DWI-FLAIR mismatch.RESULTS: In the derivation cohort of 118 patients, we retained the IQR rDWI as explanatory variable. A threshold of 0.39 was most optimal in selecting patients within 4.5 hours after stroke onset resulting in a sensitivity of 76% and specificity of 63%. The accuracy was validated in an independent cohort of 200 patients. The predictive value of the area under the curve of 0.72 (95% confidence interval 0.64-0.80) was similar to the visual DWI-FLAIR mismatch (area under the curve = 0.65; 95% confidence interval 0.58-0.72; p for difference = 0.18).CONCLUSIONS: An automated analysis of DWI performs at least as good as the visual DWI-FLAIR mismatch in selecting patients within the 4.5-hour time window.

    View details for PubMedID 29618622

  • Design and Implementation of a Novel Acute Stroke Code for the Extended Window of Endovascular Treatment Legault, C., Dujari, S., Shen, S. H., Wagner, A. M., Albers, G., Bernier, E., Callagy, P., Vora, N. LIPPINCOTT WILLIAMS & WILKINS. 2018

    View details for Web of Science ID 000453090803006

  • Time From Imaging to Endovascular Reperfusion Predicts Outcome in Acute Stroke STROKE Tsai, J. P., Mlynash, M., Christensen, S., Kemp, S., Kim, S., Mishra, N. K., Federau, C., Nogueira, R. G., Jovin, T. G., Devlin, T. G., Akhtar, N., Yavagal, D. R., Bammer, R., Straka, M., Zaharchuk, G., Marks, M. P., Albers, G. W., Lansberg, M. G., CRISP Investigators 2018; 49 (4): 952-+

    Abstract

    This study aims to describe the relationship between computed tomographic (CT) perfusion (CTP)-to-reperfusion time and clinical and radiological outcomes, in a cohort of patients who achieve successful reperfusion for acute ischemic stroke.We included data from the CRISP (Computed Tomographic Perfusion to Predict Response in Ischemic Stroke Project) in which all patients underwent a baseline CTP scan before endovascular therapy. Patients were included if they had a mismatch on their baseline CTP scan and achieved successful endovascular reperfusion. Patients with mismatch were categorized into target mismatch and malignant mismatch profiles, according to the volume of their Tmax >10s lesion volume (target mismatch, <100 mL; malignant mismatch, >100 mL). We investigated the impact of CTP-to-reperfusion times on probability of achieving functional independence (modified Rankin Scale, 0-2) at day 90 and radiographic outcomes at day 5.Of 156 included patients, 108 (59%) had the target mismatch profile, and 48 (26%) had the malignant mismatch profile. In patients with the target mismatch profile, CTP-to-reperfusion time showed no association with functional independence (P=0.84), whereas in patients with malignant mismatch profile, CTP-to-reperfusion time was strongly associated with lower probability of functional independence (odds ratio, 0.08; P=0.003). Compared with patients with target mismatch, those with the malignant mismatch profile had significantly more infarct growth (90 [49-166] versus 43 [18-81] mL; P=0.006) and larger final infarct volumes (110 [61-155] versus 48 [21-99] mL; P=0.001).Compared with target mismatch patients, those with the malignant profile experience faster infarct growth and a steeper decline in the odds of functional independence, with longer delays between baseline imaging and reperfusion. However, this does not exclude the possibility of treatment benefit in patients with a malignant profile.

    View details for PubMedID 29581341

  • Late Window Paradox STROKE Albers, G. W. 2018; 49 (3): 768–71

    View details for PubMedID 29367336

  • Effects of alteplase for acute stroke according to criteria defining the European Union and United States marketing authorizations: Individual-patient-data meta-analysis of randomized trials INTERNATIONAL JOURNAL OF STROKE Hacke, W., Lyden, P., Emberson, J., Baigent, C., Blackwell, L., Albers, G., Bluhmki, E., Brott, T., Cohen, G., Davis, S. M., Donnan, G. A., Grotta, J. C., Howard, G., Kaste, M., Koga, M., von Kummer, R., Lansberg, M. G., Lindley, R. I., Olivot, J., Parsons, M., Sandercock, P. G., Toni, D., Toyoda, K., Wahlgren, N., Wardlaw, J. M., Whiteley, W. N., del Zoppo, G., Lees, K. R., Stroke Thrombolysis Trialists' 2018; 13 (2): 175–89

    Abstract

    Background The recommended maximum age and time window for intravenous alteplase treatment of acute ischemic stroke differs between the Europe Union and United States. Aims We compared the effects of alteplase in cohorts defined by the current Europe Union or United States marketing approval labels, and by hypothetical revisions of the labels that would remove the Europe Union upper age limit or extend the United States treatment time window to 4.5 h. Methods We assessed outcomes in an individual-patient-data meta-analysis of eight randomized trials of intravenous alteplase (0.9 mg/kg) versus control for acute ischemic stroke. Outcomes included: excellent outcome (modified Rankin score 0-1) at 3-6 months, the distribution of modified Rankin score, symptomatic intracerebral hemorrhage, and 90-day mortality. Results Alteplase increased the odds of modified Rankin score 0-1 among 2449/6136 (40%) patients who met the current European Union label and 3491 (57%) patients who met the age-revised label (odds ratio 1.42, 95% CI 1.21-1.68 and 1.43, 1.23-1.65, respectively), but not in those outside the age-revised label (1.06, 0.90-1.26). By 90 days, there was no increased mortality in the current and age-revised cohorts (hazard ratios 0.98, 95% CI 0.76-1.25 and 1.01, 0.86-1.19, respectively) but mortality remained higher outside the age-revised label (1.19, 0.99-1.42). Similarly, alteplase increased the odds of modified Rankin score 0-1 among 1174/6136 (19%) patients who met the current US approval and 3326 (54%) who met a 4.5-h revised approval (odds ratio 1.55, 1.19-2.01 and 1.37, 1.17-1.59, respectively), but not for those outside the 4.5-h revised approval (1.14, 0.97-1.34). By 90 days, no increased mortality remained for the current and 4.5-h revised label cohorts (hazard ratios 0.99, 0.77-1.26 and 1.02, 0.87-1.20, respectively) but mortality remained higher outside the 4.5-h revised approval (1.17, 0.98-1.41). Conclusions An age-revised European Union label or 4.5-h-revised United States label would each increase the number of patients deriving net benefit from alteplase by 90 days after acute ischemic stroke, without excess mortality.

    View details for DOI 10.1177/1747493017744464

    View details for Web of Science ID 000426007700011

    View details for PubMedID 29171359

  • Regional Contributions to Poststroke Disability in Endovascular Therapy INTERVENTIONAL NEUROLOGY Sheth, S. A., Malhotra, K., Liebeskind, D. S., Liang, C. W., Yoo, A. J., Jahan, R., Nogueira, R. G., Pereira, V., Gralla, J., Albers, G., Goyal, M., Saver, J. L., SWIFT STAR SWIFT PRIME Investigato 2018; 7 (6): 533–43

    View details for DOI 10.1159/000492400

    View details for Web of Science ID 000447256900029

  • Regional Contributions to Poststroke Disability in Endovascular Therapy. Interventional neurology Sheth, S. A., Malhotra, K., Liebeskind, D. S., Liang, C. W., Yoo, A. J., Jahan, R., Nogueira, R. G., Pereira, V., Gralla, J., Albers, G., Goyal, M., Saver, J. L. 2018; 7 (6): 533–43

    Abstract

    The relative contribution of each Alberta Stroke Program Early CT Score (ASPECTS) region to poststroke disability likely varies across regions. Determining the relative weights of each ASPECTS region may improve patient selection for endovascular stroke therapy (EST).In the combined Solitaire Flow Restoration with the Intention for Thrombectomy (SWIFT), Solitaire Flow Restoration Thrombectomy for Acute Revascularization (STAR), and Solitaire Flow Restoration with the Intention for Thrombectomy as Primary Endovascular Treatment (SWIFT PRIME) databases, we identified patients treated with the Solitaire stent retriever. Using 24-h CT scan, a multivariate ordinal regression was used to determine the relative contribution of each ASPECTS region to clinical outcome separately in each hemisphere. The coefficients from the regression were used to create a weighted ASPECTS (wASPECTS), which was compared with the original ASPECTS to predict 90-day modified Rankin Scale disability outcomes in an independent validation cohort.Among 342 patients treated with EST, the average age was 67 years, 57% were female, and the median National Institutes of Health Stroke Scale (NIHSS) score was 17 (IQR 13-20). The median ASPECTS at presentation was 8 (IQR 7-10). The most commonly involved ASPECTS regions on 24-h CT were the lentiform nuclei (70%), insula (55%), and caudate (52%). In multivariate analysis, preservation of M6 (β = 9.7) and M4 (β = 4.4) regions in the right hemisphere was most strongly predictive of good outcome. For the left hemisphere, M6 (β = 5.5), M5 (β = 4.1), and M3 (β = 3.1) generated the greatest parameter estimates, though they did not reach statistical significance. A wASPECTS incorporating all 20 parameter estimates resulted in improved discrimination against the original ASPECTS in the independent cohort (C-statistic 0.78 vs. 0.67, right hemisphere).For both right and left hemisphere, preservation of the high cortical regions was more strongly associated with improved outcomes compared to the deep regions. Our findings support taking into consideration the location and relative weightings of the involved ASPECTS regions when evaluating a patient for EST.

    View details for PubMedID 30410533

  • Multimodal magnetic resonance imaging to identify stroke onset within 6 h in patients with large vessel occlusions. European stroke journal Wouters, A., Dupont, P., Christensen, S., Norrving, B., Laage, R., Thomalla, G., Kemp, S., Lansberg, M., Thijs, V., Albers, G. W., Lemmens, R. 2018; 3 (2): 185–92

    Abstract

    Mechanical thrombectomy within 6 h after stroke onset improves the outcome in patients with large vessel occlusions. The aim of our study was to establish a model based on diffusion weighted and perfusion weighted imaging to provide an accurate prediction for the 6 h time-window in patients with unknown time of stroke onset.A predictive model was designed based on data from the DEFUSE 2 study and validated in a subgroup of patients with large vessel occlusions from the AXIS 2 trial.We constructed the model in 91 patients from DEFUSE 2. The following parameters were independently associated with <6 h time-window and included in the model: interquartile range and median relative diffusion weighted imaging, hypoperfusion intensity ratio, core volume and the interaction between median relative diffusion weighted imaging and hypoperfusion intensity ratio as predictors of the 6 h time-window. The area under the curve was 0.80 with a positive predictive value of 0.90 (95%CI 0.79-0.96). In the validation cohort (N = 90), the area under the curve was 0.73 (P for difference = 0.4) with a positive predictive value of 0.85 (95%CI 0.69-0.95).After validation in a larger independent dataset the model can be considered to select patients for endovascular treatment in whom stroke onset is unknown.In patients with large vessel occlusion and unknown time of stroke onset an automated multivariate imaging model is able to select patients who are likely within the 6 h time-window.

    View details for PubMedID 31008349

  • Can diffusion- and perfusion-weighted imaging alone accurately triage anterior circulation acute ischemic stroke patients to endovascular therapy? Journal of neurointerventional surgery Wolman, D. N., Iv, M., Wintermark, M., Zaharchuk, G., Marks, M. P., Do, H. M., Dodd, R. L., Albers, G. W., Lansberg, M. G., Heit, J. J. 2018

    Abstract

    Acute ischemic stroke (AIS) patients who benefit from endovascular treatment have a large vessel occlusion (LVO), small core infarction, and salvageable brain. We determined if diffusion-weighted imaging (DWI) and perfusion-weighted imaging (PWI) alone can correctly identify and localize anterior circulation LVO and accurately triage patients to endovascular thrombectomy (ET).This retrospective cohort study included patients undergoing MRI for the evaluation of AIS symptoms. DWI and PWI images alone were anonymized and scored for cerebral infarction, LVO presence and LVO location, DWI-PWI mismatch, and ET candidacy. Readers were blinded to clinical data. The primary outcome measure was accurate ET triage. Secondary outcomes were detection of LVO and LVO location.Two hundred and nineteen patients were included. Seventy-three patients (33%) underwent endovascular AIS treatment. Readers correctly and concordantly triaged 70 of 73 patients (96%) to ET (κ=0.938; P=0.855) and correctly excluded 143 of 146 patients (98%; P=0.942). DWI and PWI alone had a 95.9% sensitivity and a 98.4% specificity for accurate endovascular triage. LVO were accurately localized to the ICA/M1 segment in 65 of 68 patients (96%; κ=0.922; P=0.817) and the M2 segment in 18 of 20 patients (90%; κ=0.830; P=0.529).AIS patients with anterior circulation LVO are accurately identified using DWI and PWI alone, and LVO location may be correctly inferred from PWI. MRA omission may be considered to expedite AIS triage in hyperacute scenarios or may confidently supplant non-diagnostic or artifact-limited MRA.

    View details for PubMedID 29555872

  • Reduced Intravoxel Incoherent Motion Microvascular Perfusion Predicts Delayed Cerebral Ischemia and Vasospasm After Aneurysm Rupture. Stroke Heit, J. J., Wintermark, M., Martin, B. W., Zhu, G., Marks, M. P., Zaharchuk, G., Dodd, R. L., Do, H. M., Steinberg, G. K., Lansberg, M. G., Albers, G. W., Federau, C. 2018

    Abstract

    Proximal artery vasospasm and delayed cerebral ischemia (DCI) after cerebral aneurysm rupture result in reduced cerebral perfusion and microperfusion and significant morbidity and mortality. Intravoxel incoherent motion (IVIM) magnetic resonance imaging extracts microvascular perfusion information from a multi-b value diffusion-weighted sequence. We determined whether decreased IVIM perfusion may identify patients with proximal artery vasospasm and DCI.We performed a pilot retrospective cohort study of patients with ruptured cerebral aneurysms. Consecutive patients who underwent a brain magnetic resonance imaging with IVIM after ruptured aneurysm treatment were included. Patient demographic, treatment, imaging, and outcome data were determined by electronic medical record review. Primary outcome was DCI development with proximal artery vasospasm that required endovascular treatment. Secondary outcomes included mortality and clinical outcomes at 6 months.Sixteen patients (11 females, 69%;P=0.9) were included. There were no differences in age, neurological status, or comorbidities between patients who subsequently underwent endovascular treatment of DCI (10 patients; DCI+ group) and those who did not (6 patients; DCI- group). Compared with DCI- patients, DCI+ patients had decreased IVIM perfusion fractionf(0.09±0.03 versus 0.13±0.01;P=0.03), reduced diffusion coefficientD(0.82±0.05 versus 0.92±0.07×10-3mm2/s;P=0.003), and reduced blood flow-related parameterfD* (1.18±0.40 versus 1.83±0.40×10-3mm2/s;P=0.009). IVIM pseudodiffusion coefficientD* did not differ between DCI- (0.011±0.002) and DCI+ (0.013±0.005 mm2/s;P=0.4) patients. No differences in mortality or clinical outcome were identified.Decreased IVIM perfusion fractionfand blood flow-related parameterfD* correlate with DCI and proximal artery vasospasm development after cerebral aneurysm rupture.

    View details for DOI 10.1161/STROKEAHA.117.020395

    View details for PubMedID 29439196

  • Thrombectomy for Stroke at 6 to 16 Hours with Selection by Perfusion Imaging. The New England journal of medicine Albers, G. W., Marks, M. P., Kemp, S., Christensen, S., Tsai, J. P., Ortega-Gutierrez, S., McTaggart, R. A., Torbey, M. T., Kim-Tenser, M., Leslie-Mazwi, T., Sarraj, A., Kasner, S. E., Ansari, S. A., Yeatts, S. D., Hamilton, S., Mlynash, M., Heit, J. J., Zaharchuk, G., Kim, S., Carrozzella, J., Palesch, Y. Y., Demchuk, A. M., Bammer, R., Lavori, P. W., Broderick, J. P., Lansberg, M. G. 2018; 378 (8): 708–18

    Abstract

    Thrombectomy is currently recommended for eligible patients with stroke who are treated within 6 hours after the onset of symptoms.We conducted a multicenter, randomized, open-label trial, with blinded outcome assessment, of thrombectomy in patients 6 to 16 hours after they were last known to be well and who had remaining ischemic brain tissue that was not yet infarcted. Patients with proximal middle-cerebral-artery or internal-carotid-artery occlusion, an initial infarct size of less than 70 ml, and a ratio of the volume of ischemic tissue on perfusion imaging to infarct volume of 1.8 or more were randomly assigned to endovascular therapy (thrombectomy) plus standard medical therapy (endovascular-therapy group) or standard medical therapy alone (medical-therapy group). The primary outcome was the ordinal score on the modified Rankin scale (range, 0 to 6, with higher scores indicating greater disability) at day 90.The trial was conducted at 38 U.S. centers and terminated early for efficacy after 182 patients had undergone randomization (92 to the endovascular-therapy group and 90 to the medical-therapy group). Endovascular therapy plus medical therapy, as compared with medical therapy alone, was associated with a favorable shift in the distribution of functional outcomes on the modified Rankin scale at 90 days (odds ratio, 2.77; P<0.001) and a higher percentage of patients who were functionally independent, defined as a score on the modified Rankin scale of 0 to 2 (45% vs. 17%, P<0.001). The 90-day mortality rate was 14% in the endovascular-therapy group and 26% in the medical-therapy group (P=0.05), and there was no significant between-group difference in the frequency of symptomatic intracranial hemorrhage (7% and 4%, respectively; P=0.75) or of serious adverse events (43% and 53%, respectively; P=0.18).Endovascular thrombectomy for ischemic stroke 6 to 16 hours after a patient was last known to be well plus standard medical therapy resulted in better functional outcomes than standard medical therapy alone among patients with proximal middle-cerebral-artery or internal-carotid-artery occlusion and a region of tissue that was ischemic but not yet infarcted. (Funded by the National Institute of Neurological Disorders and Stroke; DEFUSE 3 ClinicalTrials.gov number, NCT02586415 .).

    View details for PubMedID 29364767

  • Early Cerebral Vein After Endovascular Ischemic Stroke Treatment Predicts Symptomatic Reperfusion Hemorrhage. Stroke Cartmell, S. C., Ball, R. L., Kaimal, R., Telischak, N. A., Marks, M. P., Do, H. M., Dodd, R. L., Albers, G. W., Lansberg, M. G., Heit, J. J. 2018

    Abstract

    Parenchymal hemorrhage (PH) after endovascular mechanical thrombectomy in acute ischemic stroke leads to worse outcomes. Better clinical and imaging biomarkers of symptomatic reperfusion PH are needed to identify patients at risk. We identified clinical and imaging predictors of reperfusion PH after endovascular mechanical thrombectomy with attention to early cerebral veins (ECVs) on postreperfusion digital subtraction angiography.We performed a retrospective cohort study of consecutive acute ischemic stroke patients undergoing endovascular mechanical thrombectomy at our neurovascular referral center. Clinical and imaging characteristics were collected from patient health records, and random forest variable importance measures were used to identify predictors of symptomatic PH. Predictors of secondary outcomes, including 90-day mortality, functional dependence (modified Rankin Scale score, >2), and National Institutes of Health Stroke Scale shift, were also determined. Diagnostic test characteristics of ECV for symptomatic PH were determined using a receiver operating characteristic analysis. Differences between patients with and without symptomatic PH were assessed with Fisher exact test and the Wilcoxon rank sum (Mann-Whitney U test) test at the 0.05 significance level.Of 64 patients with anterior circulation large-vessel occlusion identified, 6 (9.4%) developed symptomatic PH. ECV was the strongest predictor of symptomatic PH with more than twice the importance of the next best predictor, male sex. Although ECV was also predictive of 90-day mortality and functional dependence, other characteristics were more important than ECV for these outcomes. The sensitivity and specificity of ECV alone for subsequent hemorrhage were both 0.83, with an area under the curve of 0.83 and 95% confidence interval of 0.66 to 1.00.ECV on postendovascular mechanical thrombectomy digital subtraction angiography is highly diagnostic of subsequent symptomatic reperfusion hemorrhage in this data set. This finding has important implications for post-treatment management of blood pressure and anticoagulation.

    View details for PubMedID 29739912

  • Use of Imaging to Select Patients for Late Window Endovascular Therapy. Stroke Albers, G. W. 2018; 49 (9): 2256–60

    View details for PubMedID 30355004

  • A Comparison of Relative Time to Peak and Tmax for Mismatch-Based Patient Selection FRONTIERS IN NEUROLOGY Wouters, A., Christensen, S., Straka, M., Mlynash, M., Liggins, J., Bammer, R., Thijs, V., Lemmens, R., Albers, G. W., Lansberg, M. G. 2017; 8: 539

    Abstract

    The perfusion-weighted imaging (PWI)/diffusion-weighted imaging (DWI) mismatch profile is used to select patients for endovascular treatment. A PWI map of Tmax is commonly used to identify tissue with critical hypoperfusion. A time to peak (TTP) map reflects similar hemodynamic properties with the added benefit that it does not require arterial input function (AIF) selection and deconvolution. We aimed to determine if TTP could substitute Tmax for mismatch categorization.Imaging data of the DEFUSE 2 trial were reprocessed to generate relative TTP (rTTP) maps. We identified the rTTP threshold that yielded lesion volumes comparable to Tmax > 6 s and assessed the effect of reperfusion according to mismatch status, determined based on Tmax and rTTP volumes.Among 102 included cases, the Tmax > 6 s lesion volumes corresponded most closely with rTTP > 4.5 s lesion volumes: median absolute difference 6.9 mL (IQR: 2.3-13.0). There was 94% agreement in mismatch classification between Tmax and rTTP-based criteria. When mismatch was assessed by Tmax criteria, the odds ratio (OR) for favorable clinical response associated with reperfusion was 7.4 (95% CI 2.3-24.1) in patients with mismatch vs. 0.4 (95% CI 0.1-2.6) in patients without mismatch. When mismatch was assessed with rTTP criteria, these ORs were 7.2 (95% CI 2.3-22.2) and 0.3 (95% CI 0.1-2.2), respectively.rTTP yields lesion volumes that are comparable to Tmax and reliably identifies the PWI/DWI mismatch profile. Since rTTP is void of the problems associated with AIF selection, it is a suitable substitute for Tmax that could improve the robustness and reproducibility of mismatch classification in acute stroke.

    View details for PubMedID 29081762

  • A multicenter randomized controlled trial of endovascular therapy following imaging evaluation for ischemic stroke (DEFUSE 3) INTERNATIONAL JOURNAL OF STROKE Albers, G. W., Lansberg, M. G., Kemp, S., Tsai, J. P., Lavori, P., Christensen, S., Mlynash, M., Kim, S., Hamilton, S., Yeatts, S. D., Palesch, Y., Bammer, R., Broderick, J., Marks, M. P. 2017; 12 (8): 896–905

    Abstract

    Rationale Early reperfusion in patients experiencing acute ischemic stroke is effective in patients with large vessel occlusion. No randomized data are available regarding the safety and efficacy of endovascular therapy beyond 6 h from symptom onset. Aim The aim of the study is to demonstrate that, among patients with large vessel anterior circulation occlusion who have a favorable imaging profile on computed tomography perfusion or magnetic resonance imaging, endovascular therapy with a Food and Drug Administration 510 K-cleared mechanical thrombectomy device reduces the degree of disability three months post stroke. Design The study is a prospective, randomized, multicenter, phase III, adaptive, blinded endpoint, controlled trial. A maximum of 476 patients will be randomized and treated between 6 and 16 h of symptom onset. Procedures Patients undergo imaging with computed tomography perfusion or magnetic resonance diffusion/perfusion, and automated software (RAPID) determines if the Target Mismatch Profile is present. Patients who meet both clinical and imaging selection criteria are randomized 1:1 to endovascular therapy plus medical management or medical management alone. The individual endovascular therapist chooses the specific device (or devices) employed. Study outcomes The primary endpoint is the distribution of scores on the modified Rankin Scale at day 90. The secondary endpoint is the proportion of patients with modified Rankin Scale 0-2 at day 90 (indicating functional independence). Analysis Statistical analysis for the primary endpoint will be conducted using a normal approximation of the Wilcoxon-Mann-Whitney test (the generalized likelihood ratio test).

    View details for PubMedID 28946832

  • Risk for Major Bleeding in Patients Receiving Ticagrelor Compared With Aspirin After Transient Ischemic Attack or Acute Ischemic Stroke in the SOCRATES Study (Acute Stroke or Transient Ischemic Attack Treated With Aspirin or Ticagrelor and Patient Outcomes) CIRCULATION Easton, J., Aunes, M., Albers, G. W., Amarenco, P., Bokelund-Singh, S., Denison, H., Evans, S. R., Held, P., Jahreskog, M., Jonasson, J., Minematsu, K., Molina, C. A., Wang, Y., Wong, K., Johnston, S., SOCRATES Steering Comm 2017; 136 (10): 907-+

    Abstract

    Patients with minor acute ischemic stroke or transient ischemic attack are at high risk for subsequent stroke, and more potent antiplatelet therapy in the acute setting is needed. However, the potential benefit of more intense antiplatelet therapy must be assessed in relation to the risk for major bleeding. The SOCRATES trial (Acute Stroke or Transient Ischemic Attack Treated With Aspirin or Ticagrelor and Patient Outcomes) was the first trial with ticagrelor in patients with acute ischemic stroke or transient ischemic attack in which the efficacy and safety of ticagrelor were compared with those of aspirin. The main safety objective was assessment of PLATO (Platelet Inhibition and Patient Outcomes)-defined major bleeds on treatment, with special focus on intracranial hemorrhage (ICrH).An independent adjudication committee blinded to study treatment classified bleeds according to the PLATO, TIMI (Thrombolysis in Myocardial Infarction), and GUSTO (Global Use of Strategies to Open Occluded Coronary Arteries) definitions. The definitions of ICrH and major bleeding excluded cerebral microbleeds and asymptomatic hemorrhagic transformations of cerebral infarctions so that the definitions better discriminated important events in the acute stroke population.A total of 13 130 of 13 199 randomized patients received at least 1 dose of study drug and were included in the safety analysis set. PLATO major bleeds occurred in 31 patients (0.5%) on ticagrelor and 38 patients (0.6%) on aspirin (hazard ratio, 0.83; 95% confidence interval, 0.52-1.34). The most common locations of major bleeds were intracranial and gastrointestinal. ICrH was reported in 12 patients (0.2%) on ticagrelor and 18 patients (0.3%) on aspirin. Thirteen of all 30 ICrHs (4 on ticagrelor and 9 on aspirin) were hemorrhagic strokes, and 4 (2 in each group) were symptomatic hemorrhagic transformations of brain infarctions. The ICrHs were spontaneous in 6 and 13, traumatic in 3 and 3, and procedural in 3 and 2 patients on ticagrelor and aspirin, respectively. In total, 9 fatal bleeds occurred on ticagrelor and 4 on aspirin. The composite of ICrH or fatal bleeding included 15 patients on ticagrelor and 18 on aspirin. Independently of bleeding classification, PLATO, TIMI, or GUSTO, the relative difference between treatments for major/severe bleeds was similar. Nonmajor bleeds were more common on ticagrelor.Antiplatelet therapy with ticagrelor in patients with acute ischemic stroke or transient ischemic attack showed a bleeding profile similar to that of aspirin for major bleeds. There were few ICrHs.URL: http://www.clinicaltrials.gov. Unique identifier: NCT01994720.

    View details for PubMedID 28655834

  • Microbleeds, Cerebral Hemorrhage, and Functional Outcome After Stroke Thrombolysis Individual Patient Data Meta-Analysis STROKE Charidimou, A., Turc, G., Oppenheim, C., Yan, S., Scheitz, J. F., Erdur, H., Klinger-Gratz, P. P., El-Koussy, M., Takahashi, W., Moriya, Y., Wilson, D., Kidwell, C. S., Saver, J. L., Sallem, A., Moulin, S., Edjlali-Goujon, M., Thijs, V., Fox, Z., Shoamanesh, A., Albers, G. W., Mattle, H. P., Benavente, O. R., Jaeger, H., Ambler, G., Aoki, J., Baron, J., Kimura, K., Kakuda, W., Takizawa, S., Jung, S., Nolte, C. H., Lou, M., Cordonnier, C., Werring, D. J. 2017; 48 (8): 2084-+

    Abstract

    We assessed whether the presence, number, and distribution of cerebral microbleeds (CMBs) on pre-intravenous thrombolysis MRI scans of acute ischemic stroke patients are associated with an increased risk of intracerebral hemorrhage (ICH) or poor functional outcome.We performed an individual patient data meta-analysis, including prospective and retrospective studies of acute ischemic stroke treated with intravenous tissue-type plasminogen activator. Using multilevel mixed-effects logistic regression, we investigated associations of pre-treatment CMB presence, burden (1, 2-4, ≥5, and >10), and presumed pathogenesis (cerebral amyloid angiopathy defined as strictly lobar CMBs and noncerebral amyloid angiopathy) with symptomatic ICH, parenchymal hematoma (within [parenchymal hemorrhage, PH] and remote from the ischemic area [remote parenchymal hemorrhage, PHr]), and poor 3- to 6-month functional outcome (modified Rankin score >2).In 1973 patients from 8 centers, the crude prevalence of CMBs was 526 of 1973 (26.7%). A total of 77 of 1973 (3.9%) patients experienced symptomatic ICH, 210 of 1806 (11.6%) experienced PH, and 56 of 1720 (3.3%) experienced PHr. In adjusted analyses, patients with CMBs (compared with those without CMBs) had increased risk of PH (odds ratio: 1.50; 95% confidence interval: 1.09-2.07; P=0.013) and PHr (odds ratio: 3.04; 95% confidence interval: 1.73-5.35; P<0.001) but not symptomatic ICH. Both cerebral amyloid angiopathy and noncerebral amyloid angiopathy patterns of CMBs were associated with PH and PHr. Increasing CMB burden category was associated with the risk of symptomatic ICH (P=0.014), PH (P=0.013), and PHr (P<0.00001). Five or more and >10 CMBs independently predicted poor 3- to 6-month outcome (odds ratio: 1.85; 95% confidence interval: 1.10-3.12; P=0.020; and odds ratio: 3.99; 95% confidence interval: 1.55-10.22; P=0.004, respectively).Increasing CMB burden is associated with increased risk of ICH (including PHr) and poor 3- to 6-month functional outcome after intravenous thrombolysis for acute ischemic stroke.

    View details for DOI 10.1161/STROKEAHA.116.012992

    View details for Web of Science ID 000406128300033

    View details for PubMedID 28720659

  • MR perfusion lesions after TIA or minor stroke are associated with new infarction at 7 days NEUROLOGY Lee, J., Inoue, M., Mlynash, M., Mann, S. K., Cereda, C. W., Ke, M., Albers, G. W., Olivot, J. M. 2017; 88 (24): 2254–59

    Abstract

    To investigate the relationship between acute perfusion-weighted imaging (PWI) lesions occurring within the first hours after a TIA or a minor brain infarction (BI) and the incidence of new BI detected on a systematic MRI at 1 week.Consecutive patients who experienced a TIA or BI with a neurologic deficit that lasted <24 hours, did not receive any revascularization therapy (thrombolysis/thrombectomy), and underwent DWI/PWI at baseline and fluid-attenuated inversion recovery (FLAIR)/DWI 1 week after symptom onset were enrolled. Investigators blinded to clinical information independently assessed the presence of acute ischemic lesions on baseline DWI/PWI and follow-up DWI and FLAIR. Baseline and follow-up MRIs were then compared to determine the occurrence and location of new infarctions.Sixty-four patients met the inclusion criteria. Median (IQR) ABCD2 score was 4 (3-5). Median delay from onset to baseline and follow-up MRI was 5 (2-10) hours and 6 (5-7) days, respectively. MRI revealed an acute ischemic lesion on DWI and/or PWI in 38 patients. Nine patients (14%) had a new infarction on follow-up MRI. Each had a PWI and 4 had a DWI lesion on baseline MRI. All new BIs except one were asymptomatic and in the same location as the acute PWI lesion.Our results showed that 30% of the acute focal PWI lesions detected after a TIA are associated with a new BI at 1 week. Those new BIs may result from the progression of the initial ischemic injury.

    View details for PubMedID 28500226

  • Differences in Characteristics and Outcomes Between Asian and Non-Asian Patients in the TIAregistry.org. Stroke Hoshino, T., Uchiyama, S., Wong, L. K., Sissani, L., Albers, G. W., Bornstein, N. M., Caplan, L. R., Donnan, G. A., Ferro, J. M., Hennerici, M. G., Labreuche, J., Lavallée, P. C., Molina, C., Rothwell, P. M., Steg, P. G., Touboul, P., Vicaut, É., Amarenco, P. 2017

    Abstract

    This study provides the contemporary causes and prognosis of transient ischemic attack (TIA) and minor stroke in Asians and the direct comparisons with non-Asians.The TIAregistry.org enrolled 4789 patients (1149 Asians and 3640 non-Asians) with a TIA or minor ischemic stroke within 7 days of onset. Every participating facility had systems dedicated to urgent intervention of TIA/stroke patients by specialists. The primary outcome was a composite of cardiovascular death, nonfatal stroke, and nonfatal acute coronary syndrome.Approximately 80% of patients were evaluated within 24 hours of symptom onset. At 1 year, there were no differences in the rates of composite cardiovascular events (6.8% versus 6.0%; P=0.38) and stroke (6.0% versus 4.8%; P=0.11) between Asians and non-Asians. Asians had a lower risk of cerebrovascular disease (stroke or TIA) than non-Asians (adjusted hazard ratio, 0.79; 95% confidence interval, 0.63-0.98; P=0.03); the difference was primarily driven by a lower rate of TIA in Asians (4.2% versus 8.3%; P<0.001). Moderately severe bleeding was more frequent in Asians (0.8% versus 0.3%; P=0.02). In multivariable analysis, multiple acute infarcts (P=0.005) and alcohol consumption (P=0.02) were independent predictors of stroke recurrence in Asians, whereas intracranial stenosis (P<0.001), ABCD(2) score (P<0.001), atrial fibrillation (P=0.008), extracranial stenosis (P=0.03), and previous stroke or TIA (P=0.03) were independent predictors in non-Asians.The short-term stroke risk after a TIA or minor stroke was lower than expected when urgent evidence-based care was delivered, irrespective of race/ethnicity or region. However, the predictors of stroke were different for Asians and non-Asians.

    View details for DOI 10.1161/STROKEAHA.117.016874

    View details for PubMedID 28584002

  • CT Perfusion to Predict Response to Recanalization in Ischemic Stroke. Annals of neurology Lansberg, M. G., Christensen, S., Kemp, S., Mlynash, M., Mishra, N., Federau, C., Tsai, J. P., Kim, S., Nogueria, R. G., Jovin, T., Devlin, T. G., Akhtar, N., Yavagal, D. R., Haussen, D., Dehkharghani, S., Bammer, R., Straka, M., Zaharchuk, G., Marks, M. P., Albers, G. W. 2017

    Abstract

    To assess the utility of computed tomographic (CT) perfusion for selection of patients for endovascular therapy up to 18 hours after symptom onset.We conducted a multicenter cohort study of consecutive acute stroke patients scheduled to undergo endovascular therapy within 90 minutes after a baseline CT perfusion. Patients were classified as "target mismatch" if they had a small ischemic core and a large penumbra on their baseline CT perfusion. Reperfusion was defined as >50% reduction in critical hypoperfusion between the baseline CT perfusion and the 36-hour follow-up magnetic resonance imaging.Of the 201 patients enrolled, 190 patients with an adequate baseline CT perfusion study who underwent angiography were included (mean age = 66 years, median NIH Stroke Scale [NIHSS] = 16, median time from symptom onset to endovascular therapy = 5.2 hours). Rate of reperfusion was 89%. In patients with target mismatch (n = 131), reperfusion was associated with higher odds of favorable clinical response, defined as an improvement of ≥8 points on the NIHSS (83% vs 44%; p = 0.002, adjusted odds ratio [OR] = 6.6, 95% confidence interval [CI] = 2.1-20.9). This association did not differ between patients treated within 6 hours (OR = 6.4, 95% CI = 1.5-27.8) and those treated > 6 hours after symptom onset (OR = 13.7, 95% CI = 1.4-140).The robust association between endovascular reperfusion and good outcome among patients with the CT perfusion target mismatch profile treated up to 18 hours after symptom onset supports a randomized trial of endovascular therapy in this patient population. Ann Neurol 2017;81:849-856.

    View details for DOI 10.1002/ana.24953

    View details for PubMedID 28486789

  • Symptomatic Patients Remain at Substantial Risk of Arterial Disease Complications Before and After Endarterectomy or Stenting STROKE Hobeanu, C., Lavallee, P. C., Rothwell, P. M., Sissani, L., Albers, G. W., Bornstein, N. M., Caplan, L. R., Donnan, G. A., Ferro, J. M., Hennerici, M. G., Labreuche, J., Molina, C., Steg, P. G., Touboul, P., Uchiyama, S., Vicaut, E., Wong, L. K., Amarenco, P. 2017; 48 (4): 1005-1010

    Abstract

    After carotid endarterectomy (CEA) or carotid artery stenting (CAS) in patients with transient ischemic attack or minor ischemic stroke, recurrent stroke risk falls to a low rate on modern medical treatment.We used data from 4583 patients with recent transient ischemic attack or minor stroke enrolled in the TIAregistry.org to perform a nested case-control analysis to evaluate pre- and post-CEA/CAS risk. Cases were defined as patients with a CEA/CAS during the 1-year follow-up period. For each case, 2 controls with a follow-up time greater than the time from qualifying event to CEA/CAS were randomly selected, matched by age and sex. Primary outcome was defined as major vascular events (MVE, including stroke, cardiovascular death, and myocardial infarction).The median delay from symptom onset of qualifying event to CEA/CAS was 11 days (interquartile range, 6-23). Overall, patients with CEA/CAS had a higher 1-year risk of MVE than other patients (14.8% versus 5.8%; adjusted hazard ratio, 2.40; 95% confidence interval, 1.61-3.60; P<0.001). During the matched preprocedural period, MVE occurred in 14 (7.5%) cases and in 13 (3.5%) controls, with an adjusted odds ratio =2.46 (95% confidence interval, 1.07-5.64; P=0.03). In the postprocedural period, the risk of MVE was also higher in cases than in controls (adjusted P<0.03).Patients with CEA/CAS had a higher 12-month risk of MVE, as well as during pre- and postprocedural periods. These results suggest that patients in whom CEA/CAS is anticipated are likely to be an informative population for inclusion in studies testing new antithrombotic strategies started soon after symptom onset.

    View details for DOI 10.1161/STROKEAHA.116.015171

    View details for Web of Science ID 000398207000042

    View details for PubMedID 28289241

  • Predictive Value of RAPID Assessed Perfusion Thresholds on Final Infarct Volume in SWIFT PRIME (Solitaire With the Intention for Thrombectomy as Primary Endovascular Treatment) STROKE Mokin, M., Levy, E. I., Saver, J. L., Siddiqui, A. H., Goyal, M., Bonafe, A., Cognard, C., Jahan, R., Albers, G. W. 2017; 48 (4): 932-938

    Abstract

    Computed tomography perfusion imaging can estimate the size of the ischemic core, which can be used for the selection of patients for endovascular therapy. The relative cerebral blood volume (rCBV) and relative cerebral blood flow (rCBF) thresholds chosen to identify ischemic core influence the accuracy of prediction. We aimed to analyze the accuracy of various rCBV and rCBF thresholds for predicting the 27-hour infarct volume using RAPID automated analysis software from the SWIFT PRIME trial (Solitaire With the Intention for Thrombectomy as Primary Endovascular Treatment) data.Patients from the SWIFT PRIME study who achieved complete reperfusion based on time until the residue function reached its peak >6 s perfusion maps obtained at 27 hours were included. Patients from both the intravenous tissue-type plasminogen activator only and endovascular groups were included in analysis. Final infarct volume was determined on magnetic resonance imaging (fluid-attenuated inversion recovery images) or computed tomography scans obtained 27 hours after symptom onset. The predicted ischemic core volumes on rCBV and rCBF maps using thresholds ranging between 0.2 and 0.8 were compared with the actual infarct volume to determine the most accurate thresholds.Among the 47 subjects, the following baseline computed tomography perfusion thresholds most accurately predicted the actual 27-hour infarct volume: rCBV=0.32, median absolute error (MAE)=9 mL; rCBV=0.34, MAE=9 mL; rCBF=0.30, MAE=8.8 mL; rCBF=0.32, MAE=7 mL; and rCBF=0.34, MAE=7.3.Brain regions with rCBF 0.30 to 0.34 or rCBV 0.32 to 0.34 thresholds provided the most accurate prediction of infarct volume in patients who achieved complete reperfusion with MAEs of ≤9 mL.URL: http://www.clinicaltrials.gov. Unique identifier: NCT01657461.

    View details for DOI 10.1161/STROKEAHA.116.015472

    View details for Web of Science ID 000398207000032

    View details for PubMedID 28283606

  • Efficacy and safety of ticagrelor versus aspirin in acute stroke or transient ischaemic attack of atherosclerotic origin: a subgroup analysis of SOCRATES, a randomised, double-blind, controlled trial. The Lancet. Neurology Amarenco, P., Albers, G. W., Denison, H., Easton, J. D., Evans, S. R., Held, P., Hill, M. D., Jonasson, J., Kasner, S. E., Ladenvall, P., Minematsu, K., Molina, C. A., Wang, Y., Wong, K. S., Johnston, S. C. 2017

    Abstract

    Ticagrelor is an effective antiplatelet therapy for patients with coronary atherosclerotic disease and might be more effective than aspirin in preventing recurrent stroke and cardiovascular events in patients with acute cerebral ischaemia of atherosclerotic origin. Our aim was to test for a treatment-by-ipsilateral atherosclerotic stenosis interaction in a subgroup analysis of patients in the Acute Stroke or Transient Ischaemic Attack Treated with Aspirin or Ticagrelor and Patient Outcomes (SOCRATES) trial.SOCRATES was a randomised, double-blind, controlled trial of ticagrelor versus aspirin in patients aged 40 years or older with a non-cardioembolic, non-severe acute ischaemic stroke, or high-risk transient ischaemic attack from 674 hospitals in 33 countries. We randomly allocated patients (1:1) to ticagrelor (180 mg loading dose on day 1 followed by 90 mg twice daily for days 2-90, given orally) or aspirin (300 mg on day 1 followed by 100 mg daily for days 2-90, given orally) within 24 h of symptom onset. Investigators classified all patients into atherosclerotic and non-atherosclerotic groups for the prespecified, exploratory analysis reported in this study. The primary endpoint was the time to occurrence of stroke, myocardial infarction, or death within 90 days. Efficacy analysis was by intention to treat. The SOCRATES trial is registered with ClinicalTrials.gov, number NCT01994720.Between Jan 7, 2014, and Oct 29, 2015, we randomly allocated 13 199 patients (6589 [50%] to ticagrelor and 6610 [50%] to aspirin). Potentially symptomatic ipsilateral atherosclerotic stenosis was reported in 3081 (23%) of 13 199 patients. We found a treatment-by-atherosclerotic stenosis interaction (p=0·017). 103 (6·7%) of 1542 patients with ipsilateral stenosis in the ticagrelor group and 147 (9·6%) of 1539 patients with ipsilateral stenosis in the aspirin group had an occurrence of stroke, myocardial infarction, or death within 90 days (hazard ratio 0·68 [95% CI 0·53-0·88]; p=0·003). In 10 118 patients with no ipsilateral stenosis, 339 (6·7%) of 5047 patients in the ticagrelor group had an occurrence of stroke, myocardial infarction, or death within 90 days compared with 350 (6·9%) of 5071 in the aspirin group (0·97 [0·84-1·13]; p=0·72). There were no significant differences in the proportion of life-threatening bleeding or major or minor bleeding events in patients with ipsilateral stenosis in the ticagrelor group compared with the aspirin group.In this prespecified exploratory analysis, ticagrelor was superior to aspirin at preventing stroke, myocardial infarction, or death at 90 days in patients with acute ischaemic stroke or transient ischaemic attack when associated with ipsilateral atherosclerotic stenosis. An understanding of stroke mechanisms and causes is important to deliver safe and efficacious treatments for early stroke prevention.AstraZeneca.

    View details for DOI 10.1016/S1474-4422(17)30038-8

    View details for PubMedID 28238711

  • Cost-Effectiveness of Solitaire Stent Retriever Thrombectomy for Acute Ischemic Stroke: Results From the SWIFT-PRIME Trial (Solitaire With the Intention for Thrombectomy as Primary Endovascular Treatment for Acute Ischemic Stroke). Stroke Shireman, T. I., Wang, K., Saver, J. L., Goyal, M., Bonafé, A., Diener, H., Levy, E. I., Pereira, V. M., Albers, G. W., Cognard, C., Hacke, W., Jansen, O., Jovin, T. G., Mattle, H. P., Nogueira, R. G., Siddiqui, A. H., Yavagal, D. R., Devlin, T. G., Lopes, D. K., Reddy, V. K., Du Mesnil De Rochemont, R., Jahan, R., Vilain, K. A., House, J., Lee, J., Cohen, D. J. 2017; 48 (2): 379-387

    Abstract

    Clinical trials have demonstrated improved 90-day outcomes for patients with acute ischemic stroke treated with stent retriever thrombectomy plus tissue-type plasminogen activator (SST+tPA) compared with tPA. Previous studies suggested that this strategy may be cost-effective, but models were derived from pooled data and older assumptions.In this prospective economic substudy conducted alongside the SWIFT-PRIME trial (Solitaire With the Intention for Thrombectomy as Primary Endovascular Treatment for Acute Ischemic Stroke), in-trial costs were measured for patients using detailed medical resource utilization and hospital billing data. Utility weights were assessed at 30 and 90 days using the EuroQol-5 dimension questionnaire. Post-trial costs and life-expectancy were estimated for each surviving patient using a model based on trial data and inputs derived from a contemporary cohort of ischemic stroke survivors.Index hospitalization costs were $17 183 per patient higher for SST+tPA than for tPA ($45 761 versus $28 578; P<0.001), driven by initial procedure costs. Between discharge and 90 days, costs were $4904 per patient lower for SST+tPA than for tPA ($11 270 versus $16 174; P=0.014); total 90-day costs remained higher with SST+tPA ($57 031 versus $44 752; P<0.001). Higher utility values for SST+tPA led to higher in-trial quality-adjusted life years (0.131 versus 0.105; P=0.005). In lifetime projections, SST+tPA was associated with substantial gains in quality-adjusted life years (6.79 versus 5.05), cost savings of $23 203 per patient and was economically dominant when compared with tPA in 90% of bootstrap replicates.Among patients with acute ischemic stroke enrolled in the SWIFT-PRIME trial, SST increased initial treatment costs, but was projected to improve quality-adjusted life-expectancy and reduce healthcare costs over a lifetime horizon compared with tPA.URL: http://www.clinicaltrials.gov. Unique identifier: NCT01657461.

    View details for DOI 10.1161/STROKEAHA.116.014735

    View details for PubMedID 28028150

  • Current Imaging Strategies for Patient Selection in Acute Ischemic Stroke Trials NEUROPROTECTIVE THERAPY FOR STROKE AND ISCHEMIC DISEASE Tsai, J. P., Albers, G. W., Lapchak, P. A., Zhang, J. H. 2017: 751–74

    View details for DOI 10.1007/978-3-319-45345-3_33

    View details for Web of Science ID 000414951200034

  • Ticagrelor Versus Aspirin in Acute Embolic Stroke of Undetermined Source. Stroke Amarenco, P., Albers, G. W., Denison, H., Easton, J. D., Evans, S. R., Held, P., Hill, M. D., Jonasson, J., Kasner, S. E., Ladenvall, P., Minematsu, K., Molina, C. A., Wang, Y., Wong, K. S., Johnston, S. C. 2017; 48 (9): 2480–87

    Abstract

    Ticagrelor is an effective antiplatelet therapy among patients with atherosclerotic disease and, therefore, could be more effective than aspirin in preventing recurrent stroke and cardiovascular events among patients with embolic stroke of unknown source (ESUS), which includes patients with ipsilateral stenosis <50% and aortic arch atherosclerosis.We randomized 13 199 patients with a noncardioembolic, nonsevere ischemic stroke or high-risk transient ischemic attack to ticagrelor (180 mg loading dose on day 1 followed by 90 mg twice daily for days 2-90) or aspirin (300 mg on day 1 followed by 100 mg daily for days 2-90) within 24 hours of symptom onset. In all patients, investigators informed on the presence of ipsilateral stenosis ≥50%, small deep infarct <15 mm, and on cardiac source of embolism detected after enrollment or rare causes, which allowed to construct an ESUS category in all other patients with documented brain infarction. The primary end point was the time to the occurrence of stroke, myocardial infarction, or death within 90 days.ESUS was identified in 4329 (32.8%) patients. There was no treatment-by-ESUS category interaction (P=0.83). Hazard ratio in ESUS patients was 0.87 (95% confidence interval, 0.68-1.10; P=0.24). However, hazard ratio was 0.51 (95% confidence interval, 0.29-0.90; P=0.02) in ESUS patients with ipsilateral stenosis <50% or aortic arch atherosclerosis (n=961) and 0.98 (95% confidence interval, 0.76-1.27; P=0.89) in the remaining ESUS patients (n=3368; P for heterogeneity =0.04).In this post hoc, exploratory analysis, we found no treatment-by-ESUS category interaction. ESUS subgroups have heterogeneous response to treatment (Funded by AstraZeneca).URL: http://www.clinicaltrials.gov. Unique identifier: NCT01994720.

    View details for PubMedID 28720658

  • Ticagrelor in Acute Stroke or Transient Ischemic Attack in Asian Patients From the SOCRATES Trial (Acute Stroke or Transient Ischemic Attack Treated With Aspirin or Ticagrelor and Patient Outcomes) STROKE Wang, Y., Minematsu, K., Wong, K. S., Amarenco, P., Albers, G. W., Denison, H., Easton, J. D., Evans, S. R., Held, P., Jonasson, J., Molina, C. A., Johnston, S. C. 2017; 48 (1): 167-?

    Abstract

    In the SOCRATES trial (Acute Stroke or Transient Ischemic Attack Treated With Aspirin or Ticagrelor and Patient Outcomes), ticagrelor was not superior to aspirin. Because of differences in patient demographics and stroke disease pattern in Asia, outcomes of ticagrelor versus aspirin were assessed among Asian patients in a prespecified exploratory analysis.Baseline demographics, treatment effects, and safety of ticagrelor and aspirin were assessed among Asian patients. Differences in outcomes between groups were assessed using Cox proportional hazard model.A total of 3858 (29.2%) SOCRATES participants were recruited in Asia. Among the Asian patients, the primary end point event occurred in 186 (9.6%) of the 1933 patients treated with ticagrelor, versus 224 (11.6%) of the 1925 patients treated with aspirin (hazard ratio, 0.81; 95% confidence interval, 0.67-0.99). The exploratory P value for treatment-by-region interaction was 0.27. The primary end point event rate in the Asian subgroup was numerically higher than that in the non-Asian group (10.6% versus 5.7%; nominal P<0.01). Among the Asian patients, the rate of PLATO (Platelet Inhibition and Patient Outcomes)-defined major bleeding was similar in the ticagrelor group and the aspirin group (0.6% versus 0.8%; hazard ratio, 0.76; 95% confidence interval, 0.36-1.61).The event rates were numerically higher in the Asian patients. Among the Asian patients with acute stroke or transient ischemic attacks, there was a trend toward a lower hazard ratio in reducing risk of the primary end point of stroke, myocardial infarction, or death in the ticagrelor group.URL: http://www.clinicaltrials.gov. Unique identifier: NCT01994720.

    View details for DOI 10.1161/STROKEAHA.116.014891

    View details for Web of Science ID 000391944900030

    View details for PubMedID 27899747

  • Wake-Up Stroke: Current Understanding. Topics in magnetic resonance imaging : TMRI Tsai, J. P., Albers, G. W. 2017; 26 (3): 97–102

    Abstract

    Patients with wake-up strokes account for approximately 1 in 5 individuals presenting with an acute ischemic stroke. However, they are commonly excluded from acute stroke treatment. This article reviews the current understanding of wake-up strokes. A comparison of wake-up and awake-onset strokes demonstrated that they are physiologically, clinically, and radiologically similar. Use of advanced CT and MRI techniques may help extend acute stroke treatment options to patients with wake-up stroke.

    View details for PubMedID 28277462

  • Efficacy of Stent-Retriever Thrombectomy in Magnetic Resonance Imaging Versus Computed Tomographic Perfusion-Selected Patients in SWIFT PRIME Trial (Solitaire FR With the Intention for Thrombectomy as Primary Endovascular Treatment for Acute Ischemic Stroke). Stroke Menjot de Champfleur, N., Saver, J. L., Goyal, M., Jahan, R., Diener, H. C., Bonafe, A., Levy, E. I., Pereira, V. M., Cognard, C., Yavagal, D. R., Albers, G. W. 2017; 48 (6): 1560–66

    Abstract

    The majority of patients enrolled in SWIFT PRIME trial (Solitaire FR With the Intention for Thrombectomy as Primary Endovascular Treatment for Acute Ischemic Stroke) had computed tomographic perfusion (CTP) imaging before randomization; 34 patients were randomized after magnetic resonance imaging (MRI).Patients with middle cerebral artery and distal carotid occlusions were randomized to treatment with tPA (tissue-type plasminogen activator) alone or tPA+stentriever thrombectomy. The primary outcome was the distribution of the modified Rankin Scale score at 90 days. Patients with the target mismatch profile for enrollment were identified on MRI and CTP.MRI selection was performed in 34 patients; CTP in 139 patients. Baseline National Institutes of Health Stroke Scale score was 17 in both groups. Target mismatch profile was present in 95% (MRI) versus 83% (CTP). A higher percentage of the MRI group was transferred from an outside hospital (P=0.02), and therefore, the time from stroke onset to randomization was longer in the MRI group (P=0.003). Time from emergency room arrival to randomization did not differ in CTP versus MRI-selected patients. Baseline ischemic core volumes were similar in both groups. Reperfusion rates (>90%/TICI [Thrombolysis in Cerebral Infarction] score 3) did not differ in the stentriever-treated patients in the MRI versus CTP groups. The primary efficacy analysis (90-day mRS score) demonstrated a statistically significant benefit in both subgroups (MRI, P=0.02; CTP, P=0.01). Infarct growth was reduced in the stentriever-treated group in both MRI and CTP groups.Time to randomization was significantly longer in MRI-selected patients; however, site arrival to randomization times were not prolonged, and the benefits of endovascular therapy were similar.URL: http://www.clinicaltrials.gov. Unique identifier: NCT01657461.

    View details for PubMedID 28465460

  • Power of an Adaptive Trial Design for Endovascular Stroke Studies Simulations Using IMS (Interventional Management of Stroke) III Data STROKE Lansberg, M. G., Bhat, N. S., Yeatts, S. D., Palesch, Y. Y., Broderick, J. P., Albers, G. W., Lai, T. L., Lavori, P. W. 2016; 47 (12): 2931-2937

    Abstract

    Adaptive trial designs that allow enrichment of the study population through subgroup selection can increase the chance of a positive trial when there is a differential treatment effect among patient subgroups. The goal of this study is to illustrate the potential benefit of adaptive subgroup selection in endovascular stroke studies.We simulated the performance of a trial design with adaptive subgroup selection and compared it with that of a traditional design. Outcome data were based on 90-day modified Rankin Scale scores, observed in IMS III (Interventional Management of Stroke III), among patients with a vessel occlusion on baseline computed tomographic angiography (n=382). Patients were categorized based on 2 methods: (1) according to location of the arterial occlusive lesion and onset-to-randomization time and (2) according to onset-to-randomization time alone. The power to demonstrate a treatment benefit was based on 10 000 trial simulations for each design.The treatment effect was relatively homogeneous across categories when patients were categorized based on arterial occlusive lesion and time. Consequently, the adaptive design had similar power (47%) compared with the fixed trial design (45%). There was a differential treatment effect when patients were categorized based on time alone, resulting in greater power with the adaptive design (82%) than with the fixed design (57%).These simulations, based on real-world patient data, indicate that adaptive subgroup selection has merit in endovascular stroke trials as it substantially increases power when the treatment effect differs among subgroups in a predicted pattern.

    View details for DOI 10.1161/STROKEAHA.116.015436

    View details for Web of Science ID 000389424200022

    View details for PubMedID 27895297

    View details for PubMedCentralID PMC5134921

  • Functional Neurologic Outcomes Change Over the First 6 Months After Cardiac Arrest. Critical care medicine Tong, J. T., Eyngorn, I., Mlynash, M., Albers, G. W., Hirsch, K. G. 2016; 44 (12): e1202-e1207

    Abstract

    To determine the longitudinal changes in functional outcome and compare ordinal outcome scale assessments in comatose cardiac arrest survivors.Prospective observational study of comatose cardiac arrest survivors. Subjects who survived to 1 month were included.Academic medical center ICU.Ninety-eight consecutive patients who remained comatose after resuscitation from cardiac arrest; 45 patients survived to 1 month.None.Patients' functional neurologic outcomes were assessed by phone call or in-person clinic visit at 1, 3, 6, and 12 months postcardiac arrest using the modified Rankin Scale, Glasgow Outcome Scale, and Barthel Index. A "good" outcome was defined as modified Rankin Scale 0-3, Barthel Index 70-100, and Glasgow Outcome Scale 4-5. Changes in dichotomized outcomes and shifts on each outcome scale were analyzed. The mean age of survivors was 51 ± 19 years and 18 (40%) were women. Five (19%) out of 26 patients with data available at all timepoints improved to good modified Rankin Scale outcome and none worsened to poor outcome between postarrest months 1 and 6 (p = 0.06). Thirteen patients (50%) improved on the modified Rankin Scale by 1-3 points and four (15%) worsened by 1-2 points between months 1 and 6 (overall improvement by 0.5 points; 95% CI, 0-1; p = 0.04). From postarrest months 6 to 12, there was no change in the number of patients with good versus poor outcomes. The modified Rankin Scale and Barthel Index were more sensitive to detecting changes in outcome than the Glasgow Outcome Scale.In initially comatose cardiac arrest survivors, improvements in functional status occur over the first 6 months after the event. There was no significant change in outcome between postarrest months 6 and 12. The modified Rankin Scale is a sensitive outcome scale in this population.

    View details for PubMedID 27495816

  • Optimal Computed Tomographic Perfusion Scan Duration for Assessment of Acute Stroke Lesion Volumes STROKE Kasasbeh, A. S., Christensen, S., Straka, M., Mishra, N., Mlynash, M., Bammer, R., Albers, G. W., Lansberg, M. G. 2016; 47 (12): 2966-2971

    Abstract

    The minimal scan duration needed to obtain reliable lesion volumes with computed tomographic perfusion (CTP) has not been well established in the literature.We retrospectively assessed the impact of gradual truncation of the scan duration on acute ischemic lesion volume measurements. For each scan, we identified its optimal scan time, defined as the shortest scan duration that yields measurements of the ischemic lesion volumes similar to those obtained with longer scanning, and the relative height of the fitted venous output function at its optimal scan time.We analyzed 70 computed tomographic perfusion scans of acute stroke patients. An optimal scan time could not be determined in 11 scans (16%). For the other 59 scans, the median optimal scan time was 32.7 seconds (90th percentile 52.6 seconds; 100th percentile 68.9 seconds), and the median relative height of the fitted venous output function at the optimal scan times was 0.39 (90th percentile 0.02; 100th percentile 0.00). On the basis of a linear model, the optimal scan time was T0 plus 1.6 times the width of the venous output function (P<0.001; R(2)=0.49).This study shows how the optimal duration of a computed tomographic perfusion scan relates to the arrival time and width of the contrast bolus. This knowledge can be used to optimize computed tomographic perfusion scan protocols and to determine whether a scan is of sufficient duration. Provided a baseline (T0) of 10 seconds, a total scan duration of 60 to 70 seconds, which includes the entire downslope of the venous output function in most patients, is recommended.

    View details for DOI 10.1161/STROKEAHA.116.014177

    View details for Web of Science ID 000389424200027

    View details for PubMedID 27895299

    View details for PubMedCentralID PMC5134896

  • Comparison of stroke volume evolution on diffusion-weighted imaging and fluid-attenuated inversion recovery following endovascular thrombectomy. International journal of stroke Federau, C., Christensen, S., Mlynash, M., Tsai, J., Kim, S., Zaharchuk, G., Inoue, M., Straka, M., Mishra, N. K., Kemp, S., Lansberg, M. G., Albers, G. W. 2016

    Abstract

    To compare the evolution of the infarct lesion volume on both diffusion-weighted imaging and fluid-attenuated inversion recovery in the first five days after endovascular thrombectomy.We included 109 patients from the CRISP and DEFUSE 2 studies. Stroke lesion volumes obtained on diffusion-weighted imaging and fluid-attenuated inversion recovery images both early post-procedure (median 18 h after symptom onset) and day 5, were compared using median, interquartile range, and correlation plots. Patients were dichotomized based on the time after symptom onset of their post procedure images (≥18 h vs. <18 h), and the degree of reperfusion (on Tmax>6 s; ≥ 90% vs. < 90%).Early post-procedure, median infarct lesion volume was 19 ml [(IQR) 7-43] on fluid-attenuated inversion recovery, and 23 ml [11-64] on diffusion-weighted imaging. On day 5, median infarct lesion volume was 52 ml [20-118] on fluid-attenuated inversion recovery, and 37 ml [16-91] on diffusion-weighted imaging. Infarct lesion volume on early post-procedure diffusion-weighted imaging, compared to fluid-attenuated inversion recovery, correlated better with day 5 diffusion-weighted imaging and fluid-attenuated inversion recovery lesions (r = 0.88 and 0.88 vs. 0.78 and 0.77; p < 0.0001). Median lesion growth was significantly smaller on diffusion-weighted imaging when the early post-procedure scan was obtained ≥18 h post stroke onset (5 ml [-1-13]), compared to <18 h (13 ml [2-47]; p = 0.03), but was not significantly different on fluid-attenuated inversion recovery (≥18 h: 26 ml [12-57]; <18 h: 21 ml [5-57]; p = 0.65). In the <90% reperfused group, the median infarct growth was significantly larger for diffusion-weighted imaging and fluid-attenuated inversion recovery (diffusion-weighted imaging: 23 ml [8-57], fluid-attenuated inversion recovery: 41 ml [13-104]) compared to ≥90% (diffusion-weighted imaging: 6 ml [2-24]; p = 0.003, fluid-attenuated inversion recovery: 19 ml [8-46]; p = 0.001).Early post-procedure lesion volume on diffusion-weighted imaging is a better estimate of day 5 infarct volume than fluid-attenuated inversion recovery. However, both early post-procedure diffusion-weighted imaging and fluid-attenuated inversion recovery underestimate day 5 diffusion-weighted imaging and fluid-attenuated inversion recovery lesion volumes, especially in patients who do not reperfuse.

    View details for PubMedID 27811306

  • Desmoteplase 3 to 9 Hours After Major Artery Occlusion Stroke: The DIAS-4 Trial (Efficacy and Safety Study of Desmoteplase to Treat Acute Ischemic Stroke). Stroke; a journal of cerebral circulation von Kummer, R., Mori, E., Truelsen, T., Jensen, J. S., Grønning, B. A., Fiebach, J. B., Lovblad, K., Pedraza, S., Romero, J. M., Chabriat, H., Chang, K., Dávalos, A., Ford, G. A., Grotta, J., Kaste, M., Schwamm, L. H., Shuaib, A., Albers, G. W. 2016

    Abstract

    The DIAS-3 trial (Efficacy and Safety Study of Desmoteplase to Treat Acute Ischemic Stroke [phase 3]) did not demonstrate a significant clinical benefit of desmoteplase administered 3 to 9 hours after stroke in patients with major artery occlusion. We present the results of the prematurely terminated DIAS-4 trial together with a post hoc pooled analysis of the concomitant DIAS-3, DIAS-4, and DIAS-J (Japan) trials to better understand the potential risks and benefits of intravenous desmoteplase for the treatment of ischemic stroke in an extended time window.Ischemic stroke patients with occlusion/high-grade stenosis in major cerebral arteries were randomly assigned to intravenous treatment with desmoteplase (90 μg/kg) or placebo. The primary outcome was modified Rankin Scale (mRS) score of 0 to 2 at day 90. Safety assessments included mortality, symptomatic intracranial hemorrhage, and other serious adverse events.In DIAS-4, 52 of 124 (41.9%) desmoteplase-treated and 46 of 128 (35.9%) placebo-treated patients achieved an mRS score of 0 to 2 (odds ratio, 1.45; 95% confidence interval, 0.79; 2.64; P=0.23) with equal mortality, frequency of symptomatic intracranial hemorrhage, and other serious adverse events in both the treatment arms. In the pooled analysis, mRS score of 0 to 2 was achieved by 184 of 376 (48.9%) desmoteplase-treated versus 171 of 381 (44.9%) placebo-treated patients (odds ratio, 1.33; 95% confidence interval, 0.95; 1.85; P=0.096). Treatment with desmoteplase was safe and increased the recanalization rate (107/217 [49.3%] versus 85/222 [38.3%]; odds ratio, 1.59; 95% confidence interval, 1.08-2.35; P=0.019). Recanalization was associated with favorable outcomes (mRS 0-2) at day 90 in both the treatment arms.Late treatment with intravenous 90 µg/kg desmoteplase is safe, increases arterial recanalization, but does not significantly improve functional outcome at 3 months.URL: http://www.clinicaltrials.gov. Unique identifier: NCT00856661.

    View details for PubMedID 27803391

  • Validation and comparison of imaging-based scores for prediction of early stroke risk after transient ischaemic attack: a pooled analysis of individual-patient data from cohort studies LANCET NEUROLOGY Kelly, P. J., Albers, G. W., Chatzikonstantinou, A., De Marchis, G. M., Ferrari, J., George, P., Katan, M., Knoflach, M., Kim, J. S., Li, L., Lee, E., Olivot, J., Purroy, F., Raposo, N., Rothwell, P. M., Sharma, V. K., Song, B., Tsivgoulis, G., Walsh, C., Xu, Y., Merwick, A. 2016; 15 (12): 1236-1245

    View details for Web of Science ID 000386315700019

  • A benchmarking tool to evaluate computer tomography perfusion infarct core predictions against a DWI standard JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM Cereda, C. W., Christensen, S., Campbell, B. C., Mishra, N. K., Mlynash, M., Levi, C., Straka, M., Wintermark, M., Bammer, R., Albers, G. W., Parsons, M. W., Lansberg, M. G. 2016; 36 (10): 1780-1789

    Abstract

    Differences in research methodology have hampered the optimization of Computer Tomography Perfusion (CTP) for identification of the ischemic core. We aim to optimize CTP core identification using a novel benchmarking tool. The benchmarking tool consists of an imaging library and a statistical analysis algorithm to evaluate the performance of CTP. The tool was used to optimize and evaluate an in-house developed CTP-software algorithm. Imaging data of 103 acute stroke patients were included in the benchmarking tool. Median time from stroke onset to CT was 185 min (IQR 180-238), and the median time between completion of CT and start of MRI was 36 min (IQR 25-79). Volumetric accuracy of the CTP-ROIs was optimal at an rCBF threshold of <38%; at this threshold, the mean difference was 0.3 ml (SD 19.8 ml), the mean absolute difference was 14.3 (SD 13.7) ml, and CTP was 67% sensitive and 87% specific for identification of DWI positive tissue voxels. The benchmarking tool can play an important role in optimizing CTP software as it provides investigators with a novel method to directly compare the performance of alternative CTP software packages.

    View details for DOI 10.1177/0271678X15610586

    View details for Web of Science ID 000385349400011

    View details for PubMedID 26661203

    View details for PubMedCentralID PMC5076783

  • Stroke Treatment Academic Industry Roundtable: The Next Generation of Endovascular Trials. Stroke; a journal of cerebral circulation Jovin, T. G., Albers, G. W., Liebeskind, D. S. 2016; 47 (10): 2656-2665

    Abstract

    The STAIR (Stroke Treatment Academic Industry Roundtable) meeting aims to advance acute stroke therapy development through collaboration between academia, industry, and regulatory institutions. In pursuit of this goal and building on recently available level I evidence of benefit from endovascular therapy (ET) in large vessel occlusion stroke, STAIR IX consensus recommendations were developed that outline priorities for future research in ET.Three key directions for advancing the field were identified: (1) development of systems of care for ET in large vessel occlusion stroke, (2) development of therapeutic approaches adjunctive to ET, and (3) exploring clinical benefit of ET in patient population insufficiently studied in recent trials. Methodological issues such as optimal trial design and outcome measures have also been addressed.Development of systems of care strategies should be geared both toward ensuring broad access to ET for eligible patients and toward shortening time to reperfusion to the minimum possible. Adjunctive therapy development includes neuroprotective approaches, adjuvant microcirculatory/collateral enhancing strategies, and periprocedural management. Future research priorities seeking to expand the eligible patient population are to determine benefit of ET in patients presenting beyond conventional time windows, in patients with large baseline ischemic core lesions, and in other important subgroups.Research priorities in ET for large vessel occlusion stroke are to improve systems of care, investigate effective adjuvant therapies, and explore whether patient eligibility could be expanded.

    View details for DOI 10.1161/STROKEAHA.116.013578

    View details for PubMedID 27586682

  • Prediction of Stroke Onset Is Improved by Relative Fluid-Attenuated Inversion Recovery and Perfusion Imaging Compared to the Visual Diffusion-Weighted Imaging/Fluid-Attenuated Inversion Recovery Mismatch. Stroke; a journal of cerebral circulation Wouters, A., Dupont, P., Norrving, B., Laage, R., Thomalla, G., Albers, G. W., Thijs, V., Lemmens, R. 2016; 47 (10): 2559-2564

    Abstract

    Acute stroke patients with unknown time of symptom onset are ineligible for thrombolysis. The diffusion-weighted imaging and fluid-attenuated inversion recovery (FLAIR) mismatch is a reasonable predictor of stroke within 4.5 hours of symptom onset, and its clinical usefulness in selecting patients for thrombolysis is currently being investigated. The accuracy of the visual mismatch rating is moderate, and we hypothesized that the predictive value of stroke onset within 4.5 hours could be improved by including various clinical and imaging parameters.In this study, 141 patients in whom magnetic resonance imaging was obtained within 9 hours after symptom onset were included. Relative FLAIR signal intensity was calculated in the region of nonreperfused core. Mean Tmax was calculated in the total region with Tmax >6 s. Mean relative FLAIR, mean Tmax, lesion volume with Tmax >6 s, age, site of arterial stenosis, core volume, and location of infarct were analyzed by logistic regression to predict stroke onset time before or after 4.5 hours.Receiver-operating characteristic curve analysis revealed an area under the curve of 0.68 (95% confidence interval 0.59-0.78) for the visual diffusion-weighted imaging/FLAIR mismatch, thereby correctly classifying 69% of patients with an onset time before or after 4.5 hours. Age, relative FLAIR, and Tmax increased the accuracy significantly (P<0.01) to an area under the curve of 0.82 (95% confidence interval 0.74-0.89). This new predictive model correctly categorized 77% of patients according to stroke onset before versus after 4.5 hours.In patients with unknown stroke onset, the accuracy of predicting time from symptom onset within 4.5 hours is improved by obtaining relative FLAIR and perfusion imaging.

    View details for DOI 10.1161/STROKEAHA.116.013903

    View details for PubMedID 27601375

  • Analysis of perfusion MRI in stroke: To deconvolve, or not to deconvolve. Magnetic resonance in medicine Meijs, M., Christensen, S., Lansberg, M. G., Albers, G. W., Calamante, F. 2016; 76 (4): 1282-1290

    Abstract

    There is currently controversy regarding the benefits of deconvolution-based parameters in stroke imaging, with studies suggesting a similar infarct prediction using summary parameters. We investigate here the performance of deconvolution-based parameters and summary parameters for dynamic-susceptibility contrast (DSC) MRI analysis, with particular emphasis on precision.Numerical simulations were used to assess the contribution of noise and arterial input function (AIF) variability to measurement precision. A realistic AIF range was defined based on in vivo data from an acute stroke clinical study. The simulated tissue curves were analyzed using two popular singular value decomposition (SVD) based algorithms, as well as using summary parameters.SVD-based deconvolution methods were found to considerably reduce the AIF-dependency, but a residual AIF bias remained on the calculated parameters. Summary parameters, in turn, show a lower sensitivity to noise. The residual AIF-dependency for deconvolution methods and the large AIF-sensitivity of summary parameters was greatly reduced when normalizing them relative to normal tissue.Consistent with recent studies suggesting high performance of summary parameters in infarct prediction, our results suggest that DSC-MRI analysis using properly normalized summary parameters may have advantages in terms of lower noise and AIF-sensitivity as compared to commonly used deconvolution methods. Magn Reson Med 76:1282-1290, 2016. © 2015 Wiley Periodicals, Inc.

    View details for DOI 10.1002/mrm.26024

    View details for PubMedID 26519871

  • Risk of intracerebral haemorrhage with alteplase after acute ischaemic stroke: a secondary analysis of an individual patient data meta-analysis. The Lancet. Neurology Whiteley, W. N., Emberson, J., Lees, K. R., Blackwell, L., Albers, G., Bluhmki, E., Brott, T., Cohen, G., Davis, S., Donnan, G., Grotta, J., Howard, G., Kaste, M., Koga, M., von Kummer, R., Lansberg, M. G., Lindley, R. I., Lyden, P., Olivot, J. M., Parsons, M., Toni, D., Toyoda, K., Wahlgren, N., Wardlaw, J., del Zoppo, G. J., Sandercock, P., Hacke, W., Baigent, C. 2016; 15 (9): 925-933

    Abstract

    Randomised trials have shown that alteplase improves the odds of a good outcome when delivered within 4·5 h of acute ischaemic stroke. However, alteplase also increases the risk of intracerebral haemorrhage; we aimed to determine the proportional and absolute effects of alteplase on the risks of intracerebral haemorrhage, mortality, and functional impairment in different types of patients.We used individual patient data from the Stroke Thrombolysis Trialists' (STT) meta-analysis of randomised trials of alteplase versus placebo (or untreated control) in patients with acute ischaemic stroke. We prespecified assessment of three classifications of intracerebral haemorrhage: type 2 parenchymal haemorrhage within 7 days; Safe Implementation of Thrombolysis in Stroke Monitoring Study's (SITS-MOST) haemorrhage within 24-36 h (type 2 parenchymal haemorrhage with a deterioration of at least 4 points on National Institutes of Health Stroke Scale [NIHSS]); and fatal intracerebral haemorrhage within 7 days. We used logistic regression, stratified by trial, to model the log odds of intracerebral haemorrhage on allocation to alteplase, treatment delay, age, and stroke severity. We did exploratory analyses to assess mortality after intracerebral haemorrhage and examine the absolute risks of intracerebral haemorrhage in the context of functional outcome at 90-180 days.Data were available from 6756 participants in the nine trials of intravenous alteplase versus control. Alteplase increased the odds of type 2 parenchymal haemorrhage (occurring in 231 [6·8%] of 3391 patients allocated alteplase vs 44 [1·3%] of 3365 patients allocated control; odds ratio [OR] 5·55 [95% CI 4·01-7·70]; absolute excess 5·5% [4·6-6·4]); of SITS-MOST haemorrhage (124 [3·7%] of 3391 vs 19 [0·6%] of 3365; OR 6·67 [4·11-10·84]; absolute excess 3·1% [2·4-3·8]); and of fatal intracerebral haemorrhage (91 [2·7%] of 3391 vs 13 [0·4%] of 3365; OR 7·14 [3·98-12·79]; absolute excess 2·3% [1·7-2·9]). However defined, the proportional increase in intracerebral haemorrhage was similar irrespective of treatment delay, age, or baseline stroke severity, but the absolute excess risk of intracerebral haemorrhage increased with increasing stroke severity: for SITS-MOST intracerebral haemorrhage the absolute excess risk ranged from 1·5% (0·8-2·6%) for strokes with NIHSS 0-4 to 3·7% (2·1-6·3%) for NIHSS 22 or more (p=0·0101). For patients treated within 4·5 h, the absolute increase in the proportion (6·8% [4·0% to 9·5%]) achieving a modified Rankin Scale of 0 or 1 (excellent outcome) exceeded the absolute increase in risk of fatal intracerebral haemorrhage (2·2% [1·5% to 3·0%]) and the increased risk of any death within 90 days (0·9% [-1·4% to 3·2%]).Among patients given alteplase, the net outcome is predicted both by time to treatment (with faster time increasing the proportion achieving an excellent outcome) and stroke severity (with a more severe stroke increasing the absolute risk of intracerebral haemorrhage). Although, within 4·5 h of stroke, the probability of achieving an excellent outcome with alteplase treatment exceeds the risk of death, early treatment is especially important for patients with severe stroke.UK Medical Research Council, British Heart Foundation, University of Glasgow, University of Edinburgh.

    View details for DOI 10.1016/S1474-4422(16)30076-X

    View details for PubMedID 27289487

  • Pretreatment blood-brain barrier disruption and post-endovascular intracranial hemorrhage. Neurology Leigh, R., Christensen, S., Campbell, B. C., Marks, M. P., Albers, G. W., Lansberg, M. G. 2016; 87 (3): 263-269

    Abstract

    This study sought to confirm the relationship between the degree of blood-brain barrier (BBB) damage and the severity of intracranial hemorrhage (ICH) in a population of patients who received endovascular therapy.The degree of BBB disruption on pretreatment MRI scans was analyzed, blinded to follow-up data, in the DEFUSE 2 cohort in which patients had endovascular therapy within 12 hours of stroke onset. BBB disruption was compared with ICH grade previously established by the DEFUSE 2 core lab. A prespecified threshold for predicting parenchymal hematoma (PH) was tested.Of the 108 patients in the DEFUSE 2 trial, 100 had adequate imaging and outcome data and were included in this study; 24 developed PH. Increasing amounts of BBB disruption on pretreatment MRIs was associated with increasing severity of ICH grade (p = 0.004). BBB disruption on the pretreatment scan was associated with PH (p = 0.020) with an odds ratio for developing PH of 1.69 for each 10% increase in BBB disruption (95% confidence interval 1.09-2.64), although a reliably predictive threshold was not identified.The amount of BBB disruption on pretreatment MRI is associated with the severity of ICH after acute intervention. This relationship has now been identified in patients receiving IV, endovascular, and combined therapies. Further study is needed to determine its role in guiding treatment.

    View details for DOI 10.1212/WNL.0000000000002862

    View details for PubMedID 27316247

  • Ticagrelor versus Aspirin in Acute Stroke or Transient Ischemic Attack NEW ENGLAND JOURNAL OF MEDICINE Johnston, S. C., Amarenco, P., Albers, G. W., Denison, H., Easton, J. D., Evans, S. R., Held, P., Jonasson, J., Minematsu, K., Molina, C. A., Wang, Y., Wong, K. S. 2016; 375 (1): 35-43

    Abstract

    Ticagrelor may be a more effective antiplatelet therapy than aspirin for the prevention of recurrent stroke and cardiovascular events in patients with acute cerebral ischemia.We conducted an international double-blind, controlled trial in 674 centers in 33 countries, in which 13,199 patients with a nonsevere ischemic stroke or high-risk transient ischemic attack who had not received intravenous or intraarterial thrombolysis and were not considered to have had a cardioembolic stroke were randomly assigned within 24 hours after symptom onset, in a 1:1 ratio, to receive either ticagrelor (180 mg loading dose on day 1 followed by 90 mg twice daily for days 2 through 90) or aspirin (300 mg on day 1 followed by 100 mg daily for days 2 through 90). The primary end point was the time to the occurrence of stroke, myocardial infarction, or death within 90 days.During the 90 days of treatment, a primary end-point event occurred in 442 of the 6589 patients (6.7%) treated with ticagrelor, versus 497 of the 6610 patients (7.5%) treated with aspirin (hazard ratio, 0.89; 95% confidence interval [CI], 0.78 to 1.01; P=0.07). Ischemic stroke occurred in 385 patients (5.8%) treated with ticagrelor and in 441 patients (6.7%) treated with aspirin (hazard ratio, 0.87; 95% CI, 0.76 to 1.00). Major bleeding occurred in 0.5% of patients treated with ticagrelor and in 0.6% of patients treated with aspirin, intracranial hemorrhage in 0.2% and 0.3%, respectively, and fatal bleeding in 0.1% and 0.1%.In our trial involving patients with acute ischemic stroke or transient ischemic attack, ticagrelor was not found to be superior to aspirin in reducing the rate of stroke, myocardial infarction, or death at 90 days. (Funded by AstraZeneca; ClinicalTrials.gov number, NCT01994720.).

    View details for DOI 10.1056/NEJMoa1603060

    View details for PubMedID 27160892

  • Evolution of Volume and Signal Intensity on Fluid-attenuated Inversion Recovery MR Images after Endovascular Stroke Therapy RADIOLOGY Federau, C., Mlynash, M., Christensen, S., Zaharchuk, G., Cha, B., Lansberg, M. G., Wintermark, M., Albers, G. W. 2016; 280 (1): 184-192

    Abstract

    Purpose To analyze both volume and signal evolution on magnetic resonance (MR) fluid-attenuated inversion recovery (FLAIR) images between the images after endovascular therapy and day 5 (which was the prespecified end point for infarct volume in the Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution [DEFUSE 2] trial) in a subset of patients enrolled in the DEFUSE 2 study. Materials and Methods This study was approved by the local ethics committee at all participating sites. Informed written consent was obtained from all patients. In this post hoc analysis of the DEFUSE 2 study, 35 patients with FLAIR images acquired both after endovascular therapy (median time after symptom onset, 12 hours) and at day 5 were identified. Patients were separated into two groups based on the degree of reperfusion achieved on time to maximum greater than 6-second perfusion imaging (≥90% vs <90%). After coregistration and signal normalization, lesion volumes and signal intensity were assessed by using FLAIR imaging for the initial lesion (ie, visible after endovascular therapy) and the recruited lesion (the additional lesion visible on day 5, but not visible after endovascular therapy). Statistical significance was assessed by using Wilcoxon signed-rank, Mann-Whitney U, and Fisher exact tests. Results All 35 patients had FLAIR lesion growth between the after-revascularization examination and day 5. Median lesion growth was significantly larger in patients with <90% reperfusion (27.85 mL) compared with ≥90% (8.12 mL; P = .003). In the initial lesion, normalized signal did not change between after endovascular therapy (median, 1.60) and day 5 (median, 1.58) in the ≥90% reperfusion group (P = .97), but increased in the <90% reperfusion group (from 1.60 to 1.73; P = .01). In the recruited lesion, median normalized signal increased significantly in both groups between after endovascular therapy and day 5 (after endovascular therapy, from 1.19 to 1.56, P < .001; and day 5, from 1.18 to 1.63, P < .001). Conclusion Patients with ≥90% reperfusion after endovascular therapy have significantly less lesion growth on FLAIR images between after therapy and day 5 compared with patients who have <90% reperfusion. Therefore, the effect of reperfusion therapies on lesion volumes are likely more apparent at day 5 than after therapy. (©) RSNA, 2016.

    View details for DOI 10.1148/radiol.2015151586

    View details for Web of Science ID 000378721900020

    View details for PubMedID 26761721

  • The MARINER trial of rivaroxaban after hospital discharge for medical patients at high risk of VTE Design, rationale, and clinical implications THROMBOSIS AND HAEMOSTASIS Raskob, G. E., Spyropoulos, A. C., Zrubek, J., Ageno, W., Albers, G., Elliott, C. G., Halperin, J., Haskell, L., Hiatt, W. R., Maynard, G. A., Peters, G., Spiro, T., Steg, P. G., Suh, E. Y., Weitz, J. I. 2016; 115 (6): 1240-1248

    Abstract

    Hospital-associated venous thromboembolism (VTE) is a leading cause of premature death and disability worldwide. Evidence-based guidelines recommend that anticoagulant thromboprophylaxis be given to hospitalised medical patients at risk of VTE, but suggest against routine use of thromboprophylaxis beyond the hospital stay. The MARINER study is a randomised, double-blind, placebo-controlled trial to evaluate the efficacy and safety of thromboprophylaxis using rivaroxaban, begun at hospital discharge and continued for 45 days, for preventing symptomatic VTE in high-risk medical patients. Eligible patients are identified using the International Medical Prevention Registry on Venous Thromboembolism (IMPROVE VTE) risk score, combined with a laboratory test, D-dimer. The rivaroxaban regimen is 10 mg once daily for patients with CrCl ≥ 50 ml/min, or 7.5 mg once daily for patients with CrCl ≥ 30 ml/min and < 50 ml/min. The primary efficacy outcome is the composite of symptomatic VTE (lower extremity deep-vein thrombosis and non-fatal pulmonary embolism) and VTE-related death. The principal safety outcome is major bleeding. A blinded clinical events committee adjudicates all suspected outcome events. The sample size is event-driven with an estimated total of 8,000 patients to acquire 161 primary outcome events. Study design features that distinguish MARINER from previous and ongoing thromboprophylaxis trials in medically ill patients are: (i) use of a validated risk assessment model (IMPROVE VTE) and D-dimer determination for identifying eligible patients at high risk of VTE, (ii) randomisation at the time of hospital discharge, (iii) a 45-day treatment period and (iv) restriction of the primary efficacy outcome to symptomatic VTE events.

    View details for DOI 10.1160/TH15-09-0756

    View details for Web of Science ID 000377237400020

    View details for PubMedID 26842902

  • Acute Stroke Imaging Research Roadmap III Imaging Selection and Outcomes in Acute Stroke Reperfusion Clinical Trials Consensus Recommendations and Further Research Priorities STROKE Warach, S. J., Luby, M., Albers, G. W., Bammer, R., Bivard, A., Campbell, B. C., Derdeyn, C., Heit, J. J., Khatri, P., Lansberg, M. G., Liebeskind, D. S., Majoie, C. B., Marks, M. P., Menon, B. K., Muir, K. W., Parsons, M. W., Vagal, A., Yoo, A. J., Alexandrov, A. V., Baron, J., Fiorella, D. J., Furlan, A. J., Puig, J., Schellinger, P. D., Wintermark, M. 2016; 47 (5): 1389-1398

    Abstract

    The Stroke Imaging Research (STIR) group, the Imaging Working Group of StrokeNet, the American Society of Neuroradiology, and the Foundation of the American Society of Neuroradiology sponsored an imaging session and workshop during the Stroke Treatment Academy Industry Roundtable (STAIR) IX on October 5 to 6, 2015 in Washington, DC. The purpose of this roadmap was to focus on the role of imaging in future research and clinical trials.This forum brought together stroke neurologists, neuroradiologists, neuroimaging research scientists, members of the National Institute of Neurological Disorders and Stroke (NINDS), industry representatives, and members of the US Food and Drug Administration to discuss STIR priorities in the light of an unprecedented series of positive acute stroke endovascular therapy clinical trials.The imaging session summarized and compared the imaging components of the recent positive endovascular trials and proposed opportunities for pooled analyses. The imaging workshop developed consensus recommendations for optimal imaging methods for the acquisition and analysis of core, mismatch, and collaterals across multiple modalities, and also a standardized approach for measuring the final infarct volume in prospective clinical trials.Recent positive acute stroke endovascular clinical trials have demonstrated the added value of neurovascular imaging. The optimal imaging profile for endovascular treatment includes large vessel occlusion, smaller core, good collaterals, and large penumbra. However, equivalent definitions for the imaging profile parameters across modalities are needed, and a standardization effort is warranted, potentially leveraging the pooled data resulting from the recent positive endovascular trials.

    View details for DOI 10.1161/STROKEAHA.115.012364

    View details for PubMedID 27073243

  • Diagnostic Yield of Echocardiography in Transient Ischemic Attack JOURNAL OF STROKE & CEREBROVASCULAR DISEASES Wilson, C. A., Tai, W., Desai, J. A., Mulvihill, I., Olivot, J., Murphy, S., Coutts, S. B., Albers, G. W., Kelly, P., Cucchiara, B. L. 2016; 25 (5): 1135-1140

    Abstract

    Echocardiography is often performed to identify a cardiac source of embolism (CSE) causing transient ischemic attack (TIA). However, the diagnostic yield of echocardiography in TIA remains uncertain, and its role in routine evaluation of TIA is controversial.Patients with acute TIA were prospectively enrolled at 4 stroke centers. A CSE was defined using the Causative Classification of Stroke system; patent foramen ovale was considered a relevant CSE only if the patient underwent closure or was placed on anticoagulation. Patients with a known CSE at time of admission were excluded from analysis of the yield of echocardiography.A total of 869 patients were enrolled at stroke centers, and 129 had a known CSE at presentation. Of the 740 remaining patients, 603 (81%) underwent echocardiography. A potential CSE was identified in 60 (10%) of these patients. The most common CSEs noted on echocardiography were complex aortic arch atherosclerosis and patent foramen ovale. History of coronary artery disease (P < .001), lack of prior stroke or TIA (P = .007), and presence of acute infarction on magnetic resonance imaging (MRI) (P < .001) were predictors of CSE on echocardiography. The yield of echocardiography was 29% in patients with both history of coronary artery disease and acute infarction on MRI, 14% with one of these features, and 5% with neither of these features (P < .0001). A CSE identified by echocardiography prompted initiation of anticoagulation in 15 of the 603 (2.5%) subjects.Echocardiography demonstrates a relevant CSE in a significant portion of patients with TIA. However, changes in antithrombotic therapy resulting from echocardiography are infrequent.

    View details for DOI 10.1016/j.jstrokecerebrovasdis.2016.01.011

    View details for Web of Science ID 000375144200021

    View details for PubMedID 26915604

  • One-Year Risk of Stroke after Transient Ischemic Attack or Minor Stroke NEW ENGLAND JOURNAL OF MEDICINE Amarenco, P., Lavallee, P. C., Labreuche, J., Albers, G. W., Bornstein, N. M., Canhao, P., Caplan, L. R., Donnan, G. A., Ferro, J. M., Hennerici, M. G., Molina, C., Rothwell, P. M., Sissani, L., Skoloudik, D., Steg, P. G., Touboul, P., Uchiyama, S., Vicaut, E., Wong, L. K. 2016; 374 (16): 1533-1542

    Abstract

    Previous studies conducted between 1997 and 2003 estimated that the risk of stroke or an acute coronary syndrome was 12 to 20% during the first 3 months after a transient ischemic attack (TIA) or minor stroke. The TIAregistry.org project was designed to describe the contemporary profile, etiologic factors, and outcomes in patients with a TIA or minor ischemic stroke who receive care in health systems that now offer urgent evaluation by stroke specialists.We recruited patients who had had a TIA or minor stroke within the previous 7 days. Sites were selected if they had systems dedicated to urgent evaluation of patients with TIA. We estimated the 1-year risk of stroke and of the composite outcome of stroke, an acute coronary syndrome, or death from cardiovascular causes. We also examined the association of the ABCD(2) score for the risk of stroke (range, 0 [lowest risk] to 7 [highest risk]), findings on brain imaging, and cause of TIA or minor stroke with the risk of recurrent stroke over a period of 1 year.From 2009 through 2011, we enrolled 4789 patients at 61 sites in 21 countries. A total of 78.4% of the patients were evaluated by stroke specialists within 24 hours after symptom onset. A total of 33.4% of the patients had an acute brain infarction, 23.2% had at least one extracranial or intracranial stenosis of 50% or more, and 10.4% had atrial fibrillation. The Kaplan-Meier estimate of the 1-year event rate of the composite cardiovascular outcome was 6.2% (95% confidence interval, 5.5 to 7.0). Kaplan-Meier estimates of the stroke rate at days 2, 7, 30, 90, and 365 were 1.5%, 2.1%, 2.8%, 3.7%, and 5.1%, respectively. In multivariable analyses, multiple infarctions on brain imaging, large-artery atherosclerosis, and an ABCD(2) score of 6 or 7 were each associated with more than a doubling of the risk of stroke.We observed a lower risk of cardiovascular events after TIA than previously reported. The ABCD(2) score, findings on brain imaging, and status with respect to large-artery atherosclerosis helped stratify the risk of recurrent stroke within 1 year after a TIA or minor stroke. (Funded by Sanofi and Bristol-Myers Squibb.).

    View details for DOI 10.1056/NEJMoa1412981

    View details for Web of Science ID 000374383900006

    View details for PubMedID 27096581

  • Association Between Time From Stroke Onset and Fluid-Attenuated Inversion Recovery Lesion Intensity Is Modified by Status of Collateral Circulation STROKE Wouters, A., Dupont, P., Christensen, S., Norrving, B., Laage, R., Thomalla, G., Albers, G., Thijs, V., Lemmens, R. 2016; 47 (4): 1018-1022

    View details for DOI 10.1161/STROKEAHA.115.012010

    View details for Web of Science ID 000372853200018

  • Effect of endovascular reperfusion in relation to site of arterial occlusion. Neurology Lemmens, R., Hamilton, S. A., Liebeskind, D. S., Tomsick, T. A., Demchuk, A. M., Nogueira, R. G., Marks, M. P., Jahan, R., Gralla, J., Yoo, A. J., Yeatts, S. D., Palesch, Y. Y., Saver, J. L., Pereira, V. M., Broderick, J. P., Albers, G. W., Lansberg, M. G. 2016; 86 (8): 762-770

    Abstract

    To assess whether the association between reperfusion and improved clinical outcomes after stroke differs depending on the site of the arterial occlusive lesion (AOL).We pooled data from Solitaire With the Intention for Thrombectomy (SWIFT), Solitaire FR Thrombectomy for Acute Revascularisation (STAR), Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution Study 2 (DEFUSE 2), and Interventional Management of Stroke Trial (IMS III) to compare the strength of the associations between reperfusion and clinical outcomes in patients with internal carotid artery (ICA), proximal middle cerebral artery (MCA) (M1), and distal MCA (M2/3/4) occlusions.Among 710 included patients, the site of the AOL was the ICA in 161, the proximal MCA in 389, and the distal MCA in 160 patients (M2 = 131, M3 = 23, and M4 = 6). Reperfusion was associated with an increase in the rate of good functional outcome (modified Rankin Scale [mRS] score 0-2) in patients with ICA (odds ratio [OR] 3.5, 95% confidence interval [CI] 1.7-7.2) and proximal MCA occlusions (OR 6.2, 95% CI 3.8-10.2), but not in patients with distal MCA occlusions (OR 1.4, 95% CI 0.8-2.6). Among patients with M2 occlusions, a subset of the distal MCA cohort, reperfusion was associated with excellent functional outcome (mRS 0-1; OR 2.2, 95% CI 1.0-4.7).The association between endovascular reperfusion and better clinical outcomes is more profound in patients with ICA and proximal MCA occlusions compared to patients with distal MCA occlusions. Because there are limited data from randomized controlled trials on the effect of endovascular therapy in patients with distal MCA occlusions, these results underscore the need for inclusion of this subgroup in future endovascular therapy trials.

    View details for DOI 10.1212/WNL.0000000000002399

    View details for PubMedID 26802090

  • Multi-Center Study of Diffusion-Weighted Imaging in Coma After Cardiac Arrest. Neurocritical care Hirsch, K. G., Mlynash, M., Eyngorn, I., Pirsaheli, R., Okada, A., Komshian, S., Chen, C., Mayer, S. A., Meschia, J. F., Bernstein, R. A., Wu, O., Greer, D. M., Wijman, C. A., Albers, G. W. 2016; 24 (1): 82-89

    Abstract

    The ability to predict outcomes in acutely comatose cardiac arrest survivors is limited. Brain diffusion-weighted magnetic resonance imaging (DWI MRI) has been shown in initial studies to be a simple and effective prognostic tool. This study aimed to determine the predictive value of previously defined DWI MRI thresholds in a multi-center cohort.DWI MRIs of comatose post-cardiac arrest patients were analyzed in this multi-center retrospective observational study. Poor outcome was defined as failure to regain consciousness within 14 days and/or death during the hospitalization. The apparent diffusion coefficient (ADC) value of each brain voxel was determined. ADC thresholds and brain volumes below each threshold were analyzed for their correlation with outcome.125 patients were included in the analysis. 33 patients (26 %) had a good outcome. An ADC value of less than 650 × 10(-6) mm(2)/s in ≥10 % of brain volume was highly specific [91 % (95 % CI 75-98)] and had a good sensitivity [72 % (95 % CI 61-80)] for predicting poor outcome. This threshold remained an independent predictor of poor outcome in multivariable analysis (p = 0.002). An ADC value of less than 650 × 10(-6) mm(2)/s in >22 % of brain volume was needed to achieve 100 % specificity for poor outcome.In patients who remain comatose after cardiac arrest, quantitative DWI MRI findings correlate with early recovery of consciousness. A DWI MRI threshold of 650 × 10(-6) mm(2)/s in ≥10 % of brain volume can differentiate patients with good versus poor outcome, though in this patient population the threshold was not 100 % specific for poor outcome.

    View details for DOI 10.1007/s12028-015-0179-9

    View details for PubMedID 26156112

  • Identification of imaging selection patterns in acute ischemic stroke patients and the influence on treatment and clinical trial enrollment decision making. International journal of stroke Luby, M., Warach, S. J., Albers, G. W., Baron, J., Cognard, C., Dávalos, A., Donnan, G. A., Fiebach, J. B., Fiehler, J., Hacke, W., Lansberg, M. G., Liebeskind, D. S., Mattle, H. P., Oppenheim, C., Schellinger, P. D., Wardlaw, J. M., Wintermark, M. 2016; 11 (2): 180-190

    Abstract

    For the STroke Imaging Research (STIR) and VISTA-Imaging Investigators The purpose of this study was to collect precise information on the typical imaging decisions given specific clinical acute stroke scenarios. Stroke centers worldwide were surveyed regarding typical imaging used to work up representative acute stroke patients, make treatment decisions, and willingness to enroll in clinical trials.STroke Imaging Research and Virtual International Stroke Trials Archive-Imaging circulated an online survey of clinical case vignettes through its website, the websites of national professional societies from multiple countries as well as through email distribution lists from STroke Imaging Research and participating societies. Survey responders were asked to select the typical imaging work-up for each clinical vignette presented. Actual images were not presented to the survey responders. Instead, the survey then displayed several types of imaging findings offered by the imaging strategy, and the responders selected the appropriate therapy and whether to enroll into a clinical trial considering time from onset, clinical presentation, and imaging findings. A follow-up survey focusing on 6 h from onset was conducted after the release of the positive endovascular trials.We received 548 responses from 35 countries including 282 individual centers; 78% of the centers originating from Australia, Brazil, France, Germany, Spain, United Kingdom, and United States. The specific onset windows presented influenced the type of imaging work-up selected more than the clinical scenario. Magnetic Resonance Imaging usage (27-28%) was substantial, in particular for wake-up stroke. Following the release of the positive trials, selection of perfusion imaging significantly increased for imaging strategy.Usage of vascular or perfusion imaging by Computed Tomography or Magnetic Resonance Imaging beyond just parenchymal imaging was the primary work-up (62-87%) across all clinical vignettes and time windows. Perfusion imaging with Computed Tomography or Magnetic Resonance Imaging was associated with increased probability of enrollment into clinical trials for 0-3 h. Following the release of the positive endovascular trials, selection of endovascular only treatment for 6 h increased across all clinical vignettes.

    View details for DOI 10.1177/1747493015616634

    View details for PubMedID 26783309

    View details for PubMedCentralID PMC4762013

  • Prognostic Value of Quantitative Diffusion-Weighted MRI in Patients with Traumatic Brain Injury JOURNAL OF NEUROIMAGING Shakir, A., Aksoy, D., Mlynash, M., Harris, O. A., Albers, G. W., Hirsch, K. G. 2016; 26 (1): 103-108

    View details for DOI 10.1111/jon.12286

    View details for Web of Science ID 000368012400014

  • Prediction of final infarct volume on subacute MRI by quantifying cerebral edema in ischemic stroke. Journal of cerebral blood flow and metabolism Tipirneni-Sajja, A., Christensen, S., Straka, M., Inoue, M., Lansberg, M. G., Mlynash, M., Bammer, R., Parsons, M. W., Donnan, G. A., Davis, S. M., Albers, G. W. 2016: 271678X16683960-?

    Abstract

    Final infarct volume in stroke trials is assessed on images obtained between 30 and 90 days after stroke onset. Imaging at such delayed timepoints is problematic because patients may be lost to follow-up or die before the scan. Obtaining an early assessment of infarct volume on subacute scans avoids these limitations; however, it overestimates true infarct volume because of edema. The aim of this study was to develop a novel approach to quantify edema so that final infarct volumes can be approximated on subacute scans. We analyzed data from 20 stroke patients (median age, 75 years) who had baseline, subacute (fu5d) and late (fu90d) MRI scans. Edema displaces CSF from sulci and ventricles; therefore, edema volume was estimated as change in CSF volume between baseline and spatially coregistered fu5d ADC maps. The median (interquartile range, IQR) estimated edema volume was 13.3 (7.5-37.7) mL. The fu5d lesion volumes correlated well with fu90d infarct volumes with slope: 1.24. With edema correction, fu5d infarct volumes are in close agreement, slope: 0.97 and strongly correlated with actual fu90d volumes. The median (IQR) difference between actual and predicted infarct volumes was 0.1 (-3.0-5.7) mL. In summary, this novel technique for estimation of edema allows final infarct volume to be predicted from subacute MRI.

    View details for DOI 10.1177/0271678X16683960

    View details for PubMedID 28155584

  • Magnetic resonance imaging-based endovascular versus medical stroke treatment for symptom onset up to 12?h. International journal of stroke Wouters, A., Lemmens, R., Christensen, S., Wilms, G., Dupont, P., Mlynash, M., Schneider, A., Laage, R., Cereda, C. W., Lansberg, M. G., Albers, G. W., Thijs, V. 2016; 11 (1): 127-133

    Abstract

    Recent trials have shown a clear benefit of endovascular therapy for stroke patients presenting within 6 h after stroke onset. Imaging-based selection may identify a cohort with a favorable response to endovascular therapy, in an even later time window.We performed an indirect comparison between outcomes seen in DEFUSE 2, a prospective cohort study of patients who received a baseline MRI before endovascular therapy, and a control group from AXIS 2 receiving standard medical care up to 12 h after symptom onset.Patients from AXIS 2 with a confirmed large vessel occlusion were selected as a control group for DEFUSE 2-patients. The primary endpoint was good functional outcome at day 90 (Modified Rankin Score 0-2). We performed a stratified analysis based on the presence of the target mismatch for both studies and reperfusion status in DEFUSE 2.We compared good functional outcome in 108 patients from AXIS 2 and 99 patients from DEFUSE 2. In DEFUSE 2-patients with the target mismatch profile in whom reperfusion was achieved, the rate of good functional outcome was increased compared to target mismatch patients in AXIS 2, 54% versus 29% (OR 3.2, 95% CI 1.1-9.4). In target mismatch patients treated between 6 and 12 h after stroke onset, this association between study and good functional outcome remained present (OR 9.0, 95% CI 1.1-75.8).This indirect comparison suggests that endovascular treatment resulting in substantial reperfusion is associated with improved outcome in target mismatch patients even beyond 6 h after stroke onset. Confirmation is needed from future clinical trials that randomize patients beyond the 6 h time window.

    View details for DOI 10.1177/1747493015607503

    View details for PubMedID 26763028

  • Ischemic core and hypoperfusion volumes predict infarct size in SWIFT PRIME. Annals of neurology Albers, G. W., Goyal, M., Jahan, R., Bonafe, A., Diener, H., Levy, E. I., Pereira, V. M., Cognard, C., Cohen, D. J., Hacke, W., Jansen, O., Jovin, T. G., Mattle, H. P., Nogueira, R. G., Siddiqui, A. H., Yavagal, D. R., Baxter, B. W., Devlin, T. G., Lopes, D. K., Reddy, V. K., de Rochemont, R. d., Singer, O. C., Bammer, R., Saver, J. L. 2016; 79 (1): 76-89

    Abstract

    Within the context of a prospective randomized trial (SWIFT PRIME), we assessed whether early imaging of stroke patients, primarily with computed tomography (CT) perfusion, can estimate the size of the irreversibly injured ischemic core and the volume of critically hypoperfused tissue. We also evaluated the accuracy of ischemic core and hypoperfusion volumes for predicting infarct volume in patients with the target mismatch profile.Baseline ischemic core and hypoperfusion volumes were assessed prior to randomized treatment with intravenous (IV) tissue plasminogen activator (tPA) alone versus IV tPA + endovascular therapy (Solitaire stent-retriever) using RAPID automated postprocessing software. Reperfusion was assessed with angiographic Thrombolysis in Cerebral Infarction scores at the end of the procedure (endovascular group) and Tmax > 6-second volumes at 27 hours (both groups). Infarct volume was assessed at 27 hours on noncontrast CT or magnetic resonance imaging (MRI).A total of 151 patients with baseline imaging with CT perfusion (79%) or multimodal MRI (21%) were included. The median baseline ischemic core volume was 6ml (interquartile range = 0-16). Ischemic core volumes correlated with 27-hour infarct volumes in patients who achieved reperfusion (r = 0.58, p < 0.0001). In patients who did not reperfuse (<10% reperfusion), baseline Tmax > 6-second lesion volumes correlated with 27-hour infarct volume (r = 0.78, p = 0.005). In target mismatch patients, the union of baseline core and early follow-up Tmax > 6-second volume (ie, predicted infarct volume) correlated with the 27-hour infarct volume (r = 0.73, p < 0.0001); the median absolute difference between the observed and predicted volume was 13ml.Ischemic core and hypoperfusion volumes, obtained primarily from CT perfusion scans, predict 27-hour infarct volume in acute stroke patients who were treated with reperfusion therapies. ANN NEUROL 2016;79:76-89.

    View details for DOI 10.1002/ana.24543

    View details for PubMedID 26476022

  • Inter-rater agreement analysis of the Precise Diagnostic Score for suspected transient ischemic attack. International journal of stroke Cereda, C. W., George, P. M., Inoue, M., Vora, N., Olivot, J., Schwartz, N., Lansberg, M. G., Kemp, S., Mlynash, M., Albers, G. W. 2016; 11 (1): 85-92

    Abstract

    No definitive criteria are available to confirm the diagnosis of transient ischemic attack. Inter-rater agreement between physicians regarding the diagnosis of transient ischemic attack is low, even among vascular neurologists. We developed the Precise Diagnostic Score, a diagnostic score that consists of discrete and well-defined clinical and imaging parameters, and investigated inter-rater agreement in patients with suspected transient ischemic attack.Fellowship-trained vascular neurologists, blinded to final diagnosis, independently reviewed retrospectively identical history, physical examination, routine diagnostic studies, and brain magnetic resonance imaging (diffusion and perfusion images) from consecutive patients with suspected transient ischemic attack. Each patient was rated using the 8-point Precise Diagnostic Score score, composed of a clinical score (0-4 points) and an imaging score (0-4 points). The composite Precise Diagnostic Score determines a Precise Diagnostic Score Likelihood of Brain Ischemia Scale: 0-1 = unlikely, 2 = possible, 3 = probable, 4-8 = very likely.Three raters reviewed data from 114 patients. Using Precise Diagnostic Score, all three raters scored a similar percentage of the clinical events as being "probable" or "very likely" caused by brain ischemia: 57, 55, and 58%. Agreement was high for both total Precise Diagnostic Score (intraclass correlation coefficient of 0.94) and for the Likelihood of Brain Ischemia Scale (agreement coefficient of 0.84).Compared with prior studies, inter-rater agreement for the diagnosis of transient brain ischemia appears substantially improved with the Precise Diagnostic Score scoring system. This score is the first to include specific criteria to assess the clinical relevance of diffusion-weighted imaging and perfusion lesions and supports the added value of magnetic resonance imaging for assessing patients with suspected transient ischemic attack.

    View details for DOI 10.1177/1747493015607507

    View details for PubMedID 26763024

  • Heart Rhythm Monitoring Strategies for Cryptogenic Stroke: 2015 Diagnostics and Monitoring Stroke Focus Group Report. Journal of the American Heart Association Albers, G. W., Bernstein, R. A., Brachmann, J., Camm, J., Easton, J. D., Fromm, P., Goto, S., Granger, C. B., Hohnloser, S. H., Hylek, E., Jaffer, A. K., Krieger, D. W., Passman, R., Pines, J. M., Reed, S. D., Rothwell, P. M., Kowey, P. R. 2016; 5 (3)

    View details for DOI 10.1161/JAHA.115.002944

    View details for PubMedID 27068633

  • Novel TIA biomarkers identified by mass spectrometry-based proteomics INTERNATIONAL JOURNAL OF STROKE George, P. M., Mlynash, M., Adams, C. M., Kuo, C. J., Albers, G. W., Olivot, J. 2015; 10 (8): 1204-1211

    Abstract

    Transient ischemic attacks remain a clinical diagnosis with significant variability between physicians. Finding reliable biomarkers to identify transient ischemic attacks would improve patient care and optimize treatment.Our aim is to identify novel serum TIA biomarkers through the use of mass spectroscopy-based proteomics.Patients with transient neurologic symptoms were prospectively enrolled. Mass spectrometry-based proteomics, an unbiased method to identify candidate proteins, was used to test the serum of the patients for biomarkers of cerebral ischemia. Three candidate proteins were found, and serum concentrations of these proteins were measured by enzyme-linked immunosorbent assay in a second cohort of prospectively enrolled patients. The Student's t-test was used for comparison. The Benjamini-Hochberg false discovery rate controlling procedure for multiple comparison adjustments determined significance for the proteomic screen.Patients with transient ischemic attacks (n = 20), minor strokes (n = 15), and controls (i.e. migraine, seizure, n = 12) were enrolled in the first cohort. Ceruloplasmin, complement component C8 gamma (C8γ), and platelet basic protein were significantly different between the ischemic group (transient ischemic attack and minor stroke) and the controls (P = 0·0001, P = 0·00027, P = 0·00105, respectively). A second cohort of patients with transient ischemic attack (n = 22), minor stroke (n = 20), and controls' (n = 12) serum was enrolled. Platelet basic protein serum concentrations were increased in the ischemic samples compared with control (for transient ischemic attack alone, P = 0·019, for the ischemic group, P = 0·046). Ceruloplasmin trended towards increased concentrations in the ischemic group (P = 0·127); no significant difference in C8γ (P = 0·44) was found.Utilizing mass spectrometry-based proteomics, platelet basic protein has been identified as a candidate serum biomarker for transient ischemic attack. This unbiased proteomic approach may be a promising method to identify novel biomarkers to more precisely diagnose transient ischemic attacks.

    View details for DOI 10.1111/ijs.12603

    View details for Web of Science ID 000367673700011

  • Acute Stroke or Transient Ischemic Attack Treated with Aspirin or Ticagrelor and Patient Outcomes (SOCRATES) trial: rationale and design INTERNATIONAL JOURNAL OF STROKE Johnston, S. C., Amarenco, P., Albers, G. W., Denison, H., Easton, J. D., Held, P., Jonasson, J., Minematsu, K., Molina, C. A., Wong, L. K. 2015; 10 (8): 1304-1308

    View details for DOI 10.1111/ijs.12610

    View details for Web of Science ID 000367673700027

  • The association between lesion location and functional outcome after ischemic stroke INTERNATIONAL JOURNAL OF STROKE Yassi, N., Churilov, L., Campbell, B. C., Sharma, G., Bammer, R., Desmond, P. M., Parsons, M. W., Albers, G. W., Donnan, G. A., Davis, S. M., Investigators, E. P. 2015; 10 (8): 1270-1276

    Abstract

    Infarct location has a critical effect on patient outcome after ischemic stroke, but the study of its role independent of overall lesion volume is challenging. We performed a retrospective, hypothesis-generating study of the effect of infarct location on three-month functional outcome in a pooled analysis of the EPITHET and DEFUSE studies.Posttreatment MRI diffusion lesions were manually segmented and transformed into standard-space. A novel composite brain atlas derived from three standard brain atlases and encompassing 132 cortical and sub-cortical structures was used to segment the transformed lesion into different brain regions, and calculate the percentage of each region infarcted. Classification and Regression Tree (CART) analysis was performed to determine the important regions in each hemisphere associated with nonfavorable outcome at day 90 (modified Rankin score [mRS] > 1).Overall, 152 patients (82 left hemisphere) were included. Median diffusion lesion volume was 37·0 ml, and median baseline National Institutes of Health Stroke Score was 13. In the left hemisphere, the strongest determinants of nonfavorable outcome were infarction of the uncinate fasciculus, followed by precuneus, angular gyrus and total diffusion lesion volume. In the right hemisphere, the strongest determinants of nonfavorable outcome were infarction of the parietal lobe followed by the putamen.Assessment of infarct location using CART demonstrates regional characteristics associated with poor outcome. Prognostically important locations include limbic, default-mode and language areas in the left hemisphere, and visuospatial and motor regions in the right hemisphere.

    View details for DOI 10.1111/ijs.12537

    View details for Web of Science ID 000367673700020

  • Yield of CT perfusion for the evaluation of transient ischaemic attack. International journal of stroke Kleinman, J. T., Mlynash, M., Zaharchuk, G., Ogdie, A. A., Straka, M., Lansberg, M. G., Schwartz, N. E., Singh, P., Kemp, S., Bammer, R., Albers, G. W., Olivot, J. 2015; 10: 25-29

    Abstract

    BACKGROUND: Magnetic resonance diffusion-weighted imaging and perfusion-weighted imaging are able to identify ischaemic 'footprints' in transient ischaemic attack. Computed tomography perfusion (CTP) may be useful for patient triage and subsequent management. To date, less than 100 cases have been reported, and none have compared computed tomography perfusion to perfusion-weighted imaging (PWI). We sought to define the yield of computed tomography perfusion for the evaluation of transient ischaemic attack. METHODS: Consecutive patients with a discharge diagnosis of possible or definite transient ischaemic event who underwent computed tomography perfusion were included in this study. The presence of an ischaemic lesion was assessed on noncontrast computed tomography, automatically deconvolved CTP(TMax) (Time till the residue function reaches its maximum), and when available on diffusion-weighted imaging and PWI(TMax) maps. RESULTS: Thirty-four patients were included and 17 underwent magnetic resonance imaging. Median delay between onset and computed tomography perfusion was 4·4 h (Interquartile range [IQR]: 1·9-9·6), and between computed tomography perfusion and magnetic resonance imaging was 11 h (Interquartile range: 3·8-22). Noncontrast computed tomography was negative in all cases, while CTP(TMax) identified an ischaemic lesion in 12/34 patients (35%). In the subgroup of patients with multimodal magnetic resonance imaging, an ischaemic lesion was found in six (35%) patients using CTP(TMax) versus nine (53%) on magnetic resonance imaging (five diffusion-weighted imaging, nine perfusion-weighted imaging). The additional yield of CTP(TMax) over computed tomography angiography was significant in the evaluation of transient ischaemic attack (12 vs. 3, McNemar, P = 0·004). CONCLUSIONS: CTP(TMax) found an ischaemic lesion in one-third of acute transient ischaemic attack patients. Computed tomography perfusion may be an acceptable substitute when magnetic resonance imaging is unavailable or contraindicated, and has additional yield over computed tomography angiography. Further studies evaluating the outcome of patients with computed tomography perfusion lesions in transient ischaemic attack are justified at this time.

    View details for DOI 10.1111/j.1747-4949.2012.00941.x

    View details for PubMedID 23228203

  • Relationships Between Imaging Assessments and Outcomes in Solitaire With the Intention for Thrombectomy as Primary Endovascular Treatment for Acute Ischemic Stroke STROKE Albers, G. W., Goyal, M., Jahan, R., Bonafe, A., Diener, H., Levy, E. I., Pereira, V. M., Cognard, C., Yavagal, D. R., Saver, J. L. 2015; 46 (10): 2786-2794

    View details for DOI 10.1161/STROKEAHA.115.010710

    View details for PubMedID 26316344

  • Response to endovascular reperfusion is not time-dependent in patients with salvageable tissue. Neurology Lansberg, M. G., Cereda, C. W., Mlynash, M., Mishra, N. K., Inoue, M., Kemp, S., Christensen, S., Straka, M., Zaharchuk, G., Marks, M. P., Bammer, R., Albers, G. W. 2015; 85 (8): 708-714

    Abstract

    To evaluate whether time to treatment modifies the effect of endovascular reperfusion in stroke patients with evidence of salvageable tissue on MRI.Patients from the Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution 2 (DEFUSE 2) cohort study with a perfusion-diffusion target mismatch were included. Reperfusion was defined as a decrease in the perfusion lesion volume of at least 50% between baseline and early follow-up. Good functional outcome was defined as a modified Rankin Scale score ≤2 at day 90. Lesion growth was defined as the difference between the baseline and the early follow-up diffusion-weighted imaging lesion volumes.Among 78 patients with the target mismatch profile (mean age 66 ± 16 years, 54% women), reperfusion was associated with increased odds of good functional outcome (adjusted odds ratio 3.7, 95% confidence interval 1.2-12, p = 0.03) and attenuation of lesion growth (p = 0.02). Time to treatment did not modify these effects (p value for the time × reperfusion interaction is 0.6 for good functional outcome and 0.3 for lesion growth). Similarly, in the subgroup of patients with reperfusion (n = 46), time to treatment was not associated with good functional outcome (p = 0.2).The association between endovascular reperfusion and improved functional and radiologic outcomes is not time-dependent in patients with a perfusion-diffusion mismatch. Proof that patients with mismatch benefit from endovascular therapy in the late time window should come from a randomized placebo-controlled trial.

    View details for DOI 10.1212/WNL.0000000000001853

    View details for PubMedID 26224727

  • Imaging in StrokeNet Realizing the Potential of Big Data STROKE Liebeskind, D. S., Albers, G. W., Crawford, K., Derdeyn, C. P., George, M. S., Palesch, Y. Y., Toga, A. W., Warach, S., Zhao, W., Brott, T. G., Sacco, R. L., Khatri, P., Saver, J. L., Cramer, S. C., Wolf, S. L., Broderick, J. P., Wintermark, M. 2015; 46 (7): 2000-2006

    View details for DOI 10.1161/STROKEAHA.115.009479

    View details for PubMedID 26045600

  • The growth rate of early DWI lesions is highly variable and associated with penumbral salvage and clinical outcomes following endovascular reperfusion INTERNATIONAL JOURNAL OF STROKE Wheeler, H. M., Mlynash, M., Inoue, M., Tipirnini, A., Liggins, J., Bammer, R., Lansberg, M. G., Kemp, S., Zaharchuk, G., Straka, M., Albers, G. W. 2015; 10 (5): 723-729

    Abstract

    The degree of variability in the rate of early diffusion-weighted imaging expansion in acute stroke has not been well characterized.We hypothesized that patients with slowly expanding diffusion-weighted imaging lesions would have more penumbral salvage and better clinical outcomes following endovascular reperfusion than patients with rapidly expanding diffusion-weighted imaging lesions.In the first part of this substudy of DEFUSE 2, growth curves were constructed for patients with >90% reperfusion and <10% reperfusion. Next, the initial growth rate was determined in all patients with a clearly established time of symptom onset, assuming a lesion volume of 0 ml just prior to symptom onset. Patients who achieved reperfusion (>50% reduction in perfusion-weighted imaging after endovascular therapy) were categorized into tertiles according to their initial diffusion-weighted imaging growth rates. For each tertile, penumbral salvage [comparison of final volume to the volume of perfusion-weighted imaging (Tmax > 6 s)/diffusion-weighted imaging mismatch prior to endovascular therapy], favorable clinical response (National Institutes of Health Stroke Scale improvement of ≥8 points or 0-1 at 30 days), and good functional outcome (90-day modified Rankin score of ≤2) were calculated. A multivariate model assessed whether infarct growth rates were an independent predictor of clinical outcomes.Sixty-five patients were eligible for this study; the median initial growth rate was 3·1 ml/h (interquartile range 0·7-10·7). Target mismatch patients (n = 42) had initial growth rates that were significantly slower than the growth rates in malignant profile (n = 9 patients, P < 0·001). In patients who achieved reperfusion (n = 38), slower early diffusion-weighted imaging growth rates were associated with better clinical outcomes (P < 0·05) and a trend toward more penumbral salvage (n = 31, P = 0·103). A multivariate model demonstrated that initial diffusion-weighted imaging growth rate was an independent predictor of achieving a 90-day modified Rankin score of ≤2.The growth rate of early diffusion-weighted imaging lesions in acute stroke patients is highly variable; malignant profile patients have higher growth rates than patients with target mismatch. A slower rate of early diffusion-weighted imaging growth is associated with a greater degree of penumbral salvage and improved clinical outcomes following endovascular reperfusion.

    View details for DOI 10.1111/ijs.12436

    View details for Web of Science ID 000356718000025

    View details for PubMedID 25580662

    View details for PubMedCentralID PMC4478123

  • A score based on age and DWI volume predicts poor outcome following endovascular treatment for acute ischemic stroke INTERNATIONAL JOURNAL OF STROKE Liggins, J. T., Yoo, A. J., Mishra, N. K., Wheeler, H. M., Straka, M., Leslie-Mazwi, T. M., Chaudhry, Z. A., Kemp, S., Mlynash, M., Bammer, R., Albers, G. W., Lansberg, M. G. 2015; 10 (5): 705-709

    Abstract

    The Houston Intra-Arterial Therapy score predicts poor functional outcome following endovascular treatment for acute ischemic stroke based on clinical variables. The present study sought to (a) create a predictive scoring system that included a neuroimaging variable and (b) determine if the scoring systems predict the clinical response to reperfusion.Separate datasets were used to derive (n = 110 from the Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution 2 study) and validate (n = 125 from Massachusetts General Hospital) scoring systems that predict poor functional outcome, defined as a modified Rankin Scale score of 4-6 at 90 days.Age (P < 0·001; β = 0·087) and diffusion-weighted imaging volume (P = 0·023; β = 0·025) were the independent predictors of poor functional outcome. The Stanford Age and Diffusion-Weighted Imaging score was created based on the patient's age (0-3 points) and diffusion-weighted imaging lesion volume (0-1 points). The percentage of patients with a poor functional outcome increased significantly with the number of points on the Stanford Age and Diffusion-Weighted Imaging score (P < 0·01 for trend). The area under the receiver operating characteristic curve for the Stanford Age and Diffusion-Weighted Imaging score was 0·82 in the derivation dataset. In the validation cohort, the area under the receiver operating characteristic curve was 0·69 for the Stanford Age and Diffusion-Weighted Imaging score and 0·66 for the Houston Intra-Arterial Therapy score (P = 0·45 for the difference). Reperfusion, but not the interactions between the prediction scores and reperfusion, were predictors of outcome (P > 0·5).The Stanford Age and Diffusion-Weighted Imaging and Houston Intra-Arterial Therapy scores can be used to predict poor functional outcome following endovascular therapy with good accuracy. However, these scores do not predict the clinical response to reperfusion. This limits their utility as tools to select patients for acute stroke interventions.

    View details for DOI 10.1111/ijs.12207

    View details for Web of Science ID 000356718000022

    View details for PubMedID 24207136

  • Stent-Retriever Thrombectomy after Intravenous t-PA vs. t-PA Alone in Stroke NEW ENGLAND JOURNAL OF MEDICINE Saver, J. L., Goyal, M., Bonafe, A., Diener, H., Levy, E. I., Pereira, V. M., Albers, G. W., Cognard, C., Cohen, D. J., Hacke, W., Jansen, O., Jovin, T. G., Mattle, H. P., Nogueira, R. G., Siddiqui, A. H., Yavagal, D. R., Baxter, B. W., Devlin, T. G., Lopes, D. K., Reddy, V. K., de Rochemont, R. d., Singer, O. C., Jahan, R. 2015; 372 (24): 2285-2295

    Abstract

    Among patients with acute ischemic stroke due to occlusions in the proximal anterior intracranial circulation, less than 40% regain functional independence when treated with intravenous tissue plasminogen activator (t-PA) alone. Thrombectomy with the use of a stent retriever, in addition to intravenous t-PA, increases reperfusion rates and may improve long-term functional outcome.We randomly assigned eligible patients with stroke who were receiving or had received intravenous t-PA to continue with t-PA alone (control group) or to undergo endovascular thrombectomy with the use of a stent retriever within 6 hours after symptom onset (intervention group). Patients had confirmed occlusions in the proximal anterior intracranial circulation and an absence of large ischemic-core lesions. The primary outcome was the severity of global disability at 90 days, as assessed by means of the modified Rankin scale (with scores ranging from 0 [no symptoms] to 6 [death]).The study was stopped early because of efficacy. At 39 centers, 196 patients underwent randomization (98 patients in each group). In the intervention group, the median time from qualifying imaging to groin puncture was 57 minutes, and the rate of substantial reperfusion at the end of the procedure was 88%. Thrombectomy with the stent retriever plus intravenous t-PA reduced disability at 90 days over the entire range of scores on the modified Rankin scale (P<0.001). The rate of functional independence (modified Rankin scale score, 0 to 2) was higher in the intervention group than in the control group (60% vs. 35%, P<0.001). There were no significant between-group differences in 90-day mortality (9% vs. 12%, P=0.50) or symptomatic intracranial hemorrhage (0% vs. 3%, P=0.12).In patients receiving intravenous t-PA for acute ischemic stroke due to occlusions in the proximal anterior intracranial circulation, thrombectomy with a stent retriever within 6 hours after onset improved functional outcomes at 90 days. (Funded by Covidien; SWIFT PRIME ClinicalTrials.gov number, NCT01657461.).

    View details for DOI 10.1056/NEJMoa1415061

    View details for Web of Science ID 000356019200004

    View details for PubMedID 25882376

  • Safety and efficacy of desmoteplase given 3-9 h after ischaemic stroke in patients with occlusion or high-grade stenosis in major cerebral arteries (DIAS-3): a double-blind, randomised, placebo-controlled phase 3 trial LANCET NEUROLOGY Albers, G. W., von Kummer, R., Truelsen, T., Jensen, J. S., Ravn, G. M., Gronning, B. A., Chabriat, H., Chang, K., Davalos, A. E., Ford, G. A., Grotta, J., Kaste, M., Schwamm, L. H., Shuaib, A. 2015; 14 (6): 575-584

    Abstract

    Current treatment of ischaemic stroke with thrombolytic therapy is restricted to 3-4·5 h after symptom onset. We aimed to assess the safety and efficacy of desmoteplase, a fibrin-dependent plasminogen activator, given between 3 h and 9 h after symptom onset in patients with occlusion or high-grade stenosis in major cerebral arteries.In a prospective, double-blind, multicentre, parallel-group, randomised trial, we enrolled patients from 77 hospitals in 17 countries who had ischaemic stroke and occlusion or high-grade stenosis in major cerebral arteries. We randomly assigned patients in a 1:1 ratio, using computer-generated randomisation lists with stratification for baseline National Institutes of Health Stroke Scale and age, to treatment with desmoteplase (90 μg/kg) given 3-9 h after symptom onset or to placebo. Patients, investigators, staff, and the funder were masked to treatment assignment. The primary outcome was a favourable modified Rankin Scale score (0-2) at day 90 in all treated patients who had at least one postbaseline measurement of the modified Rankin Scale. Safety was assessed in all randomly assigned patients who received study drugs. This trial is registered with ClinicalTrials.gov, number NCT00790920.Between Feb 6, 2009, and Nov 27, 2013, we enrolled 492 patients and randomly assigned 247 to desmoteplase and 245 to placebo (236 in the desmoteplase group and 237 in the placebo group were included in the analysis of the primary endpoint). Median time from stroke onset to treatment was 6·9 h (IQR 5·7-8·0) for placebo and 7·0 h (6·0-7·9) for desmoteplase. Modified Rankin Scale score (0-2) at day 90 occurred in 121 (51%) patients given desmoteplase and 118 (50%) patients given placebo (adjusted odds ratio 1·20, 95% CI 0·79-1·81, p=0·40). 24 (10%) of 240 patients given desmoteplase died compared with 23 (10%) of 238 patients given placebo. Serious adverse events occurred in 64 (27%) of 240 patients receiving desmoteplase compared with 69 (29%) of 238 patients receiving placebo; frequency of symptomatic intracranial haemorrhage (six [3%] patients in the desmoteplase group vs five [2%] in the placebo group), symptomatic cerebral oedema (five [2%] vs four [2%]), and major haemorrhage (ten [4%] vs 15 [6%]) was much the same between treatment groups.Treatment with desmoteplase did not cause safety concerns and did not improve functional outcome when given to patients who had ischaemic stroke and major cerebral artery occlusion beyond 3 h of symptom onset.H Lundbeck A/S.

    View details for DOI 10.1016/S1474-4422(15)00047-2

    View details for Web of Science ID 000354829900009

    View details for PubMedID 25937443

  • Worse stroke outcome in atrial fibrillation is explained by more severe hypoperfusion, infarct growth, and hemorrhagic transformation INTERNATIONAL JOURNAL OF STROKE Tu, H. T., Campbell, B. C., Christensen, S., Desmond, P. M., De Silva, D. A., Parsons, M. W., Churilov, L., Lansberg, M. G., Mlynash, M., Olivot, J., Straka, M., Bammer, R., Albers, G. W., Donnan, G. A., Davis, S. M. 2015; 10 (4): 534-540

    Abstract

    BACKGROUND: Atrial fibrillation is associated with greater baseline neurological impairment and worse outcomes following ischemic stroke. Previous studies suggest that greater volumes of more severe baseline hypoperfusion in patients with history of atrial fibrillation may explain this association. We further investigated this association by comparing patients with and without atrial fibrillation on initial examination following stroke using pooled multimodal magnetic resonance imaging and clinical data from the Echoplanar Imaging Thrombolytic Evaluation Trial and the Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution studies. METHODS: Echoplanar Imaging Thrombolytic Evaluation Trial was a trial of 101 ischemic stroke patients randomized to intravenous tissue plasminogen activator or placebo, and Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution was a prospective cohort of 74 ischemic stroke patients treated with intravenous tissue plasminogen activator at three to six hours following symptom onset. Patients underwent multimodal magnetic resonance imaging before treatment, at three to five days and three-months after stroke in Echoplanar Imaging Thrombolytic Evaluation Trial; before treatment, three to six hours after treatment and one-month after stroke in Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution. Patients were assessed with the National Institutes of Health Stroke Scale and the modified Rankin scale before treatment and at three-months after stroke. Patients were categorized into definite atrial fibrillation (present on initial examination), probable atrial fibrillation (history but no atrial fibrillation on initial examination), and no atrial fibrillation. Perfusion data were reprocessed with automated magnetic resonance imaging analysis software (RAPID, Stanford University, Stanford, CA, USA). Hypoperfusion volumes were defined using time to maximum delays in two-second increments from >4 to >8 s. Hemorrhagic transformation was classified according to the European Cooperative Acute Stroke Studies criteria. RESULTS: Of the 175 patients, 28 had definite atrial fibrillation, 30 probable atrial fibrillation, 111 no atrial fibrillation, and six were excluded due to insufficient imaging data. At baseline, patients with definite atrial fibrillation had more severe hypoperfusion (median time to maximum >8 s, volume 48 vs. 29 ml, P = 0·02) compared with patients with no atrial fibrillation. At outcome, patients with definite atrial fibrillation had greater infarct growth (median volume 47 vs. 8 ml, P = 0·001), larger infarcts (median volume 75 vs. 23 ml, P = 0·001), more frequent parenchymal hematoma grade hemorrhagic transformation (30% vs. 10%, P = 0·03), worse functional outcomes (median modified Rankin scale score 4 vs. 3, P = 0·03), and higher mortality (36% vs. 16%, P = 0·03) compared with patients with no atrial fibrillation. Definite atrial fibrillation was independently associated with increased parenchymal hematoma (odds ratio = 6·05, 95% confidence interval 1·60-22·83) but not poor functional outcome (modified Rankin scale 3-6, odds ratio = 0·99, 95% confidence interval 0·35-2·80) or mortality (odds ratio = 2·54, 95% confidence interval 0·86-7·49) three-months following stroke, after adjusting for other baseline imbalances. CONCLUSION: Atrial fibrillation is associated with greater volumes of more severe baseline hypoperfusion, leading to higher infarct growth, more frequent severe hemorrhagic transformation and worse stroke outcomes.

    View details for DOI 10.1111/ijs.12007

    View details for Web of Science ID 000354494000023

    View details for PubMedID 23489996

  • Reperfusion versus recanalization: the winner is…. Stroke; a journal of cerebral circulation Tsai, J. P., Albers, G. W. 2015; 46 (6): 1433-1434

    View details for DOI 10.1161/STROKEAHA.115.009268

    View details for PubMedID 25908456

  • Reperfusion of Very Low Cerebral Blood Volume Lesion Predicts Parenchymal Hematoma After Endovascular Therapy STROKE Mishra, N. K., Christensen, S., Wouters, A., Campbell, B. C., Straka, M., Mlynash, M., Kemp, S., Cereda, C. W., Bammer, R., Marks, M. P., Albers, G. W., Lansberg, M. G. 2015; 46 (5): 1245-1249

    Abstract

    Ischemic stroke patients with regional very low cerebral blood volume (VLCBV) on baseline imaging have increased risk of parenchymal hemorrhage (PH) after intravenous alteplase-induced reperfusion. We developed a method for automated detection of VLCBV and examined whether patients with reperfused-VLCBV are at increased risk of PH after endovascular reperfusion therapy.Receiver operating characteristic analysis was performed to optimize a relative CBV threshold associated with PH in patients from the Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution 2 (DEFUSE 2) study. Regional reperfused-VLCBV was defined as regions with low relative CBV on baseline imaging that demonstrated normal perfusion (Tmax <6 s) on coregistered early follow-up magnetic resonance imaging. The association between VLCBV, regional reperfused-VLCBV and PH was assessed in univariate and multivariate analyses.In 91 patients, the greatest area under the curve for predicting PH occurred at an relative CBV threshold of <0.42 (area under the curve, 0.77). At this threshold, VLCBV lesion volume ≥3.55 mL optimally predicted PH with 94% sensitivity and 63% specificity. Reperfused-VLCBV lesion volume was more specific (0.74) and equally sensitive (0.94). In total, 18 patients developed PH, of whom 17 presented with VLCBV (39% versus 2%; P=0.001), all of them had regional reperfusion (47% versus 0%; P=0.01), and 71% received intravenous alteplase. VLCBV lesion (odds ratio, 33) and bridging with intravenous alteplase (odds ratio, 3.8) were independently associated with PH. In a separate model, reperfused-VLCBV remained the single independent predictor of PH (odds ratio, 53).These results suggest that VLCBV can be used for risk stratification of patients scheduled to undergo endovascular therapy in trials and routine clinical practice.

    View details for DOI 10.1161/STROKEAHA.114.008171

    View details for PubMedID 25828235

  • Apparent diffusion coefficient threshold for delineation of ischemic core. International journal of stroke Purushotham, A., Campbell, B. C., Straka, M., Mlynash, M., Olivot, J., Bammer, R., Kemp, S. M., Albers, G. W., Lansberg, M. G. 2015; 10 (3): 348-353

    Abstract

    MRI-based selection of patients for acute stroke interventions requires rapid accurate estimation of the infarct core on diffusion-weighted MRI. Typically used manual methods to delineate restricted diffusion lesions are subjective and time consuming. These limitations would be overcome by a fully automated method that can rapidly and objectively delineate the ischemic core. An automated method would require predefined criteria to identify the ischemic core.The aim of this study is to determine apparent diffusion coefficient-based criteria that can be implemented in a fully automated software solution for identification of the ischemic core.Imaging data from patients enrolled in the Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution (DEFUSE) study who had early revascularization following intravenous thrombolysis were included. The patients' baseline restricted diffusion and 30-day T2 -weighted fluid-attenuated inversion recovery lesions were manually delineated after coregistration. Parts of the restricted diffusion lesion that corresponded with 30-day infarct were considered ischemic core, whereas parts that corresponded with normal brain parenchyma at 30 days were considered noncore. The optimal apparent diffusion coefficient threshold to discriminate core from noncore voxels was determined by voxel-based receiver operating characteristics analysis using the Youden index.51 045 diffusion positive voxels from 14 patients who met eligibility criteria were analyzed. The mean DWI lesion volume was 24 (± 23) ml. Of this, 18 (± 22) ml was ischemic core and 3 (± 5) ml was noncore. The remainder corresponded to preexisting gliosis, cerebrospinal fluid, or was lost to postinfarct atrophy. The apparent diffusion coefficient of core was lower than that of noncore voxels (P < 0·0001). The optimal threshold for identification of ischemic core was an apparent diffusion coefficient ≤620 × 10(-6 ) mm(2) /s (sensitivity 69% and specificity 78%).Our data suggest that the ischemic core can be identified with an absolute apparent diffusion coefficient threshold. This threshold can be implemented in image analysis software for fully automated segmentation of the ischemic core.

    View details for DOI 10.1111/ijs.12068

    View details for PubMedID 23802548

  • TIA triage in emergency department using acute MRI (TIA-TEAM): A feasibility and safety study. International journal of stroke Vora, N., Tung, C. E., Mlynash, M., Garcia, M., Kemp, S., Kleinman, J., Zaharchuk, G., Albers, G., Olivot, J. 2015; 10 (3): 343-347

    Abstract

    Positive diffusion weighted imaging (DWI) on MRI is associated with increased recurrent stroke risk in TIA patients. Acute MRI aids in TIA risk stratification and diagnosis.To evaluate the feasibility and safety of TIA triage directly from the emergency department (ED) with acute MRI and neurological consultation.Consecutive ED TIA patients assessed by a neurologist underwent acute MRI/MRA of head/neck per protocol and were hospitalized if positive DWI, symptomatic vessel stenosis, or per clinical judgment. Stroke neurologist adjudicated the final TIA diagnosis as definite, possible, or not a cerebrovascular event. Stroke recurrence rates were calculated at 7, 90, 365 days and compared with predicted stroke rates derived from historical DWI and ABCD(2) score data.One hundred twenty-nine enrolled patients had a mean age of 69 years (±17) and median ABCD(2) score of 3 (interquartile range [IQR] 3-4). During triage, 112 (87%) patients underwent acute MRI after a median of 16 h (IQR 10-23) from symptom onset. No patients experienced a recurrent event before imaging. Twenty-four (21%) had positive DWI and 8 (7%) had symptomatic vessel stenosis. Of the total cohort, 83 (64%) were discharged and 46 (36%) were hospitalized. By one-year follow-up, one patient in each group had experienced a stroke. Of 92 patients with MRI and index cerebrovascular event, recurrent stroke rates were 1·1% at 7 and 90 days. These were similar to predicted recurrence rates.TIA triage in the ED using a protocol with neurological consultation and acute MRI is feasible and safe. The majority of patients were discharged without hospitalization and rates of recurrent stroke were not higher than predicted.

    View details for DOI 10.1111/ijs.12390

    View details for PubMedID 25367837

  • Solitaire (TM) with the Intention for Thrombectomy as Primary Endovascular Treatment for Acute Ischemic Stroke (SWIFT PRIME) trial: protocol for a randomized, controlled, multicenter study comparing the Solitaire revascularization device with IV tPA with IV tPA alone in acute ischemic stroke INTERNATIONAL JOURNAL OF STROKE Saver, J. L., Goyal, M., Bonafe, A., Diener, H., Levy, E. I., Pereira, V. M., Albers, G. W., Cognard, C., Cohen, D. J., Hacke, W., Jansen, O., Jovin, T. G., Mattle, H. P., Nogueira, R. G., Siddiqui, A. H., Yavagal, D. R., Devlin, T. G., Lopes, D. K., Reddy, V., de Rochemont, R. d., Jahan, R. 2015; 10 (3): 439-448

    Abstract

    Early reperfusion in patients experiencing acute ischemic stroke is critical, especially for patients with large vessel occlusion who have poor prognosis without revascularization. Solitaire™ stent retriever devices have been shown to immediately restore vascular perfusion safely, rapidly, and effectively in acute ischemic stroke patients with large vessel occlusions.The aim of the study was to demonstrate that, among patients with large vessel, anterior circulation occlusion who have received intravenous tissue plasminogen activator, treatment with Solitaire revascularization devices reduces degree of disability 3 months post stroke.The study is a global multicenter, two-arm, prospective, randomized, open, blinded end-point trial comparing functional outcomes in acute ischemic stroke patients who are treated with either intravenous tissue plasminogen activator alone or intravenous tissue plasminogen activator in combination with the Solitaire device. Up to 833 patients will be enrolled.Patients who have received intravenous tissue plasminogen activator are randomized to either continue with intravenous tissue plasminogen activator alone or additionally proceed to neurothrombectomy using the Solitaire device within six-hours of symptom onset.The primary end-point is 90-day global disability, assessed with the modified Rankin Scale (mRS). Secondary outcomes include mortality at 90 days, functional independence (mRS ≤ 2) at 90 days, change in National Institutes of Health Stroke Scale at 27 h, reperfusion at 27 h, and thrombolysis in cerebral infarction 2b/3 flow at the end of the procedure.Statistical analysis will be conducted using simultaneous success criteria on the overall distribution of modified Rankin Scale (Rankin shift) and proportions of subjects achieving functional independence (mRS 0-2).

    View details for DOI 10.1111/ijs.12459

    View details for Web of Science ID 000351395300035

  • Interhospital variation in reperfusion rates following endovascular treatment for acute ischemic stroke. Journal of neurointerventional surgery Liggins, J. T., Mlynash, M., Jovin, T. G., Straka, M., Kemp, S., Bammer, R., Marks, M. P., Albers, G. W., Lansberg, M. G. 2015; 7 (4): 231-233

    Abstract

    Patients who have successful reperfusion following endovascular therapy for acute ischemic stroke have improved clinical outcomes. We sought to determine if the chance of successful reperfusion differs among hospitals, and if hospital site is an independent predictor of reperfusion.Nine hospitals recruited patients in the Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution Study 2 (DEFUSE 2), a prospective cohort study of endovascular stroke treatment conducted between 2008 and 2011. Patients were included for analysis if they had a baseline Thrombolysis in Cerebral Infarction (TICI) score of 0 or 1. Successful reperfusion was defined as a TICI reperfusion score of 2b or 3 at completion of the procedure. Collaterals were assessed using the Collateral Flow Grading System and were dichotomized as poor (0-2) or good (3-4). The association between hospital site and successful reperfusion was first assessed in an unadjusted analysis and subsequently in a multivariate analysis that adjusted for predictors of successful reperfusion.36 of 89 patients (40%) achieved successful reperfusion. The rate of reperfusion varied from 0% to 77% among hospitals in the univariate analysis (χ(2) p<0.001) but hospital site did not remain as an independent predictor of reperfusion in multivariate analysis (p=0.81) after adjustment for the presence of good collaterals (p<0.01) and use of the Merci retriever (p<0.05).Reperfusion rates vary among hospitals, which may be related to differences in treatment protocols and patient characteristics. Additional studies are needed to identify all of the factors that underlie this variability as this could lead to strategies that reduce interhospital variability in reperfusion rates and improve clinical outcomes.

    View details for DOI 10.1136/neurintsurg-2014-011115

    View details for PubMedID 24662608

  • Alberta Stroke Program Early Computed Tomographic Scoring Performance in a Series of Patients Undergoing Computed Tomography and MRI: Reader Agreement, Modality Agreement, and Outcome Prediction. Stroke; a journal of cerebral circulation McTaggart, R. A., Jovin, T. G., Lansberg, M. G., Mlynash, M., Jayaraman, M. V., Choudhri, O. A., Inoue, M., Marks, M. P., Albers, G. W. 2015; 46 (2): 407-412

    Abstract

    In this study, we compare the performance of pretreatment Alberta Stroke Program Early Computed Tomographic scoring (ASPECTS) using noncontrast CT (NCCT) and MRI in a large endovascular therapy cohort.Prospectively enrolled patients underwent baseline NCCT and MRI and started endovascular therapy within 12 hours of stroke onset. Inclusion criteria for this analysis were evaluable pretreatment NCCT, diffusion-weighted MRI (DWI), and 90-day modified Rankin Scale scores. Two expert readers graded ischemic change on NCCT and DWI using the ASPECTS. ASPECTS scores were analyzed with the full scale or were trichotomized (0-4 versus 5-7 versus 8-10) or dichotomized (0-7 versus 8-10). Good functional outcome was defined as a 90-day modified Rankin Scale score of 0 to 2.Seventy-four patients fulfilled our study criteria. The full-scale inter-rater agreement for CT-ASPECTS and DWI-ASPECTS was 0.579 and 0.867, respectively. DWI-ASPECTS correlated with functional outcome (P=0.004), whereas CT-ASPECTS did not (P=0.534). Both DWI-ASPECTS and CT-ASPECTS correlated with DWI volume. The receiver operating characteristic analysis revealed that DWI-ASPECTS outperformed both CT-ASPECTS and the time interval between symptom onset and start of the procedure for predicting good functional outcome (modified Rankin Scale score, ≤2) and DWI volume ≥70 mL.Inter-rater agreement for DWI-ASPECTS was superior to that for CT-ASPECTS. DWI-ASPECTS outperformed NCCT ASPECTS for predicting functional outcome at 90 days.

    View details for DOI 10.1161/STROKEAHA.114.006564

    View details for PubMedID 25538199

  • Transient global amnes a associated with a unilateral infarction of the fornix: case report and review of the literature FRONTIERS IN NEUROLOGY Gupta, M., Kantor, M. A., Tung, C. E., Zhang, N., Albers, G. W. 2015; 5

    View details for DOI 10.3389/fneur.2014.00291

    View details for Web of Science ID 000363751300002

  • Selection for delayed intravenous alteplase treatment based on a prognostic score INTERNATIONAL JOURNAL OF STROKE Fulton, R. L., Lees, K. R., Bluhmki, E., Biegert, G., Albers, G. W., Davis, S. M., Donnan, G. A., Grotta, J. C., Hacke, W., Kaste, M., von Kummer, R., Shuaib, A., Toni, D. 2015; 10 (1): 90-94

    Abstract

    Approved use of intravenous alteplase for ischemic stroke offers net benefit. Pooled randomized controlled trial analysis suggests additional patients could benefit but others be harmed with treatment initiated beyond 4·5 h after stroke onset. We proposed prognostic scoring methods to identify a strategy for patient selection.We selected 500 patients treated by intravenous alteplase and 500 controls from Virtual International Stroke Trials Archive, matching modified Rankin score outcomes to those from pooled randomized controlled trial 4·5-6 h data. We ranked patients by prognostic score. We chose limits to optimize our sample for a net treatment benefit significant at P = 0·01 by Cochran-Mantel-Haenszel test and by ordinal regression. For validation, we had these applied to the pooled randomized controlled trial data for 4·5-6 h, testing for net benefit by Cochran-Mantel-Haenszel test, ordinal regression, and also by dichotomized outcomes: modified Rankin score 0-1, mortality and parenchymal hemorrhage type 2 bleeds. All analyses were adjusted for age and National Institutes of Health Stroke Scale.In the training dataset, limits of 56-95 on a prognostic score retained 714 patients in whom there was net benefit significant at P = 0·01. When applied to the 1120 patients in the pooled randomized controlled trial 4·5-6 h dataset, score limits of 56-95 retained 711 patients and gave odds ratio for improved modified Rankin score distribution of 1·13, 95% confidence interval 0·87-1·47, Cochran-Mantel-Haenszel P = 0·89. More patients achieved modified Rankin score 0-1 (odds ratio 1·44, 1·02-2·05, P = 0·04) but mortality and parenchymal hemorrhage type 2 bleeds were increased: odds ratio 1·56, 1·01-2·40, P = 0·04; odds ratio 15·6, 3·7-65·8, P = 0·0002, respectively.Selection of patients between 4·5 and 6 h based on simple clinical measures failed to deliver a population in whom the alteplase effect would be safe and effective.

    View details for DOI 10.1111/j.1747-4949.2012.00943.x

    View details for Web of Science ID 000346156500024

    View details for PubMedID 23294942

  • The association between lesion location and functional outcome after ischemic stroke. International journal of stroke : official journal of the International Stroke Society Yassi, N., Churilov, L., Campbell, B. C., Sharma, G., Bammer, R., Desmond, P. M., Parsons, M. W., Albers, G. W., Donnan, G. A., Davis, S. M. 2015; 10 (8): 1270–76

    Abstract

    Infarct location has a critical effect on patient outcome after ischemic stroke, but the study of its role independent of overall lesion volume is challenging. We performed a retrospective, hypothesis-generating study of the effect of infarct location on three-month functional outcome in a pooled analysis of the EPITHET and DEFUSE studies.Posttreatment MRI diffusion lesions were manually segmented and transformed into standard-space. A novel composite brain atlas derived from three standard brain atlases and encompassing 132 cortical and sub-cortical structures was used to segment the transformed lesion into different brain regions, and calculate the percentage of each region infarcted. Classification and Regression Tree (CART) analysis was performed to determine the important regions in each hemisphere associated with nonfavorable outcome at day 90 (modified Rankin score [mRS] > 1).Overall, 152 patients (82 left hemisphere) were included. Median diffusion lesion volume was 37·0 ml, and median baseline National Institutes of Health Stroke Score was 13. In the left hemisphere, the strongest determinants of nonfavorable outcome were infarction of the uncinate fasciculus, followed by precuneus, angular gyrus and total diffusion lesion volume. In the right hemisphere, the strongest determinants of nonfavorable outcome were infarction of the parietal lobe followed by the putamen.Assessment of infarct location using CART demonstrates regional characteristics associated with poor outcome. Prognostically important locations include limbic, default-mode and language areas in the left hemisphere, and visuospatial and motor regions in the right hemisphere.

    View details for PubMedID 26045301

  • Novel TIA biomarkers identified by mass spectrometry-based proteomics. International journal of stroke : official journal of the International Stroke Society George, P. M., Mlynash, M., Adams, C. M., Kuo, C. J., Albers, G. W., Olivot, J. M. 2015; 10 (8): 1204–11

    Abstract

    Transient ischemic attacks remain a clinical diagnosis with significant variability between physicians. Finding reliable biomarkers to identify transient ischemic attacks would improve patient care and optimize treatment.Our aim is to identify novel serum TIA biomarkers through the use of mass spectroscopy-based proteomics.Patients with transient neurologic symptoms were prospectively enrolled. Mass spectrometry-based proteomics, an unbiased method to identify candidate proteins, was used to test the serum of the patients for biomarkers of cerebral ischemia. Three candidate proteins were found, and serum concentrations of these proteins were measured by enzyme-linked immunosorbent assay in a second cohort of prospectively enrolled patients. The Student's t-test was used for comparison. The Benjamini-Hochberg false discovery rate controlling procedure for multiple comparison adjustments determined significance for the proteomic screen.Patients with transient ischemic attacks (n = 20), minor strokes (n = 15), and controls (i.e. migraine, seizure, n = 12) were enrolled in the first cohort. Ceruloplasmin, complement component C8 gamma (C8γ), and platelet basic protein were significantly different between the ischemic group (transient ischemic attack and minor stroke) and the controls (P = 0·0001, P = 0·00027, P = 0·00105, respectively). A second cohort of patients with transient ischemic attack (n = 22), minor stroke (n = 20), and controls' (n = 12) serum was enrolled. Platelet basic protein serum concentrations were increased in the ischemic samples compared with control (for transient ischemic attack alone, P = 0·019, for the ischemic group, P = 0·046). Ceruloplasmin trended towards increased concentrations in the ischemic group (P = 0·127); no significant difference in C8γ (P = 0·44) was found.Utilizing mass spectrometry-based proteomics, platelet basic protein has been identified as a candidate serum biomarker for transient ischemic attack. This unbiased proteomic approach may be a promising method to identify novel biomarkers to more precisely diagnose transient ischemic attacks.

    View details for PubMedID 26307429

  • Acute Stroke or Transient Ischemic Attack Treated with Aspirin or Ticagrelor and Patient Outcomes (SOCRATES) trial: rationale and design. International journal of stroke : official journal of the International Stroke Society Johnston, S. C., Amarenco, P., Albers, G. W., Denison, H., Easton, J. D., Held, P., Jonasson, J., Minematsu, K., Molina, C. A., Wong, L. K. 2015; 10 (8): 1304–8

    Abstract

    The risk of recurrent ischemia is high in the acute period after ischemic stroke and transient ischemic attack. Aspirin is recommended by guidelines for this indication, but more intensive antiplatelet therapy may be justified.We aim to evaluate whether ticagrelor, a potent antiplatelet agent that blocks the P2Y12 receptor without requiring metabolic activation, reduces the risk of major vascular events compared with aspirin when randomization occurs within 24 h after symptom onset of a nonsevere ischemic stroke or high-risk transient ischemic attack.Acute Stroke or Transient Ischemic Attack Treated with Aspirin or Ticagrelor and Patient Outcomes (SOCRATES) is a randomized, double-blind, event-driven trial and will include an estimated 13,600 participants randomized in 33 countries worldwide to collect 844 primary events.The primary endpoint is the composite of stroke (ischemic or hemorrhagic), myocardial infarction, and death. Time to the first primary endpoint will be compared in the treatment groups during 90-day follow-up, with major hemorrhage serving as the primary safety endpoint. Participants will be followed for an additional 30 days after the randomized treatment period.The SOCRATES trial fulfills an important clinical need by evaluating a potent antiplatelet agent as a superior alternative to current standard of care in patients presenting acutely with ischemic stroke or transient ischemic attack.

    View details for PubMedID 26311628

  • Ultra-acute CT perfusion imaging: A stroke in the scanner. Neurology Christensen, S., Obi, C., Albers, G., Lansberg, M. 2015; 85 (19): 1725–26

    View details for PubMedID 26553942

  • Computed Tomography Perfusion Imaging in the Selection of Acute Stroke Patients to Undergo Emergent Carotid Endarterectomy ANNALS OF VASCULAR SURGERY Devlin, T. G., Phade, S. V., Hutson, R. K., Fugate, M. W., Major, G. R., Albers, G. W., Sirelkhatim, A. A., Sapkota, B. L., Quartfordt, S. D., Baxter, B. W. 2015; 29 (1)

    Abstract

    Severe acute stroke patients with critical carotid stenosis or occlusion without intracranial thrombus typically do not undergo emergent carotid thromboendarterectomy (CEA) because of the risk of reperfusion-related intracranial hemorrhage. Past studies have not consistently demonstrated benefit of early operative intervention. Cerebral computed tomography (CT), cervical and cerebral CT angiography (CTA), and cerebral CT perfusion (CTP) imaging may identify a subset of acute stroke patients without intracranial thrombus who may benefit from emergent CEA. Acute stroke patients underwent unenhanced brain CT imaging to exclude pathology that would contraindicate emergent therapy. Emergent CTAs of the intracranial and extracranial vessels were utilized to identify patients who presented with stroke symptoms based on the presence of isolated extracranial carotid disease in the absence of intracranial thromboembolism. CTP was then used to assess the extent of potentially reversible cerebral ischemia (penumbral tissue). Patients with isolated extracranial carotid lesions with significant reversible ischemia in the absence of large areas of irreversible cerebral damage underwent emergent CEA to salvage ischemic penumbra. In 1 year, 3 patients presented with large acute strokes in which CTA disclosed symptomatic extracranial internal carotid artery preocclusive or occlusive lesions without intracranial thromboembolic occlusions. CTP indicated a large area of ischemic penumbra with limited permanent injury. Mean age, time to presentation, and National Institutes of Health stroke score (NIHSS) were 66 years, 4.2 hr, and 19.3. All patients underwent emergent CEA with cervical carotid thrombectomy. Average time from stroke symptom onset to revascularization was 12.5 (range 5.9-19.0) hr. There were no perioperative deaths. At day 5, the mean NIHSS decreased to 7.6 and at day 30 was 4.7. The modified Rankin scale score dropped from a poststroke, preoperative level of 5 to 2.3 by day 30. Emergent CEA should be considered in patients presenting with large acute strokes based on favorable CT, CTA, and CTP findings. Emergent clot localization and physiological assessment of brain "tissue at risk" relative to irreversible cerebral infarction using CT, CTA, and CTP is now available. Utilization of this information by an experienced stroke team of neurologists, radiologists, and surgeons may aid in the recognition of a select group of patients in which emergent CEA may drive to improved outcomes.

    View details for DOI 10.1016/j.avsg.2014.07.023

    View details for Web of Science ID 000346239900027

    View details for PubMedID 25194548

  • Standards and Barriers in Acute Stroke Therapy: A Leap Forward in the Evolution of Endovascular Interventions for Stroke. Journal of the American College of Cardiology Albers, G. W., Halperin, J. L. 2015; 66 (22): 2506–9

    View details for PubMedID 26653624

  • Correlation of AOL recanalization, TIMI reperfusion and TICI reperfusion with infarct growth and clinical outcome JOURNAL OF NEUROINTERVENTIONAL SURGERY Marks, M. P., Lansberg, M. G., Mlynash, M., Kemp, S., McTaggart, R., Zaharchuk, G., Bammer, R., Albers, G. W. 2014; 6 (10): 724-728

    Abstract

    To understand how three commonly used measures of endovascular therapy correlate with clinical outcome and infarct growth.Prospectively enrolled patients underwent baseline MRI and started endovascular therapy within 12 h of stroke onset. The final angiogram was given a primary arterial occlusive lesion (AOL) recanalization score (0-3), a Thrombolysis in Myocardial Infarction (TIMI) score (0-3) and a Thrombolysis in Cerebral Infarction (TICI) score (0-3). The scores were dichotomized into poor revascularization (AOL 0-2, TIMI 0-1 and TICI 0-2a) versus good revascularization (AOL 3, TIMI 2-3, TICI 2b-3). Patients were classified according to whether or not they had target mismatch (TMM). Good outcome was defined as a 90-day modified Rankin Scale score of 0-2.Endovascular treatment was attempted in 100. A good outcome was achieved in 57% of patients with a TICI score of 2b-3 and in 24% of patients with a TICI score of 0-2a (p=0.001). Patients with TIMI scores of 2-3 and an AOL score of 3 had lower rates of good outcome (44% and 47%, respectively), which were not significantly better than those with TIMI scores of 0-1 or AOL scores of 0-2. In patients with TMM, these rates of good outcome improved with all the scoring systems and were significantly better for TIMI and TICI scores. Patients with a TICI score of 2a had rates of good functional outcome and lesion growth which were not different from those with TICI scores of 0-1 but were significantly worse than those with TICI scores of 2b-3.TIMI 2-3 and TICI 2b-3 reperfusion scores demonstrated improved outcome in patients with tissue mismatch with a small infarct core and a larger hypoperfused region but AOL scores did not. Patients with a TICI score of 2a had a poorer outcome and more lesion growth than those with TICI scores of 2b-3.

    View details for DOI 10.1136/neurintsurg-2013-010973

    View details for Web of Science ID 000344939800007

    View details for PubMedCentralID PMC4090292

  • Correlation of AOL recanalization, TIMI reperfusion and TICI reperfusion with infarct growth and clinical outcome. Journal of neurointerventional surgery Marks, M. P., Lansberg, M. G., Mlynash, M., Kemp, S., McTaggart, R., Zaharchuk, G., Bammer, R., Albers, G. W. 2014; 6 (10): 724-728

    Abstract

    To understand how three commonly used measures of endovascular therapy correlate with clinical outcome and infarct growth.Prospectively enrolled patients underwent baseline MRI and started endovascular therapy within 12 h of stroke onset. The final angiogram was given a primary arterial occlusive lesion (AOL) recanalization score (0-3), a Thrombolysis in Myocardial Infarction (TIMI) score (0-3) and a Thrombolysis in Cerebral Infarction (TICI) score (0-3). The scores were dichotomized into poor revascularization (AOL 0-2, TIMI 0-1 and TICI 0-2a) versus good revascularization (AOL 3, TIMI 2-3, TICI 2b-3). Patients were classified according to whether or not they had target mismatch (TMM). Good outcome was defined as a 90-day modified Rankin Scale score of 0-2.Endovascular treatment was attempted in 100. A good outcome was achieved in 57% of patients with a TICI score of 2b-3 and in 24% of patients with a TICI score of 0-2a (p=0.001). Patients with TIMI scores of 2-3 and an AOL score of 3 had lower rates of good outcome (44% and 47%, respectively), which were not significantly better than those with TIMI scores of 0-1 or AOL scores of 0-2. In patients with TMM, these rates of good outcome improved with all the scoring systems and were significantly better for TIMI and TICI scores. Patients with a TICI score of 2a had rates of good functional outcome and lesion growth which were not different from those with TICI scores of 0-1 but were significantly worse than those with TICI scores of 2b-3.TIMI 2-3 and TICI 2b-3 reperfusion scores demonstrated improved outcome in patients with tissue mismatch with a small infarct core and a larger hypoperfused region but AOL scores did not. Patients with a TICI score of 2a had a poorer outcome and more lesion growth than those with TICI scores of 2b-3.

    View details for DOI 10.1136/neurintsurg-2013-010973

    View details for PubMedID 24353330

  • Lipoprotein Phospholipase A2 Mass and Activity Are Not Associated with the Diagnosis of Acute Brain Ischemia CEREBROVASCULAR DISEASES Tai, W., Garcia, M., Mlynash, M., Kemp, S., Albers, G. W., Olivot, J. 2014; 38 (5): 324-327

    View details for DOI 10.1159/000368218

    View details for Web of Science ID 000348046700002

  • Effect of treatment delay, age, and stroke severity on the effects of intravenous thrombolysis with alteplase for acute ischaemic stroke: a meta-analysis of individual patient data from randomised trials LANCET Emberson, J., Lees, K. R., Lyden, P., Blackwell, L., Albers, G., Bluhmki, E., Brott, T., Cohen, G., Davis, S., Donnan, G., Grotta, J., Howard, G., Kaste, M., Koga, M., von Kummer, R., Lansberg, M., Lindley, R. I., Murray, G., Olivot, J. M., Parsons, M., Tilley, B., Toni, D., Toyoda, K., Wahlgren, N., Wardlaw, J., Whiteley, W., del Zoppo, G. J., Baigent, C., Sandercock, P., Hacke, W. 2014; 384 (9958): 1929-1935

    View details for DOI 10.1016/S0140-6736(14)60584-5

    View details for Web of Science ID 000345450100028

  • Effect of treatment delay, age, and stroke severity on the effects of intravenous thrombolysis with alteplase for acute ischaemic stroke: a meta-analysis of individual patient data from randomised trials. Lancet Emberson, J., Lees, K. R., Lyden, P., Blackwell, L., Albers, G., Bluhmki, E., Brott, T., Cohen, G., Davis, S., Donnan, G., Grotta, J., Howard, G., Kaste, M., Koga, M., von Kummer, R., Lansberg, M., Lindley, R. I., Murray, G., Olivot, J. M., Parsons, M., Tilley, B., Toni, D., Toyoda, K., Wahlgren, N., Wardlaw, J., Whiteley, W., del Zoppo, G. J., Baigent, C., Sandercock, P., Hacke, W. 2014; 384 (9958): 1929-1935

    Abstract

    Alteplase is effective for treatment of acute ischaemic stroke but debate continues about its use after longer times since stroke onset, in older patients, and among patients who have had the least or most severe strokes. We assessed the role of these factors in affecting good stroke outcome in patients given alteplase.We did a pre-specified meta-analysis of individual patient data from 6756 patients in nine randomised trials comparing alteplase with placebo or open control. We included all completed randomised phase 3 trials of intravenous alteplase for treatment of acute ischaemic stroke for which data were available. Retrospective checks confirmed that no eligible trials had been omitted. We defined a good stroke outcome as no significant disability at 3-6 months, defined by a modified Rankin Score of 0 or 1. Additional outcomes included symptomatic intracranial haemorrhage (defined by type 2 parenchymal haemorrhage within 7 days and, separately, by the SITS-MOST definition of parenchymal type 2 haemorrhage within 36 h), fatal intracranial haemorrhage within 7 days, and 90-day mortality.Alteplase increased the odds of a good stroke outcome, with earlier treatment associated with bigger proportional benefit. Treatment within 3·0 h resulted in a good outcome for 259 (32·9%) of 787 patients who received alteplase versus 176 (23·1%) of 762 who received control (OR 1·75, 95% CI 1·35-2·27); delay of greater than 3·0 h, up to 4·5 h, resulted in good outcome for 485 (35·3%) of 1375 versus 432 (30·1%) of 1437 (OR 1·26, 95% CI 1·05-1·51); and delay of more than 4·5 h resulted in good outcome for 401 (32·6%) of 1229 versus 357 (30·6%) of 1166 (OR 1·15, 95% CI 0·95-1·40). Proportional treatment benefits were similar irrespective of age or stroke severity. Alteplase significantly increased the odds of symptomatic intracranial haemorrhage (type 2 parenchymal haemorrhage definition 231 [6·8%] of 3391 vs 44 [1·3%] of 3365, OR 5·55, 95% CI 4·01-7·70, p<0·0001; SITS-MOST definition 124 [3·7%] vs 19 [0·6%], OR 6·67, 95% CI 4·11-10·84, p<0·0001) and of fatal intracranial haemorrhage within 7 days (91 [2·7%] vs 13 [0·4%]; OR 7·14, 95% CI 3·98-12·79, p<0·0001). The relative increase in fatal intracranial haemorrhage from alteplase was similar irrespective of treatment delay, age, or stroke severity, but the absolute excess risk attributable to alteplase was bigger among patients who had more severe strokes. There was no excess in other early causes of death and no significant effect on later causes of death. Consequently, mortality at 90 days was 608 (17·9%) in the alteplase group versus 556 (16·5%) in the control group (hazard ratio 1·11, 95% CI 0·99-1·25, p=0·07). Taken together, therefore, despite an average absolute increased risk of early death from intracranial haemorrhage of about 2%, by 3-6 months this risk was offset by an average absolute increase in disability-free survival of about 10% for patients treated within 3·0 h and about 5% for patients treated after 3·0 h, up to 4·5 h.Irrespective of age or stroke severity, and despite an increased risk of fatal intracranial haemorrhage during the first few days after treatment, alteplase significantly improves the overall odds of a good stroke outcome when delivered within 4·5 h of stroke onset, with earlier treatment associated with bigger proportional benefits.UK Medical Research Council, British Heart Foundation, University of Glasgow, University of Edinburgh.

    View details for DOI 10.1016/S0140-6736(14)60584-5

    View details for PubMedID 25106063

  • Transcranial Laser Therapy in Acute Stroke Treatment Results of Neurothera Effectiveness and Safety Trial 3, a Phase III Clinical End Point Device Trial STROKE Hacke, W., Schellinger, P. D., Albers, G. W., Bornstein, N. M., Dahlof, B. L., Fulton, R., Kasner, S. E., Shuaib, A., Richieri, S. P., Dilly, S. G., Zivin, J., Lees, K. R. 2014; 45 (11): 3187-3193

    View details for DOI 10.1161/STROKEAHA.114.005795

    View details for Web of Science ID 000344351500020

  • Angiographic outcome of endovascular stroke therapy correlated with MR findings, infarct growth, and clinical outcome in the DEFUSE 2 trial INTERNATIONAL JOURNAL OF STROKE Marks, M. P., Lansberg, M. G., Mlynash, M., Kemp, S., McTaggart, R. A., Zaharchuk, G., Bammer, R., Albers, G. W. 2014; 9 (7): 860-865

    Abstract

    DEFUSE 2 demonstrated that patients with magnetic resonance imaging mismatch had a favorable clinical response to tissue reperfusion assessed by magnetic resonance imaging. This study reports the endovascular results and correlates angiographic reperfusion with clinical and imaging outcomes.Prospectively enrolled ischemic stroke patients underwent baseline magnetic resonance imaging and started endovascular therapy within 12 h of onset. Patients were classified as either target mismatch or no target mismatch using magnetic resonance imaging. The pre- and postprocedure angiogram was evaluated to determine thrombolysis in cerebral infarction scores. Favorable clinical response was determined at day 30, and good functional outcome was defined as a modified Rankin Scale 0-2 at day 90.One-hundred patients had attempted endovascular treatment. At procedure end, 23% were thrombolysis in cerebral infarction 0-1, 31% thrombolysis in cerebral infarction 2A, 28% thrombolysis in cerebral infarction 2B, and 18% thrombolysis in cerebral infarction 3. More favorable thrombolysis in cerebral infarction-reperfusion scores were associated with greater magnetic resonance imaging reperfusion (P<0·001). thrombolysis in cerebral infarction scores correlated with 30-day favorable clinical response (P=0·041) and 90-day modified Rankin Scale 0-2 (P=0·008). These correlations were significant for target mismatch patients at 30 days (P=0·034) and 90 days (P=0·003). Infarct growth was strongly associated with poorer thrombolysis in cerebral infarction scores in target mismatch patients (P<0·001). Patients with thrombolysis in cerebral infarctionnfarction 2A reperfusion had less magnetic resonance imaging reperfusion (P=0·004) and poorer clinical outcome at 90 days (P=0·01) compared with thrombolysis in cerebral infarction 2B-3 patients.Thrombolysis in cerebral infarction reperfusion following endovascular therapy for ischemic stroke is highly correlated with magnetic resonance imaging reperfusion, infarct growth, and clinical outcome.

    View details for DOI 10.1111/ijs.12271

    View details for Web of Science ID 000342581900013

    View details for PubMedCentralID PMC4411961

  • Angiographic outcome of endovascular stroke therapy correlated with MR findings, infarct growth, and clinical outcome in the DEFUSE 2 trial. International journal of stroke Marks, M. P., Lansberg, M. G., Mlynash, M., Kemp, S., McTaggart, R. A., Zaharchuk, G., Bammer, R., Albers, G. W. 2014; 9 (7): 860-865

    Abstract

    DEFUSE 2 demonstrated that patients with magnetic resonance imaging mismatch had a favorable clinical response to tissue reperfusion assessed by magnetic resonance imaging. This study reports the endovascular results and correlates angiographic reperfusion with clinical and imaging outcomes.Prospectively enrolled ischemic stroke patients underwent baseline magnetic resonance imaging and started endovascular therapy within 12 h of onset. Patients were classified as either target mismatch or no target mismatch using magnetic resonance imaging. The pre- and postprocedure angiogram was evaluated to determine thrombolysis in cerebral infarction scores. Favorable clinical response was determined at day 30, and good functional outcome was defined as a modified Rankin Scale 0-2 at day 90.One-hundred patients had attempted endovascular treatment. At procedure end, 23% were thrombolysis in cerebral infarction 0-1, 31% thrombolysis in cerebral infarction 2A, 28% thrombolysis in cerebral infarction 2B, and 18% thrombolysis in cerebral infarction 3. More favorable thrombolysis in cerebral infarction-reperfusion scores were associated with greater magnetic resonance imaging reperfusion (P<0·001). thrombolysis in cerebral infarction scores correlated with 30-day favorable clinical response (P=0·041) and 90-day modified Rankin Scale 0-2 (P=0·008). These correlations were significant for target mismatch patients at 30 days (P=0·034) and 90 days (P=0·003). Infarct growth was strongly associated with poorer thrombolysis in cerebral infarction scores in target mismatch patients (P<0·001). Patients with thrombolysis in cerebral infarctionnfarction 2A reperfusion had less magnetic resonance imaging reperfusion (P=0·004) and poorer clinical outcome at 90 days (P=0·01) compared with thrombolysis in cerebral infarction 2B-3 patients.Thrombolysis in cerebral infarction reperfusion following endovascular therapy for ischemic stroke is highly correlated with magnetic resonance imaging reperfusion, infarct growth, and clinical outcome.

    View details for DOI 10.1111/ijs.12271

    View details for PubMedID 24684804

  • NeuroThera® Efficacy and Safety Trial-3 (NEST-3): a double-blind, randomized, sham-controlled, parallel group, multicenter, pivotal study to assess the safety and efficacy of transcranial laser therapy with the NeuroThera® Laser System for the treatment of acute ischemic stroke within 24?h of stroke onset. International journal of stroke Zivin, J. A., Sehra, R., Shoshoo, A., Albers, G. W., Bornstein, N. M., Dahlof, B., Kasner, S. E., Howard, G., Shuaib, A., Streeter, J., Richieri, S. P., Hacke, W. 2014; 9 (7): 950-955

    Abstract

    Transcranial laser therapy is undergoing clinical trials in patients with acute ischemic stroke. The NeuroThera® Efficacy and Safety Trial-1 was strongly positive for 90-day functional benefit with transcranial laser therapy, and post hoc analyses of the subsequent NeuroThera® Efficacy and Safety Trial-2 trial suggested a meaningful beneficial effect in patients with moderate to moderately severe ischemic stroke within 24 h of onset. These served as the basis for the NeuroThera® Efficacy and Safety Trial-3 randomized controlled trial.The purpose of this pivotal study was to demonstrate safety and efficacy of transcranial laser therapy with the NeuroThera® Laser System in the treatment of subjects diagnosed with acute ischemic stroke.NeuroThera® Efficacy and Safety Trial-3 is a double-blind, randomized, sham-controlled, parallel group, multicenter, pivotal study that will enroll 1000 subjects at up to 50 sites. All subjects will receive standard medical management based on the American Stroke Association and European Stroke Organization Guidelines. In addition to standard medical management, both groups will undergo the transcranial laser therapy procedure between 4·5 and 24 h of stroke onset. The study population will be randomized into two arms: the sham control group will receive a sham transcranial laser therapy procedure and the transcranial laser therapy group will receive an active transcranial laser therapy procedure. The randomization ratio will be 1:1 and will be stratified to ensure a balanced subject distribution between study arms.The primary efficacy end point is disability at 90 days (or the last rating), as assessed on the modified Rankin Scale, dichotomized as a success (a score of 0-2) or a failure (a score of 3 to 6).

    View details for DOI 10.1111/j.1747-4949.2012.00896.x

    View details for PubMedID 23013107

  • Fatal acanthamoeba encephalitis in a patient with a total artificial heart (syncardia) device. Open forum infectious diseases Tan, S. K., Gajurel, K., Tung, C., Albers, G., Deresinski, S., Montoya, J. G., Sheikh, A. Y., Banerjee, D., Ha, R. 2014; 1 (2): ofu057-?

    Abstract

    Acanthamoeba encephalitis is an uncommon but often fatal infection complication. Here we report the first case of Acanthamoeba encephalitis in a patient with a Total Artificial Heart device.

    View details for DOI 10.1093/ofid/ofu057

    View details for PubMedID 25734127

  • Exploratory Analysis of Glyburide as a Novel Therapy for Preventing Brain Swelling NEUROCRITICAL CARE Sheth, K. N., Kimberly, W. T., Elm, J. J., Kent, T. A., Yoo, A. J., Thomalla, G., Campbell, B., Donnan, G. A., Davis, S. M., Albers, G. W., Jacobson, S., del Zoppo, G., Simard, J. M., Stern, B. J., Mandava, P. 2014; 21 (1): 43-51

    Abstract

    Malignant infarction is characterized by the formation of cerebral edema, and medical treatment is limited. Preclinical data suggest that glyburide, an inhibitor of SUR1-TRPM4, is effective in preventing edema. We previously reported feasibility of the GAMES-Pilot study, a two-center prospective, open label, phase IIa trial of 10 subjects at high risk for malignant infarction based on diffusion weighted imaging (DWI) threshold of 82 cm(3) treated with RP-1127 (glyburide for injection). In this secondary analysis, we tested the hypothesis that RP-1127 may be efficacious in preventing poor outcome when compared to controls.Controls suffering large hemispheric infarction were obtained from the EPITHET and MMI-MRI studies. We first screened subjects for controls with the same DWI threshold used for enrollment into GAMES-Pilot, 82 cm(3). Next, to address imbalances, we applied a weighted Euclidean matching. Ninety day mRS 0-4, rate of decompressive craniectomy, and mortality were the primary clinical outcomes of interest.The mean age of the GAMES cohort was 51 years and initial DWI volume was 102 ± 23 cm(3). After Euclidean matching, GAMES subjects showed similar NIHSS, higher DWI volume, younger age and had mRS 0-4-90% versus 50% in controls p = 0.049; with a similar trend in mRS 0-3 (40 vs. 25%; p = 0.43) and trend toward lower mortality (10 vs. 35%; p = 0.21).In this pilot study, RP-1127-treated subjects showed better clinical outcomes when compared to historical controls. An adequately powered and randomized phase II trial of patients at risk for malignant infarction is needed to evaluate the potential efficacy of RP-1127.

    View details for DOI 10.1007/s12028-014-9970-2

    View details for Web of Science ID 000339350500007

    View details for PubMedID 24671831

  • Pittsburgh outcomes after stroke thrombectomy score predicts outcomes after endovascular therapy for anterior circulation large vessel occlusions. Stroke; a journal of cerebral circulation Rangaraju, S., Liggins, J. T., Aghaebrahim, A., Streib, C., Sun, C., Gupta, R., Nogueira, R., Frankel, M., Mlynash, M., Lansberg, M., Albers, G., Jadhav, A., Jovin, T. G. 2014; 45 (8): 2298-2304

    Abstract

    Prognostication tools that predict good outcome in patients with anterior circulation large vessel occlusions after endovascular therapy are lacking. We aim to develop a tool that incorporates clinical and imaging data to predict outcomes after endovascular therapy.In a derivation cohort of anterior circulation large vessel occlusion stroke patients treated with endovascular therapy within 8 hours from time last seen well (n=247), we performed logistic regression to identify independent predictors of good outcome (90-day modified Rankin Scale, 0-2). Factors were weighted based on β-coefficients to derive the Pittsburgh Outcomes After Stroke Thrombectomy (POST) score. POST was validated in an institutional endovascular database (University of Pittsburgh Medical Center, n=393) and the Diffusion-Weighted Imaging Evaluation for Understanding Stroke Evolution Study-2 (DEFUSE-2) data set (n=105), as well as in patients treated beyond 8 hours (n=194) and in octogenarians (n=111).In the derivation cohort, independent predictors (P<0.1) of good outcome included 24- to 72-hour final infarct volume (in cm(3), P<0.001), age (years, P<0.001), and parenchymal hematoma types 1 and 2 (H, P=0.01). POST was calculated as age+0.5×final infarct volume+15×H. Patients with POST score <60 had a 91% chance of good outcome compared with 4% with POST score ≥120. POST accurately predicted good outcomes in the derivation (area under the curve [AUC]=0.85) and validation cohorts (University of Pittsburgh Medical Center, AUC=0.81; DEFUSE-2, AUC=0.86), as well as in patients treated beyond 8 hours (AUC, 0.85) and octogenarians (AUC=0.76). POST had better predictive accuracy for good and poor outcome than the ischemic stroke predictive risk score (iSCORE).POST score is a validated predictor of outcome in patients with anterior circulation large vessel occlusions after endovascular therapy.

    View details for DOI 10.1161/STROKEAHA.114.005595

    View details for PubMedID 25005445

  • Predictors of Functional Dependence Despite Successful Revascularization in Large-Vessel Occlusion Strokes STROKE Shi, Z., Liebeskind, D. S., Xiang, B., Ge, S. G., Feng, L., Albers, G. W., Budzik, R., Devlin, T., Gupta, R., Jansen, O., Jovin, T. G., Killer-Oberpfalzer, M., Lutsep, H. L., Macho, J., Nogueira, R. G., Rymer, M., Smith, W. S., Wahlgren, N., Duckwiler, G. R. 2014; 45 (7): 1977-1984

    View details for DOI 10.1161/STROKEAHA.114.005603

    View details for Web of Science ID 000338129400023

  • O-034 Carotid Artery Angioplasty versus Stenting in Acute Ischemic Stroke. Journal of neurointerventional surgery Choudhri, O., Gupta, M., Feroze, A., Albers, G., Lansberg, M., Do, H., Dodd, R., Marcellus, M., Marks, M. 2014; 6: A18-9

    Abstract

    Acute ischemic stroke secondary to cervical carotid artery occlusion can lead to significant morbidity and mortality. Acute carotid occlusion may be managed by carotid angioplasty, stenting, or both. The use of carotid stents requires patients to be placed on dual antiplatelet agents, which may contribute to increased haemorrhage risk. We undertook this study to evaluate outcomes for angioplasty alone versus stenting in the setting of acute carotid occlusion.All patients treated from 2008 to 2013 with acute cervical internal carotid artery occlusions that had intervention within eight hours of symptom onset were included. NIHSS were recorded preceding intervention, and clinical outcomes were assessed using mRS at 90 days. All imaging and angiographic data were reviewed for pre-procedural ASPECT scores, pre- and post- TICI reperfusion scores, and intracranial haemorrhage as defined by PH grading score for haemorrhage. Demographic and treatment factors were correlated with good functional outcome (mRS < 2 at 90 days and a comparison was made for patients undergoing angioplasty alone versus stenting. All patients who underwent carotid stent were placed on dual antiplatelet agents while angioplasty patients received aspirin only.Twenty-four patients (15 males, 9 females; mean age, 67 years) satisfied the inclusion criteria. Seventeen patients underwent placement of carotid stent and 7 patients had angioplasty alone. Patients in both subgroups were comparable across characteristics including comorbidities, time for onset to recanalization, ASPECTS, and IV tPA use. 35% of patients who underwent stenting had good functional outcomes, versus 71% of patients treated with angioplasty alone, although these differences were not statistically significant. No differences were seen for the two treatment groups comparing time from onset to recanalization, baseline ASPECTS, and IV tPA use. Additionally, increased age (p = 0.049) and post-treatment parenchymal haemorrhage- PH1 or PH2 (p = 0.016) correlated with poor outcomes (mRS > 2). All parenchymal haemorrhages (6/17) and deaths (5/17) fell within the stenting subgroup (35.3% and 29.4%, respectively).This data suggest that patients undergoing angioplasty alone in the setting of acute internal carotid artery occlusion may have improved functional outcome at 90-day compared to those undergoing stenting. This study was limited by a small sample size and a larger study would be needed to confirm these findings.angioplasty, stenting, acute ischemic stroke, carotid occlusion.O. Choudhri: None. M. Gupta: None. A. Feroze: None. G. Albers: None. M. Lansberg: None. H. Do: None. R. Dodd: None. M. Marcellus: None. M. Marks: None.

    View details for DOI 10.1136/neurintsurg-2014-011343.34

    View details for PubMedID 25064877

  • Comparison of magnetic resonance imaging mismatch criteria to select patients for endovascular stroke therapy. Stroke; a journal of cerebral circulation Mishra, N. K., Albers, G. W., Christensen, S., Marks, M., Hamilton, S., Straka, M., Liggins, J. T., Kemp, S., Mlynash, M., Bammer, R., Lansberg, M. G. 2014; 45 (5): 1369-1374

    Abstract

    The Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution 2 (DEFUSE 2) study has shown that clinical response to endovascular reperfusion differs between patients with and without perfusion-diffusion (perfusion-weighted imaging-diffusion-weighted imaging, PWI-DWI) mismatch: patients with mismatch have a favorable clinical response to reperfusion, whereas patients without mismatch do not. This study examined whether alternative mismatch criteria can also differentiate patients according to their response to reperfusion.Patients from the DEFUSE 2 study were categorized according to vessel occlusion on magnetic resonance angiography (MRA) and DWI lesion volume criteria (MRA-DWI mismatch) and symptom severity and DWI criteria (clinical-DWI mismatch). Favorable clinical response was defined as an improvement of ≥8 points on the National Institutes of Health Stroke Scale (NIHSS) by day 30 or an NIHSS score of ≤1 at day 30. We assessed, for each set of criteria, whether the association between reperfusion and favorable clinical response differed according to mismatch status.A differential response to reperfusion was observed between patients with and without MRA-DWI mismatch defined as an internal carotid artery or M1 occlusion and a DWI lesion <50 mL. Reperfusion was associated with good functional outcome in patients who met these MRA-DWI mismatch criteria (odds ratio [OR], 8.5; 95% confidence interval [CI], 2.3-31.3), whereas no association was observed in patients who did not meet these criteria (OR, 0.5; 95% CI, 0.08-3.1; P for difference between the odds, 0.01). No differential response to reperfusion was observed with other variations of the MRA-DWI or clinical-DWI mismatch criteria.The MRA-DWI mismatch is a promising alternative to DEFUSE 2's PWI-DWI mismatch for patient selection in endovascular stroke trials.

    View details for DOI 10.1161/STROKEAHA.114.004772

    View details for PubMedID 24699054

  • Aortic arch atheroma: a plaque of a different color or more of the same? Stroke; a journal of cerebral circulation George, P. M., Albers, G. W. 2014; 45 (5): 1239-1240

    View details for DOI 10.1161/STROKEAHA.114.004827

    View details for PubMedID 24699053

  • Effect of collateral blood flow on patients undergoing endovascular therapy for acute ischemic stroke. Stroke; a journal of cerebral circulation Marks, M. P., Lansberg, M. G., Mlynash, M., Olivot, J., Straka, M., Kemp, S., McTaggart, R., Inoue, M., Zaharchuk, G., Bammer, R., Albers, G. W. 2014; 45 (4): 1035-1039

    Abstract

    Our aim was to determine the relationships between angiographic collaterals and diffusion/perfusion findings, subsequent infarct growth, and clinical outcome in patients undergoing endovascular therapy for ischemic stroke.Sixty patients with a thrombolysis in cerebral infarction (TICI) score of 0 or 1 and internal carotid artery/M1 occlusion at baseline were evaluated. A blinded reader assigned a collateral score using a previous 5-point scale, from 0 (no collateral flow) to 4 (complete/rapid collaterals to the entire ischemic territory). The analysis was dichotomized to poor flow (0-2) versus good flow (3-4). Collateral score was correlated with baseline National Institutes of Health Stroke Scale, diffusion-weighted imaging volume, perfusion-weighted imaging volume (Tmax ≥6 seconds), TICI reperfusion, infarct growth, and modified Rankin Scale score at day 90.Collateral score correlated with baseline National Institutes of Health Stroke Scale (P=0.002) and median volume of tissue at Tmax ≥6 seconds (P=0.009). Twenty-nine percent of patients with poor collateral flow had TICI 2B-3 reperfusion versus 65.5% with good flow (P=0.009). Patients with poor collaterals who reperfused (TICI 2B-3) were more likely to have a good functional outcome (modified Rankin Scale score 0-2 at 90 days) compared with patients who did not reperfuse (odds ratio, 12; 95% confidence interval, 1.6-98). There was no difference in the rate of good functional outcome after reperfusion in patients with poor collaterals versus good collaterals (P=1.0). Patients with poor reperfusion (TICI 0-2a) showed a trend toward greater infarct growth if they had poor collaterals versus good collaterals (P=0.06).Collaterals correlate with baseline National Institutes of Health Stroke Scale, perfusion-weighted imaging volume, and good reperfusion. However, target mismatch patients who reperfuse seem to have favorable outcomes at a similar rate, irrespective of the collateral score.http://www.clinicaltrials.gov. Unique identifier: NCT01349946.

    View details for DOI 10.1161/STROKEAHA.113.004085

    View details for PubMedID 24569816

  • Early diffusion-weighted imaging reversal after endovascular reperfusion is typically transient in patients imaged 3 to 6 hours after onset. Stroke; a journal of cerebral circulation Inoue, M., Mlynash, M., Christensen, S., Wheeler, H. M., Straka, M., Tipirneni, A., Kemp, S. M., Zaharchuk, G., Olivot, J., Bammer, R., Lansberg, M. G., Albers, G. W. 2014; 45 (4): 1024-1028

    Abstract

    The aim of this study was to assess the frequency and extent of early diffusion-weighted imaging (DWI) lesion reversal after endovascular therapy and to determine whether early reversal is sustained or transient.MRI with DWI perfusion imaging was performed before (DWI 1) and within 12 hours after (DWI 2) endovascular treatment; follow-up MRI was obtained on day 5. Both DWIs were coregistered to follow-up MRI. Early DWI reversal was defined as the volume of the DWI 1 lesion that was not superimposed on the DWI 2 lesion. Permanent reversal was the volume of the DWI 1 lesion not superimposed on the day 5 infarct volume. Associations between early DWI reversal and clinical outcomes in patients with and without reperfusion were assessed.A total of 110 patients had technically adequate DWI before endovascular therapy (performed median [interquartile range], 4.5 [2.8-6.2] hours after onset); 60 were eligible for this study. Thirty-two percent had early DWI reversal >10 mL; 17% had sustained reversal. The median volume of permanent reversal at 5 days was 3 mL (interquartile range, 1.7-7.0). Only 2 patients (3%) had a final infarct volume that was smaller than their baseline DWI lesion. Early DWI reversal was not an independent predictor of clinical outcome and was not associated with early reperfusion.Early DWI reversal occurred in about one third of patients after endovascular therapy; however, reversal was often transient and was not associated with a significant volume of tissue salvage or favorable clinical outcome.

    View details for DOI 10.1161/STROKEAHA.113.002135

    View details for PubMedID 24558095

  • Hypoperfusion Intensity Ratio Predicts Infarct Progression and Functional Outcome in the DEFUSE 2 Cohort. Stroke; a journal of cerebral circulation Olivot, J. M., Mlynash, M., Inoue, M., Marks, M. P., Wheeler, H. M., Kemp, S., Straka, M., Zaharchuk, G., Bammer, R., Lansberg, M. G., Albers, G. W. 2014; 45 (4): 1018-1023

    Abstract

    We evaluate associations between the severity of magnetic resonance perfusion-weighted imaging abnormalities, as assessed by the hypoperfusion intensity ratio (HIR), on infarct progression and functional outcome in the Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution Study 2 (DEFUSE 2).Diffusion-weighted magnetic resonance imaging and perfusion-weighted imaging lesion volumes were determined with the RAPID software program. HIR was defined as the proportion of TMax >6 s lesion volume with a Tmax >10 s delay and was dichotomized based on its median value (0.4) into low versus high subgroups as well as quartiles. Final infarct volumes were assessed at day 5. Initial infarct growth velocity was calculated as the baseline diffusion-weighted imaging (DWI) lesion volume divided by the delay from symptom onset to baseline magnetic resonance imaging. Total Infarct growth was determined by the difference between final infarct and baseline DWI volumes. Collateral flow was assessed on conventional angiography and dichotomized into good and poor flow. Good functional outcome was defined as modified Rankin Scale ≤2 at 90 days.Ninety-nine patients were included; baseline DWI, perfusion-weighted imaging, and final infarct volumes increased with HIR quartiles (P<0.01). A high HIR predicted poor collaterals with an area under the curve of 0.73. Initial infarct growth velocity and total infarct growth were greater among patients with a high HIR (P<0.001). After adjustment for age, DWI volume, and reperfusion, a low HIR was associated with good functional outcome: odds ratio=4.4 (95% CI, 1.3-14.3); P=0.014.HIR can be easily assessed on automatically processed perfusion maps and predicts the rate of collateral flow, infarct growth, and clinical outcome.

    View details for DOI 10.1161/STROKEAHA.113.003857

    View details for PubMedID 24595591

  • Patients with single distal MCA perfusion lesions have a high rate of good outcome with or without reperfusion INTERNATIONAL JOURNAL OF STROKE Lemmens, R., Christensen, S., Straka, M., De Silva, D. A., Mlynash, M., Campbell, B. C., Bammer, R., Olivot, J., Desmond, P., Marks, M. P., Davis, S. M., Donnan, G. A., Albers, G. W., Lansberg, M. G. 2014; 9 (2): 156-159

    Abstract

    Reperfusion is associated with good functional outcome after stroke. However, minimal data are available regarding the effect of reperfusion on clinical outcome and infarct growth in patients with distal MCA branch occlusions.The aim of this study was to evaluate this association and to determine the impact of the perfusion-diffusion mismatch.Individual patient data from three stroke studies (EPITHET, DEFUSE and DEFUSE 2) with baseline MRI profiles and reperfusion status were pooled. Patients were included if they had a single cortical perfusion lesion on their baseline MRI that was consistent with a distal MCA branch occlusion. Good functional outcome was defined as a score of 0-2 on the modified Rankin Scale at day 90 and infarct growth was defined as change in lesion volume between the baseline DWI and the final T2/FLAIR.Thirty patients met inclusion criteria. Eighteen (60%) had a good functional outcome and twenty (67%) had reperfusion. Reperfusion was not associated with good functional outcome in the overall cohort (OR: 1·0, 95% CI 0·2-4·7) and also not in the subset of patients with a PWI-DWI mismatch (n = 17; OR: 0·7, 95% CI 0·1-5·5). Median infarct growth was modest and not significantly different between patients with (0 ml) and without reperfusion (6 ml); P = 0·2.The overall high rate of good outcomes in patients with distal MCA perfusion lesions might obscure a potential benefit from reperfusion in this population. A larger pooled analysis evaluating the effect of reperfusion in patients with distal MCA branch occlusions is warranted as confirmation of our results could have implications for the design of future stroke trials.

    View details for DOI 10.1111/ijs.12230

    View details for PubMedID 24373557

  • Secondary prevention of atherothrombotic or cryptogenic stroke. Circulation Tai, W. A., Albers, G. W. 2014; 129 (4): 527-531

    View details for DOI 10.1161/CIRCULATIONAHA.112.000658

    View details for PubMedID 24470474

  • Transient global amnesia associated with a unilateral infarction of the fornix: case report and review of the literature. Frontiers in neurology Gupta, M., Kantor, M. A., Tung, C. E., Zhang, N., Albers, G. W. 2014; 5: 291-?

    Abstract

    Stroke is an extremely uncommon cause of transient global amnesia (TGA). Unilateral lesions of the fornix rarely cause amnesia and have not previously been reported to be associated with the distinctive amnesic picture of TGA. We describe the case of a 60-year-old woman who presented with acute onset, recent retrograde, and anterograde amnesia characteristic of TGA. Serial magnetic resonance imaging showed a persistent focal infarction of the body and left column of the fornix, without acute lesions in the hippocampus or other structures. Amnesia resolved in 6 h. Infarction of the fornix should thus be included in the differential diagnosis of TGA, as it changes the management of this otherwise self-limited syndrome.

    View details for DOI 10.3389/fneur.2014.00291

    View details for PubMedID 25628601

    View details for PubMedCentralID PMC4290584

  • Lipoprotein phospholipase A2 mass and activity are not associated with the diagnosis of acute brain ischemia. Cerebrovascular diseases Tai, W., Garcia, M., Mlynash, M., Kemp, S., Albers, G. W., Olivot, J. 2014; 38 (5): 324-327

    Abstract

    Elevated lipoprotein-associated phospholipase A2 (Lp-PLA2) levels are associated with both coronary artery and cerebrovascular diseases. The clinical diagnosis of neurovascular events, specifically transient ischemic attack can be challenging, although there is disagreement among vascular trained neurologists regarding this. Currently, there is no single accurate biomarker for the diagnosis of acute brain ischemia.We studied the relationship between Lp-PLA2 mass and activity levels and the diagnosis of acute brain ischemia in the acute phase among patients evaluated in the emergency department following transient focal neurological symptoms.Patients evaluated in our academic center for transient neurological symptoms of possible ischemic mechanism were enrolled with informed consent. Lp-PLA2 mass and activity levels were performed by DiaDexus, Inc.100 patients were enrolled: 58 were ischemic (30 stroke, 28 TIA), 10 were unknown, and 28 were non-ischemic. Blood samples were collected after a median delay of 23 h (IQR: 17, 36) after symptom onset. The median levels of Lp-PLA2 activity level for ischemic (stroke and TIA) versus non-ischemic events were 186.5 nmol/ml/min (IQR = 153, 216.3) and 169 nmol/ml/min (IQR = 137, 212.5), respectively. The median levels of Lp-PLA2 mass level for ischemic versus non-ischemic events were 202 ng/ml (IQR = 171.6, 226.1) and 192 ng/ml (167.8, 230). The differences in median Lp-PLA2 mass and activity levels were not statistically significant in the ischemic versus non-ischemic patients. Vessel imaging revealed a symptomatic stenosis in 14 patients (10 intracranial and 4 cervical). The median Lp-PLA2 mass and activity levels among patients with a symptomatic stenosis were not significantly higher than the levels measured in TIA/stroke patients without stenosis.The results of our study do not support the early measurement of Lp-PLA2 mass or activity levels for confirming an ischemic etiology in patients experiencing minor or transient focal neurological events.

    View details for PubMedID 25428761

  • Endovascular treatment for stroke: when does the window for good outcome close? The Lancet. Neurology Albers, G. W. 2014; 13 (6): 529–31

    View details for PubMedID 24784551

  • Pilot Study of Intravenous Glyburide in Patients With a Large Ischemic Stroke STROKE Sheth, K. N., Kimberly, W. T., Elm, J. J., Kent, T. A., Mandava, P., Yoo, A. J., Thomalla, G., Campbell, B., Donnan, G. A., Davis, S. M., Albers, G. W., Jacobson, S., Simard, J. M., Stern, B. J. 2014; 45 (1): 281-283

    Abstract

    Preclinical and retrospective clinical data indicate that glyburide, a selective inhibitor of sulfonylurea receptor 1-transient receptor potential melastatin 4, is effective in preventing edema and improving outcome after focal ischemia. We assessed the feasibility of recruiting and treating patients with severe stroke while obtaining preliminary information on the safety and tolerability of RP-1127 (glyburide for injection).We studied 10 patients with acute ischemic stroke, with baseline diffusion-weighted imaging lesion volumes of 82 to 210 cm3, whether treated with intravenous recombinant tissue-type plasminogen activator, age 18 to 80 years, and time to RP-1127≤10 hours.Recruitment was completed within 10 months. The mean age was 50.5 years, and baseline diffusion-weighted image lesion volume was 102±23 cm3. There were no serious adverse events related to drug and no symptomatic hypoglycemia. The increase in ipsilateral hemisphere volume was 50±33 cm3. The proportion of 90-day modified Rankin Scale≤4 was 90% (40% modified Rankin Scale, ≤3).RP-1127 at a dose of 3 mg/d was well tolerated and did not require any dose reductions. A clinical trial of RP-1127 is feasible.URL: http://www.clinicaltrials.gov. Unique identifier: NCT01268683.

    View details for DOI 10.1161/STROKEAHA.113.003352

    View details for PubMedID 24193798

  • Radiological examinations of transient ischemic attack. Frontiers of neurology and neuroscience Tung, C. E., Olivot, J. M., Albers, G. W. 2014; 33: 115-122

    Abstract

    Neuroimaging is critical in the evaluation of patients with TIA. CT and MRI are the two available options for imaging. Head CT is more widely available and commonly used. Diffusion MRI is the recommended modality to image an ischemic lesion. The presence of a diffusion lesion in a patient with transient neurological symptoms is an indicator of a high risk of recurrent stroke. Perfusion imaging with perfusion MRI or CT perfusion may improve the detection of ischemic lesions. Noninvasive vessel imaging may detect a symptomatic vessel lesion associated with an increased risk of stroke.

    View details for DOI 10.1159/000351913

    View details for PubMedID 24157560

  • THRIVE Score Predicts Outcomes With a Third-Generation Endovascular Stroke Treatment Device in the TREVO-2 Trial. Stroke; a journal of cerebral circulation Flint, A. C., Xiang, B., Gupta, R., Nogueira, R. G., Lutsep, H. L., Jovin, T. G., Albers, G. W., Liebeskind, D. S., Sanossian, N., Smith, W. S. 2013; 44 (12): 3370-3375

    Abstract

    Several outcome prediction scores have been tested in patients receiving acute stroke treatment with previous generations of endovascular stroke treatment devices. The TREVO-2 trial was a randomized controlled trial comparing a novel endovascular stroke treatment device (the Trevo device) to a previous-generation endovascular stroke treatment device (the Merci device).We used data from the TREVO-2 trial to validate the Totaled Health Risks in Vascular Events (THRIVE) score in patients receiving treatment with a third-generation endovascular stroke treatment device and to compare THRIVE to other predictive scores. We used logistic regression to model outcomes and compared score performance with receiver operating characteristic curve analysis.In the TREVO-2 trial, the THRIVE score strongly predicts clinical outcome and mortality. The relationship between THRIVE score and outcome is not influenced by either success of recanalization or the type of device used (Trevo versus Merci). The superiority of the Trevo device to the Merci device is evident particularly among patients with a low-to-moderate THRIVE score (0-5; 53.8% good outcome with Trevo versus 27.5% good outcome with Merci). In receiver operating characteristic curve analysis, the THRIVE score was comparable or superior to several other outcome prediction scores (HIAT, HIAT-2, SPAN-100, and iScore).The THRIVE score strongly predicts clinical outcome and mortality in the TREVO-2 trial. Taken together with THRIVE validation data from patients receiving intravenous tissue-type plasminogen activator or no acute treatment, the THRIVE score has broad predictive power in patients with acute ischemic stroke, which is likely because THRIVE reflects a set of strong nonmodifiable predictors of stroke outcome. A free Web calculator for the THRIVE score is available at http://www.thrivescore.org.

    View details for DOI 10.1161/STROKEAHA.113.002796

    View details for PubMedID 24072003

  • Stroke Treatment Academic Industry Roundtable Research Priorities in the Assessment of Neurothrombectomy Devices STROKE Saver, J. L., Jovin, T. G., Smith, W. S., Albers, G. W. 2013; 44 (12): 3596-3601

    Abstract

    The goal of the Stroke Treatment Academic Industry Roundtable (STAIR) meetings is to advance the development of stroke therapies. At STAIR VIII, consensus recommendations were developed for clinical trial strategies to demonstrate the benefit of endovascular reperfusion therapies for acute ischemic stroke.Prospects for success with forthcoming endovascular trials are robust, because new neurothrombectomy devices have superior reperfusion efficacy compared with earlier-generation interventions. Specific recommendations are provided for trial designs in 3 populations: (1) patients undergoing intravenous fibrinolysis, (2) early patients ineligible for or having failed intravenous fibrinolysis, and (3) wake-up and other late-presenting patients. Among intravenous fibrinolysis-eligible patients, key principles are that CT or MRI confirmation of target arterial occlusions should precede randomization; endovascular intervention should be pursued with the greatest rapidity possible; and combined intravenous and neurothrombectomy therapy is more promising than neurothrombectomy alone. Among patients ineligible for or having failed intravenous fibrinolysis, scientific equipoise was affirmed and the need to randomize all eligible patients emphasized. Vessel imaging to confirm occlusion is mandatory, and infarct core and penumbral imaging is desirable in later time windows. Additional STAIR VIII recommendations include approaches to test multiple devices in a single trial, utility weighting of disability end points, and adaptive designs to delineate time and tissue injury thresholds at which benefits from intervention no longer accrue.Endovascular research priorities in acute ischemic stroke are to perform trials testing new, highly effective neuro thrombectomy devices rapidly deployed in patients confirmed to have target vessel occlusions.

    View details for DOI 10.1161/STROKEAHA.113.002769

    View details for PubMedID 24193797

  • Imaging recommendations for acute stroke and transient ischemic attack patients: A joint statement by the American Society of Neuroradiology, the American College of Radiology, and the Society of NeuroInterventional Surgery. AJNR. American journal of neuroradiology Wintermark, M., Sanelli, P. C., Albers, G. W., Bello, J., Derdeyn, C., Hetts, S. W., Johnson, M. H., Kidwell, C., Lev, M. H., Liebeskind, D. S., Rowley, H., Schaefer, P. W., Sunshine, J. L., Zaharchuk, G., Meltzer, C. C. 2013; 34 (11): E117-27

    Abstract

    Stroke is a leading cause of death and disability worldwide. Imaging plays a critical role in evaluating patients suspected of acute stroke and transient ischemic attack, especially before initiating treatment. Over the past few decades, major advances have occurred in stroke imaging and treatment, including Food and Drug Administration approval of recanalization therapies for the treatment of acute ischemic stroke. A wide variety of imaging techniques has become available to assess vascular lesions and brain tissue status in acute stroke patients. However, the practical challenge for physicians is to understand the multiple facets of these imaging techniques, including which imaging techniques to implement and how to optimally use them, given available resources at their local institution. Important considerations include constraints of time, cost, access to imaging modalities, preferences of treating physicians, availability of expertise, and availability of endovascular therapy. The choice of which imaging techniques to employ is impacted by both the time urgency for evaluation of patients and the complexity of the literature on acute stroke imaging. Ideally, imaging algorithms should incorporate techniques that provide optimal benefit for improved patient outcomes without delaying treatment.

    View details for DOI 10.3174/ajnr.A3690

    View details for PubMedID 23907247

  • Imaging Recommendations for Acute Stroke and Transient Ischemic Attack Patients JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY Wintermark, M., Sanelli, P. C., Albers, G. W., Bello, J. A., Derdeyn, C. P., Hetts, S. W., Johnson, M. H., Kidwell, C. S., Lev, M. H., Liebeskind, D. S., Rowley, H. A., Schaefer, P. W., Sunshine, J. L., Zaharchuk, G., Meltzer, C. C. 2013; 10 (11): 828-832

    Abstract

    In the article entitled "Imaging Recommendations for Acute Stroke and Transient Ischemic Attack Patients: A Joint Statement by the American Society of Neuroradiology, the American College of Radiology and the Society of NeuroInterventional Surgery", we are proposing a simple, pragmatic approach that will allow the reader to develop an optimal imaging algorithm for stroke patients at their institution.

    View details for DOI 10.1016/j.jacr.2013.06.019

    View details for Web of Science ID 000327418100009

  • Reduction in Early Stroke Risk in Carotid Stenosis With Transient Ischemic Attack Associated With Statin Treatment STROKE Merwick, A., Albers, G. W., Arsava, E. M., Ay, H., Calvet, D., Coutts, S. B., Cucchiara, B. L., Demchuk, A. M., Giles, M. F., Mas, J., Olivot, J. M., Purroy, F., Rothwell, P. M., Saver, J. L., Sharma, V. K., Tsivgoulis, G., Kelly, P. J. 2013; 44 (10): 2814-2820

    Abstract

    Statins reduce stroke risk when initiated months after transient ischemic attack (TIA)/stroke and reduce early vascular events in acute coronary syndromes, possibly via pleiotropic plaque stabilization. Few data exist on acute statin use in TIA. We aimed to determine whether statin pretreatment at TIA onset modified early stroke risk in carotid stenosis.We analyzed data from 2770 patients with TIA from 11 centers, 387 with ipsilateral carotid stenosis. ABCD2 score, abnormal diffusion weighted imaging, medication pretreatment, and early stroke were recorded.In patients with carotid stenosis, 7-day stroke risk was 8.3% (95% confidence interval [CI], 5.7-11.1) compared with 2.7% (CI, 2.0%-3.4%) without stenosis (P<0.0001; 90-day risks 17.8% and 5.7% [P<0.0001]). Among carotid stenosis patients, nonprocedural 7-day stroke risk was 3.8% (CI, 1.2%-9.7%) with statin treatment at TIA onset, compared with 13.2% (CI, 8.5%-19.8%) in those not statin pretreated (P=0.01; 90-day risks 8.9% versus 20.8% [P=0.01]). Statin pretreatment was associated with reduced stroke risk in patients with carotid stenosis (odds ratio for 90-day stroke, 0.37; CI, 0.17-0.82) but not nonstenosis patients (odds ratio, 1.3; CI, 0.8-2.24; P for interaction, 0.008). On multivariable logistic regression, the association remained after adjustment for ABCD2 score, smoking, antiplatelet treatment, recent TIA, and diffusion weighted imaging hyperintensity (adjusted P for interaction, 0.054).In acute symptomatic carotid stenosis, statin pretreatment was associated with reduced stroke risk, consistent with findings from randomized trials in acute coronary syndromes. These data support the hypothesis that statins started acutely after TIA symptom onset may also be beneficial to prevent early stroke. Randomized trials addressing this question are required.

    View details for DOI 10.1161/STROKEAHA.113.001576

    View details for Web of Science ID 000324831900038

    View details for PubMedID 23908061

  • Acute Stroke Imaging Research Roadmap II STROKE Wintermark, M., Albers, G. W., Broderick, J. P., Demchuk, A. M., Fiebach, J. B., Fiehler, J., Grotta, J. C., Houser, G., Jovin, T. G., Lees, K. R., Lev, M. H., Liebeskind, D. S., Luby, M., Muir, K. W., Parsons, M. W., von Kummer, R., Wardlaw, J. M., Wu, O., Yoo, A. J., Alexandrov, A. V., Alger, J. R., Aviv, R. I., Bammer, R., Baron, J., Calamante, F., Campbell, B. C., Carpenter, T. C., Christensen, S., Copen, W. A., Derdeyn, C. P., Haley, C., Khatri, P., Kudo, K., Lansberg, M. G., Latour, L. L., Lee, T., Leigh, R., Lin, W., Lyden, P., Mair, G., Menon, B. K., Michel, P., Mikulik, R., Nogueira, R. G., Ostergaard, L., Pedraza, S., Riedel, C. H., Rowley, H. A., Sanelli, P. C., Sasaki, M., Saver, J. L., Schaefer, P. W., Schellinger, P. D., Tsivgoulis, G., Wechsler, L. R., White, P. M., Zaharchuk, G., Zaidat, O. O., Davis, S. M., Donnan, G. A., Furlan, A. J., Hacke, W., Kang, D., Kidwell, C., Thijs, V. N., Thomalla, G., Warach, S. J. 2013; 44 (9): 2628-2639

    View details for DOI 10.1161/STROKEAHA.113.002015

    View details for Web of Science ID 000329982500063

    View details for PubMedID 23860298

  • Recommendations on Angiographic Revascularization Grading Standards for Acute Ischemic Stroke A Consensus Statement STROKE Zaidat, O. O., Yoo, A. J., Khatri, P., Tomsick, T. A., von Kummer, R., Saver, J. L., Marks, M. P., Prabhakaran, S., Kallmes, D. F., Fitzsimmons, B. M., Mocco, J., Wardlaw, J. M., Barnwell, S. L., Jovin, T. G., Linfante, I., Siddiqui, A. H., Alexander, M. J., Hirsch, J. A., Wintermark, M., Albers, G., Woo, H. H., Heck, D. V., Lev, M., Aviv, R., Hacke, W., Warach, S., Broderick, J., Derdeyn, C. P., Furlan, A., Nogueira, R. G., Yavagal, D. R., Goyal, M., Demchuk, A. M., Bendszus, M., Liebeskind, D. S. 2013; 44 (9): 2650-2663

    View details for DOI 10.1161/STROKEAHA.113.001972

    View details for Web of Science ID 000329982500066

    View details for PubMedID 23920012

  • Comparison of the response to endovascular reperfusion in relation to site of arterial occlusion. Neurology Lemmens, R., Mlynash, M., Straka, M., Kemp, S., Bammer, R., Marks, M. P., Albers, G. W., Lansberg, M. G. 2013; 81 (7): 614-618

    Abstract

    We explored the relationship between the site of vascular occlusion and the response to endovascular treatment in patients with acute ischemic stroke and also considered the impact of mismatch profile.DEFUSE-2 was a prospective cohort study of patients treated with endovascular therapy. Patients with internal carotid artery (ICA) and middle cerebral artery (MCA) involvement were included in this substudy. Mismatch and reperfusion status was assessed on MRI. Favorable clinical response was defined as an improvement of at least 8 points on the NIH Stroke Scale.Reperfusion rates were comparable in both groups (61% for ICA and 59% for MCA). In the setting of reperfusion, percentages of favorable clinical response were similar between patients with stroke due to ICA (65%) and MCA (63%) occlusions. When reperfusion was not achieved, favorable outcomes were less frequent with obstructions of the ICA (9%) than the MCA (52%). Among target mismatch patients, the adjusted odds ratio for favorable clinical response associated with reperfusion was 39.7 (95% confidence interval 1.4-1,132.8) for ICA occlusions vs 5.1 (95% confidence interval 1.4-19.3) for MCA occlusions.Endovascular reperfusion is associated with favorable clinical response regardless of the location of the arterial occlusion. This association is strongest for target mismatch patients with ICA occlusions. Target mismatch patients with either ICA or MCA occlusions appear to be good candidates for endovascular reperfusion therapy.

    View details for DOI 10.1212/WNL.0b013e3182a08f07

    View details for PubMedID 23851962

  • Impact of diffusion-weighted imaging lesion volume on the success of endovascular reperfusion therapy. Stroke; a journal of cerebral circulation Olivot, J., Mosimann, P. J., Labreuche, J., Inoue, M., Meseguer, E., Desilles, J., Rouchaud, A., Klein, I. F., Straka, M., Bammer, R., Mlynash, M., Amarenco, P., Albers, G. W., Mazighi, M. 2013; 44 (8): 2205-2211

    Abstract

    BACKGROUND AND PURPOSE: Diffusion-weighted imaging (DWI) lesion volume is associated with poor outcome after thrombolysis, and it is unclear whether endovascular therapies are beneficial for large DWI lesion. Our aim was to assess the impact of pretreatment DWI lesion volume on outcomes after endovascular therapy, with a special emphasis on patients with complete recanalization. METHODS: We analyzed data collected between April 2007 and November 2011 in a prospective clinical registry. All acute ischemic stroke patients with complete occlusion of internal carotid artery or middle cerebral artery treated by endovascular therapy were included. DWI lesion volumes were measured by the RAPID software. Favorable outcome was defined by modified Rankin Scale of 0 to 2 at 90 days. RESULTS: A total of 139 acute ischemic stroke patients were included. Median DWI lesion volume was 14 cc (interquartile range, 5-43) after a median onset time to imaging of 110 minutes (interquartile range, 77-178). Higher volume was associated with less favorable outcome (adjusted odds ratio, 0.55; 95% confidence interval, 0.31-0.96). A complete recanalization was achieved in 65 (47%) patients after a median onset time of 238 minutes (interquartile range, 206-285). After adjustment for volume, complete recanalization was associated with more favorable outcome (adjusted odds ratio, 6.32; 95% confidence interval, 2.90-13.78). After stratification of volume by tertiles, complete recanalization was similarly associated with favorable outcome in the upper 2 tertiles (P<0.005). CONCLUSIONS: Our results emphasize the importance of initial DWI volume and recanalization on clinical outcome after endovascular treatment. Large DWI lesions may still benefit from recanalization in selected patients.

    View details for DOI 10.1161/STROKEAHA.113.000911

    View details for PubMedID 23760215

  • Validating Imaging Biomarkers of Cerebral Edema in Patients With Severe Ischemic Stroke JOURNAL OF STROKE & CEREBROVASCULAR DISEASES Yoo, A. J., Sheth, K. N., Kimberly, W. T., Chaudhry, Z. A., Elm, J. J., Jacobson, S., Davis, S. M., Donnan, G. A., Albers, G. W., Stern, B. J., Gonzalez, R. G. 2013; 22 (6): 742-749

    Abstract

    There is no validated neuroimaging marker for quantifying brain edema. We sought to test whether magnetic resonance imaging (MRI)-based metrics would reliably change during the early subacute period in a manner consistent with edema and whether they would correlate with relevant clinical endpoints.Serial MRI studies from patients in the Echoplanar Imaging Thrombolytic Evaluation Trial with initial diffusion-weighted imaging (DWI) lesion volume >82 cm(3) were analyzed. Two independent readers outlined the hemisphere and lateral ventricle on the involved side and calculated respective volumes at baseline and days 3 to 5. We assessed interrater agreement, volume change between scans, and the association of volume change with early neurologic deterioration (National Institutes of Health Stroke Scale score worsening of ≥ 4 points), a 90-day modified Rankin scale (mRS) score of 0 to 4, and mortality.Of 12 patients who met study criteria, average baseline and follow-up DWI lesion size was 138 cm(3) and 234 cm(3), respectively. The mean time to follow-up MRI was 62 hours. Concordance correlation coefficients between readers were >0.90 for both hemisphere and ventricle volume assessment. Mean percent hemisphere volume increase was 16.2 ± 8.3% (P < .0001), and the mean percent ventricle volume decrease was 45.6 ± 16.9% (P < .001). Percent hemisphere growth predicted early neurologic deterioration (area under the curve [AUC] 0.92; P = .0005) and 90-day mRS 0 to 4 (AUC 0.80; P = .02).In this exploratory analysis of severe ischemic stroke patients, statistically significant changes in hemisphere and ventricular volumes within the first week are consistent with expected changes of cerebral edema. MRI-based analysis of hemisphere growth appears to be a suitable biomarker for edema formation.

    View details for DOI 10.1016/j.jstrokecerebrovasdis.2012.01.002

    View details for Web of Science ID 000323497700008

    View details for PubMedID 22325573

    View details for PubMedCentralID PMC3529850

  • Clinical outcomes strongly associated with the degree of reperfusion achieved in target mismatch patients: pooled data from the diffusion and perfusion imaging evaluation for understanding stroke evolution studies. Stroke; a journal of cerebral circulation Inoue, M., Mlynash, M., Straka, M., Kemp, S., Jovin, T. G., Tipirneni, A., Hamilton, S. A., Marks, M. P., Bammer, R., Lansberg, M. G., Albers, G. W. 2013; 44 (7): 1885-1890

    Abstract

    BACKGROUND AND PURPOSE: To investigate relationships between the degree of early reperfusion achieved on perfusion-weighted imaging and clinical outcomes in the Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution studies. We hypothesized that there would be a strong correlation between the degree of reperfusion achieved and clinical outcomes in target mismatch (TMM) patients. METHODS: The degree of reperfusion was calculated on the basis of the difference in perfusion-weighted imaging volumes (time to maximum of tissue residue function [Tmax]>6 s) between the baseline MRI and the early post-treatment follow-up scan. Patients were grouped into quartiles, on the basis of degree of reperfusion achieved, and the association between the degree of reperfusion and clinical outcomes in TMM and no TMM patients was assessed. Favorable clinical response was determined at day 30 on the basis of the National Institutes of Health Stroke Scale and good functional outcome was defined as a modified Rankin Scale score ≤2 at day 90. RESULTS: This study included 121 patients; 98 of these had TMM. The median degree of reperfusion achieved was not different in TMM patients (60%) versus No TMM patients (64%; P=0.604). The degree of reperfusion was strongly correlated with both favorable clinical response (P<0.001) and good functional outcome (P=0.001) in TMM patients; no correlation was present in no TMM. The frequency of achieving favorable clinical response or good functional outcome was significantly higher in TMM patients in the highest reperfusion quartile versus the lower 3 quartiles (88% versus 41% as odds ratio, 10.3; 95% confidence interval, 2.8-37.5; and 75% versus 34% as odds ratio, 5.9; 95% confidence interval, 2.1-16.7, respectively). A receiver operating characteristic curve analysis identified 90% as the optimal reperfusion threshold for predicting good functional outcomes. CONCLUSIONS: The degree of reperfusion documented on perfusion-weighted imaging after reperfusion therapies corresponds closely with clinical outcomes in TMM patients. Reperfusion of ≥90% of the perfusion lesion is an appropriate goal for reperfusion therapies to aspire to.

    View details for DOI 10.1161/STROKEAHA.111.000371

    View details for PubMedID 23704106

  • MR RESCUE Is the Glass Half-Full or Half-Empty? STROKE Parsons, M. W., Albers, G. W. 2013; 44 (7): 2055-2057

    View details for DOI 10.1161/STROKEAHA.113.001443

    View details for Web of Science ID 000330527500058

    View details for PubMedID 23760218

  • Impact of Recanalization, Reperfusion, and Collateral Flow on Clinical Efficacy 28th Princeton Conference Albers, G. W. LIPPINCOTT WILLIAMS & WILKINS. 2013: S11–S12

    View details for DOI 10.1161/STROKEAHA.111.000258

    View details for Web of Science ID 000319459000005

    View details for PubMedID 23709700

  • Details of a prospective protocol for a collaborative meta-analysis of individual participant data from all randomized trials of intravenous rt-PA vs. control: statistical analysis plan for the Stroke Thrombolysis Trialists' Collaborative meta-analysis INTERNATIONAL JOURNAL OF STROKE Emberson, J., Lees, K. R., Howard, G., Bluhmki, E., Tilley, B., Albers, G., Baigent, C., Blackwell, L., Davis, S., Donnan, G., Grotta, J., Hacke, W., Kaste, M., von Kummer, R., Lansberg, M., Lindley, R., Lyden, P., Sandercock, P., Toni, D., Wahlgren, N., Wardlaw, J., Whiteley, W., del Zoppo, G. J. 2013; 8 (4): 278-283

    View details for DOI 10.1111/ijs.12040

    View details for Web of Science ID 000319398900023

  • Imaging-based selection for intra-arterial stroke therapies. Journal of neurointerventional surgery Morais, L. T., Leslie-Mazwi, T. M., Lev, M. H., Albers, G. W., Yoo, A. J. 2013; 5: i13-20

    View details for DOI 10.1136/neurintsurg-2013-010733

    View details for PubMedID 23572461

  • Advanced imaging improves prediction of hemorrhage after stroke thrombolysis ANNALS OF NEUROLOGY Campbell, B. C., Christensen, S., Parsons, M. W., Churilov, L., Desmond, P. M., Barber, P. A., Butcher, K. S., Levi, C. R., De Silva, D. A., Lansberg, M. G., Mlynash, M., Olivot, J., Straka, M., Bammer, R., Albers, G. W., Donnan, G. A., Davis, S. M. 2013; 73 (4): 510-519

    View details for DOI 10.1002/ana.23837

    View details for Web of Science ID 000319523800012

  • Selection of patients for intra-arterial therapy--authors' reply. Lancet neurology Lansberg, M. G., Albers, G. W. 2013; 12 (3): 225-226

    View details for DOI 10.1016/S1474-4422(13)70019-X

    View details for PubMedID 23415563

  • Early Diffusion-Weighted Imaging and Perfusion-Weighted Imaging Lesion Volumes Forecast Final Infarct Size in DEFUSE 2 STROKE Wheeler, H. M., Mlynash, M., Inoue, M., Tipirneni, A., Liggins, J., Zaharchuk, G., Straka, M., Kemp, S., Bammer, R., Lansberg, M. G., Albers, G. W. 2013; 44 (3): 681-685

    Abstract

    It is hypothesized that early diffusion-weighted imaging (DWI) lesions accurately estimate the size of the irreversibly injured core and thresholded perfusion-weighted imaging (PWI) lesions (time to maximum of tissue residue function [Tmax] >6 seconds) approximate the volume of critically hypoperfused tissue. With incomplete reperfusion, the union of baseline DWI and posttreatment PWI is hypothesized to predict infarct volume.This is a substudy of Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution Study 2 (DEFUSE 2); all patients with technically adequate MRI scans at 3 time points were included. Baseline DWI and early follow-up PWI lesion volumes were determined by the RAPID software program. Final infarct volumes were assessed with 5-day fluid-attenuated inversion recovery and were corrected for edema. Reperfusion was defined on the basis of the reduction in PWI lesion volume between baseline and early follow-up MRI. DWI and PWI volumes were correlated with final infarct volumes.Seventy-three patients were eligible. Twenty-six patients with >90% reperfusion show a high correlation between early DWI volume and final infarct volume (r=0.95; P<0.001). Nine patients with <10% reperfusion have a high correlation between baseline PWI (Tmax >6 seconds) volume and final infarct volume (r=0.86; P=0.002). Using all 73 patients, the union of baseline DWI and early follow-up PWI is highly correlated with final infarct volume (r=0.94; P<0.001). The median absolute difference between observed and predicted final volumes is 15 mL (interquartile range, 5.5-30.2).Baseline DWI and early follow-up PWI (Tmax >6 seconds) volumes provide a reasonable approximation of final infarct volume after endovascular therapy.

    View details for DOI 10.1161/STROKEAHA.111.000135

    View details for Web of Science ID 000315447400024

    View details for PubMedID 23390119

    View details for PubMedCentralID PMC3625664

  • The Effects of Alteplase 3 to 6 Hours After Stroke in the EPITHET-DEFUSE Combined Dataset Post Hoc Case-Control Study STROKE Ogata, T., Christensen, S., Nagakane, Y., Ma, H., Campbell, B. C., Churilov, L., Lansberg, M. G., Straka, M., De Silva, D. A., Mlynash, M., Bammer, R., Olivot, J., Desmond, P. M., Albers, G. W., Davis, S. M., Donnan, G. A. 2013; 44 (1): 87-93

    Abstract

    Two phase 2 studies of alteplase in acute ischemic stroke 3 to 6 hours after onset, Echoplanar Imaging Thrombolytic Evaluation Trial (EPITHET; a randomized, controlled, double-blinded trial), and Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution Study (DEFUSE; open-label, treatment only) using MR imaging-based outcomes have been conducted. We have pooled individual patient data from these to assess the response to alteplase. The primary hypothesis was that alteplase would significantly attenuate infarct growth compared with placebo in mismatch-selected patients using coregistration techniques.The EPITHET-DEFUSE study datasets were pooled while retaining the original inclusion and exclusion criteria. Significant hypoperfusion was defined as a Tmax delay >6 seconds), and coregistration techniques were used to define MR diffusion-weighted imaging/perfusion-weighted imaging mismatch. Neuroimaging, parameters including reperfusion, recanalization, symptomatic intracerebral hemorrhage, and clinical outcomes were assessed. Alteplase and placebo groups were compared for the primary outcome of infarct growth as well for secondary outcome measures.From 165 patients with adequate MR scans in the EPITHET-DEFUSE pooled data, 121 patients (73.3%) were found to have mismatch. For the primary outcome analysis, 60 patients received alteplase and 41 placebo. Mismatch patients receiving alteplase had significantly attenuated infarct growth compared with placebo (P=0.025). The reperfusion rate was also increased (62.7% vs 31.7%; P=0.003). Mortality and clinical outcomes were not different between groups.The data provide further evidence that alteplase significantly attenuates infarct growth and increases reperfusion compared with placebo in the 3- to 6- hour time window in patients selected based on MR penumbral imaging.

    View details for DOI 10.1161/STROKEAHA.112.668301

    View details for Web of Science ID 000312883800016

    View details for PubMedID 23250996

  • Advanced Imaging to Extend the Therapeutic Time Window of Acute Ischemic Stroke ANNALS OF NEUROLOGY Fisher, M., Albers, G. W. 2013; 73 (1): 4-9

    Abstract

    Reperfusion therapy for acute stroke has evolved from the initial use of intravenous tissue plasminogen activator (tPA) within 3 hours of symptom onset to more recent guideline-recommended use up to 4.5 hours. In addition, endovascular therapy is increasingly utilized for stroke treatment and is typically initiated up to 8 hours after onset. Recent studies demonstrate that imaging of the ischemic penumbra with diffusion/perfusion magnetic resonance imaging (MRI) can identify subgroups of patients who are likely to improve following successful reperfusion (Target Mismatch profile) and others who are at increased risk for hemorrhage and poor clinical outcomes (Malignant profile). New data indicate that stent retriever devices provide better recanalization efficacy and clinical outcomes than the previously available mechanical thrombectomy devices. Going forward, we believe that the use of penumbral imaging with validated MRI techniques, as well as the currently less well-validated computed tomography (CT) perfusion approach, will maximize benefit and reduce the risk of adverse events and poor outcomes when used both early after stroke onset and at later time points. New trials that feature diffusion/perfusion MRI or CT perfusion-based patient selection for treatment with intravenous tPA and or endovascular therapies versus nonreperfused control groups are planned or in progress. We predict that these trials will confirm the hypothesis that penumbral imaging can enhance patient selection and extend the therapeutic time window for acute ischemic stroke.

    View details for DOI 10.1002/ana.23744

    View details for Web of Science ID 000314660800005

    View details for PubMedID 23378323

  • Oral Antithrombotic Agents for the Prevention of Stroke in Nonvalvular Atrial Fibrillation A Science Advisory for Healthcare Professionals From the American Heart Association/American Stroke Association STROKE Furie, K. L., Goldstein, L. B., Albers, G. W., Khatri, P., Neyens, R., Turakhia, M. P., Turan, T. N., Wood, K. A. 2012; 43 (12): 3442-3453

    View details for Web of Science ID 000311497600063

    View details for PubMedID 22858728

  • Trevo versus Merci retrievers for thrombectomy revascularisation of large vessel occlusions in acute ischaemic stroke (TREVO 2): a randomised trial LANCET Nogueira, R. G., Lutsep, H. L., Gupta, R., Jovin, T. G., Albers, G. W., Walker, G. A., Liebeskind, D. S., Smith, W. S. 2012; 380 (9849): 1231-1240

    Abstract

    Present mechanical devices are unable to achieve recanalisation in up to 20-40% of large vessel occlusion strokes. We compared efficacy and safety of the Trevo Retriever, a new stent-like device, with its US Food and Drug Administration-cleared predecessor, the Merci Retriever.In this open-label randomised controlled trial, we recruited patients at 26 sites in the USA and one in Spain. We included adults aged 18-85 years with angiographically confirmed large vessel occlusion strokes and US National Institutes of Health Stroke Scale (NIHSS) scores of 8-29 within 8 h of symptom onset. We randomly assigned patients (1:1) with sequentially numbered sealed envelopes to thrombectomy with Trevo or Merci devices. Randomisation was stratified by age (≤68 years vs 69-85 years) and NIHSS scores (≤18 vs 19-29) with alternating blocks of various sizes. The primary efficacy endpoint, assessed by an unmasked core laboratory, was thrombolysis in cerebral infarction (TICI) scores of 2 or greater reperfusion with the assigned device alone. The primary safety endpoint was a composite of procedure-related adverse events. Analyses were done by intention to treat. This study is registered with ClinicalTrials.gov, number NCT01270867.Between Feb 3, 2011, and Dec 1, 2011, we randomly assigned 88 patients to the Trevo Retriever group and 90 patients to Merci Retriever group. 76 (86%) patients in the Trevo group and 54 (60%) in the Merci group met the primary endpoint after the assigned device was used (odds ratio 4·22, 95% CI 1·92-9·69; p(superiority)<0·0001). Incidence of the primary safety endpoint did not differ between groups (13 [15%] patients in the Trevo group vs 21 [23%] in the Merci group; p=0·1826).Patients who have had large vessel occlusion strokes but are ineligible for (or refractory to) intravenous tissue plasminogen activator should be treated with the Trevo Retriever in preference to the Merci Retriever.Stryker Neurovascular.

    View details for DOI 10.1016/S0140-6736(12)61299-9

    View details for Web of Science ID 000309817500030

    View details for PubMedID 22932714

  • MRI profile and response to endovascular reperfusion after stroke (DEFUSE 2): a prospective cohort study LANCET NEUROLOGY Lansberg, M. G., Straka, M., Kemp, S., Mlynash, M., Wechsler, L. R., Jovin, T. G., Wilder, M. J., Lutsep, H. L., Czartoski, T. J., Bernstein, R. A., Chang, C. W., Warach, S., Fazekas, F., Inoue, M., Tipirneni, A., Hamilton, S. A., Zaharchuk, G., Marks, M. P., Bammer, R., Albers, G. W. 2012; 11 (10): 860-867

    Abstract

    Whether endovascular stroke treatment improves clinical outcomes is unclear because of the paucity of data from randomised placebo-controlled trials. We aimed to establish whether MRI can be used to identify patients who are most likely to benefit from endovascular reperfusion.In this prospective cohort study we consecutively enrolled patients scheduled to have endovascular treatment within 12 h of onset of stroke at eight centres in the USA and one in Austria. Aided by an automated image analysis computer program, investigators interpreted a baseline MRI scan taken before treatment to establish whether the patient had an MRI profile (target mismatch) that suggested salvageable tissue was present. Reperfusion was assessed on an early follow-up MRI scan (within 12 h of the revascularisation procedure) and defined as a more than 50% reduction in the volume of the lesion from baseline on perfusion-weighted MRI. The primary outcome was favourable clinical response, defined as an improvement of 8 or more on the National Institutes of Health Stroke Scale between baseline and day 30 or a score of 0-1 at day 30. The secondary clinical endpoint was good functional outcome, defined as a modified Rankin scale score of 2 or less at day 90. Analyses were adjusted for imbalances in baseline predictors of outcome. Investigators assessing outcomes were masked to baseline data.138 patients were enrolled. 110 patients had catheter angiography and of these 104 had an MRI profile and 99 could be assessed for reperfusion. 46 of 78 (59%) patients with target mismatch and 12 of 21 (57%) patients without target mismatch had reperfusion after endovascular treatment. The adjusted odds ratio (OR) for favourable clinical response associated with reperfusion was 8·8 (95% CI 2·7-29·0) in the target mismatch group and 0·2 (0·0-1·6) in the no target mismatch group (p=0·003 for difference between ORs). Reperfusion was associated with increased good functional outcome at 90 days (OR 4·0, 95% CI 1·3-12·2) in the target mismatch group, but not in the no target mismatch group (1·9, 0·2-18·7).Target mismatch patients who had early reperfusion after endovascular stroke treatment had more favourable clinical outcomes. No association between reperfusion and favourable outcomes was present in patients without target mismatch. Our data suggest that a randomised controlled trial of endovascular treatment for patients with the target mismatch profile is warranted.National Institute for Neurological Disorders and Stroke.

    View details for DOI 10.1016/S1474-4422(12)70203-X

    View details for PubMedID 22954705

  • The Desmoteplase in Acute Ischemic Stroke (DIAS) clinical trial program INTERNATIONAL JOURNAL OF STROKE von Kummer, R., Albers, G. W., Mori, E. 2012; 7 (7): 589-596

    Abstract

    Desmoteplase is a novel, highly fibrin-specific thrombolytic agent in phase III of clinical development. In comparison to alteplase, it has high fibrin selectivity, is associated with minimal or no neurotoxicity, and has no apparent negative effect on the blood-brain barrier. The safety and efficacy of desmoteplase is being studied in the Desmoteplase in Acute Ischemic Stroke clinical trial program. Three studies (Dose Escalation Study of Desmoteplase in Acute Ischemic Stroke, Desmoteplase in Acute Ischemic Stroke, and Desmoteplase in Acute Ischemic Stroke-2) have been completed, two large randomized, double-blind, placebo-controlled, phase III trials are ongoing at >200 sites worldwide (Desmoteplase in Acute Ischemic Stroke-3 and Desmoteplase in Acute Ischemic Stroke-4, n = 800; DIAS-3 and DIAS-4), and a randomized, double-blind, placebo-controlled, dose-escalation phase II trial is ongoing in Japan (Desmoteplase in Acute Ischemic Stroke-Japan, n = 48; DIAS-J).The objective of DIAS-3 and DIAS-4 is to evaluate the safety and efficacy of a single IV bolus injection of 90 μg/kg desmoteplase given three- to nine-hours after onset of ischemic stroke (National Institutes of Health Stroke Scale 4-24, age 18-85 years). The objective of DIAS-J is to evaluate the safety and tolerability of desmoteplase 70 and 90 μg/kg three- to nine-hours after ischemic stroke onset in Japanese patients.Patients are included with occlusion or high-grade stenosis (thrombolysis in myocardial infarction 0-1) in proximal cerebral arteries on magnetic resonance or computed tomography angiography but excluded with extended ischemic edema on computed tomography or diffusion-weighted imaging.Desmoteplase is the only thrombolytic agent in late-stage development for acute ischemic stroke that is now tested in patients with proven stroke pathology. The results of the Desmoteplase in Acute Ischemic Stroke clinical trial program will show whether patients with major artery occlusions but not extended ischemic brain damage can be safely and effectively treated up to nine-hours after onset.

    View details for DOI 10.1111/j.1747-4949.2012.00910.x

    View details for Web of Science ID 000308968100021

    View details for PubMedID 22989394

  • Patients With the Malignant Profile Within 3 Hours of Symptom Onset Have Very Poor Outcomes After Intravenous Tissue-Type Plasminogen Activator Therapy STROKE Inoue, M., Mlynash, M., Straka, M., Lansberg, M. G., Zaharchuk, G., Bammer, R., Albers, G. W. 2012; 43 (9): 2494-2496

    Abstract

    The malignant profile has been associated with poor outcomes after reperfusion in the 3- to 6-hour time window. The aim of this study was to estimate the incidence and prognostic implications of the malignant profile, as identified by CT perfusion, in intravenous tissue-type plasminogen activator-treated patients who were imaged <3 hours from stroke onset.The incidence of the malignant profile, based on the previously published optimal perfusion-weighted imaging definition, was assessed in consecutive patients using a fully automated software program (RApid processing of Perfusion and Diffusion [RAPID]). A receiver operating characteristic curve analysis was done to identify time to maximum and core volume thresholds that optimally identify patients with poor outcome (modified Rankin Scale 5-6).Forty-two patients had an interpretable CT perfusion performed within 3 hours of symptom onset. Mean age was 74±14 years and median (interquartile range) National Institutes of Stroke Scale score was 13 (6-19). Four patients (9.5%) met the prespecified criteria for the malignant profile and all 4 had poor outcome. Receiver operating characteristic analysis determined that the best CT perfusion measure to identify patients with poor outcome was a cerebral blood flow based infarct core >53 mL (100% specificity and 67% sensitivity). This criterion identified 5 patients as malignant (12%). The poor outcome rate in these patients was 100% versus 7.1% in the 37 nonmalignant patients (P<0.001).The incidence of the malignant profile on CT perfusion is approximately 10% in tissue-type plasminogen activator-eligible patients imaged within 3 hours of symptom onset. The clinical outcome of these patients is very poor despite intravenous tissue-type plasminogen activator therapy.

    View details for DOI 10.1161/STROKEAHA.112.653329

    View details for Web of Science ID 000308416300050

    View details for PubMedID 22811464

  • Clinical Assessment of Standard and Generalized Autocalibrating Partially Parallel Acquisition Diffusion Imaging: Effects of Reduction Factor and Spatial Resolution AMERICAN JOURNAL OF NEURORADIOLOGY Andre, J. B., Zaharchuk, G., Fischbein, N. J., Augustin, M., Skare, S., Straka, M., Rosenberg, J., Lansberg, M. G., Kemp, S., Wijman, C. A., Albers, G. W., Schwartz, N. E., Bammer, R. 2012; 33 (7): 1337-1342

    Abstract

    PI improves routine EPI-based DWI by enabling higher spatial resolution and reducing geometric distortion, though it remains unclear which of these is most important. We evaluated the relative contribution of these factors and assessed their ability to increase lesion conspicuity and diagnostic confidence by using a GRAPPA technique.Four separate DWI scans were obtained at 1.5T in 48 patients with independent variation of in-plane spatial resolution (1.88 mm(2) versus 1.25 mm(2)) and/or reduction factor (R = 1 versus R = 3). A neuroradiologist with access to clinical history and additional imaging sequences provided a reference standard diagnosis for each case. Three blinded neuroradiologists assessed scans for abnormalities and also evaluated multiple imaging-quality metrics by using a 5-point ordinal scale. Logistic regression was used to determine the impact of each factor on subjective image quality and confidence.Reference standard diagnoses in the patient cohort were acute ischemic stroke (n = 30), ischemic stroke with hemorrhagic conversion (n = 4), intraparenchymal hemorrhage (n = 9), or no acute lesion (n = 5). While readers preferred both a higher reduction factor and a higher spatial resolution, the largest effect was due to an increased reduction factor (odds ratio, 47 ± 16). Small lesions were more confidently discriminated from artifacts on R = 3 images. The diagnosis changed in 5 of 48 scans, always toward the reference standard reading and exclusively for posterior fossa lesions.PI improves DWI primarily by reducing geometric distortion rather than by increasing spatial resolution. This outcome leads to a more accurate and confident diagnosis of small lesions.

    View details for DOI 10.3174/ajnr.A2980

    View details for Web of Science ID 000307628200025

    View details for PubMedID 22403781

  • Combined spin- and gradient-echo perfusion-weighted imaging MAGNETIC RESONANCE IN MEDICINE Schmiedeskamp, H., Straka, M., Newbould, R. D., Zaharchuk, G., Andre, J. B., Olivot, J., Moseley, M. E., Albers, G. W., Bammer, R. 2012; 68 (1): 30-40

    Abstract

    In this study, a spin- and gradient-echo echo-planar imaging (SAGE EPI) MRI pulse sequence is presented that allows simultaneous measurements of gradient-echo and spin-echo dynamic susceptibility-contrast perfusion-weighted imaging data. Following signal excitation, five readout trains were acquired using spin- and gradient-echo echo-planar imaging, all of them with echo times of less than 100 ms. Contrast agent concentrations in brain tissue were determined based on absolute R2* and R(2) estimates rather than relative changes in the signals of individual echo trains, producing T(1)-independent dynamic susceptibility-contrast perfusion-weighted imaging data. Moreover, this acquisition technique enabled vessel size imaging through the simultaneous quantification of R2* and R(2), without an increase in acquisition time. In this work, the concepts of SAGE EPI pulse sequence and results in stroke and tumor imaging are presented. Overall, SAGE EPI combined the advantages of higher sensitivity to contrast agent passage of gradient-echo perfusion-weighted imaging with better microvascular selectivity of spin-echo perfusion-weighted imaging.

    View details for DOI 10.1002/mrm.23195

    View details for Web of Science ID 000305119100004

    View details for PubMedID 22114040

    View details for PubMedCentralID PMC3374915

  • Comparison of Arterial Spin Labeling and Bolus Perfusion-Weighted Imaging for Detecting Mismatch in Acute Stroke STROKE Zaharchuk, G., El Mogy, I. S., Fischbein, N. J., Albers, G. W. 2012; 43 (7): 1843-1848

    Abstract

    The perfusion-weighted imaging (PWI)-diffusion-weighted imaging (DWI) mismatch paradigm is widely used in stroke imaging studies. Arterial spin labeling (ASL) is an alternative perfusion method that does not require contrast. This study compares the agreement of ASL-DWI and PWI-DWI mismatch classification in patients with stroke.This was a retrospective study drawn from all 1.5-T MRI studies performed in 2010 at a single institution. Inclusion criteria were: symptom onset<5 days, DWI lesion>10 mL, and acquisition of both PWI and ASL. DWI and PWI time to maximum>6 seconds lesion volumes were determined using automated software. Patients were classified into reperfused, matched, or mismatch groups. Two radiologists classified ASL-DWI qualitatively into the same categories blinded to DWI-PWI. Agreement between both individual readers and methods was assessed.Fifty-one studies met the inclusion criteria. Seven cases were excluded (1 due to PWI susceptibility artifact, 2 due to motion, and 4 due to severe ASL border zone sign), resulting in 44 studies for comparison. Interrater agreement for ASL-DWI mismatch status was high (κ=0.92; 95% CI, 0.80-1.00). ASL-DWI and PWI-DWI mismatch categories agreed in 25 of 44 cases (57%). In the 16 of 19 discrepant cases (84%), ASL overestimated the PWI lesion size. In 34 of 44 cases (77%), they agreed regarding the presence of mismatch versus no mismatch.Mismatch classification based on ASL and PWI agrees frequently but not perfectly. ASL tends to overestimate the PWI time to maximum lesion volume. Improved ASL methodologies and/or higher field strength are necessary before ASL can be recommended for routine use in acute stroke.

    View details for DOI 10.1161/STROKEAHA.111.639773

    View details for Web of Science ID 000305882000030

    View details for PubMedID 22539548

    View details for PubMedCentralID PMC3383868

  • Automated Perfusion Imaging for the Evaluation of Transient Ischemic Attack STROKE Kleinman, J. T., Zaharchuk, G., Mlynash, M., Ogdie, A. A., Straka, M., Lansberg, M. G., Schwartz, N. E., Kemp, S., Bammer, R., Albers, G. W., Olivot, J. 2012; 43 (6): 1556-1560

    Abstract

    Diffusion-weighted imaging (DWI) is recommended for the evaluation of transient ischemic attack. Perfusion imaging can increase the yield of MRI in transient ischemic attack. We evaluated automated bolus perfusion (the time when the residue function reaches its maximum [TMax] and mean transit time [MTT]) and arterial spin labeling (ASL) sequences for the detection of ischemic lesions in patients with transient ischemic attack.We enrolled consecutive patients evaluated for suspicion of acute transient ischemic attack by multimodal MRI within 36 hours of symptom onset. Two independent raters assessed the presence and location of ischemic lesions blinded to the clinical presentation. The prevalence of ischemic lesions and the interrater agreement were 1,410 assessed.From January 2010 to 2011, 93 patients were enrolled and 90 underwent perfusion imaging (69 bolus perfusion and 76 ASL). Overall, 25 of 93 patients (27%) were DWI-positive and 14 (15%) were perfusion-positive but DWI-negative (ASL n=9; TMax n=9; MTT n=2). MTT revealed an ischemic lesion in fewer patients than TMax (7 versus 20, P=0.004). Raters agreed on 89% of diffusion-weighted imaging cases, 89% of TMax, 87% o10f010 MTT, and 90% of ASL cases. The interrater agreement was good for DWI, TMax, and ASL (κ=0.73, 0.72, and 0.74, respectively) and fair for MTT (κ=0.43). Diffusion and/or perfusion were positive in 39 of 69 (57%) patients with a discharge diagnosis of possible ischemic event.Our results suggest that in patients referred for suspicion of transient ischemic attack, automated TMax is more sensitive than MTT, and both ASL and TMax increase the yield of MRI for the detection of ischemic lesions.

    View details for DOI 10.1161/STROKEAHA.111.644971

    View details for Web of Science ID 000304523800025

    View details for PubMedID 22474058

  • Hemisphere Volume Is Associated with Neurological Deterioration and Outcome after Malignant Infarction 64th Annual Meeting of the American-Academy-of-Neurology (AAN) Sheth, K., Yoo, A., Gonzalez, R., Kimberly, W., Chaudhry, Z., Elm, J., Jacobson, S., Davis, S., Donnan, G., Albers, G., Stern, B. LIPPINCOTT WILLIAMS & WILKINS. 2012

    View details for Web of Science ID 000303204804024

  • Closure or Medical Therapy for Cryptogenic Stroke with Patent Foramen Ovale NEW ENGLAND JOURNAL OF MEDICINE Furlan, A. J., Reisman, M., Massaro, J., Mauri, L., Adams, H., Albers, G. W., Felberg, R., Herrmann, H., Kar, S., Landzberg, M., Raizner, A., Wechsler, L. 2012; 366 (11): 991-999

    Abstract

    The prevalence of patent foramen ovale among patients with cryptogenic stroke is higher than that in the general population. Closure with a percutaneous device is often recommended in such patients, but it is not known whether this intervention reduces the risk of recurrent stroke.We conducted a multicenter, randomized, open-label trial of closure with a percutaneous device, as compared with medical therapy alone, in patients between 18 and 60 years of age who presented with a cryptogenic stroke or transient ischemic attack (TIA) and had a patent foramen ovale. The primary end point was a composite of stroke or transient ischemic attack during 2 years of follow-up, death from any cause during the first 30 days, or death from neurologic causes between 31 days and 2 years.A total of 909 patients were enrolled in the trial. The cumulative incidence (Kaplan-Meier estimate) of the primary end point was 5.5% in the closure group (447 patients) as compared with 6.8% in the medical-therapy group (462 patients) (adjusted hazard ratio, 0.78; 95% confidence interval, 0.45 to 1.35; P=0.37). The respective rates were 2.9% and 3.1% for stroke (P=0.79) and 3.1% and 4.1% for TIA (P=0.44). No deaths occurred by 30 days in either group, and there were no deaths from neurologic causes during the 2-year follow-up period. A cause other than paradoxical embolism was usually apparent in patients with recurrent neurologic events.In patients with cryptogenic stroke or TIA who had a patent foramen ovale, closure with a device did not offer a greater benefit than medical therapy alone for the prevention of recurrent stroke or TIA. (Funded by NMT Medical; ClinicalTrials.gov number, NCT00201461.).

    View details for Web of Science ID 000301482800002

    View details for PubMedID 22417252

  • Arterial Spin Labeling Imaging Findings in Transient Ischemic Attack Patients: Comparison with Diffusion- and Bolus Perfusion-Weighted Imaging CEREBROVASCULAR DISEASES Zaharchuk, G., Olivot, J., Fischbein, N. J., Bammer, R., Straka, M., Kleinman, J. T., Albers, G. W. 2012; 34 (3): 221-228

    Abstract

    Since transient ischemic attacks (TIAs) can predict future stroke, it is important to distinguish true vascular events from non-vascular etiologies. Arterial spin labeling (ASL) is a non-contrast magnetic resonance (MR) method that is sensitive to cerebral perfusion and arterial arrival delays. Due to its high sensitivity to minor perfusion alterations, we hypothesized that ASL abnormalities would be identified frequently in TIA patients, and could therefore help increase clinicians' confidence in the diagnosis.We acquired diffusion-weighted imaging (DWI), intracranial MR angiography (MRA), and ASL in a prospective cohort of TIA patients. A subset of these patients also received bolus contrast perfusion-weighted imaging (PWI). Two neuroradiologists evaluated the images in a blinded fashion to determine the frequency of abnormalities on each imaging sequence. Kappa (ĸ) statistics were used to assess agreement, and the χ(2) test was used to detect differences in the proportions of abnormal studies.76 patients met the inclusion criteria, 48 (63%) of whom received PWI. ASL was abnormal in 62%, a much higher frequency compared with DWI (24%) and intracranial MRA (13%). ASL significantly increased the MR imaging yield above the combined DWI and MRA yield (62 vs. 32%, p < 0.05). Arterial transit artifact in vascular borderzones was the most common ASL abnormality (present in 51%); other abnormalities included focal high or low ASL signal (11%). PWI was abnormal in 31% of patients, and in these, ASL was abnormal in 14 out of 15 cases (93%). In hemispheric TIA patients, both PWI and ASL findings were more common in the symptomatic hemisphere. Agreement between neuroradiologists regarding abnormal studies was good for ASL and PWI [ĸ = 0.69 (95% CI 0.53-0.86) and ĸ = 0.66 (95% CI 0.43-0.89), respectively].In TIA patients, perfusion-related alterations on ASL were more frequently detected compared with PWI or intracranial MRA and were most frequently associated with the symptomatic hemisphere. Almost all cases with a PWI lesion also had an ASL lesion. These results suggest that ASL may aid in the workup and triage of TIA patients, particularly those who cannot undergo a contrast study.

    View details for DOI 10.1159/000339682

    View details for Web of Science ID 000313654100007

    View details for PubMedID 23006669

  • The infarct core is well represented by the acute diffusion lesion: sustained reversal is infrequent JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM Campbell, B. C., Purushotham, A., Christensen, S., Desmond, P. M., Nagakane, Y., Parsons, M. W., Lansberg, M. G., Mlynash, M., Straka, M., De Silva, D. A., Olivot, J., Bammer, R., Albers, G. W., Donnan, G. A., Davis, S. M. 2012; 32 (1): 50-56

    Abstract

    Diffusion-weighted imaging (DWI) is commonly used to assess irreversibly infarcted tissue but its accuracy is challenged by reports of diffusion lesion reversal (DLR). We investigated the frequency and implications for mismatch classification of DLR using imaging from the EPITHET (Echoplanar Imaging Thrombolytic Evaluation Trial) and DEFUSE (Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution) studies. In 119 patients (83 treated with IV tissue plasminogen activator), follow-up images were coregistered to acute diffusion images and the lesions manually outlined to their maximal visual extent in diffusion space. Diffusion lesion reversal was defined as voxels of acute diffusion lesion that corresponded to normal brain at follow-up (i.e., final infarct, leukoaraiosis, and cerebrospinal fluid (CSF) voxels were excluded from consideration). The appearance of DLR was visually checked for artifacts, the volume calculated, and the impact of adjusting baseline diffusion lesion volume for DLR volume on perfusion-diffusion mismatch analyzed. Median DLR volume reduced from 4.4 to 1.5 mL after excluding CSF/leukoaraiosis. Visual inspection verified 8/119 (6.7%) with true DLR, median volume 2.33 mL. Subtracting DLR from acute diffusion volume altered perfusion-diffusion mismatch (T(max)>6 seconds, ratio>1.2) in 3/119 (2.5%) patients. Diffusion lesion reversal between baseline and 3 to 6 hours DWI was also uncommon (7/65, 11%) and often transient. Clinically relevant DLR is uncommon and rarely alters perfusion-diffusion mismatch. The acute diffusion lesion is generally a reliable signature of the infarct core.

    View details for DOI 10.1038/jcbfm.2011.102

    View details for Web of Science ID 000299010000008

    View details for PubMedID 21772309

    View details for PubMedCentralID PMC3323290

  • MRI guides diagnostic approach for ischaemic stroke JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY Kumar, M. A., Vangala, H., Tong, D. C., Campbell, D. M., Balgude, A., Eyngorn, I., Beraud, A. S., Olivot, J. M., Hsia, A. W., Bernstein, R. A., Wijman, C. A., Lansberg, M. G., Mlynash, M., Hamilton, S., Moseley, M. E., Albers, G. W. 2011; 82 (11): 1201-1205

    Abstract

    Identification of ischaemic stroke subtype currently relies on clinical evaluation supported by various diagnostic studies. The authors sought to determine whether specific diffusion-weighted MRI (DWI) patterns could reliably guide the subsequent work-up for patients presenting with acute ischaemic stroke symptoms.273 consecutive patients with acute ischaemic stroke symptoms were enrolled in this prospective, observational, single-centre NIH-sponsored study. Electrocardiogram, non-contrast head CT, brain MRI, head and neck magnetic resonance angiography (MRA) and transoesophageal echocardiography were performed in this prespecified order. Stroke neurologists determined TOAST (Trial of Org 10172 in Acute Stroke Treatment) classification on admission and on discharge. Initial TOAST stroke subtypes were compared with the final TOAST subtype. If the final subtype differed from the initial assessment, the diagnostic test deemed the principal determinant of change was recorded. These principal determinants of change were compared between a CT-based and an MRI-based classification schema.Among patients with a thromboembolic DWI pattern, transoesophageal echocardiography was the principal determinant of diagnostic change in 8.8% versus 0% for the small vessel group and 1.7% for the other group (p<0.01). Among patients with the combination of a thromboembolic pattern on MRI and a negative cervical MRA, transoesophageal echocardiography led to a change in diagnosis in 12.1%. There was no significant difference between groups using a CT-based scheme.DWI patterns appear to predict stroke aetiologies better than conventional methods. The study data suggest an MRI-based diagnostic algorithm that can potentially obviate the need for echocardiography in one-third of stroke patients and may limit the number of secondary extracranial vascular imaging studies to approximately 10%.

    View details for DOI 10.1136/jnnp.2010.237941

    View details for Web of Science ID 000295920000006

    View details for PubMedID 21551473

  • Greater Effect of Stroke Thrombolysis in the Presence of Arterial Obstruction ANNALS OF NEUROLOGY De Silva, D. A., Churilov, L., Olivot, J., Christensen, S., Lansberg, M. G., Mlynash, M., Campbell, B. C., Desmond, P., Straka, M., Bammer, R., Albers, G. W., Davis, S. M., Donnan, G. A. 2011; 70 (4): 601-605

    Abstract

    Recanalization of arterial obstruction is associated with improved clinical outcomes. There are no controlled data demonstrating whether arterial obstruction status predicts the treatment effect of intravenous (IV) tissue plasminogen activator (tPA). We aimed to determine if the presence of arterial obstruction improves the treatment effect of IV tPA over placebo in attenuating infarct growth.We analyzed 175 ischemic stroke patients treated in the 3-6 hour time window from the Echoplanar Imaging Thrombolytic Evaluation Trial (EPITHET) trial (randomized to IV tPA or placebo) and Diffusion and perfusion imaging Evaluation For Understanding Stroke Evolution (DEFUSE) study (all treated with IV tPA). Infarct growth was calculated as the difference between baseline diffusion-weighted imaging (DWI) and final T2 lesion volumes. Baseline arterial obstruction of large intracranial arteries was graded on magnetic resonance angiography (MRA).Among the 116 patients with adequate baseline MRA and final lesion assessment, 72 had arterial obstruction (48 tPA, 24 placebo) and 44 no arterial obstruction (33 tPA, 11 placebo). Infarct growth was lower in the tPA than placebo group (median difference 26ml, 95% confidence interval [CI], 1-50) in patients with arterial obstruction, but was similar in patients with no arterial obstruction (median difference 5ml, 95%CI, -3 to 9). Infarct growth attenuation with tPA over placebo treatment was greater among patients with arterial obstruction than those without arterial obstruction by a median of 32ml (95%CI, 21-43, p < 0.001).The treatment effect of IV tPA over placebo was greater with baseline arterial obstruction, supporting arterial obstruction status as a consideration in selecting patients more likely to benefit from IV thrombolysis.

    View details for DOI 10.1002/ana.22444

    View details for Web of Science ID 000296396700013

    View details for PubMedID 22028220

    View details for PubMedCentralID PMC3205432

  • Heterogeneity in the penumbra JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM del Zoppo, G. J., Sharp, F. R., Heiss, W., Albers, G. W. 2011; 31 (9): 1836-1851

    Abstract

    Original experimental studies in nonhuman primate models of focal ischemia showed flow-related changes in evoked potentials that suggested a circumferential zone of low regional cerebral blood flow with normal K(+) homeostasis, around a core of permanent injury in the striatum or the cortex. This became the basis for the definition of the ischemic penumbra. Imaging techniques of the time suggested a homogeneous core of injury, while positing a surrounding 'penumbral' region that could be salvaged. However, both molecular studies and observations of vascular integrity indicate a more complex and dynamic situation in the ischemic core that also changes with time. The microvascular, cellular, and molecular events in the acute setting are compatible with heterogeneity of the injury within the injury center, which at early time points can be described as multiple 'mini-cores' associated with multiple 'mini-penumbras'. These observations suggest the progression of injury from many small foci to a homogeneous defect over time after the onset of ischemia. Recent observations with updated imaging techniques and data processing support these dynamic changes within the core and the penumbra in humans following focal ischemia.

    View details for DOI 10.1038/jcbfm.2011.93

    View details for Web of Science ID 000294524300003

    View details for PubMedID 21731034

  • Stroke Treatment Academic Industry Roundtable (STAIR) Recommendations for Maximizing the Use of Intravenous Thrombolytics and Expanding Treatment Options With Intra-arterial and Neuroprotective Therapies STROKE Albers, G. W., Goldstein, L. B., Hess, D. C., Wechsler, L. R., Furie, K. L., Gorelick, P. B., Hurn, P., Liebeskind, D. S., Nogueira, R. G., Saver, J. L. 2011; 42 (9): 2645-2650

    Abstract

    The goal of the Stroke Treatment Academic Industry Roundtable (STAIR) meetings is to advance the development of acute and restorative stroke therapies. Summary of Review- At the STAIR VII recommendations for strategies to maximize the use of intravenous thrombolytics through targeting public education, and the refinement of current treatment exclusion criteria were proposed. Increased utilization of mechanical devices for intra-arterial recanalization can be achieved by obtaining more definitive evidence of efficacy in randomized clinical trials, identification of patient characteristics associated with treatment efficacy, optimization of technical approaches, clarification of effective time windows, and development of approaches to limit complications. Neuroprotective strategies remain viable; recommendations for further study of these agents include an emphasis on rapid administration, consideration of the systemic effects of ischemic stroke, prevention of complications associated with early reperfusion, a focus on agents with multiple mechanisms of action, and consideration of possible interactions between neuroprotective and thrombolytic therapies.Extending intravenous thrombolysis to a broader patient population, clarifying the risk and benefits of intra-arterial reperfusion therapies, and further development of neuroprotective therapies were the key recommendations from STAIR VII.

    View details for DOI 10.1161/STROKEAHA.111.618850

    View details for Web of Science ID 000294342800061

    View details for PubMedID 21852620

  • Improving the Accuracy of Perfusion Imaging in Acute Ischemic Stroke ANNALS OF NEUROLOGY Albers, G. W., Fisher, M. 2011; 70 (3): 347-349

    View details for DOI 10.1002/ana.22524

    View details for Web of Science ID 000294816800007

    View details for PubMedID 21905076

  • Early stroke risk and ABCD2 score performance in tissue- vs time-defined TIA A multicenter study NEUROLOGY Giles, M. F., Albers, G. W., Amarenco, P., Arsava, E. M., Asimos, A. W., Ay, H., Calvet, D., Coutts, S. B., Cucchiara, B. L., Demchuk, A. M., Johnston, S. C., Kelly, P. J., Kim, A. S., Labreuche, J., Lavallee, P. C., Mas, J., Merwick, A., Olivot, J. M., Purroy, F., Rosamond, W. D., Sciolla, R., Rothwell, P. M. 2011; 77 (13): 1222-1228

    Abstract

    Stroke risk immediately after TIA defined by time-based criteria is high, and prognostic scores (ABCD2 and ABCD3-I) have been developed to assist management. The American Stroke Association has proposed changing the criteria for the distinction between TIA and stroke from time-based to tissue-based. Research using these definitions is lacking. In a multicenter observational cohort study, we have investigated prognosis and performance of the ABCD2 score in TIA, subcategorized as tissue-positive or tissue-negative on diffusion-weighted imaging (DWI) or CT imaging according to the newly proposed criteria.Twelve centers provided data on ABCD2 scores, DWI or CT brain imaging, and follow-up in cohorts of patients with TIA diagnosed by time-based criteria. Stroke rates at 7 and 90 days were studied in relation to tissue-positive or tissue-negative subcategorization, according to the presence or absence of brain infarction. The predictive power of the ABCD2 score was determined using area under receiver operator characteristic curve (AUC) analyses.A total of 4,574 patients were included. Among DWI patients (n = 3,206), recurrent stroke rates at 7 days were 7.1%(95% confidence interval 5.5-9.1) after tissue-positive and 0.4% (0.2-0.7) after tissue-negative events (p diff < 0.0001). Corresponding rates in CT-imaged patients were 12.8% (9.3-17.4) and 3.0% (2.0-4.2), respectively (p diff < 0.0001). The ABCD2 score had predictive value in tissue-positive and tissue-negative events (AUC = 0.68 [95% confidence interval 0.63-0.73] and 0.73 [0.67-0.80], respectively; p sig < 0.0001 for both results, p diff = 0.17). Tissue-positive events with low ABCD2 scores and tissue-negative events with high ABCD2 scores had similar stroke risks, especially after a 90-day follow-up.Our findings support the concept of a tissue-based definition of TIA and stroke, at least on prognostic grounds.

    View details for DOI 10.1212/WNL.0b013e3182309f91

    View details for Web of Science ID 000295253800008

    View details for PubMedID 21865578

    View details for PubMedCentralID PMC3179650

  • Systemic augmentation of alpha B-crystallin provides therapeutic benefit twelve hours post-stroke onset via immune modulation PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Arac, A., Brownell, S. E., Rothbard, J. B., Chen, C., Ko, R. M., Pereira, M. P., Albers, G. W., Steinman, L., Steinberg, G. K. 2011; 108 (32): 13287-13292

    Abstract

    Tissue plasminogen activator is the only treatment option for stroke victims; however, it has to be administered within 4.5 h after symptom onset, making its use very limited. This report describes a unique target for effective treatment of stroke, even 12 h after onset, by the administration of αB-crystallin (Cryab), an endogenous immunomodulatory neuroprotectant. In Cryab(-/-) mice, there was increased lesion size and diminished neurologic function after stroke compared with wild-type mice. Increased plasma Cryab was detected after experimental stroke in mice and after stroke in human patients. Administration of Cryab even 12 h after experimental stroke reduced both stroke volume and inflammatory cytokines associated with stroke pathology. Cryab is an endogenous anti-inflammatory and neuroprotectant molecule produced after stroke, whose beneficial properties can be augmented when administered therapeutically after stroke.

    View details for DOI 10.1073/pnas.1107368108

    View details for Web of Science ID 000293691400065

    View details for PubMedID 21828004

    View details for PubMedCentralID PMC3156222

  • TWO ACES Transient Ischemic Attack Work-Up as Outpatient Assessment of Clinical Evaluation and Safety STROKE Olivot, J., Wolford, C., Castle, J., Mlynash, M., Schwartz, N. E., Lansberg, M. G., Kemp, S., Albers, G. W. 2011; 42 (7): 1839-1843

    Abstract

    To evaluate a novel emergency department-based TIA triage system.We developed an approach to TIA triage and management based on risk assessment using the ABCD(2) score in combination with early cervical and intracranial vessel imaging. It was anticipated that this triage system would avoid hospitalization for the majority of TIA patients and result in a low rate of recurrent stroke. We hypothesized that the subsequent stroke rate among consecutively encountered patients managed with this approach would be lower than predicted based on their ABCD2 scores.From June 2007 to December 2009, 224 consecutive patients evaluated in the Stanford emergency department for a possible TIA were enrolled in the study. One hundred fifty-seven were discharged to complete their evaluation at the outpatient TIA clinic; 67 patients were hospitalized. One hundred sixteen patients had a final diagnosis of TIA/minor stroke or possible TIA. The stroke rates at 7, 30, and 90 days were 0.6% (0.1%-3.5%) for patients referred to the TIA clinic and 1.5% (0.3%-8.0%) for the hospitalized patients. Combining both groups, the overall stroke rate was 0.9% (0.3%-3.2%), which is significantly less than expected based on ABCD2 scores (P=0.034 at 7 days and P=0.001 at 90 days).This emergency department-based inpatient versus outpatient TIA triage system led to a low rate of hospitalization (30%). Recurrent stroke rates were low for both the hospitalized and outpatient subgroups.

    View details for DOI 10.1161/STROKEAHA.110.608380

    View details for Web of Science ID 000292090900019

    View details for PubMedID 21617143

  • RAPID Automated Patient Selection for Reperfusion Therapy A Pooled Analysis of the Echoplanar Imaging Thrombolytic Evaluation Trial (EPITHET) and the Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution (DEFUSE) Study STROKE Lansberg, M. G., Lee, J., Christensen, S., Straka, M., De Silva, D. A., Mlynash, M., Campbell, B. C., Bammer, R., Olivot, J., Desmond, P., Davis, S. M., Donnan, G. A., Albers, G. W. 2011; 42 (6): 1608-1614

    Abstract

    The aim of this study was to determine if automated MRI analysis software (RAPID) can be used to identify patients with stroke in whom reperfusion is associated with an increased chance of good outcome.Baseline diffusion- and perfusion-weighted MRI scans from the Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution study (DEFUSE; n=74) and the Echoplanar Imaging Thrombolytic Evaluation Trial (EPITHET; n=100) were reprocessed with RAPID. Based on RAPID-generated diffusion-weighted imaging and perfusion-weighted imaging lesion volumes, patients were categorized according to 3 prespecified MRI profiles that were hypothesized to predict benefit (Target Mismatch), harm (Malignant), and no effect (No Mismatch) from reperfusion. Favorable clinical response was defined as a National Institutes of Health Stroke Scale score of 0 to 1 or a ≥ 8-point improvement on the National Institutes of Health Stroke Scale score at Day 90.In Target Mismatch patients, reperfusion was strongly associated with a favorable clinical response (OR, 5.6; 95% CI, 2.1 to 15.3) and attenuation of infarct growth (10 ± 23 mL with reperfusion versus 40 ± 44 mL without reperfusion; P<0.001). In Malignant profile patients, reperfusion was not associated with a favorable clinical response (OR, 0.74; 95% CI, 0.1 to 5.8) or attenuation of infarct growth (85 ± 74 mL with reperfusion versus 95 ± 79 mL without reperfusion; P=0.7). Reperfusion was also not associated with a favorable clinical response (OR, 1.05; 95% CI, 0.1 to 9.4) or attenuation of lesion growth (10 ± 15 mL with reperfusion versus 17 ± 30 mL without reperfusion; P=0.9) in No Mismatch patients.MRI profiles that are associated with a differential response to reperfusion can be identified with RAPID. This supports the use of automated image analysis software such as RAPID for patient selection in acute stroke trials.

    View details for DOI 10.1161/STROKEAHA.110.609008

    View details for PubMedID 21493916

  • A Topographic Study of the Evolution of the MR DWI/PWI Mismatch Pattern and Its Clinical Impact A Study by the EPITHET and DEFUSE Investigators STROKE Ogata, T., Nagakane, Y., Christensen, S., Ma, H., Campbell, B. C., Churilov, L., Olivot, J., Desmond, P. M., Albers, G. W., Davis, S. M., Donnan, G. A. 2011; 42 (6): 1596-1601

    Abstract

    The ischemic penumbra may be classical, with complete annular configuration around the infarct core, or nonclassical with a more fragmented pattern. We tested the hypotheses that these penumbral patterns may: be associated with specific predictive factors, influence infarct growth and clinical outcome, and influence the effect of tissue plasminogen activator (t-PA).Using the EPITHET/DEFUSE data set, in which patients received alteplase or placebo 3 to 6 hours poststroke, perfusion-weighted imaging and diffusion-weighted imaging images were analyzed. These mismatch patterns were defined as "classical" or "nonclassical." Multivariate analysis was used to identify variables associated with mismatch patterns, the effect of t-PA, as well as the relationship between mismatch patterns, infarct growth, and clinical outcomes.We included 158 patients (median age, 74 years; median National Institute of Health Stroke Scale score, 12). Multivariate analysis indicated that the factors associated with classical mismatch pattern type were large mismatch volume (P<0.001) and cortical infarct location (P=0.036). Infarct growth, clinical outcome, and the efficacy of t-PA were not statistically different between patterns.Coregistered mismatch volume and cortical location of infarction were the important factors associated with presence of the classical mismatch pattern. The lack of effect of the type of mismatch patterns on infarct growth, clinical outcomes, or the benefit of t-PA would suggest that mismatch topography is less important during the hyperacute phase of ischemic stroke than during subacute phase.

    View details for DOI 10.1161/STROKEAHA.110.609016

    View details for Web of Science ID 000291032700036

    View details for PubMedID 21512174

  • Refining the Definition of the Malignant Profile Insights From the DEFUSE-EPITHET Pooled Data Set STROKE Mlynash, M., Lansberg, M. G., De Silva, D. A., Lee, J., Christensen, S., Straka, M., Campbell, B. C., Bammer, R., Olivot, J., Desmond, P., Donnan, G. A., Davis, S. M., Albers, G. W. 2011; 42 (5): 1270-1275

    Abstract

    To refine the definition of the malignant magnetic resonance imaging profile in acute stroke patients using baseline diffusion-weighted magnetic resonance imaging (DWI) and perfusion-weighted magnetic resonance imaging (PWI) findings from the pooled DEFUSE/EPITHET database.Patients presenting with acute stroke within 3 to 6 hours from symptom onset were treated with tissue plasminogen activator or placebo. Baseline and follow-up DWI and PWI images from both studies were reprocessed using the same software program. A receiver operating characteristic curve analysis was used to identify Tmax and DWI volumes that optimally predicted poor outcomes (modified Rankin Scale 5-6) at 90 days in patients who achieved reperfusion.Sixty-five patients achieved reperfusion and 46 did not reperfuse. Receiver operating characteristic analysis identified a PWI (Tmax>8 s) volume of >85 mL as the optimal definition of the malignant profile. Eighty-nine percent of malignant profile patients had poor outcome with reperfusion versus 39% of patients without reperfusion (P=0.02). Parenchymal hematomas occurred more frequently in malignant profile patients who experienced reperfusion versus no reperfusion (67% versus 11%, P<0.01). DWI analysis identified a volume of 80 mL as the best DWI threshold, but this definition was less sensitive than were PWI-based definitions.Stroke patients likely to suffer parenchymal hemorrhages and poor outcomes following reperfusion can be identified from baseline magnetic resonance imaging findings. The current analysis demonstrates that a PWI threshold (Tmax>8 s) of approximately 100 mL is appropriate for identifying these patients. Exclusion of malignant profile patients from reperfusion therapies may substantially improve the efficacy and safety of reperfusion therapies. Clinical Trial Registration Information- URL: http://www.clinicaltrials.gov. Unique identifier: NCT00238537.

    View details for DOI 10.1161/STROKEAHA.110.601609

    View details for Web of Science ID 000289835900023

    View details for PubMedID 21474799

    View details for PubMedCentralID PMC3248048

  • Role of Diffusion and Perfusion MRI in Selecting Patients for Reperfusion Therapies NEUROIMAGING CLINICS OF NORTH AMERICA Grigoryan, M., Tung, C. E., Albers, G. W. 2011; 21 (2): 247-?

    Abstract

    After onset of ischemic stroke, potentially viable tissue at risk (ischemic penumbra) may be salvageable. Currently, intravenous alteplase is approved for up to 4.5 hours after symptom onset of acute ischemic stroke. Increasing this time window may allow many more patients to be treated. The ability to use MRI to help define the irreversibly damaged brain (infarct core) and the reversible ischemic penumbra shows great promise for stroke treatment. Recent advances in penumbral imaging technology may enable a phase III trial of an intravenous thrombolytic to be performed beyond 4.5 hours using techniques to select patients with penumbral tissue.

    View details for DOI 10.1016/j.nic.2011.01.002

    View details for Web of Science ID 000292007900006

    View details for PubMedID 21640298

  • National Stroke Association Recommendations for Systems of Care for Transient Ischemic Attack ANNALS OF NEUROLOGY Johnston, S. C., Albers, G. W., Gorelick, P. B., Cumbler, E., Klingman, J., Ross, M. A., Briggs, M., Carlton, J., Sloan, E. P., Vaince, U. 2011; 69 (5): 872-877

    Abstract

    Transient ischemic attacks (TIAs) are common and portend a high short-term risk of stroke. Evidence-based recommendations for the urgent evaluation and treatment of patients with TIA have been published. However, implementation of these recommendations reliably and consistently will require changes in the systems of care established for TIA. The National Stroke Association convened a multidisciplinary panel of experts to develop recommendations for the essential components of systems of care at hospitals to improve the quality of care provided to patients with TIA. The panel recommends that hospitals establish standardized protocols to assure rapid and complete evaluation and treatment for patients with TIA, with particular attention to urgency and close observation in patients at high risk of stroke.

    View details for DOI 10.1002/ana.22332

    View details for Web of Science ID 000290156300014

    View details for PubMedID 21391236

  • A 5-Item Scale to Predict Stroke Outcome After Cortical Middle Cerebral Artery Territory Infarction Validation From Results of the Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution (DEFUSE) Study STROKE Vora, N. A., Shook, S. J., Schumacher, H. C., Tievsky, A. L., Albers, G. W., Wechsler, L. R., Gupta, R. 2011; 42 (3): 645-649

    Abstract

    Various clinical, laboratory, and radiographic parameters have been identified as predictors of outcome for ischemic stroke. The purpose of this study was to combine these parameters into a validated scale for outcome prognostication in patients with a middle cerebral artery territory infarction.We retrospectively reviewed 129 patients over a 2-year period and considered demographic, clinical, laboratory, and radiographic parameters as potential predictors of outcome. Inclusion criteria were unilateral hemispheric infarcts within the middle cerebral artery territory >15 mm in diameter. Our primary outcome measure was a favorable recovery defined as a modified Rankin Score was ≤2 at 30 days. A multivariable model was used to determine independent predictors of outcome and weighted to create a 5-item scale to predict stroke recovery. External validation of this model was done using data from the Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution (DEFUSE) study.The 5 independent predictors of outcome were as follows: age (OR, 1.09; 95% CI, 1.03 to 1.14; P=0.001), National Institutes of Health Stroke Scale score (OR, 1.17; 95% CI, 1.06 to 1.30; P=0.003), infarct volume (OR, 1.01; 95% CI, 1.00 to 1.02; P=0.03), admission white blood cell count (8.5×10(3)/mm(3); OR, 1.16; 95% CI, 1.03 to 1.27; P=0.04), and presence of hyperglycemia (OR, 4.2; 95% CI, 1.1 to 16.4; P=0.04). Combining these variables into a point scale significantly improved prediction over the individual variables accounted alone as evidenced by the area underneath the receiver operating curve (OR, 0.91; 95% CI, 0.87 to 0.96; P=0.0001). When applied to the DEFUSE study population for validation, the model achieved a sensitivity of 83% and specificity of 86%.With validation from a prospective study of similar patients, this model serves as a useful clinical and research tool to predict stroke recovery after cortical middle cerebral artery territory infarction.

    View details for DOI 10.1161/STROKEAHA.110.596312

    View details for Web of Science ID 000287479401453

    View details for PubMedID 21273564

  • TIA Clinic Triage Strategy Reduces the Cost of TIA Evaluation International Stroke Conference Mlynash, M., Castle, J., Olivot, J., Wolford, C., Schwartz, N. E., Lansberg, M. G., Edwards, G., Kemp, S., Albers, G. W. LIPPINCOTT WILLIAMS & WILKINS. 2011: E250–E250

    View details for Web of Science ID 000287479401072

  • Worse Stroke Outcome In Atrial Fibrillation Links To More Severe Hypoperfusion International Stroke Conference Tu, H. T., Campbell, B. C., Christensen, S., De Silva, D. A., Parsons, M. W., Churilov, L., Olivot, J., Lansberg, M. G., Mlynash, M., Straka, M., Bammer, R., Albers, G. W., Desmond, P. M., Donnan, G. A., Davis, S. M. LIPPINCOTT WILLIAMS & WILKINS. 2011: E119–E119

    View details for Web of Science ID 000287479400248

  • The Combination Of Reperfusion And Recanalization Predicts Favorable Outcome Better Than Reperfusion Or Recanalization Alone In Target Mismatch Patients International Stroke Conference Lee, J., Lansberg, M. G., Mlynash, M., De Silva, D. A., Christensen, S., Straka, M., Campbell, B. C., Bammer, R., Olivot, J., Desmond, P., Donnan, G. A., Davis, S. M., Albers, G. W. LIPPINCOTT WILLIAMS & WILKINS. 2011: E66–E67

    View details for Web of Science ID 000287479400088

  • Higher rCBV Values In The PWI/DWI Mismatch Area Predict Favorable Clinical Outcome In Acute Ischemic Stroke International Stroke Conference Lee, J., Lansberg, M. G., Mlynash, M., Straka, M., Bammer, R., Olivot, J., Kemp, S., Albers, G. W. LIPPINCOTT WILLIAMS & WILKINS. 2011: E112–E112

    View details for Web of Science ID 000287479400228

  • Mri Based Tia Triage Study International Stroke Conference Wolford, C., Mlynash, M., Schwartz, N. E., Purushotham, A., Lansberg, M., Kemp, S., Albers, G. W., Olivot, J. LIPPINCOTT WILLIAMS & WILKINS. 2011: E210–E210

    View details for Web of Science ID 000287479400572

  • The Acute Diffusion Lesion Reliably Represents Infarct Core: Clinically Relevant Reversibility Is Rare International Stroke Conference Campbell, B. C., Purushotham, A., Christensen, S., Desmond, P. M., Nagakane, Y., Parsons, M. W., Lansberg, M. G., Mlynash, M., Straka, M., De Silva, D. A., Olivot, J., Bammer, R., Albers, G. W., Donnan, G. A., Davis, S. M. LIPPINCOTT WILLIAMS & WILKINS. 2011: E71–E71

    View details for Web of Science ID 000287479400102

  • Postthrombolysis hemorrhage risk is affected by stroke assessment bias between hemispheres NEUROLOGY Audebert, H. J., Singer, O. C., Gotzler, B., Vatankhah, B., Boy, S., Fiehler, J., Lansberg, M. G., Albers, G. W., Kastrup, A., Rovira, A., Gass, A., Rosso, C., Derex, L., Kim, J. S., Heuschmann, P. 2011; 76 (7): 629-636

    Abstract

    Stroke symptoms in right hemispheric stroke tend to be underestimated in clinical assessment scales, resulting in greater infarct volumes in right as compared to left hemispheric strokes despite similar clinical stroke severity. We hypothesized that patients with right hemispheric nonlacunar stroke are at higher risk for secondary intracerebral hemorrhage after thrombolysis despite similar stroke severity.We analyzed data of 2 stroke cohorts with CT-based and MRI-based imaging before thrombolysis. Initial stroke severity was measured with the NIH Stroke Scale (NIHSS). Lacunar strokes were excluded through either the presence of cortical symptoms (CT cohort) or restriction to patients with prestroke diffusion-weighted imaging (DWI) lesion size >3.75 mL (MRI cohort). Probabilities of having a parenchymal hematoma were determined using multivariate logistic regression.A total of 392 patients in the CT cohort and 400 patients in the MRI cohort were evaluated. Although NIHSS scores were similar in strokes of both hemispheres (median NIHSS: CT: 15 vs 13, MRI: 14 vs 16), the frequencies of parenchymal hematoma were higher in right hemispheric compared to left hemispheric strokes (CT: 12.4% vs 5.7%, MRI: 10.4% vs 6.8%). After adjustment for potential confounders (but not pretreatment lesion volume), the probability of parenchymal hematoma was higher in right hemispheric nonlacunar strokes (CT: odds ratio [OR] 2.3; 95% confidence interval [CI] 1.08-4.89; p = 0.032) and showed a borderline significant effect in the MRI cohort (OR 2.1; 95% CI 0.98-4.49; p = 0.057). Adjustment for pretreatment DWI lesion size eliminated hemispheric differences in hemorrhage risk.Higher hemorrhage rates in right hemispheric nonlacunar strokes despite similar stroke severity may be caused by clinical underestimation of the proportion of tissue at bleeding risk.

    View details for DOI 10.1212/WNL.0b013e31820ce505

    View details for Web of Science ID 000287363800010

    View details for PubMedID 21248275

  • Diffusion-perfusion MRI for triaging transient ischemic attack and acute cerebrovascular syndromes CURRENT OPINION IN NEUROLOGY Olivot, J., Albers, G. W. 2011; 24 (1): 44-49

    Abstract

    Time from symptom onset to treatment is considered to be the key variable that influences the indication of recanalization therapy for treatment of acute brain infarction. Symptom duration less than 24 h defines transient ischemic attack (TIA). The evolution of multimodal brain MRI demonstrates that neuroimaging findings of tissue injury may be more important predictors of clinical outcomes than arbitrary time thresholds.Preliminaries studies suggest that stroke victims with a significant penumbra estimated by the diffusion/perfusion mismatch on MRI benefit from thrombolysis beyond the currently recommended time window of 4.5 h. New software programs can automatically produce reliable perfusion and diffusion maps for use in clinical practice. Combined diffusion and perfusion MRI reveals an acute ischemic lesion in about 60% of TIA patients. Patients with transient symptoms and a restricted diffusion lesion on MRI are considered by the American Heart Association (AHA) scientific committee to have suffered a brain infarction and have a very high risk of early stroke recurrence.Multimodal MRI provides critical real-time information about ongoing tissue injury as well as the risk of additional ischemic damage. It is becoming an essential tool for the diagnosis, management and triage of acute TIA and brain infarction.

    View details for DOI 10.1097/WCO.0b013e328341f8a5

    View details for Web of Science ID 000285742400008

    View details for PubMedID 21157338

  • Fluid-Attenuated Inversion Recovery Hyperintensity in Acute Ischemic Stroke May Not Predict Hemorrhagic Transformation CEREBROVASCULAR DISEASES Campbell, B. C., Costello, C., Christensen, S., Ebinger, M., Parsons, M. W., Desmond, P. M., Barber, P. A., Butcher, K. S., Levi, C. R., De Silva, D. A., Lansberg, M. G., Mlynash, M., Olivot, J., Straka, M., Bammer, R., Albers, G. W., Donnan, G. A., Davis, S. M. 2011; 32 (4): 401-405

    Abstract

    Fluid-attenuated inversion recovery (FLAIR) hyperintensity within an acute cerebral infarct may reflect delayed onset time and increased risk of hemorrhage after thrombolysis. Given the important implications for clinical practice, we examined the prevalence of FLAIR hyperintensity in patients 3-6 h from stroke onset and its relationship to parenchymal hematoma (PH).Baseline DWI and FLAIR imaging with subsequent hemorrhage detection (ECASS criteria) were prospectively obtained in patients 3-6 h after stroke onset from the pooled EPITHET and DEFUSE trials. FLAIR hyperintensity within the region of the acute DWI lesion was rated qualitatively (dichotomized as visually obvious or subtle (i.e. only visible after careful windowing)) and quantitatively (using relative signal intensity (RSI)). The association of FLAIR hyperintensity with hemorrhage was then tested alongside established predictors (very low cerebral blood volume (VLCBV) and diffusion (DWI) lesion volume) in logistic regression analysis.There were 49 patients with pre-treatment FLAIR imaging (38 received tissue plasminogen activator (tPA), 5 developed PH). FLAIR hyperintensity within the region of acute DWI lesion occurred in 48/49 (98%) patients, was obvious in 18/49 (37%) and subtle in 30/49 (61%). Inter-rater agreement was 92% (κ = 0.82). The prevalence of obvious FLAIR hyperintensity did not differ between studies obtained in the 3-4.5 h and 4.5-6 h time periods (40% vs. 33%, p = 0.77). PH was poorly predicted by obvious FLAIR hyperintensity (sensitivity 40%, specificity 64%, positive predictive value 11%). In univariate logistic regression, VLCBV (p = 0.02) and DWI lesion volume (p = 0.03) predicted PH but FLAIR lesion volume (p = 0.87) and RSI (p = 0.11) did not. In ordinal logistic regression for hemorrhage grade adjusted for age and baseline stroke severity (NIHSS), increased VLCBV (p = 0.002) and DWI lesion volume (p = 0.003) were associated with hemorrhage but FLAIR lesion volume (p = 0.66) and RSI (p = 0.35) were not.Visible FLAIR hyperintensity is almost universal 3-6 h after stroke onset and did not predict subsequent hemorrhage in this dataset. Our findings question the value of excluding patients with FLAIR hyperintensity from reperfusion therapies. Larger studies are required to clarify what implications FLAIR-positive lesions have for patient selection.

    View details for DOI 10.1159/000331467

    View details for Web of Science ID 000299642300014

    View details for PubMedID 21986096

    View details for PubMedCentralID PMC3214893

  • Guidelines for the Prevention of Stroke in Patients With Stroke or Transient Ischemic Attack A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association STROKE Furie, K. L., Kasner, S. E., Adams, R. J., Albers, G. W., Bush, R. L., Fagan, S. C., Halperin, J. L., Johnston, S. C., Katzan, I., Kernan, W. N., Mitchell, P. H., Ovbiagele, B., Palesch, Y. Y., Sacco, R. L., Schwamm, L. H., Wassertheil-Smoller, S., Turan, T. N., Wentworth, D. 2011; 42 (1): 227-276

    Abstract

    The aim of this updated statement is to provide comprehensive and timely evidence-based recommendations on the prevention of ischemic stroke among survivors of ischemic stroke or transient ischemic attack. Evidence-based recommendations are included for the control of risk factors, interventional approaches for atherosclerotic disease, antithrombotic treatments for cardioembolism, and the use of antiplatelet agents for noncardioembolic stroke. Further recommendations are provided for the prevention of recurrent stroke in a variety of other specific circumstances, including arterial dissections; patent foramen ovale; hyperhomocysteinemia; hypercoagulable states; sickle cell disease; cerebral venous sinus thrombosis; stroke among women, particularly with regard to pregnancy and the use of postmenopausal hormones; the use of anticoagulation after cerebral hemorrhage; and special approaches to the implementation of guidelines and their use in high-risk populations.

    View details for DOI 10.1161/STR.0b013e3181f7d043

    View details for Web of Science ID 000285636400046

    View details for PubMedID 20966421

  • Study Design of the CLOSURE I Trial A Prospective, Multicenter, Randomized, Controlled Trial to Evaluate the Safety and Efficacy of the STARFlex Septal Closure System Versus Best Medical Therapy in Patients With Stroke or Transient Ischemic Attack Due to Presumed Paradoxical Embolism Through a Patent Foramen Ovale STROKE Furlan, A. J., Reisman, M., Massaro, J., Mauri, L., Adams, H., Albers, G. W., Felberg, R., Herrmann, H., Kar, S., Landzberg, M., Raizner, A., Wechsler, L. 2010; 41 (12): 2872-2883

    Abstract

    Some strokes of unknown etiology may be the result of a paradoxical embolism traversing through a nonfused foramen ovale (patent foramen ovale [PFO]). The utility of percutaneously placed devices for treatment of patients with cryptogenic stroke or transient ischemic attack (TIA) and PFO is unknown. In addition, there are no clear data about the utility of medical interventions or other surgical procedures in this situation. Despite limited data, many patients are being treated with PFO closure devices. Thus, there is a strong need for clinical trials that test the potential efficacy of PFO occlusive devices in this situation. To address this gap in medical knowledge, we designed the CLOSURE I trial, a randomized, clinical trial comparing the use of a percutaneously placed PFO occlusive device and best medical therapy versus best medical therapy alone for prevention of recurrent ischemic neurologic symptoms among persons with TIA or ischemic stroke.This prospective, multicenter, randomized, controlled trial has finished enrollment. Two-year follow-up for all 910 patients is required. The primary end point is the 2-year incidence of stroke or TIA, all-cause mortality for the first 30 days, and neurologic mortality from ≥ 31 days of follow-up, as adjudicated by a panel of physicians who are unaware of treatment allocation. This article describes the rationale and study design of CLOSURE I.This trial should provide information as to whether the STARFlex septal closure system is safe and more effective than best medical therapy alone in preventing recurrent stroke/TIA and mortality in patients with PFO and whether the STARFlex septal closure device can demonstrate superiority compared with best medical therapy alone. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT00201461.

    View details for DOI 10.1161/STROKEAHA.110.593376

    View details for Web of Science ID 000284685600032

    View details for PubMedID 21051670

  • MRI Profile of the Perihematomal Region in Acute Intracerebral Hemorrhage STROKE Olivot, J., Mlynash, M., Kleinman, J. T., Straka, M., Venkatasubramanian, C., Bammer, R., Moseley, M. E., Albers, G. W., Wijman, C. A. 2010; 41 (11): 2681-2683

    Abstract

    The pathophysiology of the presumed perihematomal edema immediately surrounding an acute intracerebral hemorrhage is poorly understood, and its composition may influence clinical outcome. Method-Twenty-three patients from the Diagnostic Accuracy of MRI in Spontaneous intracerebral Hemorrhage (DASH) study were prospectively enrolled and studied with MRI. Perfusion-weighted imaging, diffusion-weighted imaging, and fluid-attenuated inversion recovery sequences were coregistered. TMax (the time when the residue function reaches its maximum) and apparent diffusion coefficient values in the presumed perihematomal edema regions of interest were compared with contralateral mirror and remote ipsilateral hemispheric regions of interest.Compared with mirror and ipsilateral hemispheric regions of interest, TMax (the time when the residue function reaches its maximum) and apparent diffusion coefficient were consistently increased in the presumed perihematomal edema. Two thirds of the patients also exhibited patchy regions of restricted diffusion in the presumed perihematomal edema.The MRI profile of the presumed perihematomal edema in acute intracerebral hemorrhage exhibits delayed perfusion and increased diffusivity mixed with areas of reduced diffusion.

    View details for DOI 10.1161/STROKEAHA.110.590638

    View details for PubMedID 20947849

  • Real-Time Diffusion-Perfusion Mismatch Analysis in Acute Stroke JOURNAL OF MAGNETIC RESONANCE IMAGING Straka, M., Albers, G. W., Bammer, R. 2010; 32 (5): 1024-1037

    Abstract

    Diffusion-perfusion mismatch can be used to identify acute stroke patients that could benefit from reperfusion therapies. Early assessment of the mismatch facilitates necessary diagnosis and treatment decisions in acute stroke. We developed the RApid processing of PerfusIon and Diffusion (RAPID) for unsupervised, fully automated processing of perfusion and diffusion data for the purpose of expedited routine clinical assessment. The RAPID system computes quantitative perfusion maps (cerebral blood volume, CBV; cerebral blood flow, CBF; mean transit time, MTT; and the time until the residue function reaches its peak, T(max)) using deconvolution of tissue and arterial signals. Diffusion-weighted imaging/perfusion-weighted imaging (DWI/PWI) mismatch is automatically determined using infarct core segmentation of ADC maps and perfusion deficits segmented from T(max) maps. The performance of RAPID was evaluated on 63 acute stroke cases, in which diffusion and perfusion lesion volumes were outlined by both a human reader and the RAPID system. The correlation of outlined lesion volumes obtained from both methods was r(2) = 0.99 for DWI and r(2) = 0.96 for PWI. For mismatch identification, RAPID showed 100% sensitivity and 91% specificity. The mismatch information is made available on the hospital's PACS within 5-7 min. Results indicate that the automated system is sufficiently accurate and fast enough to be used for routine care as well as in clinical trials.

    View details for DOI 10.1002/jmri.22338

    View details for Web of Science ID 000284190200002

    View details for PubMedID 21031505

    View details for PubMedCentralID PMC2975404

  • Addition of brain and carotid imaging to the ABCD(2) score to identify patients at early risk of stroke after transient ischaemic attack: a multicentre observational study LANCET NEUROLOGY Merwick, A., Albers, G. W., Amarenco, P., Arsava, E. M., Ay, H., Calvet, D., Coutts, S. B., Cucchiara, B. L., Demchuk, A. M., Furie, K. L., Giles, M. F., Labreuche, J., Lavallee, P. C., Mas, J., Olivot, J. M., Purroy, F., Rothwell, P. M., Saver, J. L., Sheehan, O. C., Stack, J. P., Walsh, C., Kelly, P. J. 2010; 9 (11): 1060-1069

    Abstract

    The ABCD² score improves stratification of patients with transient ischaemic attack by early stroke risk. We aimed to develop two new versions of the score: one that was based on preclinical information and one that was based on imaging and other secondary care assessments.We analysed pooled data from patients with clinically defined transient ischaemic attack who were investigated while in secondary care. Items that contribute to the ABCD² score (age, blood pressure, clinical weakness, duration, and diabetes), other clinical variables, carotid stenosis, and abnormal acute diffusion-weighted imaging (DWI) were recorded and were included in multivariate logistic regression analysis of stroke occurrence at early time intervals after onset of transient ischaemic attack. Scores based on the findings of this analysis were validated in patients with transient ischaemic attack from two independent population-based cohorts.3886 patients were included in the study: 2654 in the derivation sample and 1232 in the validation sample. We derived the ABCD³ score (range 0-9 points) by assigning 2 points for dual transient ischaemic attack (an earlier transient ischaemic attack within 7 days of the index event). C statistics (which indicate discrimination better than chance at >0·5) for the ABCD³ score were 0·78 at 2 days, 0·80 at 7 days, 0·79 at 28 days, and 0·77 at 90 days, compared with C statistics for the ABCD² score of 0·71 at 2 days (p=0·083), 0·71 at 7 days (p=0·012), 0·71 at 28 days (p=0·021), and 0·69 at 90 days (p=0·018). We included stenosis of at least 50% on carotid imaging (2 points) and abnormal DWI (2 points) in the ABCD³-imaging (ABCD³-I) score (0-13 points). C statistics for the ABCD³-I score were 0·90 at 2 days (compared with ABCD² score p=0·035), 0·92 at 7 days (p=0·001), 0·85 at 28 days (p=0·028), and 0·79 at 90 days (p=0·073). The 90-day net reclassification improvement compared with ABCD² was 29·1% for ABCD³ (p=0·0003) and 39·4% for ABCD³-I (p=0·034). In the validation sample, the ABCD³ and ABCD³-I scores predicted early stroke at 7, 28, and 90 days. However, discrimination and net reclassification of patients with early stroke were similar with ABCD³ compared with ABCD².The ABCD³-I score can improve risk stratification after transient ischaemic attack in secondary care settings. However, use of ABCD³ cannot be recommended without further validation.Health Research Board of Ireland, Irish Heart Foundation, and Irish National Lottery.

    View details for DOI 10.1016/S1474-4422(10)70240-4

    View details for Web of Science ID 000284246800014

    View details for PubMedID 20934388

  • Capsular warning syndrome caused by middle cerebral artery stenosis JOURNAL OF THE NEUROLOGICAL SCIENCES Lee, J., Albers, G. W., Marks, M. P., Lansberg, M. G. 2010; 296 (1-2): 115-120

    Abstract

    The capsular warning syndrome is a term used to describe recurrent stereotyped lacunar transient ischemic attacks (TIAs). This syndrome is associated with a high risk of developing a completed stroke. The presumed mechanism for this syndrome is angiopathy of a lenticulostriate artery. We describe the case of a 33-year-old man who presented with the capsular warning syndrome who was successfully treated with angioplasty. The patient's capsular warning syndrome manifested as recurrent episodes of transient left hemiparesis. Symptoms recurred one to three times daily despite treatment with antithrombotics. Cerebral angiography demonstrated stenosis of the right middle cerebral artery (MCA) with decreased flow to a dominant lenticulostriate artery. Angioplasty of the right middle cerebral artery increased flow to the lenticulostriate artery and the TIAs resolved following the procedure. In select cases intracranial angioplasty, may be an effective treatment for patients with capsular warning syndrome.

    View details for DOI 10.1016/j.jns.2010.06.003

    View details for PubMedID 20619422

  • Addition of Brain Infarction to the ABCD(2) Score (ABCD(2)I) A Collaborative Analysis of Unpublished Data on 4574 Patients STROKE Giles, M. F., Albers, G. W., Amarenco, P., Arsava, M. M., Asimos, A., Ay, H., Calvet, D., Coutts, S., Cucchiara, B. L., Demchuk, A. M., Johnston, S. C., Kelly, P. J., Kim, A. S., Labreuche, J., Lavallee, P. C., Mas, J., Merwick, A., Olivot, J. M., Purroy, F., Rosamond, W. D., Sciolla, R., Rothwell, P. M. 2010; 41 (9): 1907-1913

    Abstract

    The ABCD system was developed to predict early stroke risk after transient ischemic attack. Incorporation of brain imaging findings has been suggested, but reports have used inconsistent methods and been underpowered. We therefore performed an international, multicenter collaborative study of the prognostic performance of the ABCD(2) score and brain infarction on imaging to determine the optimal weighting of infarction in the score (ABCD(2)I).Twelve centers provided unpublished data on ABCD(2) scores, presence of brain infarction on either diffusion-weighted imaging or CT, and follow-up in cohorts of patients with transient ischemic attack diagnosed by World Health Organization criteria. Optimal weighting of infarction in the ABCD(2)I score was determined using area under the receiver operating characteristic curve analyses and random effects meta-analysis.Among 4574 patients with TIA, acute infarction was present in 884 (27.6%) of 3206 imaged with diffusion-weighted imaging and new or old infarction was present in 327 (23.9%) of 1368 imaged with CT. ABCD(2) score and presence of infarction on diffusion-weighted imaging or CT were both independently predictive of stroke (n=145) at 7 days (after adjustment for ABCD(2) score, OR for infarction=6.2, 95% CI=4.2 to 9.0, overall; 14.9, 7.4 to 30.2, for diffusion-weighted imaging; 4.2, 2.6 to 6.9, for CT; all P<0.001). Incorporation of infarction in the ABCD(2)I score improved predictive power with an optimal weighting of 3 points for infarction on CT or diffusion-weighted imaging. Pooled areas under the curve increased from 0.66 (0.53 to 0.78) for the ABCD(2) score to 0.78 (0.72 to 0.85) for the ABCD(2)I score.In secondary care, incorporation of brain infarction into the ABCD system (ABCD(2)I score) improves prediction of stroke in the acute phase after transient ischemic attack.

    View details for DOI 10.1161/STROKEAHA.110.578971

    View details for Web of Science ID 000281503000011

    View details for PubMedID 20634480

  • Agreement Regarding Diagnosis of Transient Ischemic Attack Fairly Low Among Stroke-Trained Neurologists STROKE Castle, J., Mlynash, M., Lee, K., Caulfield, A. F., Wolford, C., Kemp, S., Hamilton, S., Albers, G. W., Olivot, J. 2010; 41 (7): 1367-1370

    Abstract

    Agreement between physicians to define the likelihood of a transient ischemic attack (TIA) remains poor. Several studies have compared neurologists with nonneurologists, and neurologists among themselves, but not between fellowship-trained stroke neurologists. We investigated the diagnostic agreement in 55 patients with suspected TIA.The history and physical examination findings of 55 patients referred to the Stanford TIA clinic from the Stanford emergency room were blindly reviewed by 3 fellowship-trained stroke neurologists who had no knowledge of any test results or patient outcomes. Each patient's presentation was rated as to the likelihood that the presentation was consistent with TIA. We used 3 different scales (2-, 3-, and 4-point scales) to define TIA likelihood. We assessed global agreement between the raters and evaluated the biases related to individual raters and scale type.The agreement between fellowship-trained stroke neurologists remained poor regardless of the rating system used and the statistical test used to measure it. Difference in rating bias among all raters was significant for each scale: P=0.001, 0.012, and <0.001. In addition, for each reviewer, the rate of labeling an event an "unlikely TIA" progressively decreased with the number of points that composed the scale.TIA remains a highly subjective diagnosis, even among stroke subspecialists. The use of confirmatory testing beyond clinical judgment is needed to help solidify the diagnosis. Caution should be used when diagnosing an event as a possible TIA.

    View details for DOI 10.1161/STROKEAHA.109.577650

    View details for Web of Science ID 000279272200013

    View details for PubMedID 20508192

  • Combined Arterial Spin Label and Dynamic Susceptibility Contrast Measurement of Cerebral Blood Flow MAGNETIC RESONANCE IN MEDICINE Zaharchuk, G., Straka, M., Marks, M. P., Albers, G. W., Moseley, M. E., Bammer, R. 2010; 63 (6): 1548-1556

    Abstract

    Dynamic susceptibility contrast (DSC) and arterial spin labeling (ASL) are both used to measure cerebral blood flow (CBF), but neither technique is ideal. Absolute DSC-CBF quantitation is challenging due to many uncertainties, including partial- volume errors and nonlinear contrast relaxivity. ASL can measure quantitative CBF in regions with rapidly arriving flow, but CBF is underestimated in regions with delayed arrival. To address both problems, we have derived a patient-specific correction factor, the ratio of ASL- and DSC-CBF, calculated only in short-arrival-time regions (as determined by the DSC-based normalized bolus arrival time [Tmax]). We have compared the combined CBF method to gold-standard xenon CT in 20 patients with cerebrovascular disease, using a range of Tmax threshold levels. Combined ASL and DSC CBF demonstrated quantitative accuracy as good as the ASL technique but with improved correlation in voxels with long Tmax. The ratio of MRI-based CBF to xenon CT CBF (coefficient of variation) was 90 +/- 30% (33%) for combined ASL and DSC CBF, 43 +/- 21% (47%) for DSC, and 91 +/- 31% (34%) for ASL (Tmax threshold 3 sec). These findings suggest that combining ASL and DSC perfusion measurements improves quantitative CBF measurements in patients with cerebrovascular disease.

    View details for DOI 10.1002/mrm.22329

    View details for PubMedID 20512858

  • Using advanced MRI techniques for patient selection before acute stroke therapy. Current treatment options in cardiovascular medicine Olivot, J., Albers, G. W. 2010; 12 (3): 230-239

    Abstract

    OPINION STATEMENT: Results of acute MRI studies may help guide the management of acute stroke. Patients with a malignant MRI pattern may be poor candidates for reperfusion therapies yet may benefit from hemicraniectomy. Preliminary data suggest that patients with a carefully identified diffusion weighted imaging (DWI)/perfusion weighted imaging (PWI) mismatch may benefit from intravenous recombinant tissue plasminogen activator in a 3- to 6-hour time window; however, confirmatory studies with larger sample sizes are required before clinical use of this strategy can be generally recommended. Post hoc analyses of recent studies suggest that PWI techniques that use a threshold to exclude benign oligemia from penumbra and DWI techniques that use apparent diffusion coefficient thresholds to exclude reversible DWI lesions to distinguish the ischemic core from penumbra appear to provide more accurate determinations of the volume of salvageable tissue. New automated software programs are now implementing these techniques to generate quantitative PWI and DWI maps within minutes. Prospective trials are in progress to investigate these new techniques. The results of these studies will further refine the application of MRI to select patients for acute recanalization therapies.

    View details for DOI 10.1007/s11936-010-0072-y

    View details for PubMedID 20842546

  • Dabigatran Challenges Warfarin's Superiority for Stroke Prevention in Atrial Fibrillation STROKE Schwartz, N. E., Albers, G. W. 2010; 41 (6): 1307-1309

    View details for DOI 10.1161/STROKEAHA.110.584557

    View details for Web of Science ID 000278019400041

    View details for PubMedID 20395603

  • Time to treatment with intravenous alteplase and outcome in stroke: an updated pooled analysis of ECASS, ATLANTIS, NINDS, and EPITHET trials LANCET Lees, K. R., Bluhmki, E., von Kummer, R., Brott, T. G., Toni, D., Grotta, J. C., Albers, G. W., Kaste, M., Marler, J. R., Hamilton, S. A., Tilley, B. C., Davis, S. M., Donnan, G. A., Hacke, W., Ninds, E. A. 2010; 375 (9727): 1695-1703

    Abstract

    Early administration of intravenous recombinant tissue plasminogen activator (rt-PA) after ischaemic stroke improves outcome. Previous analysis of combined data from individual patients suggested potential benefit beyond 3 h from stroke onset. We re-examined the effect of time to treatment with intravenous rt-PA (alteplase) on therapeutic benefit and clinical risk by adding recent trial data to the analysis.We added data from ECASS III (821 patients) and EPITHET (100 patients) to a pool of common data elements from six other trials of alteplase for acute stroke (2775 patients). We used multivariate logistic regression to assess the relation of stroke onset to start of treatment (OTT) with treatment on favourable 3-month outcome (defined as modified Rankin score 0-1), mortality, and occurrence and outcome of clinically relevant parenchymal haemorrhage. The presence of an arterial occlusion was inferred from the patient's symptoms and absence of haemorrhage or other causes of ischaemic stroke. Vascular imaging was not a requirement in the trials. All patients with confirmed OTT within 360 min were included in the analysis.Treatment was started within 360 min of stroke onset in 3670 patients randomly allocated to alteplase (n=1850) or to placebo (n=1820). Odds of a favourable 3-month outcome increased as OTT decreased (p=0.0269) and no benefit of alteplase treatment was seen after around 270 min. Adjusted odds of a favourable 3-month outcome were 2.55 (95% CI 1.44-4.52) for 0-90 min, 1.64 (1.12-2.40) for 91-180 min, 1.34 (1.06-1.68) for 181-270 min, and 1.22 (0.92-1.61) for 271-360 min in favour of the alteplase group. Large parenchymal haemorrhage was seen in 96 (5.2%) of 1850 patients assigned to alteplase and 18 (1.0%) of 1820 controls, with no clear relation to OTT (p=0.4140). Adjusted odds of mortality increased with OTT (p=0.0444) and were 0.78 (0.41-1.48) for 0-90 min, 1.13 (0.70-1.82) for 91-180 min, 1.22 (0.87-1.71) for 181-270 min, and 1.49 (1.00-2.21) for 271-360 min.Patients with ischaemic stroke selected by clinical symptoms and CT benefit from intravenous alteplase when treated up to 4.5 h. To increase benefit to a maximum, every effort should be taken to shorten delay in initiation of treatment. Beyond 4.5 h, risk might outweigh benefit.None.

    View details for Web of Science ID 000277890200031

    View details for PubMedID 20472172

  • Validation of the Malignant Profile in the DEFUSE-EPITHET Pooled Database International Stroke Conference Lee, J., Lansberg, M. G., Mlynash, M., De Silva, D. A., Christensen, S., Straka, M., Campbell, B. C., Bammer, R., Olivot, J., Donnan, G. A., Davis, S. M., Albers, G. W. LIPPINCOTT WILLIAMS & WILKINS. 2010: E258–E258

    View details for Web of Science ID 000276106100270

  • Factors Predicting the Presence of Acute Ischemic Lesions on Diffusion Weighted in the Stanford TIA Study (Two Aces) International Stroke Conference Olivot, J. M., Wolford, C., Mlynash, M., Castle, J., Lansberg, M., Schwartz, N., Kemp, S., Albers, G. W. LIPPINCOTT WILLIAMS & WILKINS. 2010: E273–E273

    View details for Web of Science ID 000276106100329

  • Diagnostic Accuracy of MRI in Spontaneous Intra-cerebral Hemorrhage (DASH): Initial Results International Stroke Conference Wijman, C. A., Snider, R. W., Venkatasubramanian, C., Caulfield, A. F., Buckwalter, M., Eyngorn, I., Fischbein, N., Gean, A., Schwartz, N., Lansberg, M., Mlynash, M., Kemp, S., Thai, D., Narayana, R. K., Marks, M., Bammer, R., Moseley, M., Albers, G. W. LIPPINCOTT WILLIAMS & WILKINS. 2010: E210–E211

    View details for Web of Science ID 000276106100102

  • Large and Severe Baseline PWI Volumes Predict Poor Response to Intravenous tPA vs. Placebo in the Pooled DEFUSE-EPITHET Database International Stroke Conference De Silva, D. A., Mlynash, M., Lansberg, M. G., Lee, J., Christensen, S., Straka, M., Campbell, B. C., Bammer, R., Olivot, J. M., Donnan, G. A., Davis, S. M., Albers, G. A. LIPPINCOTT WILLIAMS & WILKINS. 2010: E208–E208

    View details for Web of Science ID 000276106100092

  • Symptomatic Intracranial Hemorrhage Rates With IV tPA Treatment by Stroke Subtype International Stroke Conference De Silva, D. A., Thomalla, G., Oppenheim, C., Albers, G. W., Lansberg, M. G., Kang, D., Hjort, N., Liebeskind, D. S., Hao, Q., Neumann-Haefelin, T., Singer, O. C., Nighoghossian, N., Derex, L., Shara, N., Donnan, G. A., Davis, S. M., Kidwell, C. S. LIPPINCOTT WILLIAMS & WILKINS. 2010: E363–E363

    View details for Web of Science ID 000276106100673

  • DEFUSE and EPITHET: Two Different Studies With One Consistent Message International Stroke Conference Lansberg, M. G., Lee, J., Christensen, S., Straka, M., De Silva, D. A., Mlynash, M., Campbell, B. C., Bammer, R., Olivot, J., Davis, S. M., Donnan, G. A., Albers, G. W. LIPPINCOTT WILLIAMS & WILKINS. 2010: E295–E295

    View details for Web of Science ID 000276106100410

  • Optimal Definition of the Malignant Profile in the DEFUSE-EPITHET Pooled Database International Stroke Conference Mlynash, M., De Silva, D. A., Lansberg, M. G., Lee, J., Christensen, S., Straka, M., Campbell, B. C., Bammer, R., Olivot, J., Donnan, G. A., Davis, S. M., Albers, G. W. LIPPINCOTT WILLIAMS & WILKINS. 2010: E207–E207

    View details for Web of Science ID 000276106100088

  • Optimal Perfusion Thresholds for Prediction of Tissue Destined for Infarction in the Combined EPITHET and DEFUSE Dataset International Stroke Conference Christensen, S., Campbell, B. C., de la Ossa, N. P., Lansberg, M., Straka, M., De Silva, D. A., Nagakane, Y., Ogata, T., Mlynash, M., Bammer, R., Olivot, J., Desmond, P., Albers, G. W., Donnan, G. A., Davis, S. M. LIPPINCOTT WILLIAMS & WILKINS. 2010: E297–E297

    View details for Web of Science ID 000276106100416

  • Does Presence of Arterial Obstruction Influence the Treatment Effect of Intravenous tPA Over Placebo in the 3-6 Hour Time Window? International Stroke Conference De Silva, D. A., Churilov, L., Olivot, J. M., Christensen, S., Lansberg, M. G., Mlynash, M., Straka, M., Campbell, B. C., Bammer, R., Albers, G. W., Davis, S. M., Donnan, G. A. LIPPINCOTT WILLIAMS & WILKINS. 2010: E207–E208

    View details for Web of Science ID 000276106100091

  • Mismatch-Based Delayed Thrombolysis A Meta-Analysis STROKE Mishra, N. K., Albers, G. W., Davis, S. M., Donnan, G. A., Furlan, A. J., Hacke, W., Lees, K. R. 2010; 41 (1): E25-E33

    Abstract

    Clinical benefit from thrombolysis is reduced as stroke onset to treatment time increases. The use of "mismatch" imaging to identify patients for delayed treatment has face validity and has been used in case series and clinical trials. We undertook a meta-analysis of relevant trials to examine whether present evidence supports delayed thrombolysis among patients selected according to mismatch criteria.We collated outcome data for patients who were enrolled after 3 hours of stroke onset in thrombolysis trials and had mismatch on pretreatment imaging. We selected the trials on the basis of a systematic search of the Web of Knowledge. We compared favorable outcome, reperfusion and/or recanalization, mortality, and symptomatic intracerebral hemorrhage between the thrombolyzed and nonthrombolyzed groups of patients and the probability of a favorable outcome among patients with successful reperfusion and clinical findings for 3 to 6 versus 6 to 9 hours from poststroke onset. Results are expressed as adjusted odds ratios (a-ORs) with 95% CIs. Heterogeneity was explored by test statistics for clinical heterogeneity, I(2) (inconsistency), and L'Abbé plot.We identified articles describing the DIAS, DIAS II, DEDAS, DEFUSE, and EPITHET trials, giving a total of 502 mismatch patients thrombolyzed beyond 3 hours. The combined a-ORs for favorable outcomes were greater for patients who had successful reperfusion (a-OR=5.2; 95% CI, 3 to 9; I(2)=0%). Favorable clinical outcome was not significantly improved by thrombolysis (a-OR=1.3; 95% CI, 0.8 to 2.0; I(2)=20.9%). Odds for reperfusion/recanalization were increased among patients who received thrombolytic therapy (a-OR=3.0; 95% CI, 1.6 to 5.8; I(2)=25.7%). The combined data showed a significant increase in mortality after thrombolysis (a-OR=2.4; 95% CI, 1.2 to 4.9; I(2)=0%), but this was not confirmed when we excluded data from desmoteplase doses that were abandoned in clinical development (a-OR=1.6; 95% CI, 0.7 to 3.7; I(2)=0%). Symptomatic intracerebral hemorrhage was significantly increased after thrombolysis (a-OR=6.5; 95% CI, 1.2 to 35.4; I(2)=0%) but not significant after exclusion of abandoned doses of desmoteplase (a-OR=5.4; 95% CI, 0.9 to 31.8; I(2)=0%).Delayed thrombolysis amongst patients selected according to mismatch imaging is associated with increased reperfusion/recanalization. Recanalization/reperfusion is associated with improved outcomes. However, delayed thrombolysis in mismatch patients was not confirmed to improve clinical outcome, although a useful clinical benefit remains possible. Thrombolysis carries a significant risk of symptomatic intracerebral hemorrhage and possibly increased mortality. Criteria to diagnose mismatch are still evolving. Validation of the mismatch selection paradigm is required with a phase III trial. Pending these results, delayed treatment, even according to mismatch selection, cannot be recommended as part of routine care.

    View details for DOI 10.1161/STROKEAHA.109.566869

    View details for Web of Science ID 000273093400041

    View details for PubMedID 19926836

  • Stroke: more protection for patients with atrial fibrillation LANCET NEUROLOGY Albers, G. W. 2010; 9 (1): 2-4

    View details for Web of Science ID 000273199700002

    View details for PubMedID 20083021

  • Challenges in childhood arterial ischaemic stroke LANCET NEUROLOGY Massicotte, M. P., Bauman, M. E., Albers, G. W. 2009; 8 (12): 1079-1081

    View details for DOI 10.1016/S1474-4422(09)70269-8

    View details for Web of Science ID 000272106100005

    View details for PubMedID 19801205

  • Neurological Outcomes in Patients With Ischemic Stroke Receiving Enoxaparin or Heparin for Venous Thromboembolism Prophylaxis Subanalysis of the Prevention of VTE After Acute Ischemic Stroke With LMWH (PREVAIL) Study STROKE Kase, C. S., Albers, G. W., Bladin, C., Fieschi, C., Gabbai, A. A., O'Riordan, W., Pineo, G. F. 2009; 40 (11): 3532-3540

    Abstract

    The Prevention of VTE after Acute Ischemic Stroke with LMWH (PREVAIL) study demonstrated that enoxaparin was superior to unfractionated heparin (UFH) in preventing venous thromboembolism in patients with ischemic stroke and was associated with a small but statistically significant increase in extracranial hemorrhage rates. In this PREVAIL subanalysis, we evaluate the long-term neurological outcomes associated with the use of enoxaparin compared with UFH. We also determine predictors of stroke progression.Acute ischemic stroke patients aged >or=18 years, who could not walk unassisted, were randomized to receive enoxaparin (40 mg once daily) or UFH (5000 U every 12 hours) for 10 days. Patients were stratified according to baseline stroke severity using the National Institutes of Health Stroke Scale score. End points for this analysis included stroke progression (>or=4-point increase in National Institutes of Health Stroke Scale score), neurological outcomes up to 3 months postrandomization (assessed using National Institutes of Health Stroke Scale score and modified Rankin Scale score), and incidence of intracranial hemorrhage.Stroke progression occurred in 45 of 877 (5.1%) patients in the enoxaparin group and 42 of 872 (4.8%) of those receiving UFH. Similar improvements in National Institutes of Health Stroke Scale and modified Rankin Scale scores were observed in both groups over the 90-day follow-up period. Incidence of intracranial hemorrhage was comparable between groups (20 of 877 [2.3%] and 22 of 872 [2.5%] in enoxaparin and UFH groups, respectively). Baseline National Institutes of Health Stroke Scale score, hyperlipidemia, and Hispanic ethnicity were independent predictors of stroke progression.The clinical benefits associated with use of enoxaparin for venous thromboembolism prophylaxis in patients with acute ischemic stroke are not associated with poorer long-term neurological outcomes or increased rates of symptomatic intracranial hemorrhage compared with UFH.

    View details for DOI 10.1161/STROKEAHA.109.555003

    View details for Web of Science ID 000271160300021

    View details for PubMedID 19696423

  • Clinical and Radiographic Natural History of Cervical Artery Dissections JOURNAL OF STROKE & CEREBROVASCULAR DISEASES Schwartz, N. E., Vertinsky, A. T., Hirsch, K. G., Albers, G. W. 2009; 18 (6): 416-423

    Abstract

    Cervical artery dissection (CADsx) is a common cause of stroke in young patients, but long-term clinical and radiographic follow-up from a large population is lacking.Epidemiologic data, treatment, recurrence, and other features were extracted from the records of all patients seen at our stroke center with confirmed CAD during a 15-year period. A subset of cases was examined to provide detailed information about vessel status.In all, 177 patients (mean age 44.0 +/- 11.1 years) were identified, with the male patients being older than the female patients. Almost 60% of dissections were spontaneous, whereas the remainder involved some degree of head and/or neck trauma. More than 70% of patients were treated with anticoagulation. During follow-up (mean 18.2 months; 0-220 months) there were 15 cases (8.5%) of recurrent ischemic events, and two cases (1.1%) of a recurrent dissection. About half of recurrent stroke/transient ischemic attack events occurred within 2 weeks of presentation. There was no clear association between the choice of antithrombotic agent and recurrent ischemic events. Detailed analysis of imaging findings was performed in 51 cases. Some degree of recanalization was seen in 58.8% of patients overall, and was more frequent in women. The average time to total or near-total recanalization was 4.7 +/- 2.5 months. Patients with complete occlusions at presentation tended not to recanalize.This large series from a single institution highlights many of the features of CAD. A relatively benign course with low recurrence rate is supported, independent of the type and duration of antithrombotic therapy.

    View details for DOI 10.1016/j.jstrokecerebrovasdis.2008.11.016

    View details for Web of Science ID 000272114400002

    View details for PubMedID 19900642

  • Improving Dynamic Susceptibility Contrast MRI Measurement of Quantitative Cerebral Blood Flow using Corrections for Partial Volume and Nonlinear Contrast Relaxivity: A Xenon Computed Tomographic Comparative Study JOURNAL OF MAGNETIC RESONANCE IMAGING Zaharchuk, G., Bammer, R., Straka, M., Newbould, R. D., Rosenberg, J., Olivot, J., Mlynash, M., Lansberg, M. G., Schwartz, N. E., Marks, M. M., Albers, G. W., Moseley, M. E. 2009; 30 (4): 743-752

    Abstract

    To test whether dynamic susceptibility contrast MRI-based CBF measurements are improved with arterial input function (AIF) partial volume (PV) and nonlinear contrast relaxivity correction, using a gold-standard CBF method, xenon computed tomography (xeCT).Eighteen patients with cerebrovascular disease underwent xeCT and MRI within 36 h. PV was measured as the ratio of the area under the AIF and the venous output function (VOF) concentration curves. A correction was applied to account for the nonlinear relaxivity of bulk blood (BB). Mean CBF was measured with both techniques and regression analyses both within and between patients were performed.Mean xeCT CBF was 43.3 +/- 13.7 mL/100g/min (mean +/- SD). BB correction decreased CBF by a factor of 4.7 +/- 0.4, but did not affect precision. The least-biased CBF measurement was with BB but without PV correction (45.8 +/- 17.2 mL/100 g/min, coefficient of variation [COV] = 32%). Precision improved with PV correction, although absolute CBF was mildly underestimated (34.3 +/- 10.8 mL/100 g/min, COV = 27%). Between patients correlation was moderate even with both corrections (R = 0.53).Corrections for AIF PV and nonlinear BB relaxivity improve bolus MRI-based CBF maps. However, there remain challenges given the moderate between-patient correlation, which limit diagnostic confidence of such measurements in individual patients.

    View details for DOI 10.1002/jmri.21908

    View details for PubMedID 19787719

  • Geography, Structure, and Evolution of Diffusion and Perfusion Lesions in Diffusion and Perfusion Imaging Evaluation For Understanding Stroke Evolution (DEFUSE) STROKE Olivot, J., Mlynash, M., Thijs, V. N., Purushotham, A., Kemp, S., Lansberg, M. G., Wechsler, L., Gold, G. E., Bammer, R., Marks, M. P., Albers, G. W. 2009; 40 (10): 3245-3251

    Abstract

    The classical representation of acute ischemic lesions on MRI is a central diffusion-weighted imaging (DWI) lesion embedded in a perfusion-weighted imaging (PWI) lesion. We investigated spatial relationships between final infarcts and early DWI/PWI lesions before and after intravenous thrombolysis in the Diffusion and perfusion imaging Evaluation For Understanding Stroke Evolution (DEFUSE) study.Baseline and follow-up DWI and PWI lesions and 30-day fluid-attenuated inversion recovery scans of 32 patients were coregistered. Lesion geography was defined by the proportion of the DWI lesion superimposed by a Tmax (time when the residue function reaches its maximum) >4 seconds PWI lesion; Type 1: >50% overlap and Type 2: < or = 50% overlap. Three-dimensional structure was dichotomized into a single lesion (one DWI and one PWI lesion) versus multiple lesions. Lesion reversal was defined by the percentage of the baseline DWI or PWI lesion not superimposed by the early follow-up DWI or PWI lesion. Final infarct prediction was estimated by the proportion of the final infarct superimposed on the union of the DWI and PWI lesions.Single lesion structure with Type 1 geography was present in only 9 patients (28%) at baseline and 4 (12%) on early follow-up. In these patients, PWI and DWI lesions were more likely to correspond with the final infarcts. DWI reversal was greater among patients with Type 2 geography at baseline. Patients with multiple lesions and Type 2 geography at early follow-up were more likely to have early reperfusion.Before thrombolytic therapy in the 3- to 6-hour time window, Type 2 geography is predominant and is associated with DWI reversal. After thrombolysis, both Type 2 geography and multiple lesion structure are associated with reperfusion.

    View details for DOI 10.1161/STROKEAHA.109.558635

    View details for PubMedID 19679845

  • Stroke Therapy Academic Industry Roundtable (STAIR) Recommendations for Extended Window Acute Stroke Therapy Trials STROKE Saver, J. L., Albers, G. W., Dunn, B., Johnston, K. C., Fisher, M. 2009; 40 (7): 2594-2600

    Abstract

    The Stroke Therapy Academic Industry Roundtable (STAIR) meetings focus on helping to advance the development of acute stroke therapies. Further extending the time window for acute stroke therapies is an important endeavor for increasing the number of stroke patients who might benefit from treatment. The STAIR group recommends that future extended time window trials initially should focus on selected patient groups most likely to respond to investigational therapies and that penumbral imaging is one tool that may identify such patients. The control group in these trials should receive best locally available medical care; if regulatory approval for intravenous (i.v.) tPA is extended to 4.5 hours, then tPA will become the most appropriate comparator in trials conducted within this time window. In future well-designed extended window clinical trials randomization is appropriate and should not be precluded by using unproven treatment with intraarterial (i.a.) thrombolysis or mechanical devices. For proof of concept, extended time window, phase II trials of i.v. thrombolysis, or mechanical devices in which early recanalization/reperfusion is the primary end point, rescue therapy/bailout treatment with i.a. thrombolysis or devices may be acceptable. Statistical considerations and definitions of successful recanalization/reperfusion are suggested for these trials.

    View details for DOI 10.1161/STROKEAHA.109.552554

    View details for Web of Science ID 000267467900056

    View details for PubMedID 19478212

    View details for PubMedCentralID PMC2761073

  • Effect of Clopidogrel Added to Aspirin in Patients with Atrial Fibrillation NEW ENGLAND JOURNAL OF MEDICINE Connolly, S. J., Yusuf, S., Camm, J., Chrolavicius, S., Commerford, P., Flather, M., Hart, R. G., Hohnloser, S. H., Joyner, C., Pfeffer, M., Gaudin, C., Blumenthal, M., Marchese, C., Pogue, J., Hart, R., Hohnloser, S., Anand, I., Arthur, H., Avezum, A., BUDAJ, A., CEREMUZYNSKI, L., De Caterina, R., Diaz, R., Dorian, P., Flaker, G., Fox, K. A., Franzosi, M. G., Goldhaber, S., Golitsyn, S., Granger, C., Halon, D., Hermosillo, A., HUNT, D., Jansky, P., Karatzas, N., Keltai, M., Kozan, O., Lanas, F., Lau, P., Le Heuzey, J. Y., Lewis, B. S., Morais, J., Morillo, C., PAOLASSO, E., Peters, R. J., Pfisterer, M., Piegas, L., PIPILIS, A., Sitkei, E., Swedberg, K., Talajic, M., Valentin, V., Van Mieghem, W., Varigos, J., Ameriso, S., Atra, M., Avezum, A., Berwanger, O., Bonilla, C., Bornstein, N., BUDAJ, A., Chamiec, T., Chan, Y. K., Cottin, Y., Csiba, L., Cybulski, J., Czepiel, A., De Raedt, H., Diaz, R., Dvorakova, H., Eikelboom, J., Ergene, O., Fodor, G., Galli, M., Gardinale, E., Golitsyn, S., Granger, C., Gross, B., Goodfield, P., Halon, D., Happola, O., Healey, J., Himbert, D., HUNT, D., Jacobsson, F., Jansky, P., Kalvach, P., Karatzas, N., Keltai, M., Kies, B., Laine, M., Lam, A., Le Heuzey, J. Y., Lewis, B. S., Lewis, S., Leys, D., Maggioni, A. P., Massaro, A., Mayosi, B. M., Norrving, B., Okay, T., Olah, L., Osende, J. O., Oto, A., Peeters, A., Penicka, M., Perakis, A., Piegas, L., PIPILIS, A., Pizzolato, G., RAFTI, F., Renkin, J., Siva, A., Steg, P. G., STOCKINS, B., Strozynska, E., Swedberg, K., Turazza, F., VANDERHOVEN, L., Vizel, S., Widimsky, P., Zaborski, J., Albers, G., Hankey, G., Norrving, B., Shuaib, A., Silva, J., Wyse, D. G., Cairns, J. A., Gent, M., Hirsh, J., Marler, J., Pritchett, E., Wittes, J., Beresh, H., Floyd, L., Gasic, Z., Holadyk-Gris, I., Lawrence, M., Moro, I., Perry, S., Roberts, J., Rodrigues, T., Robinson, L., Stevens, C., WORTHY, L., Yuan, F., Guerrero, R. A., Allall, O., Amuchastegui, L. M., Boskis, M., Labarta, M. H., Castellanos, C. R., Chiale, P., CUNEO, C. A., Czcczuo, A., Gabito, A. J., Garrido, M., GUZMAN, L. A., Hasban, E. G., Hershson, A. R., Hominal, M. A., Krauss, J. G., Luciardi, H. L., Marzetti, E. M., Montana, O. R., Rabinovich, R. F., Ramos, H. R., Sanchez, A. S., Schygiel, P. O., Sumay, G. M., Vogel, D. R., Zaidman, C. J., Aroney, G. M., Ashby, D. T., Barlow, M. A., Cooke, P., Cross, D. B., Fitzpatrick, M. A., Garrahy, P., Karrasch, J., Nelson, G. I., Rees, D., Roger, S. D., Rogers, J., Singh, B. B., STICKLAND, J. F., WAITES, J. H., Walsh, W. F., Eichinger, J., Huber, K., Leisch, F., Boland, J., Conraads, V. M., Cools, F. J., De Roy, L., El Allaf, D., Mairesse, G. H., Vankelecom, B., Abrantes, J., Armaganijan, D., Atie, J., Blacher, C., Bodanese, L. C., Braga, J. C., Braile, M. V., Chaves, H., Coelho, O. R., CUNHA, C. L., De Lima, G. G., de Paola, A. A., Esteves, J. P., Francischetti, A., Francischetti, A. E., Lorga-Filho, A. M., Maia, L. N., Marcussi, D. M., Marin-Neto, J. A., Meneghelo, Z. M., Rocha, R. M., Nogueira, P. R., Oigman, W., Paiva, M., Precoma, D. B., Rabelo, W., Rabelo, A., Rassi, S., Rassi, A., Reis, G., Rossi, P. R., Neto, J. M., Saraiva, J. K., Sobral-Filho, D. C., Zimmermann, S. L., Ashton, T. A., Bhargava, R., Carroll, S., Chehayeb, R., Connors, S. P., Constance, C., Costi, P., Coutu, B., Crystal, E., Douketis, J. D., Fortin, C., Fox, B. A., Gupta, M. K., Krahn, A. D., Kuritzky, R., Kwok, K., Leader, R., Ma, P., Mangat, I., MARANDA, C. R., MATANGI, M. F., Moddel, G., Mukherjee, A., Nawaz, S., PALAIC, M., Pandey, A. S., Rebane, T. M., Ruel, M., Sapp, J. L., Senaratne, M. P., St-Hilaire, R., Talbot, P., To, T. B., Vakani, M., WEIGEL, M. A., Wulffhart, Z., Yao, L., Zaniol, D., Conejeros, C. R., Corbalan, R., DUSSAILLANT, G. R., ESCOBAR, E., Hassi, M. E., Parra, C. A., STOCKINS, B. A., Varleta, P. E., Berka, L., Dedek, V., Florian, J., Hejhal, O., Herold, M., Klimsa, Z., Kotik, I., Simon, J., Smetana, K., Spinar, J., Spinarova, L., Tousek, F., Husted, S., Nielsen, T., Pehrson, S., Tuxen, C., Harjola, V. P., Huikuri, H. V., Kettunen, R. V., Melin, J. H., Peuhkurinen, K., Carlioz, R., Coisne, D., Decoulx, E., Defaye, P., DEMARCQ, J. M., Gacem, K., Galley, D. L., Lardoux, H. M., Mabo, P., Mansour, M., Olive, T. G., Poulard, J. E., Pruvot, C. F., Rey, J. L., Bauer, W. R., Baumann, G., Berghoefer, G., Boehm, G., Borggrefe, M. M., Bruecker, G., Darius, H., Duray, G. Z., Felix, S. B., Fink, P., Fritz, H., Haberl, R., Hoffmann, S., Horacek, T., Kalusche, D. W., Kasper, W., Katus, H. A., KLEPZIG, H. H., Loos, U., Merher, R., Munzel, T., Neuzner, J., Ochs, H. R., Pieske, B., POLLOCK, B. W., Schmidt, A., Schumacher, M., Seidl, K., Speier, U., Spitzer, S. G., STENZEL, G., Volkmann, H., Wunderlich, J., Zacharzowsky, U., Antonakoudis, H., Georgakopoulos, N., Goudevenos, J. A., Iliopoulos, T. A., Kallikazaros, I., Pyrgakis, V. N., Skoufas, P., Chan, W. K., Chan, H. W., Fung, J. W., Li, S. K., Wong, K. S., Forster, T., Karpati, P., Keltai, K., Kovacs, A., Kurta, G., Laszlo, Z., RAPI, J., Regos, L., ROSTAS, L., Szakal, I., Tomcsanyi, J., Toth, C., Bloch, L., Khader, N., Klainman, E., Koukoui, D., Lotan, C., Marmor, A., Omary, M. Z., Reisin, L. H., Vered, Z., Zeltser, D., Zimlichman, R., Bianconi, L., Bicego, D., Cosmi, D., Filigheddu, F., Garini, A., Lunati, M., Moretti, L., Mos, L., Pontiroli, A. E., Renda, G., Ricci, S., Rossi, P., Santonastaso, M., Scioli, G. A., Stramba-Badiale, M., Terrosu, P., Omar, R., Ong, T. K., Ahmad, W. A., ALVARADO, R., Calvo, C., Cordero-Cabra, J. A., HERNANDEZ, I., Jerjes-Sanchez, C., Lara, S., Lopez Rosas, E., Molina, L., Morales, E., Petersen-Aranguren, F., Picos Bovio, E. M., Pozas, G., Robles Torres, F. J., HOLWERDA, K., Lok, D. J., Nierop, R., PIETERSE, M. G., van der Heijden, R., Van Kempen, L., OIE, B. K., Omland, T. M., Otterstad, J., von Brandis, C., Bronisz, M., Chizynski, K., Czerski, T., Dluzniewski, M., Gessek, J., Gieroba, A., Gniot, J. R., Gorny, J., Halaczuiewicz, H., Janik, K., Janion, M., Jerzykowska, O., Kawka-Urbanek, T., Kincel, K., KOCON, S., Kopaczewski, J., Krasowski, W., Makuch, M., Malinowski, S., Miastkowski, Z., Mickiewicz-Pawlowska, M., Miekus, P., Obrebska-Tabaczka, E., Ogorek, M., Piasecka-Krysiak, E., Piepiorka, A. W., Piotrowski, W., Pluta, W., Puzio, E., Rekosz, J., Sinkiewicz, W., Stopinski, M., Szelemej, R., Tendera, M., Trusz-Gluza, M., Wilkoszynski, M., Zalska, B., Antunes, E., CARRAGETA, M. O., de Sousa, J., Martins, L., Mendonca, M. I., Silvestre, I., Akatova, E. V., Aleksandrov, V., Antuch, E. A., Arutyunov, G., Bart, B., Belousov, Y. B., Chernichka, I. I., Dovgalevsky, P., Gratsiansky, N., Ivleva, A. Y., Kislyak, O. A., Mareyev, V. Y., Maykov, E. B., Milyagin, V., Novikova, T. N., Panchenko, E. P., Reshetko, O., Semernin, E., Sidorenko, B. A., Sinopalnikov, A., Skvortsova, V., Solomatin, A., Sukhinina, T. S., Suslina, Z. A., Titkov, Y., Tsyrline, V., Chan, B., Foo, D., Omar, A. R., Teo, W. S., Brown, B. G., Ebrahim, I. O., Gibson, G. J., Klug, E., Marx, J. D., Mntla, P. S., Okreglicki, A., Pretorius, M., ROOS, J. S., Snyders, F., Van, L. J., Cano, L., Garcia-Puig, J., Hernandez-Madrid, A., Mostaza, J. M., Orriach, M. D., Sabate, X., Vinolas, X., Blomstrom, P., Jacobsson, F., Johansson, L., Klintberg, L., LYCKSELL, M., Nilsson, O., Rasmanis, G., Nilehn, K. E., Ulvenstam, G., Baumgartner, R. W., Francois, M., Gallino, A., MOCCETTI, T., Tettenborn, B. E., Chou, H., Kuo, J., Lai, W., Lin, J. L., Lin, L., Ueng, K. C., Yeih, D., Bakar, M., Ilerigelen, B., Kumral, E., Nisanci, Y., Savas, Z. I., Adgey, Y., Brack, M. J., Cleland, J., Davey, P. P., DAVIES, J., Glen, S. K., Jennings, K., Levy, T., Lip, G. Y., MORIARTY, A. J., Pearson, C., PURVIS, J. A., Pye, M. P., Savelieva, I., Senior, R., Trouton, T. G., Ahmed, I. S., Amin, M., Anderson, J. L., BAUERNFEIND, R. A., Belew, K., Bilazarian, S. D., Black, R. A., Burton, M. E., Cebe, J. E., Chandrashekhar, Y. S., Chen, C., Das, D., Denny, D. M., Desai, V., FAHMY, R. N., Fishbein, G. J., GELERNT, M. D., Gerber, J., Goldberg, M. C., Grena, P. G., HONAN, M. B., Hunter, J. J., Jacobson, J., Jarmukli, N. F., Klancke, K., KOBAYASHI, J. F., Lewis, S. J., Little, T., Mallis, I., Marani, A. M., Marshall, J. J., MELTZER, P., Menapace, F. J., O'Neill, P. G., Pearce, D. J., Quick, A., Ravipudi, S., Rivera, E., Sackett, M., Salerno, D. M., Schussheim, A., Sheikh, K., Shettigar, U. R., Treasure, C. B., Vidaillet, H., Vijay, N., Wagner, D., Walker, J. L., Winters, S. L., Young, D. R., Zoble, R. G. 2009; 360 (20): 2066-2078

    View details for DOI 10.1056/NEJMoa0901301

    View details for Web of Science ID 000266011200005

  • Hyperfibrinogenemia and Functional Outcome From Acute Ischemic Stroke 80th Annual Scientific Session of the American-Heart-Association (AHA) del Zoppo, G. J., Levy, D. E., Wasiewski, W. W., Pancioli, A. M., Demchuk, A. M., Trammel, J., Demaerschalk, B. M., Kaste, M., Albers, G. W., Ringelstein, E. B. LIPPINCOTT WILLIAMS & WILKINS. 2009: 1687–91

    Abstract

    Epidemiological studies have found strong correlations between elevated plasma fibrinogen levels and both ischemic stroke incidence and stroke mortality. Little is known about the influence of fibrinogen levels on functional stroke outcome.Placebo data from the Stroke Treatment with Ancrod Trial (STAT) and European Stroke Treatment with Ancrod Trial (ESTAT) were analyzed. Fibrinogen levels were determined within 3 hours (STAT) or 6 hours (ESTAT) of stroke onset and at preset intervals throughout 5 days of intravenous infusions. Barthel Index scores at 90 days quantified functional outcomes. The association between initial fibrinogen levels and functional outcomes was evaluated using a multiple logistic regression analysis.Fibrinogen levels increased gradually over the first 24 hours from a pretreatment median value of 340 mg/dL to a 24-hour median value of 376 mg/dL. In a univariate analysis, the proportion of patients with good functional outcome decreased with increasing quartiles of initial fibrinogen levels in both STAT (36.0% to 26.2%) and ESTAT (53.8% to 24.8%). In a multifactorial analysis, the same trend was observed. Patients with initial fibrinogen levels <450 mg/dL had better outcomes in both studies; the difference (42.0% versus 21.6%) was significant in ESTAT (P=0.0006), even when corrected for age and initial stroke severity.The independent association of higher initial fibrinogen levels with poor outcome needs to be verified using a larger acute stroke dataset. Even in the present small populations, the apparent association of these 2 variables suggests that treatments designed to reduce fibrinogen levels could potentially be important in treating acute ischemic stroke.

    View details for DOI 10.1161/STROKEAHA.108.527804

    View details for Web of Science ID 000265579800026

    View details for PubMedID 19299642

    View details for PubMedCentralID PMC2774454

  • Relationships Between Cerebral Perfusion and Reversibility of Acute Diffusion Lesions in DEFUSE Insights from RADAR STROKE Olivot, J., Mlynash, M., Thijs, V. N., Purushotham, A., Kemp, S., Lansberg, M. G., Wechsler, L., Bammer, R., Marks, M. P., Albers, G. W. 2009; 40 (5): 1692-1697

    Abstract

    Acute ischemic lesions with restricted diffusion can resolve after early recanalization. The impact of superimposed perfusion abnormalities on the fate of acute diffusion lesions is unclear.Data were obtained from DEFUSE, a prospective multicenter study of patients treated with IV tPA 3 to 6 hours after stroke onset. Thirty-two patients with baseline diffusion and perfusion lesions and 30 day FLAIR scans were coregistered. The acute diffusion lesion was divided into 3 regions according to the Tmax delay of the superimposed perfusion lesion: normal baseline perfusion; mild-moderately hypoperfused (2 s8 s). The reversal rate was calculated as the percentage of the acute diffusion lesion that did not overlap with the final infarct on 30-day FLAIR. Diffusion reversal rates were compared based on whether a favorable clinical response occurred and whether early recanalization was achieved.On average, 54% of the acute diffusion lesion volume had normal perfusion. Diffusion reversal rates were significantly increased among cases with favorable clinical response and in patients with early recanalization, especially in regions with normal baseline perfusion. The portion of the diffusion lesion with normal perfusion had significantly higher mean apparent diffusion coefficient values and reversal rates.Acute ischemic lesions with restricted diffusion are most likely to recover if reperfusion occurs within 6 hours of symptom onset, and reversibility is associated with early recanalization and favorable clinical outcome. We propose the term RADAR (Reversible Acute Diffusion lesion Already Reperfused) to describe regions of acute restricted diffusion with normal perfusion.

    View details for DOI 10.1161/STROKEAHA.108.538082

    View details for PubMedID 19299632

  • Effectiveness and Safety of Transcranial Laser Therapy for Acute Ischemic Stroke STROKE Zivin, J. A., Albers, G. W., Bornstein, N., Chippendale, T., Dahlof, B., Devlin, T., Fisher, M., Hacke, W., Holt, W., Ilic, S., Kasner, S., Lew, R., Nash, M., Perez, J., Rymer, M., Schellinger, P., Schneider, D., Schwab, S., Veltkamp, R., Walker, M., Streeter, J. 2009; 40 (4): 1359-1364

    Abstract

    We hypothesized that transcranial laser therapy (TLT) can use near-infrared laser technology to treat acute ischemic stroke. The NeuroThera Effectiveness and Safety Trial-2 (NEST-2) tested the safety and efficacy of TLT in acute ischemic stroke.This double-blind, randomized study compared TLT treatment to sham control. Patients receiving tissue plasminogen activator and patients with evidence of hemorrhagic infarct were excluded. The primary efficacy end point was a favorable 90-day score of 0 to 2 assessed by the modified Rankin Scale. Other 90-day end points included the overall shift in modified Rankin Scale and assessments of change in the National Institutes of Health Stroke Scale score.We randomized 660 patients: 331 received TLT and 327 received sham; 120 (36.3%) in the TLT group achieved favorable outcome versus 101 (30.9%), in the sham group (P=0.094), odds ratio 1.38 (95% CI, 0.95 to 2.00). Comparable results were seen for the other outcome measures. Although no prespecified test achieved significance, a post hoc analysis of patients with a baseline National Institutes of Health Stroke Scale score of <16 showed a favorable outcome at 90 days on the primary end point (P<0.044). Mortality rates and serious adverse events did not differ between groups with 17.5% and 17.4% mortality, 37.8% and 41.8% serious adverse events for TLT and sham, respectively.TLT within 24 hours from stroke onset demonstrated safety but did not meet formal statistical significance for efficacy. However, all predefined analyses showed a favorable trend, consistent with the previous clinical trial (NEST-1). Both studies indicate that mortality and adverse event rates were not adversely affected by TLT. A definitive trial with refined baseline National Institutes of Health Stroke Scale exclusion criteria is planned.

    View details for DOI 10.1161/STROKEAHA.109.547547

    View details for Web of Science ID 000264709500052

    View details for PubMedID 19233936

  • SENSE Diffusion-weighted Imaging Improves Diagnostic Sensitivity in Acute Ischemic Stroke American-Association-International-Stroke Conference 2009 Schwartz, N. E., Newbould, R. D., Skare, S., Zaharchuk, G., Mlynash, M., Olivot, J., Lansberg, M. G., Eyngorn, I., Thai, D., Albers, G. W., Bammer, R. LIPPINCOTT WILLIAMS & WILKINS. 2009: E115–E115

    View details for Web of Science ID 000264709500133

  • Prognostic Value of Brain Diffusion-Weighted Imaging after Cardiac Arrest ANNALS OF NEUROLOGY Wijman, C. A., Mlynash, M., Caulfield, A. F., Hsia, A. W., Eyngorn, I., Bammer, R., Fischbein, N., Albers, G. W., Moseley, M. 2009; 65 (4): 394-402

    Abstract

    Outcome prediction is challenging in comatose postcardiac arrest survivors. We assessed the feasibility and prognostic utility of brain diffusion-weighted magnetic resonance imaging (DWI) during the first week.Consecutive comatose postcardiac arrest patients were prospectively enrolled. AWI data of patients who met predefined specific prognostic criteria were used to determine distinguishing apparent diffusion coefficient (ADC) thresholds. Group 1 criteria were death at 6 months and absent motor response or absent pupillary reflexes or bilateral absent cortical responses at 72 hours or vegetative at 1 month. Group 2 criterion was survival at 6 months with a Glasgow Outcome Scale score of 4 or 5 (group 2A) or 3 (group 2B). The percentage of voxels below different ADC thresholds was calculated at 50 x 10(-6) mm(2)/sec intervals.Overall, 86% of patients underwent DWI. Fifty-one patients with 62 brain DWIs were included. Forty patients met the specific prognostic criteria. The percentage of brain volume with an ADC value less than 650 to 700 x 10(-6)mm(2)/sec best differentiated between Group 1 and Groups 2A and 2B combined (p < 0.001), whereas the 400 to 450 x 10(-6)mm(2)/sec threshold best differentiated between Groups 2A and 2B (p = 0.003). The ideal time window for prognostication using DWI was between 49 and 108 hours after the arrest. When comparing DWI in this time window with the 72-hour neurological examination, DWI improved the sensitivity for predicting poor outcome by 38% while maintaining 100% specificity (p = 0.021).Quantitative DWI in comatose postcardiac arrest survivors holds promise as a prognostic adjunct.

    View details for DOI 10.1002/ana.21632

    View details for Web of Science ID 000265656200008

    View details for PubMedID 19399889

    View details for PubMedCentralID PMC2677115

  • Perfusion MRI (Tmax and MTT) correlation with xenon CT cerebral blood flow in stroke patients NEUROLOGY Olivot, J., Mlynash, M., Zaharchuk, G., Straka, M., Bammer, R., Schwartz, N., Lansberg, M. G., Moseley, M. E., Albers, G. W. 2009; 72 (13): 1140-1145

    Abstract

    While stable xenon CT (Xe-CT) cerebral blood flow (CBF) is an accepted standard for quantitative assessment of cerebral hemodynamics, the accuracy of magnetic resonance perfusion-weighted imaging (PWI-MRI) is unclear. The Improved PWI Methodology in Acute Clinical Stroke Study compares PWI findings with Xe-CT CBF values in patients experiencing symptomatic severe cerebral hypoperfusion.We compared mean transit time (MTT) and Tmax PWI-MRI with the corresponding Xe-CT CBF values in 25 coregistered regions of interest (ROIs) of multiple sizes and locations in nine subacute stroke patients. Comparisons were performed with Pearson correlation coefficients (R). We performed receiver operating characteristic (ROC) curve analyses to define the threshold of Tmax and absolute MTT that could best predict a Xe-CT CBF <20 mL/100 g/minute.The subjects' mean (SD) age was 50 (15) years, the median (interquartile range [IQR]) NIH Stroke Scale score was 2 (2-6), and the median (IQR) time between MRI and Xe-CT was 12 (-7-19) hours. The total number of ROIs was 225, and the median (IQR) ROI size was 550 (360-960) pixels. Tmax correlation with Xe-CT CBF (R = 0.63, p < 0.001) was stronger than absolute MTT (R = 0.55, p < 0.001), p = 0.049. ROC curve analysis found that Tmax >4 seconds had 68% sensitivity, 80% specificity, and 77% accuracy and MTT >10 seconds had 68% sensitivity, 77% specificity, and 75% accuracy for predicting ROIs with Xe-CT CBF <20 mL/100 g/minute.Our results suggest that in subacute ischemic stroke patients, Tmax correlates better than absolute mean transit time (MTT) with xenon CT cerebral blood flow (Xe-CT CBF) and that both Tmax >4 seconds and MTT >10 seconds are strongly associated with Xe-CT CBF <20 mL/100 g/minute. CBF = cerebral blood flow; DBP = diastolic blood pressure; DEFUSE = Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution; DWI = diffusion-weighted imaging; EPITHET = Echoplanar Imaging Thrombolytic Evaluation Trial; FOV = field of view; ICA = internal carotid artery; IQR = interquartile range; MCA = middle cerebral artery; MTT = mean transit time; NIHSS = NIH Stroke Scale; PWI = perfusion-weighted imaging; PWI-MRI = magnetic resonance perfusion-weighted imaging; ROC = receiver operating characteristic; ROI = region of interest; SBP = systolic blood pressure; SVD = singular value decomposition; Xe-CT = xenon CT.

    View details for DOI 10.1212/01.wnl.0000345372.49233.e3

    View details for Web of Science ID 000264709000007

    View details for PubMedID 19332690

    View details for PubMedCentralID PMC2680065

  • Yield of combined perfusion and diffusion MR imaging in hemispheric TIA NEUROLOGY Mlynash, M., Olivot, J., Tong, D. C., Lansberg, M. G., Eyngorn, I., Kemp, S., Moseley, M. E., Albers, G. W. 2009; 72 (13): 1127-1133

    Abstract

    Transient ischemic attacks (TIA) predict future stroke. However, there are no sensitive and specific diagnostic criteria for TIA and interobserver agreement regarding the diagnosis is poor. Diffusion-weighted MRI (DWI) demonstrates acute ischemic lesions in approximately 30% of TIA patients; the yield of perfusion-weighted MRI (PWI) is unclear.We prospectively performed both DWI and PWI within 48 hours of symptom onset in consecutive patients admitted with suspected hemispheric TIAs of <24 hours symptom duration. Two independent raters, blinded to clinical features, assessed the presence and location of acute DWI and PWI lesions. Lesions were correlated with suspected clinical localization and baseline characteristics. Clinical features predictive of a PWI lesion were assessed.Forty-three patients met the inclusion criteria. Thirty-three percent had a PWI lesion and 35% had a DWI lesion. Seven patients (16%) had both PWI and DWI lesions and 7 (16%) had only PWI lesions. The combined yield for identification of either a PWI or a DWI was 51%. DWI lesions occurred in the clinically suspected hemisphere in 93% of patients; PWI lesions in 86%. PWI lesions occurred more frequently when the MRI was performed within 12 hours of symptom resolution, in patients with symptoms of speech impairment, and among individuals younger than 60 years.The combination of early diffusion-weighted MRI and perfusion-weighted MRI can document the presence of a cerebral ischemic lesion in approximately half of all patients who present with a suspected hemispheric transient ischemic attack (TIA). MRI has the potential to improve the accuracy of TIA diagnosis. ACA = anterior cerebral artery; CI = confidence interval; DWI = diffusion-weighted MRI; ICA = internal carotid artery; MCA = middle cerebral artery; MRA = magnetic resonance angiography; MTT = mean transit time; OR = odds ratios; PCA = posterior cerebral artery; PWI = perfusion-weighted MRI; RR = risk ratios; TIA = transient ischemic attacks; TOAST = Trial of Org 10172 in Acute Stroke Treatment.

    View details for DOI 10.1212/01.wnl.0000340983.00152.69

    View details for Web of Science ID 000264709000005

    View details for PubMedID 19092109

  • Optimal Tmax Threshold for Predicting Penumbral Tissue in Acute Stroke STROKE Olivot, J., Mlynash, M., Thijs, V. N., Kemp, S., Lansberg, M. G., Wechsler, L., Bammer, R., Marks, M. P., Albers, G. W. 2009; 40 (2): 469-475

    Abstract

    We sought to assess whether the volume of the ischemic penumbra can be estimated more accurately by altering the threshold selected for defining perfusion-weighting imaging (PWI) lesions.DEFUSE is a multicenter study in which consecutive acute stroke patients were treated with intravenous tissue-type plasminogen activator 3 to 6 hours after stroke onset. Magnetic resonance imaging scans were obtained before, 3 to 6 hours after, and 30 days after treatment. Baseline and posttreatment PWI volumes were defined according to increasing Tmax delay thresholds (>2, >4, >6, and >8 seconds). Penumbra salvage was defined as the difference between the baseline PWI lesion and the final infarct volume (30-day fluid-attenuated inversion recovery sequence). We hypothesized that the optimal PWI threshold would provide the strongest correlations between penumbra salvage volumes and various clinical and imaging-based outcomes.Thirty-three patients met the inclusion criteria. The correlation between infarct growth and penumbra salvage volume was significantly better for PWI lesions defined by Tmax >6 seconds versus Tmax >2 seconds, as was the difference in median penumbra salvage volume in patients with a favorable versus an unfavorable clinical response. Among patients who did not experience early reperfusion, the Tmax >4 seconds threshold provided a more accurate prediction of final infarct volume than the >2 seconds threshold.Defining PWI lesions based on a stricter Tmax threshold than the standard >2 seconds delay appears to provide more a reliable estimate of the volume of the ischemic penumbra in stroke patients imaged between 3 and 6 hours after symptom onset. A threshold between 4 and 6 seconds appears optimal for early identification of critically hypoperfused tissue.

    View details for DOI 10.1161/STROKEAHA.108.526954

    View details for PubMedID 19109547

  • Use of MRI to Estimate the Therapeutic Window in Acute Stroke Is Perfusion-Weighted Imaging/Diffusion-Weighted Imaging Mismatch an EPITHET for Salvageable Ischemic Brain Tissue? STROKE Toth, G., Albers, G. W. 2009; 40 (1): 333-335

    View details for DOI 10.1161/STROKEAHA.108.525683

    View details for Web of Science ID 000262059400057

    View details for PubMedID 18845795

  • Risk of Symptomatic Intracerebral Hemorrhage in Patients Treated with Intra-Arterial Thrombolysis CEREBROVASCULAR DISEASES Singer, O. C., Berkefeld, J., Lorenz, M. W., Fiehler, J., Albers, G. W., Lansberg, M. G., Kastrup, A., Rovira, A., Liebeskind, D. S., Gass, A., Rosso, C., Derex, L., Kim, J. S., Neumann-Haefelin, T. 2009; 27 (4): 368-374

    Abstract

    In intra-arterial (IA) thrombolysis trials, higher rates of symptomatic intracerebral haemorrhage (sICH) were found than in trials with intravenous (IV) recombinant tissue plasminogen activator (tPA); this observation could have been due to the inclusion of more severely affected patients in IA thrombolysis trials. In the present study, we investigated the rate of sICH in IA and combined IV + IA thrombolysis versus IV thrombolysis after adjusting for differences in clinical and MRI parameters.In this multicenter study, we systematically analyzed data from 645 patients with anterior-circulation strokes treated with either IV or IA thrombolysis within 6 h following symptom onset. Thrombolytic regimens included (1) IV tPA treatment (n = 536) and (2) IA treatment with either tPA or urokinase (n = 74) or (3) combined IV + IA treatment with either tPA or urokinase (n = 35).44 (6.8%) patients developed sICH. sICH patients had significantly higher scores on the National Institutes of Health Stroke Scale (NIHSS) at admission and pretreatment DWI lesions. The sICH risk was 5.2% (n = 28) in IV thrombolysis, which is significantly lower than in IA (12.5%, n = 9) or IV + IA thrombolysis (20%, n = 7). In a binary logistic regression analysis including age, NIHSS score, time to thrombolysis, initial diffusion weighted imaging lesion size, mode of thrombolytic treatment and thrombolytic agent, the mode of thrombolytic treatment remained an independent predictor for sICH. The odds ratio for IA or IV + IA versus IV treatment was 3.466 (1.19-10.01, 95% CI, p < 0.05).In this series, IA and IV + IA thrombolysis is associated with an increased sICH risk as compared to IV thrombolysis, and this risk is independent of differences in baseline parameters such as age, initial NIHSS score or pretreatment lesion size.

    View details for DOI 10.1159/000202427

    View details for Web of Science ID 000264862500010

    View details for PubMedID 19218803

    View details for PubMedCentralID PMC2715450

  • Antithrombotic agents for stroke prevention. Handbook of clinical neurology Schwartz, N. E., Diener, H., Albers, G. W. 2009; 94: 1277-1294

    View details for DOI 10.1016/S0072-9752(08)94064-1

    View details for PubMedID 18793901

  • Acute strokes in the setting of a persistent primitive trigeminal artery. BMJ case reports Schwartz, N. E., Albers, G. W. 2009; 2009: bcr2006111773-?

    View details for DOI 10.1136/bcr.2006.111773

    View details for PubMedID 21687235

    View details for PubMedCentralID PMC3105872

  • Patients with Acute Stroke Treated with Intravenous tPA 3-6 Hours after Stroke Onset: Correlations between MR Angiography Findings and Perfusion- and Diffusion-weighted Imaging in the DEFUSE Study RADIOLOGY Marks, M. P., Olivot, J., Kemp, S., Lansberg, M. G., Bammer, R., Wechsler, L. R., Albers, G. W., Thijs, V. 2008; 249 (2): 614-623

    Abstract

    To study magnetic resonance (MR) angiography findings in patients with acute stroke treated with intravenous tissue plasminogen activator (tPA) in relationship to perfusion- and diffusion-weighted imaging changes and clinical outcome.Patients treated with intravenous tPA 3-6 hours after stroke onset (with informed consent) were evaluated in a HIPAA-compliant multicenter prospective study approved by all institutional review boards. MR imaging and MR angiography studies were performed before and 3-6 hours after treatment. MR angiography studies that were technically adequate at both time points were evaluated for occlusion, decreased flow, any early recanalization, and degree of recanalization. These results were compared with favorable clinical response (an improvement in National Institutes of Health Stroke Scale score of >or=8 points at 30 days or a modified Rankin scale score of 0 or 1 at 30 days) in patients with and those without mismatch between perfusion- and diffusion-weighted imaging at baseline.Seventy-four patients were enrolled in the initial investigation; pre- and posttreatment MR angiography studies were both technically adequate in 62 patients. MR angiography demonstrated occlusion or decreased flow in 46 patients. Patients with isolated middle cerebral artery (MCA) occlusion and early recanalization at MR angiography had higher rates of favorable clinical response than those with tandem internal carotid artery-MCA occlusion and early recanalization (P = .05). Any early recanalization was not associated with favorable clinical response, but degree of recanalization did correlate with favorable clinical response (P = .048). Favorable clinical response was more frequently seen in patients with mismatch between perfusion- and diffusion-weighted imaging findings at baseline who experienced early recanalization than in those who did not have early recanalization (odds ratio = 6.2; 95% confidence interval: 1.3, 30.2; P = .021). No relationship between early recanalization and favorable clinical response was seen in patients without mismatch.Early recanalization seen at MR angiography before and after treatment coupled with diffusion- and perfusion-weighted imaging data may predict clinical outcome in patients with stroke treated with tPA 3-6 hours after symptom onset.

    View details for DOI 10.1148/radiol.2492071751

    View details for PubMedID 18936316

  • Effects of aspirin plus extended-release dipyridamole versus clopidogrel and telmisartan on disability and cognitive function after recurrent stroke in patients with ischaemic stroke in the Prevention Regimen for Effectively Avoiding Second Strokes (PRoFESS) trial: a double-blind, active and placebo-controlled study LANCET NEUROLOGY Dienert, H., Saccot, R. L., Yusuft, S., Cotton, D., Ounpuu, S., Lawton, W. A., Palesch, Y., Martin, R. H., Albers, G. W., Bath, P., Bornstein, N., Chan, B. P., Chen, S., Cunha, L., Dahlof, B., De Keyser, J., Donnan, G. A., Estol, C., Gorelick, P., Gu, V., Hermansson, K., Hilbrich, L., Kaste, M., Lu, C., Machnig, T., Pais, P., Roberts, R., Skvortsova, V., Teal, P., Toni, D., VanderMaelen, C., Voigt, T., Weber, M., Yoon, B. 2008; 7 (10): 875-884

    Abstract

    The treatment of ischaemic stroke with neuroprotective drugs has been unsuccessful, and whether these compounds can be used to reduce disability after recurrent stroke is unknown. The putative neuroprotective effects of antiplatelet compounds and the angiotensin II receptor antagonist telmisartan were investigated in the Prevention Regimen for Effectively Avoiding Second Strokes (PRoFESS) trial.Patients who had had an ischaemic stroke were randomly assigned in a two by two factorial design to receive either 25 mg aspirin (ASA) and 200 mg extended-release dipyridamole (ER-DP) twice a day or 75 mg clopidogrel once a day, and either 80 mg telmisartan or placebo once per day. The predefined endpoints for this substudy were disability after a recurrent stroke, assessed with the modified Rankin scale (mRS) and Barthel index at 3 months, and cognitive function, assessed with the mini-mental state examination (MMSE) score at 4 weeks after randomisation and at the penultimate visit. Analysis was by intention to treat. The study was registered with ClinicalTrials.gov, number NCT00153062.20,332 patients (mean age 66 years) were randomised and followed-up for a median of 2.4 years. Recurrent strokes occurred in 916 (9%) patients randomly assigned to ASA with ER-DP and 898 (9%) patients randomly assigned to clopidogrel; 880 (9%) patients randomly assigned to telmisartan and 934 (9%) patients given placebo had recurrent strokes. mRS scores were not statistically different in patients with recurrent stroke who were treated with ASA and ER-DP versus clopidogrel (p=0.38), or with telmisartan versus placebo (p=0.61). There was no significant difference in the proportion of patients with recurrent stroke with a good outcome, as measured with the Barthel index, across all treatment groups. Additionally, there was no significant difference in the median MMSE scores, the percentage of patients with an MMSE score of 24 points or less, the percentage of patients with a drop in MMSE score of 3 points or more between 1 month and the penultimate visit, and the number of patients with dementia among the treatment groups. There were no significant differences in the proportion of patients with cognitive impairment or dementia among the treatment groups.Disability due to recurrent stroke and cognitive decline in patients with ischaemic stroke were not different between the two antiplatelet regimens and were not affected by the preventive use of telmisartan.

    View details for DOI 10.1016/S1474-4422(08)70198-4

    View details for Web of Science ID 000259725700011

    View details for PubMedID 18757238

  • Comparison of Multidetector CT Angiography and MR Imaging of Cervical Artery Dissection AMERICAN JOURNAL OF NEURORADIOLOGY Vertinsky, A. T., Schwartz, N. E., Fischbein, N. J., Rosenberg, J., Albers, G. W., Zaharchuk, G. 2008; 29 (9): 1753-1760

    Abstract

    Conventional angiography has been historically considered the gold standard for the diagnosis of cervical artery dissection, but MR imaging/MR angiography (MRA) and CT/CT angiography (CTA) are commonly used noninvasive alternatives. The goal of this study was to compare the ability of multidetector CT/CTA and MR imaging/MRA to detect common imaging findings of dissection.Patients in the data base of our Stroke Center between 2003 and 2007 with dissections who had CT/CTA and MR imaging/MRA on initial work-up were reviewed retrospectively. Two neuroradiologists evaluated the images for associated findings of dissection, including acute ischemic stroke, luminal narrowing, vessel irregularity, wall thickening/hematoma, pseudoaneurysm, and intimal flap. The readers also subjectively rated each vessel on the basis of whether the imaging findings were more clearly displayed with CT/CTA or MR imaging/MRA or were equally apparent.Eighteen patients with 25 dissected vessels (15 internal carotid arteries [ICA] and 10 vertebral arteries [VA]) met the inclusion criteria. CT/CTA identified more intimal flaps, pseudoaneurysms, and high-grade stenoses than MR imaging/MRA. CT/CTA was preferred for diagnosis in 13 vessels (5 ICA, 8 VA), whereas MR imaging/MRA was preferred in 1 vessel (ICA). The 2 techniques were deemed equal in the remaining 11 vessels (9 ICA, 2 VA). A significant preference for CT/CTA was noted for VA dissections (P < .05), but not for ICA dissections.Multidetector CT/CTA visualized more features of cervical artery dissection than MR imaging/MRA. CT/CTA was subjectively favored for vertebral dissection, whereas there was no technique preference for ICA dissection. In many cases, MR imaging/MRA provided complementary or confirmatory information, particularly given its better depiction of ischemic complications.

    View details for DOI 10.3174/ajnr.A1189

    View details for Web of Science ID 000260023800029

    View details for PubMedID 18635617

  • Telmisartan to prevent recurrent stroke and cardiovascular events NEW ENGLAND JOURNAL OF MEDICINE Yusuf, S., Diener, H., Sacco, R. L., Cotton, D., Ounpuu, S., Lawton, W. A., Palesch, Y., Martin, R. H., Albers, G. W., Bath, P., Bornstein, N., Chan, B. P., Chen, S., Cunha, L., Dahlof, B., De Keyser, J., Donnan, G. A., Estol, C., Gorelick, P., Gu, V., Hermansson, K., Hilbrich, L., Kaste, M., Lu, C., Machnig, T., Pais, P., Roberts, R., Skvortsova, V., Teal, P., Toni, D., VanderMaelen, C., Voigt, T., Weber, M., Yoon, B. 2008; 359 (12): 1225-1237

    Abstract

    Prolonged lowering of blood pressure after a stroke reduces the risk of recurrent stroke. In addition, inhibition of the renin-angiotensin system in high-risk patients reduces the rate of subsequent cardiovascular events, including stroke. However, the effect of lowering of blood pressure with a renin-angiotensin system inhibitor soon after a stroke has not been clearly established. We evaluated the effects of therapy with an angiotensin-receptor blocker, telmisartan, initiated early after a stroke.In a multicenter trial involving 20,332 patients who recently had an ischemic stroke, we randomly assigned 10,146 to receive telmisartan (80 mg daily) and 10,186 to receive placebo. The primary outcome was recurrent stroke. Secondary outcomes were major cardiovascular events (death from cardiovascular causes, recurrent stroke, myocardial infarction, or new or worsening heart failure) and new-onset diabetes.The median interval from stroke to randomization was 15 days. During a mean follow-up of 2.5 years, the mean blood pressure was 3.8/2.0 mm Hg lower in the telmisartan group than in the placebo group. A total of 880 patients (8.7%) in the telmisartan group and 934 patients (9.2%) in the placebo group had a subsequent stroke (hazard ratio in the telmisartan group, 0.95; 95% confidence interval [CI], 0.86 to 1.04; P=0.23). Major cardiovascular events occurred in 1367 patients (13.5%) in the telmisartan group and 1463 patients (14.4%) in the placebo group (hazard ratio, 0.94; 95% CI, 0.87 to 1.01; P=0.11). New-onset diabetes occurred in 1.7% of the telmisartan group and 2.1% of the placebo group (hazard ratio, 0.82; 95% CI, 0.65 to 1.04; P=0.10).Therapy with telmisartan initiated soon after an ischemic stroke and continued for 2.5 years did not significantly lower the rate of recurrent stroke, major cardiovascular events, or diabetes. (ClinicalTrials.gov number, NCT00153062.)

    View details for Web of Science ID 000259259900006

    View details for PubMedID 18753639

  • Aspirin and extended-release dipyridamole versus clopidogrel for recurrent stroke NEW ENGLAND JOURNAL OF MEDICINE Sacco, R. L., Diener, H., Yusuf, S., Cotton, D., Ounpuu, S., Lawton, W. A., Palesch, Y., Martin, R. H., Albers, G. W., Bath, P., Bornstein, N., Chan, B. P., Chen, S., Cunha, L., Dahlof, B., De Keyser, J., Donnan, G. A., Estol, C., Gorelick, P., Gu, V., Hermansson, K., Hilbrich, L., Kaste, M., Lu, C., Machnig, T., Pais, P., Roberts, R., Skvortsova, V., Teal, P., Toni, D., VanderMaelen, C., Voigt, T., Weber, M., Yoon, B. 2008; 359 (12): 1238-1251

    Abstract

    Recurrent stroke is a frequent, disabling event after ischemic stroke. This study compared the efficacy and safety of two antiplatelet regimens--aspirin plus extended-release dipyridamole (ASA-ERDP) versus clopidogrel.In this double-blind, 2-by-2 factorial trial, we randomly assigned patients to receive 25 mg of aspirin plus 200 mg of extended-release dipyridamole twice daily or to receive 75 mg of clopidogrel daily. The primary outcome was first recurrence of stroke. The secondary outcome was a composite of stroke, myocardial infarction, or death from vascular causes. Sequential statistical testing of noninferiority (margin of 1.075), followed by superiority testing, was planned.A total of 20,332 patients were followed for a mean of 2.5 years. Recurrent stroke occurred in 916 patients (9.0%) receiving ASA-ERDP and in 898 patients (8.8%) receiving clopidogrel (hazard ratio, 1.01; 95% confidence interval [CI], 0.92 to 1.11). The secondary outcome occurred in 1333 patients (13.1%) in each group (hazard ratio for ASA-ERDP, 0.99; 95% CI, 0.92 to 1.07). There were more major hemorrhagic events among ASA-ERDP recipients (419 [4.1%]) than among clopidogrel recipients (365 [3.6%]) (hazard ratio, 1.15; 95% CI, 1.00 to 1.32), including intracranial hemorrhage (hazard ratio, 1.42; 95% CI, 1.11 to 1.83). The net risk of recurrent stroke or major hemorrhagic event was similar in the two groups (1194 ASA-ERDP recipients [11.7%], vs. 1156 clopidogrel recipients [11.4%]; hazard ratio, 1.03; 95% CI, 0.95 to 1.11).The trial did not meet the predefined criteria for noninferiority but showed similar rates of recurrent stroke with ASA-ERDP and with clopidogrel. There is no evidence that either of the two treatments was superior to the other in the prevention of recurrent stroke. (ClinicalTrials.gov number, NCT00153062.)

    View details for Web of Science ID 000259259900007

    View details for PubMedID 18753638

  • The MRA-DWI mismatch identifies patients with stroke who are likely to benefit from reperfusion STROKE Lansberg, M. G., Thijs, V. N., Bammer, R., Olivot, J., Marks, M. P., Wechsler, L. R., Kemp, S., Albers, G. W. 2008; 39 (9): 2491-2496

    Abstract

    The aim of this exploratory analysis was to evaluate if a combination of MR angiography (MRA) and diffusion-weighted imaging (DWI) selection criteria can be used to identify patients with acute stroke who are likely to benefit from early reperfusion.Data from DEFUSE, a study of 74 patients with stroke who received intravenous tissue plasminogen activator in the 3- to 6-hour time window and underwent MRIs before and approximately 4 hours after treatment were analyzed. The MRA-DWI mismatch model was defined as (1) a DWI lesion volume less than 25 mL in patients with a proximal vessel occlusion; or (2) a DWI lesion volume less than 15 mL in patients with proximal vessel stenosis or an abnormal finding of a distal vessel. Favorable clinical response was defined as an improvement on the National Institutes of Health Stroke Scale score of at least 8 points between baseline and 30 days or a National Institutes of Health Stroke Scale score

    View details for DOI 10.1161/STROKEAHA.107.508572

    View details for Web of Science ID 000258727000015

    View details for PubMedID 18635861

  • Relationships between infarct growth, clinical outcome, and early recanalization in Diffusion and perfusion imaging For Understanding Stroke Evolution (DEFUSE) STROKE Olivot, J., Mlynash, M., Thijs, V. N., Kemp, S., Lansberg, M. G., Wechsler, L., Schlaug, G., Bammer, R., Marks, M. P., Albers, G. W. 2008; 39 (8): 2257-2263

    Abstract

    The purpose of this study was to determine the relationships between ischemic lesion growth, recanalization, and clinical response in stroke patients with and without a perfusion/diffusion mismatch.DEFUSE is an open label multicenter study in which 74 consecutive acute stroke patients were treated with intravenous tPA 3 to 6 hours after stroke onset. Magnetic resonance imaging (MRI) scans were obtained before, 3 to 6 hours after, and 30 days after treatment. Lesion growth was defined as the difference between the final infarct volume (30 day FLAIR) and the baseline diffusion lesion. Baseline MRI profiles were used to categorize 44 patients into Mismatch versus Absence of Mismatch subgroups. Early recanalization was assessed in 28 patients with an initial vessel lesion on magnetic resonance angiography. Infarct growth was compared based on whether a favorable clinical response (FCR) occurred and whether early recanalization was achieved.In the Mismatch subgroup, FCR was associated with less infarct growth P=0.03 and early recanalization was predictive of both FCR (odds ratio: 22, P=0.047) and reduced infarct growth P=0.024. There was no significant relationship between recanalization, infarct growth, and clinical outcome in the Absence of Mismatch subgroup. A threshold of <7 cc of growth had the highest sensitivity and specificity for predicting a FCR in Mismatch patients (odds ratio: 65, P=0.015, sensitivity 82%, specificity 75%).In contrast to Absence of Mismatch patients, significant associations between recanalization, reduced infarct growth, and favorable clinical response were documented in patients with a perfusion/diffusion mismatch who were treated with tPA within 3 to 6 hours after stroke onset. These findings support the Mismatch hypothesis but require validation in a larger study.

    View details for DOI 10.1161/STROKEAHA.107.511535

    View details for PubMedID 18566302

  • Optimal outcome measures for detecting clinical benefits of early reperfusion: insights from the DEFUSE Study. Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association Kakuda, W., Hamilton, S., Thijs, V. N., Lansberg, M. G., Kemp, S., Skalabrin, E., Albers, G. W. 2008; 17 (4): 235-240

    Abstract

    There is no consensus regarding which clinical outcome scales are the most sensitive indicators of early reperfusion in patients with acute stroke.Patients with acute stroke enrolled in the Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution (DEFUSE) study with a perfusion-/diffusion-weighted imaging mismatch at baseline magnetic resonance imaging were studied. Prespecified secondary outcome measures were evaluated at both 30 and 90 days after treatment with intravenous tissue plasminogen activator. A nonparametric recursive partitioning algorithm was also used to identify the optimal dichotomous splits for differentiating patients who experienced early reperfusion from those who did not.In all, 34 of the 74 patients enrolled in DEFUSE met the inclusion criteria for this study. Statistically significant benefits of reperfusion were documented on multiple outcome measures. The most powerful predefined outcome measure was improvement in the National Institutes of Health Stroke Scale (NIHSS) score of greater than or equal to 11 points between baseline and day 90 and/or a day-90 NIHSS score of 0 to 1 (odds ratio 22.5, P = .0021). The recursive partitioning algorithm analysis identified an improvement of greater than or equal to 10 on the NIHSS score between baseline and 30 days and an NIHSS score of less than or equal to 2 at 30 days as optimal end points.For patients with stroke and a perfusion-/diffusion-weighted imaging mismatch treated with intravenous tissue plasminogen activator at 3 to 6 hours, a substantial change in the baseline NIHSS score (> or =10 points) is a potent discriminator of patients who experience early reperfusion from those who do not. In addition, an NIHSS score of less than or equal to 2 appears to be an excellent end point for phase II studies of reperfusion therapies.

    View details for DOI 10.1016/j.jstrokecerebrovasdis.2008.03.001

    View details for PubMedID 18589345

  • Antithrombotic and thrombolytic therapy: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest Hirsh, J., Guyatt, G., Albers, G. W., Harrington, R., Schünemann, H. J., American College of Chest Physician 2008; 133 (6): 110S-112S

    Abstract

    Since publication of the seventh American College of Chest Physicians (ACCP) supplement on antithrombotic and thrombolytic therapy, the results of clinical trials have provided important new information on the management of thromboembolic disorders, and the science of developing recommendations has advanced. In the accompanying supplement, we provide the new and updated recommendations and review several important changes that we have made in our guideline development process. We again made a conscious effort to increase the participation of female authors and contributors from outside North America, the latter reflecting the widespread use and dissemination of these guidelines internationally. The grading system for the recommendations was adopted in 2006 by the ACCP for all its guidelines, is similar to the increasingly widely used Grades of Recommendation, Assessment, Development, and Evaluation approach, and is described in detail in one of the introductory chapters. While most of the evidence on which recommendations are made remains low quality in fields of pediatric thrombosis, thrombosis in pregnancy, and thrombosis in valvular heart disease, rigorous studies in other fields have resulted in new and strong evidence-based recommendations for many indications.

    View details for DOI 10.1378/chest.08-0652

    View details for PubMedID 18574260

  • Comparison of 12 risk stratification schemes to predict stroke in patients with nonvalvular atrial fibrillation STROKE Hart, R. G., Pearce, L. A., Halperin, J. L., Hylek, E. M., Albers, G. W., Anderson, D. C., Connolly, S. J., Friday, G. H., Gage, B. F., Go, A. S., Goldstein, L. B., Gronseth, G., Lip, G. Y., Sherman, D. G., Singer, D. E., van Walraven, C. 2008; 39 (6): 1901-1910

    Abstract

    More than a dozen schemes for stratifying stroke risk in patients with nonvalvular atrial fibrillation have been published. Differences among these schemes lead to inconsistent stroke risk estimates for many atrial fibrillation patients, resulting in confusion among clinicians and nonuniform use of anticoagulation.Twelve published schemes stratifying stroke risk in patients with nonvalvular atrial fibrillation are analyzed, and observed stroke rates in independent test cohorts are compared with predicted risk status.Seven schemes were based directly on event-rate analyses, whereas 5 resulted from expert consensus. Four considered only clinical features, whereas 7 schemes included echocardiographic variables. The number of variables per scheme ranged from 4 to 8 (median, 6). The most frequently included features were previous stroke/TIA (100% of schemes), patient age (83%), hypertension (83%), and diabetes (83%), and 8 additional variables were included in >/=1 schemes. Based on published test cohorts, all 8 tested schemes stratified stroke risk, but the absolute stroke rates varied widely. Observed rates for those categorized as low risk ranged from 0% to 2.3% per year and those categorized as high risk ranged from 2.5% to 7.9% per year. When applied to the same cohorts, the fractions of patients categorized by the different schemes as low risk varied from 9% to 49% and those categorized by the different schemes as high-risk varied from 11% to 77%.There are substantial, clinically relevant differences among published schemes designed to stratify stroke risk in patients with atrial fibrillation. Additional research to identify an optimum scheme for primary prevention and subsequent standardization of recommendations may lead to more uniform selection of patients for anticoagulant prophylaxsis.

    View details for DOI 10.1161/STROKEAHA.107.501825

    View details for Web of Science ID 000256162600046

    View details for PubMedID 18420954

  • Antithrombotic and thrombolytic therapy CHEST Hirsh, J., Guyatt, G., Albers, G. W., Harrington, R., Schunemann, H. J. 2008; 133 (6): 110S-112S

    View details for DOI 10.1378/chest.08-0652

    View details for Web of Science ID 000257151800002

  • American College of Chest Physicians evidence-based clinical practice guidelines (8th edition) CHEST Hirsh, J., Guyatt, G., Albers, G. W., Harrington, R., Schunemann, H. J. 2008; 133 (6): 71S-109S

    View details for DOI 10.1378/chest.08-0693

    View details for Web of Science ID 000257151800001

  • Executive summary: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest Hirsh, J., Guyatt, G., Albers, G. W., Harrington, R., Schünemann, H. J. 2008; 133 (6): 71S-109S

    View details for DOI 10.1378/chest.08-0693

    View details for PubMedID 18574259

  • Antithrombotic therapy in atrial fibrillation CHEST Singer, D. E., Albers, G. W., Dalen, J. E., Fang, M. C., Go, A. S., Halperin, J. L., Lip, G. Y., Manning, W. J. 2008; 133 (6): 546S-592S

    Abstract

    This chapter about antithrombotic therapy in atrial fibrillation (AF) is part of the American College of Chest Physicians Evidence-Based Guidelines Clinical Practice Guidelines (8th Edition). Grade 1 recommendations indicate that most patients would make the same choice and Grade 2 suggests that individual patient's values may lead to different choices (for a full understanding of the grading see Guyatt et al, CHEST 2008; 133[suppl]:123S-131S). Among the key recommendations in this chapter are the following (all vitamin K antagonist [VKA] recommendations have a target international normalized ratio [INR] of 2.5; range 2.0-3.0, unless otherwise noted). In patients with AF, including those with paroxysmal AF, who have had a prior ischemic stroke, transient ischemic attack (TIA), or systemic embolism, we recommend long-term anticoagulation with an oral VKA, such as warfarin, because of the high risk of future ischemic stroke faced by this set of patients (Grade 1A). In patients with AF, including those with paroxysmal AF, who have two or more of the risk factors for future ischemic stroke listed immediately below, we recommend long-term anticoagulation with an oral VKA (Grade 1A). Two or more of the following risk factors apply: age >75 years, history of hypertension, diabetes mellitus, moderately or severely impaired left ventricular systolic function and/or heart failure. In patients with AF, including those with paroxysmal AF, with only one of the risk factors listed immediately above, we recommend long-term antithrombotic therapy (Grade 1A), either as anticoagulation with an oral VKA, such as warfarin (Grade 1A), or as aspirin, at a dose of 75-325 mg/d (Grade 1B). In these patients at intermediate risk of ischemic stroke we suggest a VKA rather than aspirin (Grade 2A). In patients with AF, including those with paroxysmal AF, age < or =75 years and with none of the other risk factors listed above, we recommend long-term aspirin therapy at a dose of 75-325 mg/d (Grade 1B), because of their low risk of ischemic stroke. For patients with atrial flutter, we recommend that antithrombotic therapy decisions follow the same risk-based recommendations as for AF (Grade 1C). For patients with AF and mitral stenosis, we recommend long-term anticoagulation with an oral VKA (Grade 1B). For patients with AF and prosthetic heart valves we recommend long-term anticoagulation with an oral VKA at an intensity appropriate for the specific type of prosthesis (Grade 1B). See CHEST 2008; 133(suppl):593S-629S. For patients with AF of > or =48 h or of unknown duration for whom pharmacologic or electrical cardioversion is planned, we recommend anticoagulation with an oral VKA, such as warfarin, for 3 weeks before elective cardioversion and for at least 4 weeks after sinus rhythm has been maintained (Grade 1C). For patients with AF of > or = 48 h or of unknown duration undergoing pharmacological or electrical cardioversion, we also recommend either immediate anticoagulation with unfractionated IV heparin, or low-molecular-weight heparin (LMWH), or at least 5 days of warfarin by the time of cardioversion (achieving an INR of 2.0-3.0) as well as a screening multiplane transesophageal echocardiography (TEE). If no thrombus is seen, cardioversion is successful, and sinus rhythm is maintained, we recommend anticoagulation for at least 4 weeks. If a thrombus is seen on TEE, then cardioversion should be postponed and anticoagulation should be continued indefinitely. We recommend obtaining a repeat TEE before attempting later cardioversion (Grade 1B addressing the equivalence of TEE-guided vs non-TEE-guided cardioversion). For patients with AF of known duration <48 h, we suggest cardioversion without prolonged anticoagulation (Grade 2C). However, in patients without contraindications to anticoagulation, we suggest beginning IV heparin or LMWH at presentation (Grade 2C).

    View details for DOI 10.1378/chest.08-0678

    View details for Web of Science ID 000257151800015

    View details for PubMedID 18574273

  • Antithrombotic and thrombolytic therapy for ischemic stroke CHEST Albers, G. W., Amarenco, P., Easton, J. D., Sacco, R. L., Teal, P. 2008; 133 (6): 630S-669S

    Abstract

    This article about treatment and prevention of stroke is part of the Antithrombotic and Thrombolytic Therapy: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Grade 1 recommendations are strong and indicate that the benefits do, or do not, outweigh risks, burden, and costs. Grade 2 suggests that individual patients' values may lead to different choices (for a full understanding of the grading, see the "Grades of Recommendations" chapter by Guyatt et al, CHEST 2008; 133:123S-131S). Among the key recommendations in this chapter are the following: For patients with acute ischemic stroke, we recommend administration of IV tissue plasminogen activator (tPA) if treatment is initiated within 3 h of clearly defined symptom onset (Grade 1A). For patients with acute ischemic stroke of > 3 h but < 4.5 h, we suggest clinicians do not use IV tPA (Grade 2A). For patients with acute stroke onset of > 4.5 h, we recommend against the use of IV tPA (Grade 1A). For patients with acute ischemic stroke who are not receiving thrombolysis, we recommend early aspirin therapy (Grade 1A). For acute ischemic stroke patients with restricted mobility, we recommend prophylactic low-dose subcutaneous heparin or low-molecular-weight heparins (Grade 1A). For long-term stroke prevention in patients with noncardioembolic stroke or transient ischemic attack (TIA) [ie, atherothrombotic, lacunar, or cryptogenic], we recommend treatment with an antiplatelet agent (Grade 1A), including aspirin (recommended dose, 50-100 mg/d), the combination of aspirin and extended-release dipyridamole (25 mg/200 mg bid), or clopidogrel (75 mg qd). In these patients, we recommend use of the combination of aspirin and extended-release dipyridamole (25/200 mg bid) over aspirin (Grade 1A) and suggest clopidogrel over aspirin (Grade 2B), and recommend avoiding long-term use of the combination of aspirin and clopidogrel (Grade 1B). For patients who are allergic to aspirin, we recommend clopidogrel (Grade 1A). In patients with atrial fibrillation and a recent stroke or TIA, we recommend long-term oral anticoagulation (target international normalized ratio, 2.5; range, 2.0 to 3.0) [Grade 1A]. In patients with venous sinus thrombosis, we recommend unfractionated heparin (Grade 1B) or low-molecular-weight heparin (Grade 1B) over no anticoagulant therapy during the acute phase.

    View details for DOI 10.1378/chest.08-0720

    View details for Web of Science ID 000257151800017

    View details for PubMedID 18574275

  • Optimal definition for PWI/DWI mismatch in acute ischemic stroke patients JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM Kakuda, W., Lansberg, M. G., Thijs, V. N., Kemp, S. M., Bammer, R., Wechsler, L. R., Moseley, M. E., Parks, M. P., Albers, G. W. 2008; 28 (5): 887-891

    Abstract

    Although the perfusion-weighted imaging/diffusion-weighted imaging (PWI/DWI) mismatch model has been proposed to identify acute stroke patients who benefit from reperfusion therapy, the optimal definition of a mismatch is uncertain. We evaluated the odds ratio for a favorable clinical response in mismatch patients with reperfusion compared with no reperfusion for various mismatch ratio thresholds in patients enrolled in the diffusion and perfusion imaging evaluation for understanding stroke evolution (DEFUSE) study. A mismatch ratio of 2.6 provided the highest sensitivity (90%) and specificity (83%) for identifying patients in whom reperfusion was associated with a favorable response. Defining mismatch with a larger PWI/DWI ratio may provide greater power for detecting beneficial effects of reperfusion.

    View details for DOI 10.1038/sj.jcbfm.9600604

    View details for Web of Science ID 000255261300003

    View details for PubMedID 18183031

  • Update to the AHA/ASA recommendations for the prevention of stroke in patients with stroke and transient ischemic attack STROKE Adams, R. J., Albers, G., Alberts, M. J., Benavente, O., Furie, K., Goldstein, L. B., Gorelick, P., Halperin, J., Harbaugh, R., Johnston, S. C., Katzan, I., Kelly-Hayes, M., Kenton, E. J., Marks, M., Sacco, R. L., Schwamm, L. H. 2008; 39 (5): 1647-1652

    View details for DOI 10.1161/STROKEAHA.107.189063

    View details for Web of Science ID 000255393100046

    View details for PubMedID 18322260

  • Acute stroke imaging research roadmap. AJNR. American journal of neuroradiology Wintermark, M., Albers, G. W., Alexandrov, A. V., Alger, J. R., Bammer, R., Baron, J., Davis, S., Demaerschalk, B. M., Derdeyn, C. P., Donnan, G. A., Eastwood, J. D., Fiebach, J. B., Fisher, M., Furie, K. L., Goldmakher, G. V., Hacke, W., Kidwell, C. S., Kloska, S. P., Köhrmann, M., Koroshetz, W., Lee, T., Lees, K. R., Lev, M. H., Liebeskind, D. S., Ostergaard, L., Powers, W. J., Provenzale, J., Schellinger, P., Silbergleit, R., Sorensen, A. G., Wardlaw, J., Wu, O., Warach, S. 2008; 29 (5): e23-30

    Abstract

    The recent "Advanced Neuroimaging for Acute Stroke Treatment" meeting on September 7 and 8, 2007 in Washington DC, brought together stroke neurologists, neuroradiologists, emergency physicians, neuroimaging research scientists, members of the National Institute of Neurological Disorders and Stroke (NINDS), the National Institute of Biomedical Imaging and Bioengineering (NIBIB), industry representatives, and members of the US Food and Drug Administration (FDA) to discuss the role of advanced neuroimaging in acute stroke treatment. The goals of the meeting were to assess state-of-the-art practice in terms of acute stroke imaging research and to propose specific recommendations regarding: (1) the standardization of perfusion and penumbral imaging techniques, (2) the validation of the accuracy and clinical utility of imaging markers of the ischemic penumbra, (3) the validation of imaging biomarkers relevant to clinical outcomes, and (4) the creation of a central repository to achieve these goals. The present article summarizes these recommendations and examines practical steps to achieve them.

    View details for PubMedID 18477656

  • Effect of ximelagatran and warfarin on Stroke subtypes in atrial fibrillation CANADIAN JOURNAL OF NEUROLOGICAL SCIENCES Teitelbaum, J. S., von Kummer, R., Gjesdal, K., Kristinsson, A., Gahn, G., Albers, G. W. 2008; 35 (2): 160-165

    Abstract

    The most common stroke subtype among atrial fibrillation (AF) patients not receiving anticoagulants is cardioembolic. In the SPORTIF III and V trials, the oral direct thrombin inhibitor ximelagatran was as effective as warfarin in reducing the risk of stroke in patients with nonvalvular AF. We assessed any differential effect of warfarin versus ximelagatran on the risk and outcome of cardioembolic and noncardioembolic stroke.7329 patients with AF and > or = 1 risk factors for stroke were randomized to treatment with warfarin (target international normalized ratio 2.0--3.0) or fixed-dose ximelagatran. Strokes were classified into specific subtypes. Therapeutic effect of warfarin and ximelagatran, adverse events, and stroke outcomes were assessed according to stroke subtype.The annual stroke rate was low for both cardioembolic (ximelagatran, 0.39%; warfarin, 0.47%) and noncardioembolic stroke (ximelagatran, 0.57%; warfarin, 0.37%). In ischemic strokes, 33.9% (ximelagatran) and 34.3% (warfarin) had strokes of presumed cardioembolic origin. When fatal stroke, disabling stroke, myocardial infarction, and death from any cause were combined as poor outcome, patients with cardioembolic strokes had the highest rate of poor outcome (40%) but this was non- significant.In SPORTIF III and V the efficacy of warfarin and ximelagatran were similar for prevention of cardioembolic and noncardioembolic strokes. Overall outcome tended to be worse following cardioembolic stroke. Ximelagatran has been withdrawn from the market due to hepatic side effects, but similar compounds are presently being studied.

    View details for Web of Science ID 000256184600009

    View details for PubMedID 18574928

  • Rapid assessment and intervention at specialist outpatient clinics - time for a new standard in TIA care? NATURE CLINICAL PRACTICE NEUROLOGY Albers, G. W. 2008; 4 (4): 184-185

    View details for DOI 10.1038/ncpneuro0733

    View details for Web of Science ID 000254581200004

    View details for PubMedID 18227824

  • Yield of transesophageal echocardiography in ischemic stroke patients by age and lesion pattern on diffusion-weighted MRI 33rd International Stroke Conference Campbell, D. M., Beraud, A., Mlynash, M., Schnittger, I., Eyngorn, I., Kumar, M. A., Tong, D. C., Moseley, M., Albers, G. W., Wijman, C. A. LIPPINCOTT WILLIAMS & WILKINS. 2008: 575–76

    View details for Web of Science ID 000252726100246

  • MRI-based diagnostic evaluation has substantial impact on final stroke diagnosis 33rd International Stroke Conference Kumar, M. A., Campbell, D. M., Vangala, H. L., Eyngorn, I., Olivot, J. M., Beraud, A. S., Belgude, A., Lansberg, M. G., Schnittger, I., Wijman, C. A., Tong, D. C., Mlynash, M., Albers, G. W., Moseley, M. LIPPINCOTT WILLIAMS & WILKINS. 2008: 569–69

    View details for Web of Science ID 000252726100222

  • Use of antiplatelet agents to prevent stroke: What is the role for combinations of medications? CURRENT NEUROLOGY AND NEUROSCIENCE REPORTS Schwartz, N. E., Albers, G. W. 2008; 8 (1): 29-34

    Abstract

    Antiplatelet agents are the medications of choice for preventing non-cardioembolic strokes. The diverse pathways involved in platelet function suggest the possibility of synergistic effects by combining various agents. In heart disease and in the setting of coronary artery stents, antiplatelet therapy with clopidogrel and aspirin has established benefits. Although it is tempting to extrapolate the benefits of this combination for stroke prevention, recent clinical trials have not borne this out. Unacceptable bleeding risks without additional efficacy weigh against the routine use of clopidogrel with aspirin for stroke prophylaxis. The combination of aspirin and extended-release dipyridamole has demonstrated superiority over aspirin in two large secondary stroke prevention trials.

    View details for Web of Science ID 000256319000004

    View details for PubMedID 18367036

  • Risk for symptomatic intracerebral hemorrhage after thrombolysis assessed by diffusion-weighted magnetic resonance imaging ANNALS OF NEUROLOGY Singer, O. C., Humpich, M. C., Fiehler, J., Albers, G. W., Lansberg, M. G., Kastrup, A., Rovira, A., Liebeskind, D. S., Gass, A., Rosso, C., Derex, L., Kim, J. S., Neumann-Haefelin, T. 2008; 63 (1): 52-60

    Abstract

    The risk for symptomatic intracerebral hemorrhage (sICH) associated with thrombolytic treatment has not been evaluated in large studies using diffusion-weighted imaging (DWI). Here, we investigated the relation between pretreatment DWI lesion size and the risk for sICH after thrombolysis.In this retrospective multicenter study, prospectively collected data from 645 patients with anterior circulation stroke treated with intravenous or intraarterial thrombolysis within 6 hours (<3 hours: n = 320) after symptom onset were pooled. Patients were categorized according to the pretreatment DWI lesion size into three prespecified groups: small (< or =10 ml; n = 218), moderate (10-100 ml; n = 371), and large (>100 ml; n = 56) DWI lesions.In total, 44 (6.8%) patients experienced development of sICH. The sICH rate was significantly different between subgroups: 2.8, 7.8, and 16.1% in patients with small, moderate, and large DWI lesions, respectively (p < 0.05). This translates to a 5.8 (2.8)-fold greater sICH risk for patients with large DWI lesions as compared with patients with small (or moderate) DWI lesions. The results were similar in the large subgroup (n = 536) of patients treated with intravenous tissue plasminogen activator. DWI lesion size remained an independent risk factor when including National Institutes of Health Stroke Scale, age, time to thrombolysis, and leukoariosis in a logistic regression analysis.This multicenter study provides estimates of sICH risk in potential candidates for thrombolysis. The sICH risk increases gradually with increasing DWI lesion size, indicating that the potential benefit of therapy needs to be balanced carefully against the risk for sICH, especially in patients with large DWI lesions.

    View details for DOI 10.1002/ana.21222

    View details for Web of Science ID 000253008700008

    View details for PubMedID 17880020

  • Is there a role for combinations of antiplatelet agents in stroke prevention? Current treatment options in neurology Schwartz, N. E., Albers, G. W. 2007; 9 (6): 442-450

    Abstract

    Antiplatelet medications are the agents of choice for secondary prevention of noncardioembolic ischemic strokes. Multiple clinical trials have proven their reliable albeit modest clinical benefits and relatively good safety profile. The most commonly recommended antiplatelet agents for secondary stroke prevention in North America and Europe are aspirin, clopidogrel, and the combination of aspirin and extended-release dipyridamole. Because of the multiple pharmacologic mechanisms available for platelet inhibition, combination antiplatelet agents have the potential for synergistic effects. However, combinations of antithrombotic agents do not necessarily improve clinical efficacy and are typically associated with increased toxicity. Clopidogrel and aspirin have been used in combination in patients with diverse arterial vascular diseases. Combination antiplatelet therapy with clopidogrel and aspirin has established clinical benefits, particularly in coronary disease and in patients who have undergone coronary stenting. Although it is tempting to extrapolate the benefits of clopidogrel and aspirin to the setting of secondary stroke prevention, recent clinical trials have failed to document significant clinical benefits in cerebrovascular patients. This failure has occurred because of a lack of significant efficacy for prevention of vascular events and a substantial increase in bleeding risk. Therefore, the clopidogrel and aspirin combination is not recommended for recurrent stroke prevention. In general, when clopidogrel is used for cerebrovascular patients, the addition of aspirin should be avoided unless there is a specific cardiac indication such as recent acute coronary syndrome or a coronary stent. The combination of aspirin and extended-release dipyridamole is supported by Class I data from two large studies demonstrating superiority over aspirin alone for recurrent stroke prevention. Although dual antiplatelet therapy with clopidogrel and aspirin has never been directly compared with the combination of aspirin and extended-release dipyridamole, clinical trial results favor the latter for secondary stroke prevention. Currently, there are no data for primary stroke prevention with dual antiplatelet agents regarding aspirin and extended-release dipyridamole. Limited data from the recent Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization Management and Avoidance (CHARISMA) trial indicate that the combination of clopidogrel and aspirin may be harmful, compared with aspirin alone.

    View details for PubMedID 18173943

  • Bleeding Risk Analysis in Stroke Imaging before ThromboLysis (BRASIL) - Pooled analysis of t2*-weighted magnetic resonance imaging data from 570 patients STROKE Fiehler, J., Albers, G. W., Boulanger, J., Derex, L., Gass, A., Hjort, N., Kim, J. S., Liebeskind, D. S., Neumann-Haefelin, T., Pedraza, S., Rother, J., Rothwell, P., Rovira, A., Schellinger, P. D., Trenkler, J. 2007; 38 (10): 2738-2744

    Abstract

    There has been speculation that the risk of secondary symptomatic intracranial hemorrhage (SICH) may be increased after thrombolytic therapy in ischemic stroke patients who have cerebral microbleeds (CMBs) on T2*-weighted magnetic resonance imaging. Because of this concern, some centers withhold potentially beneficial thrombolytic therapy from these patients.We analyzed magnetic resonance imaging data acquired within 6 hours after symptom onset from 570 ischemic stroke patients treated with intravenous tissue plasminogen activator in 13 centers in Europe, North America, and Asia. Baseline T2*-weighted magnetic resonance images were evaluated for the presence of CMBs. The primary end point was SICH, defined as clinical deterioration with an increase in the National Institutes of Health Stroke Scale score by >or=4 points, temporally related to a parenchymal hematoma on follow-up-imaging.A total of 242 CMBs were detected in 86 of 570 patients (15.1%). The number of CMBs ranged from 1 to 77 in the individual patient, with >or=5 CMBs in 6 of 570 patients (1.1%). Proportions of patients with SICH were 5.8% (95% CI, 1.9 to 13.0) in the presence of CMBs and 2.7% (95% CI, 1.4 to 4.5) in patients without CMBs (P=0.170, Fisher's exact test), resulting in no significant absolute increase in the risk of SICH of 3.1% (95% CI, -2.0 to 8.3).The data suggest that if there is any increased risk of SICH attributable to CMBs, it is likely to be small and unlikely to exceed the benefits of thrombolytic therapy. No reliable conclusion regarding risk in the rare patient with multiple CMBs can be reached.

    View details for DOI 10.1161/STROKEAHA.106.480848

    View details for Web of Science ID 000249694900021

    View details for PubMedID 17717319

  • Warfarin prevails for stroke prevention in atrial fibrillation-even in octogenarians LANCET NEUROLOGY Albers, G. W. 2007; 6 (10): 844-846

    View details for Web of Science ID 000250035600005

    View details for PubMedID 17884669

  • Independent predictors of stroke in patients with atrial fibrillation - A systematic review NEUROLOGY Hart, R. G., Pearce, L. A., Albers, G. W., Connolly, S. J., Friday, G. H., Gage, B. F., Go, A. S., Goldstein, L. B., Gronseth, G., Halperin, J. L., Hylek, E. M., Lip, G. Y., Sherman, D. G., Singer, D. E., van Walraven, C. 2007; 69 (6): 546-554

    Abstract

    Absolute stroke rates vary widely among patients with nonvalvular atrial fibrillation. To balance the benefits and risks of chronic antithrombotic prophylaxis, it is important to estimate the absolute risk of stroke for individual patients.Systematic review of studies using multivariate regression techniques to identify independent risk factors for stroke in patients with atrial fibrillation was conducted, and reports of absolute stroke rates in subgroups of patients with these risk factors collected. A summary estimate of the relative risk associated with each independent risk factor was calculated using maximum likelihood methods.Seven studies (including six entirely independent cohorts) were identified. Prior stroke/TIA (relative risk 2.5, 95% CI 1.8 to 3.5), increasing age (relative risk 1.5 per decade, 95% CI 1.3 to 1.7), a history of hypertension (relative risk 2.0, 95% CI 1.6 to 2.5), and diabetes mellitus (relative risk 1.7, 95% CI 1.4 to 2.0) were the strongest, most consistent independent risk factors. Observed absolute stroke rates for nonanticoagulated patients with single independent risk factors were in the range of 6 to 9% per year for prior stroke/TIA, 1.5 to 3% per year for history of hypertension, 1.5 to 3% per year for age >75, and 2.0 to 3.5% per year for diabetes. Female sex was inconsistently associated with stroke risk, whereas the evidence was inconclusive that either heart failure or coronary artery disease is independently predictive of stroke.Four clinical features (prior stroke/TIA, advancing age, hypertension, diabetes) are consistent independent risk factors for stroke in atrial fibrillation patients. Prior stroke/TIA is the most powerful risk factor and reliably confers a high stroke risk (>5% per year, averaging 10% per year). Absolute stroke rates associated with other individual risk factors are difficult to precisely estimate from available data.

    View details for Web of Science ID 000248573000007

    View details for PubMedID 17679673

  • Risk factors of symptomatic intracerebral hemorrhage after tPA therapy for acute stroke STROKE Lansberg, M. G., Thijs, V. N., Bammer, R., Kemp, S., Wijman, C. A., Marks, M. P., Albers, G. W. 2007; 38 (8): 2275-2278

    Abstract

    Studies evaluating predictors of tPA-associated symptomatic intracerebral hemorrhage (SICH) have typically focused on clinical and CT-based variables. MRI-based variables have generally not been included in predictive models, and little is known about the influence of reperfusion on SICH risk.Seventy-four patients were prospectively enrolled in an open-label study of intravenous tPA administered between 3 and 6 hours after symptom onset. An MRI was obtained before and 3 to 6 hours after tPA administration. The association between several clinical and MRI-based variables and tPA-associated SICH was determined using multivariate logistic regression analysis. SICH was defined as a > or = 2 point change in National Institutes of Health Stroke Scale Score (NIHSSS) associated with any degree of hemorrhage on CT or MRI. Reperfusion was defined as a decrease in PWI lesion volume of at least 30% between baseline and the early follow-up MRI.SICH occurred in 7 of 74 (9.5%) patients. In univariate analysis, NIHSSS, DWI lesion volume, PWI lesion volume, and reperfusion status were associated with an increased risk of SICH (P<0.05). In multivariate analysis, DWI lesion volume was the single independent baseline predictor of SICH (odds ratio 1.42; 95% CI 1.13 to 1.78 per 10 mL increase in DWI lesion volume). When early reperfusion status was included in the predictive model, the interaction between DWI lesion volume and reperfusion status was the only independent predictor of SICH (odds ratio 1.77; 95% CI 1.25 to 2.50 per 10 mL increase in DWI lesion volume).Patients with large baseline DWI lesion volumes who achieve early reperfusion appear to be at greatest risk of SICH after tPA therapy.

    View details for DOI 10.1161/STROKEAHA.106.480475

    View details for PubMedID 17569874

  • Neurological picture. Acute strokes in the setting of a persistent primitive trigeminal artery. Journal of neurology, neurosurgery, and psychiatry Schwartz, N. E., Albers, G. W. 2007; 78 (7): 745-?

    View details for PubMedID 17575019

  • Perfusion mapping with multiecho multishot parallel imaging EPI MAGNETIC RESONANCE IN MEDICINE Newbould, R. D., Skare, S. T., Jochimsen, T. H., Alley, M. T., Moseley, M. E., Albers, G. W., Bammer, R. 2007; 58 (1): 70-81

    Abstract

    Echo-planar imaging (EPI) is the standard technique for dynamic susceptibility-contrast (DSC) perfusion MRI. However, EPI suffers from well-known geometric distortions, which can be reduced by increasing the k-space phase velocity. Moreover, the long echo times (TEs) used in DSC lead to signal saturation of the arterial input signal, and hence to severe quantitation errors in the hemodynamic information. Here, through the use of interleaved shot acquisition and parallel imaging (PI), rapid volumetric EPI is performed using pseudo-single-shot (ss)EPI with the effective T(*)(2) blur and susceptibility distortions of a multishot EPI sequence. The reduced readout lengths permit multiple echoes to be acquired with temporal resolution and spatial coverage similar to those obtained with a single-echo method. Multiecho readouts allow for unbiased R(*)(2) mapping to avoid incorrect estimation of tracer concentration due to signal saturation or T(1) shortening effects. Multiecho perfusion measurement also mitigates the signal-to-noise ratio (SNR) reduction that results from utilizing PI. Results from both volunteers and clinical stroke patients are presented. This acquisition scheme can aid most rapid time-series acquisitions. The use of this method for DSC addresses the problem of signal saturation and T(1) contamination while it improves image quality, and is a logical step toward better quantitative MR PWI.

    View details for DOI 10.1002/mrm.21255

    View details for Web of Science ID 000248488400009

    View details for PubMedID 17659630

  • Identifying systematic errors in quantitative dynamic-susceptibility contrast perfusion imaging by high-resolution multi-echo parallel EPI NMR IN BIOMEDICINE Jochimsen, T. H., Newbould, R. D., Skare, S. T., Clayton, D. B., Albers, G. W., Moseley, M. E., Bammer, R. 2007; 20 (4): 429-438

    Abstract

    Several obstacles usually confound a straightforward perfusion analysis using dynamic-susceptibility contrast-based magnetic resonance imaging (DSC-MRI). In this work, it became possible to eliminate some of these sources of error by combining a multiple gradient-echo technique with parallel imaging (PI): first, the large dynamic range of tracer concentrations could be covered satisfactorily with multiple echo times (TE) which would otherwise result in overestimation of image magnitude in the presence of noise. Second, any bias from T(1) relaxation could be avoided by fitting to the signal magnitude of multiple TEs. Finally, with PI, a good tradeoff can be achieved between number of echoes, brain coverage, temporal resolution and spatial resolution. The latter reduces partial voluming, which could distort calculation of the arterial input function. Having ruled out these sources of error, a 4-fold overestimation of cerebral blood volume and flow remained, which was most likely due to the completely different relaxation mechanisms that are effective in arterial voxels compared with tissue. Hence, the uniform tissue-independent linear dependency of relaxation rate upon tracer concentration, which is usually assumed, must be questioned. Therefore, DSC-MRI requires knowledge of the exact dependency of transverse relaxation rate upon tracer concentration in order to calculate truly quantitative perfusion maps.

    View details for DOI 10.1002/nbm.1107

    View details for Web of Science ID 000246767000004

    View details for PubMedID 17044140

  • Evaluation of the clinical-diffusion and perfusion-diffusion mismatch models in DEFUSE STROKE Lansberg, M. G., Thijs, V. N., Hamilton, S., Schlaug, G., Bammer, R., Kemp, S., Albers, G. W. 2007; 38 (6): 1826-1830

    Abstract

    The perfusion-diffusion mismatch (PDM) model has been proposed as a tool to select acute stroke patients who are most likely to benefit from reperfusion therapy. The clinical-diffusion mismatch (CDM) model is an alternative method that is technically less challenging because it does not require perfusion-weighted imaging. This study is an evaluation of these 2 models in the DEFUSE dataset.DEFUSE is an open-label multicenter study in which acute stroke patients were treated with intravenous tPA between 3 and 6 hours after symptoms onset and an MRI was obtained before and 3 to 6 hours after treatment. Presence of PDM and CDM was determined for each patient.Based on conventional predefined mismatch criteria, PDM was present in 54% of the DEFUSE population and CDM in 62%. There was no agreement beyond chance between the 2 mismatch models (kappa 0.07). The presence of PDM was associated with an increased chance of favorable clinical response after reperfusion (OR, 5.4; P=0.039). Reperfusion was not associated with a significant increase in the rate of favorable clinical response in patients with CDM (OR, 2.2; P=0.34). Using optimized mismatch criteria, determined retrospectively based on DEFUSE data, the OR for favorable clinical response was 70 (P=0.001) for PDM and 5.1 (P=0.066) for CDM.The PDM model appears to be more accurate than the CDM model for selecting patients who are likely to benefit from reperfusion therapy in the 3- to 6-hour time window.

    View details for DOI 10.1161/STROKEA.HA.106.480145

    View details for Web of Science ID 000246827100026

    View details for PubMedID 17495217

  • Transient isolated vertigo secondary to an acute stroke of the cerebellar nodulus ARCHIVES OF NEUROLOGY Schwartz, N. E., Venkat, C., Albers, G. W. 2007; 64 (6): 897-898

    View details for Web of Science ID 000247143500018

    View details for PubMedID 17562941

  • Clinical multishot DW-EPI through parallel imaging with considerations of susceptibility, motion, and noise MAGNETIC RESONANCE IN MEDICINE Skare, S., Newbould, R. D., Clayton, D. B., Albers, G. W., Nagle, S., Bammer, R. 2007; 57 (5): 881-890

    Abstract

    Geometric distortions and poor image resolution are well known shortcomings of single-shot echo-planar imaging (ss-EPI). Yet, due to the motion immunity of ss-EPI, it remains the most common sequence for diffusion-weighted imaging (DWI). Moreover, both navigated DW interleaved EPI (iEPI) and parallel imaging (PI) methods, such as sensitivity encoding (SENSE) and generalized autocalibrating parallel acquisitions (GRAPPA), can improve the image quality in EPI. In this work, DW-EPI accelerated by PI is proposed as a self-calibrated and unnavigated form of interleaved acquisition. The PI calibration is performed on the b = 0 s/mm2 data and applied to each shot in the rest of the DW data set, followed by magnitude averaging. Central in this study is the comparison of GRAPPA and SENSE in the presence of off-resonances and motion. The results show that GRAPPA is more robust than SENSE against both off-resonance and motion-related artifacts. The SNR efficiency was also investigated, and it is shown that the SNR/scan time ratio is equally high for one- to three-shot high-resolution diffusion scans due to the shortened EPI readout train length. The image quality improvements without SNR efficiency loss, together with motion tolerance, make the GRAPPA-driven DW-EPI sequence clinically attractive.

    View details for DOI 10.1002/mrm.21176

    View details for Web of Science ID 000246052800010

    View details for PubMedID 17457876

  • The efficacy and safety of enoxaparin versus unfractionated heparin for the prevention of venousthromboembolism after acute ischaemic stroke (PREVAIL Study): an open-label randomised comparison LANCET Sherman, D. G., Albers, G. W., Bladin, C., Fieschi, C., Gabbai, A. A., Kase, C. S., O'Riordan, W., Pineo, G. F. 2007; 369 (9570): 1347-1355

    Abstract

    Venous thromboembolism prophylaxis with low molecular weight heparin or unfractionated heparin is recommended in acute ischaemic stroke, but which regimen provides optimum treatment is uncertain. We aimed to compare the efficacy and safety of enoxaparin with that of unfractionated heparin for patients with stroke.1762 patients with acute ischaemic stroke who were unable to walk unassisted were randomly assigned within 48 h of symptoms to receive either enoxaparin 40 mg subcutaneously once daily or unfractionated heparin 5000 U subcutaneously every 12 h for 10 days (range 6-14). Patients were stratified by National Institutes of Health Stroke Scale (NIHSS) score (severe stroke > or =14, less severe stroke <14). The primary efficacy endpoint was the composite of symptomatic or asymptomatic deep vein thrombosis, symptomatic pulmonary embolism, or fatal pulmonary embolism. Primary safety endpoints were symptomatic intracranial haemorrhage, major extracranial haemorrhage, and all-cause mortality. This study is registered with ClinicalTrials.gov, number NCT00077805.In the efficacy population (ie, one or more dose received, presence of deep vein thrombosis or pulmonary embolism, or assessment for venous thromboembolism), enoxaparin (n=666) and unfractionated heparin (669) were given for 10.5 days (SD 3.2). Enoxaparin reduced the risk of venous thromboembolism by 43% compared with unfractionated heparin (68 [10%] vs 121 [18%]; relative risk 0.57, 95% CI 0.44-0.76, p=0.0001; difference -7.9%, -11.6 to -4.2); this reduction was consistent for patients with an NIHSS score of 14 or more (26 [16%] vs 52 [30%]; p=0.0036) or less than 14 (42 [8%] vs 69 [14%]; p=0.0044). The occurrence of any bleeding was similar with enoxaparin (69 [8%]) or unfractionated heparin (71 [8%]; p=0.83). The frequency of the composite of symptomatic intracranial and major extracranial haemorrhage was small and closely similar between groups (enoxaparin 11 [1%] vs unfractionated heparin 6 [1%]; p=0.23). We noted no difference for symptomatic intracranial haemorrhage between groups (4 [1%] vs 6 [1%], respectively; p=0.55); the rate of major extracranial bleeding was higher with enoxaparin than with unfractionated heparin (7 [1%] vs 0; p=0.015).Our results suggest that for patients with acute ischaemic stroke, enoxaparin is preferable to unfractionated heparin for venous thromboembolism prophylaxis in view of its better clinical benefits to risk ratio and convenience of once daily administration.

    View details for Web of Science ID 000245856100027

    View details for PubMedID 17448820

  • Secondary stroke prevention with ximelagatran versus warfarin in patients with atrial fibrillation - Pooled analysis of SPORTIF III and V clinical trials 14th European Stroke Conference Akins, P. T., Feldman, H. A., Zoble, R. G., Newman, D., Spitzer, S. G., Diener, H., Albers, G. W. LIPPINCOTT WILLIAMS & WILKINS. 2007: 874–80

    Abstract

    Patients with nonvalvular atrial fibrillation and prior stroke or transient ischemic attack (TIA) are at high risk for recurrent stroke. We investigated whether ximelagatran was noninferior to warfarin in patients with prior stroke or TIA.We analyzed pooled data from the SPORTIF III and V trials in patients with prior stroke/TIA. The primary outcome was the composite annual rate of both ischemic and hemorrhagic strokes and systemic embolic events. Secondary analyses considered ischemic and hemorrhagic strokes separately, bleeding, and nonrandomized, concomitant therapy with aspirin < or =100 mg/d.Patients from SPORTIF III (n=3407) and SPORTIF V (n=3922) trials were categorized by prior stroke/TIA (21%) versus no prior stroke/TIA (79%) and by treatment group (ximelagatran vs warfarin). The primary event rate in patients with prior stroke/TIA was 2.83%/y with ximelagatran and 3.27%/y with warfarin (absolute difference, -0.44%; 95% CI, -1.88 to1.01; P=0.625). In those without prior stroke/TIA, the primary event rate was 1.31%/y with ximelagatran and 1.26%/y with warfarin (P=NS). Ischemic strokes outnumbered cerebral hemorrhages with both warfarin (31 of 36) and ximelagatran (30 of 32) treatment (difference between treatments was not significant). Combining aspirin with either anticoagulant was associated with higher rates of major bleeding (1.5%/y with warfarin and 4.95%/y with warfarin plus aspirin, P=0.004; 2.35%/y with ximelagatran and 5.09%/y with ximelagatran plus aspirin, P=0.046) but not lower rates of primary events.Ximelagatran was at least as effective as well-controlled warfarin for the secondary prevention of stroke. The nonrandomized, concomitant treatment with aspirin and anticoagulation was associated with increased bleeding without evidence of a reduction in primary outcome events.

    View details for DOI 10.1161/01.STR.0000258004.64840.0b

    View details for Web of Science ID 000244482500017

    View details for PubMedID 17255547

  • Can the ESPRIT results end the antiplatelet battle between neurologists and cardiologists? NATURE CLINICAL PRACTICE CARDIOVASCULAR MEDICINE Albers, G. W. 2007; 4 (3): 118-119

    View details for DOI 10.1038/ncpcardio0803

    View details for Web of Science ID 000244378000002

    View details for PubMedID 17330124

  • Comparison of outcomes among patients randomized to warfarin therapy according to anticoagulant control - Results from SPORTIF III and IV ARCHIVES OF INTERNAL MEDICINE White, H. D., Gruber, M., Feyzi, J., Kaatz, S., Tse, H., Husted, S., Albers, G. W. 2007; 167 (3): 239-245

    Abstract

    Warfarin sodium reduces stroke risk in patients with atrial fibrillation, but international normalized ratio (INR) monitoring is required. Target INRs are frequently not achieved, and the risk of death, bleeding, myocardial infarction (MI), and stroke or systemic embolism event (SEE) may be related to INR control.We analyzed the relationship between INR control and the rates of death, bleeding, MI, and stroke or SEE among 3587 patients with atrial fibrillation randomized to receive warfarin treatment in the SPORTIF (Stroke Prevention Using an Oral Thrombin Inhibitor in Atrial Fibrillation) III and V trials. The mean+/-SD follow-up was 16.6 +/- 6.3 months. Patients were divided into 3 equal groups (those with good control [>75%], those with moderate control [60%-75%], or those with poor control [<60%]) according to the percentage time with an INR of 2.0 to 3.0. Outcomes were compared according to INR control. The main outcome measures were death, bleeding, MI, and stroke or SEE.The poor control group had higher rates of annual mortality (4.20%) and major bleeding (3.85%) compared with the moderate control group (1.84% and 1.96%, respectively) and the good control group (1.69% and 1.58%, respectively) (P<.01 for all). Compared with the good control group, the poor control group had higher rates of MI (1.38% vs 0.62%, P = .04) and of stroke or SEE (2.10% vs 1.07%, P = .02).In patients with atrial fibrillation taking warfarin, the risks of death, MI, major bleeding, and stroke or SEE are related to INR control. Good INR control is important to improve patient outcomes.

    View details for Web of Science ID 000244163200003

    View details for PubMedID 17296878

  • A multicenter pooled, patient-level data analysis of diffusion-weighted MRI in TIA patients 32nd International Stroke Conference Shah, S. H., Saver, J. L., Kidwell, C. S., Albers, G., Rothwell, P., Ay, H., Koroshetz, W. J., Inatomi, Y., Uchino, M., Demchuk, A. M., Coutts, S. B., Purroy, F., Alvarez-Sabin, J., Sander, K., Sander, D., Restrepo, L., Wityk, R. J., Marx, J. J., Easton, J. D. LIPPINCOTT WILLIAMS & WILKINS. 2007: 463–63

    View details for Web of Science ID 000244122600103

  • Clinical and radiographic history of cervical artery dissections 32nd International Stroke Conference Hirsch, K., Vertinsky, T., Albers, G. W., Schwartz, N. E. LIPPINCOTT WILLIAMS & WILKINS. 2007: 587–87

    View details for Web of Science ID 000244122600671

  • Intravenous alteplase for ischaemic stroke LANCET Albers, G. W., Olivot, J. 2007; 369 (9558): 249-250

    View details for Web of Science ID 000243912000004

    View details for PubMedID 17258646

  • Symptomatic intracerebral hemorrhage following thrombolytic therapy for acute ischemic stroke: A review of the risk factors CEREBROVASCULAR DISEASES Lansberg, M. G., Albers, G. W., Wijman, C. A. 2007; 24 (1): 1-10

    Abstract

    Symptomatic intracerebral hemorrhage (SICH) following thrombolytic therapy for acute ischemic stroke is associated with a high rate of morbidity and mortality. Knowledge of the risk factors associated with SICH following thrombolyitc therapy may provide insight into the pathophysiological mechanisms underlying the development of SICH, lead to the development of treatments that reduce the risk of SICH and have implications for the design of future stroke trials.Relevant studies were identified through a search in Pubmed. Included studies used multivariate analyses to identify independent risk factors for SICH following thrombolytic therapy. For each variable that was found to have a significant association with SICH, a secondary literature search was conducted to identify additional reports on the specific relationship between that variable and SICH.Twelve studies met inclusion criteria for the systematic review. Extent of hypoattenuated brain parenchyma on pretreatment CT and elevated serum glucose or history of diabetes were independent risk factors for thrombolysis-associated SICH in six of the twelve studies. Symptom severity was an independent risk factor in three of the studies and advanced age, increased time to treatment, high systolic blood pressure, low platelets, history of congestive heart failure and low plasminogen activator inhibitor levels were found to be independent risk factors for SICH in a single study. Although these data should not alter the current guidelines for the use of rt-PA in acute stroke, they may help develop future strategies aimed at reducing the rate of thrombolysis-associated SICH.

    View details for DOI 10.1159/000103110

    View details for Web of Science ID 000247435300001

    View details for PubMedID 17519538

  • Safety and tolerability of arundic acid in acute ischemic stroke JOURNAL OF THE NEUROLOGICAL SCIENCES Pettigrew, L. C., Kasner, S. E., Albers, G. W., Gorman, M., Grotta, J. C., Sherman, D. G., Funakoshi, Y., Ishibashi, H. 2006; 251 (1-2): 50-56

    Abstract

    Arundic acid (AA; ONO-2506), a novel modulator of astrocyte activation, may improve neuronal survival after stroke. We conducted a multicenter, dose-escalating, randomized, double-blind Phase I trial of AA in acute ischemic stroke. Subjects were randomized to treatment with AA or placebo in sequential dose tiers of 2-12 mg/kg/h (10-16 patients/group) within 24 h of stroke onset. Study drug was infused for 1 h daily over 7 days, and follow-up terminated at 40 days. Neurological and functional outcomes were evaluated through Day 40 as exploratory endpoints. A total of 92 subjects were enrolled with no dose-related pattern of serious adverse events (AEs). Premature terminations caused by AEs occurred in four (8.2%) patients treated with AA and five (11.6%) treated with placebo. Two subjects treated with AA (4.1%) and four given placebo (9.3%) died. Exploratory efficacy analysis showed a trend toward improvement in the change from baseline National Institutes of Health Stroke Scale (NIHSS) in the 8 mg/kg/h AA group on Days 3 (p=0.023 vs. placebo), 7 (p=0.002), 10 (p=0.003), and 40 (p=0.018). A dose of 8 mg/kg/h AA produced a favorable trend in reduction of NIHSS that should be confirmed in a future clinical trial.

    View details for DOI 10.1016/j.jns.2006.09.001

    View details for Web of Science ID 000243059000009

    View details for PubMedID 17095018

  • Magnetic resonance imaging profiles predict clinical response to early reperfusion: The diffusion and perfusion imaging evaluation for understanding stroke evolution (DEFUSE) study ANNALS OF NEUROLOGY Albers, G. W., Thijs, V. N., Wechsle, L., Kemp, S., Schlaug, G., Skalabrin, E., Bammer, R., Kakuda, W., Lansberg, M. G., Shuaib, A., Coplin, W., Hamilton, S., Moseley, M., Marks, M. P. 2006; 60 (5): 508-517

    Abstract

    To determine whether prespecified baseline magnetic resonance imaging (MRI) profiles can identify stroke patients who have a robust clinical response after early reperfusion when treated 3 to 6 hours after symptom onset.We conducted a prospective, multicenter study of 74 consecutive stroke patients admitted to academic stroke centers in North America and Europe. An MRI scan was obtained immediately before and 3 to 6 hours after treatment with intravenous tissue plasminogen activator 3 to 6 hours after symptom onset. Baseline MRI profiles were used to categorize patients into subgroups, and clinical responses were compared based on whether early reperfusion was achieved.Early reperfusion was associated with significantly increased odds of achieving a favorable clinical response in patients with a perfusion/diffusion mismatch (odds ratio, 5.4; p = 0.039) and an even more favorable response in patients with the Target Mismatch profile (odds ratio, 8.7; p = 0.011). Patients with the No Mismatch profile did not appear to benefit from early reperfusion. Early reperfusion was associated with fatal intracranial hemorrhage in patients with the Malignant profile.For stroke patients treated 3 to 6 hours after onset, baseline MRI findings can identify subgroups that are likely to benefit from reperfusion therapies and can potentially identify subgroups that are unlikely to benefit or may be harmed.

    View details for DOI 10.1002/ana.20976

    View details for PubMedID 17066483

  • Acute cerebrovascular syndrome: time for new terminology for acute brain ischemia NATURE CLINICAL PRACTICE CARDIOVASCULAR MEDICINE Albers, G. W. 2006; 3 (10): 521-521

    View details for DOI 10.1038/ncpcardio0679

    View details for Web of Science ID 000240850900001

    View details for PubMedID 16990832

  • Proof-of-principle phase II MRI studies in stroke - Sample size estimates from dichotomous and continuous data STROKE Donnan, G. A., Davis, S. M., Phan, T. G., Ludbrook, J., Byrnes, G., Parsons, M., Barber, A. P., Reutens, D. C., Rose, S. E., Chalk, J., Demchuk, A. M., Coutts, S. B., Simon, J. E., Tomanek, A., Roether, J., Weiller, C., Fiehler, J., Thomalla, G., Kucinski, T., Schellinger, P. D., Hacke, W., Gass, A., Szabo, K., Hennerici, M., Siebler, M., Villringer, A., Junge-Huelsing, G. J., Pedraza, S., Davalos, A., Castillo, J., Albers, G. W., Lansberg, M. G., Thijs, V. N., Bammer, R., Moseley, M. E., Marks, M., Warach, S., Baird, A., Kidwell, C., Saver, J., Sorensen, G., Fisher, M., Nighoghossian, N., Muir, K. 2006; 37 (10): 2521-2525

    Abstract

    Since the failure of a number of phase III trials of neuroprotection in ischemic stroke, the need for smaller phase II studies with MRI surrogates has emerged. There is, however, little information available about sample size requirements for such phase II trials and rarely enough patients in single studies to make robust estimates. We have formed an international collaborative group to assemble larger datasets and from these have generated sample size tables for MRI-based infarct expansion as the outcome measure.Twelve centers from Australia, Europe, and North America contributed data from patients with hemispheric ischemic stroke. Infarct expansion was defined from initial diffusion-weighted images and later fluid-attenuated inversion recover or T2 images. Sample size estimates were calculated from data on infarct expansion ratios treated as dichotomous or continuous variables. A nonparametric approach was used because the distribution of infarct expansion was resistant to all forms of transformation.As an example, a 20% absolute reduction in infarct expansion ratio (< or = 1), 80% power, and alpha = 0.05 requires 99 patients in each arm. To achieve an equivalent effect size with a continuous approach requires 61 patients.These tables will be useful in planning phase II trials of therapy with the use of MRI outcome measures. For positive studies, biologically plausible surrogates such as these may provide a rationale for proceeding to phase III trials.

    View details for DOI 10.1161/01.STR.0000239696.61545.4b

    View details for Web of Science ID 000240938700021

    View details for PubMedID 16931782

  • Trials and tribulations of noninferiority: The ximelagatran experience JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Albers, G. W., Diener, H., Frison, L., Grind, M., Horrow, J., Nevinson, M., Olsson, S. B., Partridge, S., Petersen, P., Vahanian, A., Halperin, J. L. 2006; 48 (5): 1058-1058

    View details for DOI 10.1016/j.jacc.2006.06.004

    View details for Web of Science ID 000240324500025

    View details for PubMedID 16949503

  • National stroke association guidelines for the management of transient ischemic attacks ANNALS OF NEUROLOGY Johnston, S. C., Nguyen-Huynh, M. N., Schwarz, M. E., Fuller, K., Williams, C. E., Josephson, S. A. 2006; 60 (3): 301-313

    Abstract

    Transient ischemic attacks are common and important harbingers of subsequent stroke. Management varies widely, and most published guidelines have not been updated in several years. We sought to create comprehensive, unbiased, evidence-based guidelines for the management of patients with transient ischemic attacks.Fifteen expert panelists were selected based on objective criteria, using publication metrics that predicted nomination by practitioners in the field. Prior published guidelines were identified through systematic review, and recommendations derived from them were rated independently for quality by the experts. Highest quality recommendations were selected and subsequently edited by the panelists using a modified Delphi approach with multiple iterations of questionnaires to reach consensus on new changes. Experts were provided systematic reviews of recent clinical studies and were asked to justify wording changes based on new evidence and to rate the final recommendations based on level of evidence and quality. No expert was allowed to contribute to recommendations on a topic for which there could be any perception of a conflict of interest.Of 257 guidelines documents identified by systematic review, 13 documents containing 137 recommendations met all entry criteria. Six iterations of questionnaires were required to reach consensus on wording of 53 final recommendations. Final recommendations covered initial management, evaluation, medical treatment, surgical treatment, and risk factor management.The final recommendations on the care of patients with transient ischemic attacks emphasize the importance of urgent evaluation and treatment. The novel approach used to develop these guidelines is feasible, allows for rapid updating, and may reduce bias.

    View details for DOI 10.1002/ana.20942

    View details for Web of Science ID 000241007600007

    View details for PubMedID 16912978

  • Dose escalation of desmoteplase for acute ischemic stroke (DEDAS) - Evidence of safety and efficacy 3 to 9 hours after stroke onset STROKE Furlan, A. J., Eyding, D., Albers, G. W., Al-Rawi, Y., Lees, K. R., Rowley, H. A., Sachara, C., Soehngen, M., Warach, S., Hacke, W. 2006; 37 (5): 1227-1231

    Abstract

    Desmoteplase is a novel plasminogen activator with favorable features in vitro compared with available agents. This study evaluated safety and efficacy of intravenous (IV) desmoteplase in patients with perfusion/diffusion mismatch on MRI 3 to 9 hours after onset of acute ischemic stroke.DEDAS was a placebo-controlled, double-blind, randomized, dose-escalation study investigating doses of 90 microg/kg and 125 microg/kg desmoteplase. Eligibility criteria included baseline National Institute of Health Stroke Scale (NIHSS) scores of 4 to 20 and MRI evidence of perfusion/diffusion mismatch. The safety end point was the rate of symptomatic intracranial hemorrhage. Primary efficacy co-end points were MRI reperfusion 4 to 8 hours after treatment and good clinical outcome at 90 days. The primary analyses were intent-to-treat. Before unblinding, a target population, excluding patients violating specific MRI criteria, was defined.Thirty-seven patients were randomized and received treatment (intent-to-treat; placebo: n=8; 90 microg/kg: n=14; 125 microg/kg: n=15). No symptomatic intracranial hemorrhage occurred. Reperfusion was achieved in 37.5% (95% CI [8.5; 75.5]) of placebo patients, 18.2% (2.3; 51.8) of patients treated with 90 microg/kg desmoteplase, and 53.3% (26.6; 78.7) of patients treated with 125 microg/kg desmoteplase. Good clinical outcome at 90 days occurred in 25.0% (3.2; 65.1) treated with placebo, 28.6% (8.4; 58.1) treated with 90 microg/kg desmoteplase and 60.0% (32.3; 83.7) treated with 125 microg/kg desmoteplase. In the target population (n=25), the difference compared with placebo increased and was statistically significant for good clinical outcome with 125 microg/kg desmoteplase (P=0.022).Treatment with IV desmoteplase 3 to 9 hours after ischemic stroke onset appears safe. At a dose of 125 microg/kg desmoteplase appeared to improve clinical outcome, especially in patients fulfilling all MRI criteria. The results of DEDAS generally support the results of its predecessor study, Desmoteplase in Acute Ischemic Stroke (DIAS).

    View details for DOI 10.1161/01.STR.0000217403.66996.6d

    View details for Web of Science ID 000237053900028

    View details for PubMedID 16574922

  • MRI characteristics of cerebral air embolism from a venous source NEUROLOGY Caulfield, A. F., Lansberg, M. G., Marks, M. P., Albers, G. W., Wijman, C. A. 2006; 66 (6): 945-946

    View details for Web of Science ID 000236292300037

    View details for PubMedID 16567722

  • Guidelines for prevention of stroke in patients with ischemic stroke or transient ischemic attack - A statement for healthcare professionals from the American Heart Association/American Stroke Association Council on Stroke - Co-sponsored by the Council on Cardiovascular Radiology and Intervention - The American Academy of Neurology affirms the value of this guideline. CIRCULATION Sacco, R. L., Adams, R., Albers, G., Alberts, M. J., Benavente, O., Furie, K., Goldstein, L. B., Gorelick, P., Halperin, J., Harbaugh, R., Johnston, S. C., Katzan, I., Kelly-Hayes, M., Kenton, E. J., Marks, M., Schwamm, L. H., Tomsick, T. 2006; 113 (10): E409-E449

    Abstract

    The aim of this new statement is to provide comprehensive and timely evidence-based recommendations on the prevention of ischemic stroke among survivors of ischemic stroke or transient ischemic attack. Evidence-based recommendations are included for the control of risk factors, interventional approaches for atherosclerotic disease, antithrombotic treatments for cardioembolism, and the use of antiplatelet agents for noncardioembolic stroke. Further recommendations are provided for the prevention of recurrent stroke in a variety of other specific circumstances, including arterial dissections; patent foramen ovale; hyperhomocysteinemia; hypercoagulable states; sickle cell disease; cerebral venous sinus thrombosis; stroke among women, particularly with regard to pregnancy and the use of postmenopausal hormones; the use of anticoagulation after cerebral hemorrhage; and special approaches for the implementation of guidelines and their use in high-risk populations.

    View details for Web of Science ID 000235971600025

    View details for PubMedID 16534023

  • Mechanical thrombectomy following intravenous thrombolysis in the treatment of acute stroke ARCHIVES OF NEUROLOGY Lansberg, M. G., Fields, J. D., Albers, G. W., Jayaraman, M. V., Do, H. M., Marks, M. P. 2005; 62 (11): 1763-1765

    Abstract

    The efficacy of intravenous thrombolytics in acute stroke is limited by low rates of recanalization of occluded arteries. Treatment with intravenous thrombolytics followed by mechanical thrombectomy is a novel approach that may increase recanalization rates without compromising time to initiation of treatment.To report our experience with 2 patients who received this combination therapy and outline plans for a prospective pilot study.Case studies at a university hospital.Patients treated with intravenous thrombolytics within 3 hours of symptom onset subsequently underwent computed tomographic angiography. If an occlusion of a proximal cerebral vessel was shown by a computed tomographic angiogram, mechanical thrombectomy was performed. Patients were observed for 1 month after treatment.National Institutes of Health Stroke Scale (NIHSS) score.The computed tomographic angiography of 2 patients showed complete occlusion of the M1 branch of the middle cerebral artery following administration of intravenous thrombolytics. The NIHSS scores were 21 and 13. In both cases, blood flow through the occluded artery was restored with mechanical thrombectomy and dramatic neurologic improvement occurred. There were no complications. The NIHSS scores were 0 and 2 at 1-month follow-up.Treatment with intravenous thrombolytics followed by mechanical thrombectomy may improve outcomes in acute stroke patients and a pilot safety trial is warranted.

    View details for PubMedID 16286552

  • Clinical importance of microbleeds in patients receiving IV thrombolysis NEUROLOGY Kakuda, W., Thijs, V. N., Lansberg, M. G., Bammer, R., Wechsler, L., Kemp, S., Moseley, M. E., Marks, M. P., Albers, G. W. 2005; 65 (8): 1175-1178

    Abstract

    Cerebral microbleeds (MBs) detected on gradient echo (GRE) imaging may be a risk factor for hemorrhagic complications in patients with stroke treated with IV tissue plasminogen activator (tPA).The authors prospectively evaluated patients with acute ischemic stroke treated with IV tPA between 3 and 6 hours of symptom onset. MRI scans, including GRE imaging, were performed prior to tPA treatment, 3 to 6 hours after treatment and at day 30. The authors compared the frequency of hemorrhagic complications after thrombolysis in patients with and without MBs on their baseline GRE imaging.Seventy consecutive patients (mean age, 71 +/- 29 years; 31 men, 39 women) were included. MBs were identified in 11 patients (15.7%) on baseline GRE imaging. There was no significant difference in the frequency of either symptomatic or asymptomatic hemorrhagic complications after thrombolysis between patients with and without MBs at baseline. None of the 11 patients with MBs (0%) at baseline had a symptomatic intracerebral hemorrhage compared with 7 of 59 patients who did not have baseline MBs (11.9%). In addition, no patients with baseline MBs had asymptomatic hemorrhagic transformation observed at the site of any pre-treatment MB.The presence of cerebral microbleeds on gradient echo imaging does not appear to substantially increase the risk of either symptomatic or asymptomatic brain hemorrhage following IV tissue plasminogen activator administered between 3 and 6 hours after stroke onset.

    View details for Web of Science ID 000232813600008

    View details for PubMedID 16247042

  • Enhancing the development and approval of acute stroke therapies - Stroke Therapy Academic Industry Roundtable STROKE Fisher, M. 2005; 36 (8): 1808-1813

    Abstract

    Previous Stroke Therapy Academic Industry Roundtable (STAIR) meetings focused on preclinical evidence of drug efficacy and enhancing acute stroke trial design and performance. A fourth (STAIR-IV) was held to discuss relevant issues related to acute stroke drug development and regulatory approval.The STAIR-IV meeting had 3 main focus areas. The first topic was novel approaches to statistical design of acute stroke trials and appropriate outcome measures. The second focus was the need for better cooperation among participants in stroke therapy development that may be addressed through a national consortium of stroke trial centers in the United States and elsewhere. Lastly, regulatory issues related to the approval of novel mono and multiple acute stroke therapies were discussed.The development of additional acute stroke therapies represents a large unmet need with many remaining challenges and also opportunities to incorporate novel approaches to clinical trial design that will lead to regulatory approval. The STAIR-IV meeting explored new concepts of trial methodology and data analysis, initiatives for implementing a US clinical trialist consortium, and pertinent regulatory issues to expedite approval of novel therapies.

    View details for DOI 10.1161/01.STR.0000173403.60553.27

    View details for Web of Science ID 000230817600033

    View details for PubMedID 16020764

  • Mechanical thrombectomy for acute stroke AMERICAN JOURNAL OF NEURORADIOLOGY Versnick, E. J., Do, H. M., Albers, G. W., Tong, D. C., Marks, M. P. 2005; 26 (4): 875-879

    Abstract

    We evaluated a mechanical thrombectomy protocol to treat acute stroke and report the angiographic results and clinical outcomes.Patients with anterior circulation strokes <8 hours and posterior circulation strokes <12 hours were treated at a single center over 10 months. Patients were excluded if they were candidates for intravenous tissue plasminogen activator (tPA). Treatment involved one of two mechanical thrombectomy devices. Retrieval was augmented by low-dose intra-arterial tPA if needed. Outcome was measured by using the Modified Rankin score.Ten patients were treated: five with anterior circulation strokes, four with posterior circulation strokes, and one with embolic strokes involving both circulations. Mean National Institutes of Health Stroke Scale score at presentation was 24.6 +/- 10.9. In eight patients (80%), revascularization was successful (Thrombolysis in Acute Myocardial Infarction score, 3). Mean time from symptom onset to initiation of the procedure was 6 hours (5.3 hours for anterior circulation and 7.0 hours for posterior circulation). Mean time for recanalization from the start of the procedure was 1.17 +/- 0.58 hours for the six anterior circulation strokes and 2.75 +/- 1.34 hours in the two posterior circulation strokes. Five patients died within 48 hours; all had posterior circulation strokes. Mean Modified Rankin score at 90 days was 1.4.In this small series, mechanical thrombectomy of acute stroke appeared to improve recanalization rates compared with intra-arterial thrombolysis. No hemorrhagic complications occurred. Further study is required to determine the role of these techniques.

    View details for PubMedID 15814937

  • Intracranial Angioplasty without stenting for symptomatic atherosclerotic stenosis: Long-term follow-up AMERICAN JOURNAL OF NEURORADIOLOGY Marks, M. P., Marcellus, M. L., Do, H. M., Schraedley-Desmond, P. K., Steinberg, G. K., Tong, D. C., Albers, G. W. 2005; 26 (3): 525-530

    Abstract

    Angioplasty and stent placement have been reported for the treatment of intracranial stenosis. This study was undertaken to assess the efficacy and long-term clinical outcome of angioplasty without stent placement for patients with symptomatic intracranial stenosis.A retrospective study was done to evaluate 36 patients with 37 symptomatic atherosclerotic intracranial stenosis who underwent primary balloon angioplasty. All patients had symptoms despite medical therapy. Thirty-four patients were available for follow-up ranging from 6 to 128 months. Mean follow-up was 52.9 months.Mean pretreatment stenosis was 84.2% before angioplasty and 43.3% after angioplasty. The periprocedural death and stroke rate was 8.3% (two deaths and one minor stroke). Two patients had strokes in the territory of angioplasty at 2 and 37 months after angioplasty. The annual stroke rate in the territory appropriate to the site of angioplasty was 3.36%, and for those patients with a residual stenosis of > or =50% it was 4.5%. Patients with iatrogenic dissection (n=11) did not have transient ischemic attacks or strokes after treatment.Results of long-term follow-up suggest that intracranial angioplasty without stent placement reduces the risk of further stroke in symptomatic patients.

    View details for PubMedID 15760860

  • Oral antiplatelet therapy JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Bernstein, R. A., Albers, G. W. 2005; 293 (7): 793-794

    View details for Web of Science ID 000226984600012

    View details for PubMedID 15713763

  • Ximelagatran vs warfarin for stroke prevention in patients with nonvalvular atrial fibrillation - A Randomized trial JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Albers, G. W., Diener, H. C., Frison, L., Grind, M., Nevinson, M., Partridge, S., Halperin, J. L., Horrow, J., Olsson, S. B., Petersen, P., Vahanian, A. 2005; 293 (6): 690-698

    Abstract

    In patients with nonvalvular atrial fibrillation, warfarin prevents ischemic stroke, but dose adjustment, coagulation monitoring, and bleeding limit its use.To compare the efficacy of the oral direct thrombin inhibitor ximelagatran with warfarin for prevention of stroke and systemic embolism.Double-blind, randomized, multicenter trial (2000-2001) conducted at 409 North American sites, involving 3922 patients with nonvalvular atrial fibrillation and additional stroke risk factors.Adjusted-dose warfarin (aiming for an international normalized ratio [INR] 2.0 to 3.0) or fixed-dose oral ximelagatran, 36 mg twice daily.The primary end point was all strokes (ischemic or hemorrhagic) and systemic embolic events. The primary analysis was based on demonstrating noninferiority within an absolute margin of 2.0% per year according to the intention-to-treat model.During 6405 patient-years (mean 20 months) of follow-up, 88 patients experienced primary events. The mean (SD) INR with warfarin (2.4 [0.8]) was within target during 68% of the treatment period. The primary event rate with ximelagatran was 1.6% per year and with warfarin was 1.2% per year (absolute difference, 0.45% per year; 95% confidence interval, -0.13% to 1.03% per year; P<.001 for the predefined noninferiority hypothesis). When all-cause mortality was included in addition to stroke and systemic embolic events, the rate difference was 0.10% per year (95% confidence interval, -0.97% to 1.2% per year; P = .86). There was no difference between treatment groups in rates of major bleeding, but total bleeding (major and minor) was lower with ximelagatran (37% vs 47% per year; 95% confidence interval for the difference, -14% to -6.0% per year; P<.001). Serum alanine aminotransferase levels rose to greater than 3 times the upper limit of normal in 6.0% of patients treated with ximelagatran, usually within 6 months and typically declined whether or not treatment continued; however, one case of documented fatal liver disease and one other suggestive case occurred.The results establish the efficacy of fixed-dose oral ximelagatran without coagulation monitoring compared with well-controlled warfarin for prevention of thromboembolism in patients with atrial fibrillation requiring chronic anticoagulant therapy, but the potential for hepatotoxicity requires further investigation.

    View details for Web of Science ID 000226842200022

    View details for PubMedID 15701910

  • Who is most likely to benefit from tPA? The perfusion-diffusion and clinical-diffusion mismatch models disagree 30th International Stroke Conference Lansberg, M. G., Thijs, V. N., Bammer, R., Wechsler, L. R., O'Donnell, M. J., Olshen, R. A., Wijman, C. A., Kemp, S. M., Albers, G. W. LIPPINCOTT WILLIAMS & WILKINS. 2005: 437–37

    View details for Web of Science ID 000227523800098

  • The Desmoteplase In Acute Ischemic Stroke Trial (DIAS) - A phase II MRI-based 9-hour window acute stroke thrombolysis trial with intravenous desmoteplase STROKE Hacke, W., Albers, G., Al-Rawi, Y., Bogousslavsky, J., Davalos, A., Eliasziw, M., Fischer, M., Furlan, A., Kaste, M., Lees, K. R., Soehngen, M., Warach, S. 2005; 36 (1): 66-73

    Abstract

    Most acute ischemic stroke patients arrive after the 3-hour time window for recombinant tissue plasminogen activator (rtPA) administration. The Desmoteplase In Acute Ischemic Stroke trial (DIAS) was a dose-finding randomized trial designed to evaluate the safety and efficacy of intravenous desmoteplase, a highly fibrin-specific and nonneurotoxic thrombolytic agent, administered within 3 to 9 hours of ischemic stroke onset in patients with perfusion/diffusion mismatch on MRI.DIAS was a placebo-controlled, double-blind, randomized, dose-finding phase II trial. Patients with National Institute of Health Stroke Scale (NIHSS) scores of 4 to 20 and MRI evidence of perfusion/diffusion mismatch were eligible. Of 104 patients, the first 47 (referred to as Part 1) were randomized to fixed doses of desmoteplase (25 mg, 37.5 mg, or 50 mg) or placebo. Because of an excessive rate of symptomatic intracranial hemorrhage (sICH), lower weight-adjusted doses escalating through 62.5 microg/kg, 90 microg/kg, and 125 microg/kg were subsequently investigated in 57 patients (referred to as Part 2). The safety endpoint was the rate of sICH. Efficacy endpoints were the rate of reperfusion on MRI after 4 to 8 hours and clinical outcome as assessed by NIHSS, modified Rankin scale, and Barthel Index at 90 days.Part 1 was terminated prematurely because of high rates of sICH with desmoteplase (26.7%). In Part 2, the sICH rate was 2.2%. No sICH occurred with placebo in either part. Reperfusion rates up to 71.4% (P=0.0012) were observed with desmoteplase (125 microg/kg) compared with 19.2% with placebo. Favorable 90-day clinical outcome was found in 22.2% of placebo-treated patients and between 13.3% (62.5 microg/kg; P=0.757) and 60.0% (125 microg/kg; P=0.0090) of desmoteplase-treated patients. Early reperfusion correlated favorably with clinical outcome (P=0.0028). Favorable outcome occurred in 52.5% of patients experiencing reperfusion versus 24.6% of patients without reperfusion.Intravenous desmoteplase administered 3 to 9 hours after acute ischemic stroke in patients selected with perfusion/diffusion mismatch is associated with a higher rate of reperfusion and better clinical outcome compared with placebo. The sICH rate with desmoteplase was low, using doses up to 125 microg/kg.

    View details for DOI 10.1161/01.STR.0000149938.08731.2c

    View details for Web of Science ID 000225944800018

    View details for PubMedID 15569863

  • Optimizing oral anticoagulation in managed care AMERICAN JOURNAL OF MANAGED CARE Schaecher, K., Albers, G. W., Caro, J. J. 2004; 10 (14): S474-S477

    View details for Web of Science ID 000226142200006

    View details for PubMedID 15696911

  • Stroke prevention in atrial fibrillation: Pooled analysis of SPORTIF III and V trials 5th World Stroke Congress Albers, G. W. MANAGED CARE & HEALTHCARE COMMUNICATIONS LLC. 2004: S462–S469

    Abstract

    This article will review 2 clinical trials that recently compared the safety and efficacy of the oral direct thrombin inhibitor ximelagatran (fixed dose, 36 mg twice daily) with warfarin (adjusted dose, target international normalized ratio [INR] 2.0-3.0) in patients with nonvalvular atrial fibrillation and at least 1 risk factor for stroke. These noninferiority trials involved 7329 patients and a mean exposure to study drug of 18.5 months. The Stroke Prevention Using Oral Thrombin Inhibitor in Atrial Fibrillation (SPORTIF) III (open-label, N = 3407) and V trials (double-blind, N = 3922) were designed for pooled analysis, and the data showed the efficacy of ximelagatran therapy was comparable (noninferior) with extremely well-controlled warfarin therapy in preventing stroke and systemic embolic events; the primary event rates were 1.65% per year and 1.62% per year in the warfarin and ximelagatran groups, respectively (P = .941). In patients with a history of stroke or transient ischemic attack (about 20% of the SPORTIF population), the event rates were 3.27% per year and 2.83% per year in the warfarin and ximelagatran groups, respectively (P = .625). The distribution of stroke subtypes was similar in the 2 treatment groups. Intracranial hemorrhage occurred at a rate of 0.20% per year with warfarin and 0.11% per year with ximelagatran. Combined rates of minor and major bleeding were significantly lower with ximelagatran than with warfarin (32% per year vs 39% per year; P < .0001). The myocardial infarction rates were the same in the pooled database (no difference between agents). The aspirin data will be the subject of two substudy papers. Oral ximelagatran administered without coagulation monitoring or dose adjustment was as effective as well-controlled, adjusted-dose warfarin for prevention of stroke and systemic embolic events and was associated with significantly less total bleeding. This oral direct thrombin inhibitor is a potentially promising treatment option for the prevention of thromboembolism.

    View details for Web of Science ID 000226142200004

    View details for PubMedID 15696910

  • Antithrombotic and thrombolytic therapy for ischemic stroke: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest Albers, G. W., Amarenco, P., Easton, J. D., Sacco, R. L., Teal, P. 2004; 126 (3): 483S-512S

    Abstract

    This chapter about treatment and prevention of stroke is part of the 7th ACCP Conference on Antithrombotic and Thrombolytic Therapy: Evidence Based Guidelines. Grade 1 recommendations are strong and indicate that the benefits do, or do not, outweigh risks, burden, and costs. Grade 2 suggests that individual patients' values may lead to different choices (for a full understanding of the grading see Guyatt et al). Among the key recommendations in this chapter are the following: For patients with acute ischemic stroke (AIS), we recommend administration of i.v. tissue plasminogen activator (tPA), if treatment is initiated within 3 h of clearly defined symptom onset (Grade 1A). For patients with extensive and clearly identifiable hypodensity on CT, we recommend against thrombolytic therapy (Grade 1B). For unselected patients with AIS of > 3 h but < 6 h, we suggest clinicians not use i.v. tPA (Grade 2A). For patients with AIS, we recommend against streptokinase (Grade 1A) and suggest clinicians not use full-dose anticoagulation with i.v. or subcutaneous heparins or heparinoids (Grade 2B). For patients with AIS who are not receiving thrombolysis, we recommend early aspirin therapy, 160 to 325 mg qd (Grade 1A). For AIS patients with restricted mobility, we recommend prophylactic low-dose subcutaneous heparin or low molecular weight heparins or heparinoids (Grade 1A); and for patients who have contraindications to anticoagulants, we recommend use of intermittent pneumatic compression devices or elastic stockings (Grade 1C). In patients with acute intracerebral hematoma, we recommend the initial use of intermittent pneumatic compression (Grade 1C+). In patients with noncardioembolic stroke or transient ischemic attack (TIA) [ie, atherothrombotic, lacunar or cryptogenic], we recommend treatment with an antiplatelet agent (Grade 1A) including aspirin, 50 to 325 mg qd; the combination of aspirin and extended-release dipyridamole, 25 mg/200 mg bid; or clopidogrel, 75 mg qd. In these patients, we suggest use of the combination of aspirin and extended-release dipyridamole, 25/200 mg bid, over aspirin (Grade 2A) and clopidogrel over aspirin (Grade 2B). For patients who are allergic to aspirin, we recommend clopidogrel (Grade 1C+). In patients with atrial fibrillation and a recent stroke or TIA, we recommend long-term oral anticoagulation (target international normalized ratio, 2.5; range, 2.0 to 3.0) [Grade 1A]. In patients with venous sinus thrombosis, we recommend unfractionated heparin (Grade 1B) or low molecular weight heparin (Grade 1B) over no anticoagulant therapy during the acute phase.

    View details for PubMedID 15383482

  • Antithrombotic and thrombolytic therapy for ischemic stroke CHEST Albers, G. W., Amarenco, P., Easton, J. D., Sacco, R. L., Teal, P. 2004; 126 (3): 483S-512S

    View details for Web of Science ID 000224298900014

  • Antithrombotic therapy in atrial fibrillation CHEST Singer, D. E., Albers, G. W., Dalen, J. E., Go, A. S., Halperin, J. L., Manning, W. J. 2004; 126 (3): 429S-456S

    View details for Web of Science ID 000224298900012

  • Diffusion-weighted MR imaging in acute ischemia: Value of apparent diffusion coefficient and signal intensity thresholds in predicting tissue at risk and final infarct size AMERICAN JOURNAL OF NEURORADIOLOGY Na, D. G., Thijs, V. N., Albers, G. W., Moseley, M. E., Marks, M. P. 2004; 25 (8): 1331-1336

    Abstract

    Identifying tissue at risk for infarction is an important goal of stroke imaging. This study was performed to determine whether pixel-based apparent diffusion coefficient (ADC) and signal intensity ratio are helpful diffusion-weighted (DW) imaging metrics to predict tissue at risk for infarction.Twelve patients presenting with acute hemispheric strokes underwent DW imaging within 7 hours of symptom onset. Region of interest (ROI), pixel-based ADC, and signal intensity analyses were performed at initial DW imaging to assess area of infarct growth, final infarct area, and normal tissue.Pixel-based analysis was less accurate than ROI-based analysis for evaluating infarct growth or final infarct with ADC, ADC ratio, and signal intensity ratios. In pixel-based analysis, signal intensity ratios were better than ADCs or ADC ratios for identifying tissue at risk (accuracy, 67.4%) and for predicting final infarct (accuracy, 79.9%). Linear regression analysis demonstrated a strong correlation between lesion volume on quantitative DW images or ADC maps and final infarct volume (P < .001). When receiver operating characteristic (ROC) curves were used to determine optimal cutoffs for ADC and DW image values, the region of infarct growth was significantly correlated with only the mismatch between initial qualitative DW image and quantitative DW image signal intensity ratio (cutoff value, 1.19; R = 0.652; P = .022).Pixel-based thresholds applied to ADC or DW image signal intensity maps were not accurate prognostic measures of tissue at risk. Quantitative DW images or ADC maps may provide added information not obtained by visual inspection of the qualitative DW image map.

    View details for PubMedID 15466327

  • Proceedings of the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy: evidence-based guidelines. Chest 2004; 126 (3): 172S-696S

    Abstract

    Since the Sixth American College of Chest Physicians Consensus Conference on Antithrombotic Therapy, the results of clinical trials have provided important new information on the management of thromboembolic disorders, and the science of developing recommendations has advanced. In the accompanying supplement, we provide the new and previously existing recommendations and review several important changes that we have made in our guideline development process. We made a conscious effort to increase the participation of female authors and of contributors from outside North America, with the latter reflecting the widespread use and dissemination of these guidelines internationally. The change in the title from a conference emphasizing consensus to "ACCP Conference on Antithrombotic and Thrombolytic Therapy: Evidence-Based Guidelines" reflects the evidence-based approach to making recommendations. The recommendations follow the grading system described in the 2001 recommendations. If the guideline developers are very certain that benefits do, or do not, outweigh risks, burdens, and costs, they will make a strong recommendation (in our formulation, Grade 1). If they are less certain of the magnitude of the benefits and the risks, burdens, and costs, and thus of their relative impact, they make a weaker Grade 2 recommendation. Consistent results from RCTs generate Grade A recommendations, observational studies with very strong effects or secure generalizations from randomized clinical trials (RCTs) generate Grade C+ recommendations, inconsistent results from RCTs generate Grade B recommendations, and observational studies generate Grade C recommendations. We now use the language "we recommend" for strong recommendations (ie, Grades 1A, 1C+, 1B, and 1C) and "we suggest" for weaker recommendations (ie, Grades 2A, 2C+, 2B, and 2C). While evidence on which recommendation are made remains weak in the fields of pediatric thrombosis, thrombosis in pregnancy, and thrombosis in valvular heart disease, rigorous studies in other fields have resulted in new and strong evidence-based recommendations for many indications.

    View details for PubMedID 15383469

  • Antithrombotic therapy in atrial fibrillation: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest Singer, D. E., Albers, G. W., Dalen, J. E., Go, A. S., Halperin, J. L., Manning, W. J. 2004; 126 (3): 429S-456S

    Abstract

    This chapter about antithrombotic therapy in atrial fibrillation (AF) is part of the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy: Evidence Based Guidelines. Grade 1 recommendations are strong and indicate that the benefits do, or do not, outweigh risks, burden, and costs. Grade 2 suggests that individual patients' values may lead to different choices (for a full understanding of the grading see Guyatt et al, CHEST 2004; 126:179S-187S). Among the key recommendations in this chapter are the following (all vitamin K antagonist [VKA] recommendations have a target international normalized ratio [INR] of 2.5; range, 2.0 to 3.0): In patients with persistent or paroxysmal AF (PAF) [intermittent AF] at high risk of stroke (ie, having any of the following features: prior ischemic stroke, transient ischemic attack, or systemic embolism, age > 75 years, moderately or severely impaired left ventricular systolic function and/or congestive heart failure, history of hypertension, or diabetes mellitus), we recommend anticoagulation with an oral VKA, such as warfarin (Grade 1A). In patients with persistent AF or PAF, age 65 to 75 years, in the absence of other risk factors, we recommend antithrombotic therapy with either an oral VKA or aspirin, 325 mg/d, in this group of patients who are at intermediate risk of stroke (Grade 1A). In patients with persistent AF or PAF < 65 years old and with no other risk factors, we recommend aspirin, 325 mg/d (Grade 1B). For patients with AF and mitral stenosis, we recommend anticoagulation with an oral VKA (Grade 1C+). For patients with AF and prosthetic heart valves, we recommend anticoagulation with an oral VKA (Grade 1C+); the target INR may be increased and aspirin added depending on valve type and position, and on patient factors. For patients with AF of > or = 48 h or of unknown duration for whom pharmacologic or electrical cardioversion is planned, we recommend anticoagulation with an oral VKA for 3 weeks before and for at least 4 weeks after successful cardioversion (Grade 1C+). For patients with AF of > or = 48 h or of unknown duration undergoing pharmacologic or electrical cardioversion, an alternative strategy is anticoagulation and screening multiplane transesophageal echocardiography (Grade 1B). If no thrombus is seen and cardioversion is successful, we recommend anticoagulation for at least 4 weeks (Grade 1B). For patients with AF of known duration < 48 h, we suggest cardioversion without anticoagulation (Grade 2C). However, in patients without contraindications to anticoagulation, we suggest beginning IV heparin or low molecular weight heparin at presentation (Grade 2C).

    View details for PubMedID 15383480

  • A review of published TIA treatment recommendations NEUROLOGY Albers, G. W. 2004; 62 (8): S26-S28

    View details for Web of Science ID 000221202700008

    View details for PubMedID 15111654

  • Discussion: Reconsideration of TIA terminology and definitions. Neurology Easton, J. D., Albers, G. W., Caplan, L. R., Saver, J. L., Sherman, D. G. 2004; 62 (8): S29-34

    View details for PubMedID 15111655

  • Comparing the guidelines: Anticoagulation therapy to optimize stroke prevention in patients with atrial fibrillation JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Rockson, S. G., Albers, G. W. 2004; 43 (6): 929-935

    Abstract

    Atrial fibrillation (AF) is an important risk factor for stroke. According to a pooled analysis of controlled clinical trials with warfarin, anticoagulation therapy reduces stroke risk by 62%. However, clinicians must decide whether the benefit of long-term anticoagulation therapy with available agents outweighs the risk of bleeding for individual patients. Guidelines issued by the American College of Chest Physicians and by the joint American College of Cardiology, American Heart Association, and the European Society of Cardiology task force recommend antithrombotic therapy to protect AF patients from stroke based on risk-stratification algorithms. Risk factors for stroke AF patients include age > or =75 years; hypertension; thyrotoxicosis; diabetes; cardiovascular disease; congestive heart failure; and history of stroke, transient ischemic attack, or thromboembolism. Patients at high risk for stroke experience greater absolute benefit from anticoagulation therapy than patients at low risk. The guidelines are consistent in recommendations for high-risk patients (warfarin therapy, international normalized ratio 2.0 to 3.0) and low-risk patients (aspirin 325 mg), but differ for intermediate-risk patients with diabetes or heart disease. The guidelines continue to evolve, and future guidelines are likely to incorporate new clinical data, including the CHADS(2) algorithm for determining risk and the results of the Atrial Fibrillation Follow-up Investigation of Rhythm Management trial, the Rate Control versus Electrical Cardioversion for Persistent Atrial Fibrillation study, and the Stroke Prevention Using an Oral Thrombin Inhibitor in Atrial Fibrillation II to V trials.

    View details for DOI 10.1016/j.jacc.2003.11.028

    View details for PubMedID 15028346

  • Association of outcome with early stroke treatment: pooled analysis of ATLANTIS, ECASS, and NINDS rt-PA stroke trials LANCET Hacke, W., Donnan, G., Fieschi, C., Kaste, M., von Kummer, R., Broderick, J. P., Brott, T., Frankel, M., Grotta, J. C., Haley, E. C., Kwiatkowski, T., Levine, S. R., Lewandowski, C., Lu, M., Lyden, P., Marler, J. R., Patel, S., Tilley, B. C., Albers, G., Brott, T., Grotta, J., Bluhmki, P. E., Wilhelm, M., Hamilton, S. 2004; 363 (9411): 768-774

    Abstract

    Quick administration of intravenous recombinant tissue plasminogen activator (rt-PA) after stroke improved outcomes in previous trials. We aimed to analyse combined data for individual patients to confirm the importance of rapid treatment.We pooled common data elements from six randomised placebo-controlled trials of intravenous rt-PA. Using multivariable logistic regression we assessed the relation of the interval from stroke onset to start of treatment (OTT) on favourable 3-month outcome and on the occurrence of clinically relevant parenchymal haemorrhage.Treatment was started within 360 min of onset of stroke in 2775 patients randomly allocated to rt-PA or placebo. Median age was 68 years, median baseline National Institute of Health Stroke Scale (NIHSS) 11, and median OTT 243 min. Odds of a favourable 3-month outcome increased as OTT decreased (p=0.005). Odds were 2.8 (95% CI 1.8-4.5) for 0-90 min, 1.6 (1.1-2.2) for 91-180 min, 1.4 (1.1-1.9) for 181-270 min, and 1.2 (0.9-1.5) for 271-360 min in favour of the rt-PA group. The hazard ratio for death adjusted for baseline NIHSS was not different from 1.0 for the 0-90, 91-180, and 181-270 min intervals; for 271-360 min it was 1.45 (1.02-2.07). Haemorrhage was seen in 82 (5.9%) rt-PA patients and 15 (1.1%) controls (p<0.0001). Haemorrhage was not associated with OTT but was with rt-PA treatment (p=0.0001) and age (p=0.0002).The sooner that rt-PA is given to stroke patients, the greater the benefit, especially if started within 90 min. Our results suggest a potential benefit beyond 3 h, but this potential might come with some risks.

    View details for Web of Science ID 000220092000007

    View details for PubMedID 15016487

  • Influence of arterial input function on hypoperfusion volumes measured with perfusion-weighted imaging STROKE Thijs, V. N., Somford, D. M., Bammer, R., Robberecht, W., Moseley, M. E., Albers, G. W. 2004; 35 (1): 94-98

    Abstract

    The arterial input function (AIF) is critical in determining hemodynamic parameters quantitatively with bolus-tracking MRI. We studied the effect of varying the location of measurement of AIF on the volume of hypoperfusion. We compared the volumes of hypoperfusion obtained with different AIFs with the final ischemic lesion volume.We included 13 patients with acute cerebral ischemia in the anterior circulation who underwent diffusion- (DWI) and perfusion (PWI)-weighted imaging within 8 hours after symptom onset and exhibited DWI lesion expansion between baseline and follow-up. AIF was measured at 4 locations: near both middle cerebral arteries (MCAs), in MCA branches adjacent to the largest DWI abnormality, and at the same level on the opposite hemisphere. Hypoperfusion lesion volumes were compared with the DWI volume at follow-up.Large variations in PWI lesion size were found with different AIF locations. The largest PWI lesions were found when AIF was measured at the contralateral MCA. Smaller PWI lesions were found when AIF was measured in the other locations. There was no significant difference between PWI lesion area at baseline and follow-up DWI lesion when AIF was measured at the contralateral MCA. The other PWI lesions significantly underestimated follow-up DWI lesion size.AIF is an important determinant of the size of hypoperfusion lesions measured with PWI. PWI lesion volumes determined with AIF from the contralateral MCA are associated with follow-up lesion volume.

    View details for DOI 10.1161/01.STR.0000106136.15163.73

    View details for Web of Science ID 000187630500020

    View details for PubMedID 14671249

  • Safety and tolerability of ONO-2506 in acute ischemic stroke. 29th International Stroke Conference Pettigrew, L. C., Kasner, S. E., Kwiatkowski, T., Albers, G. W., Gorman, M., Grotta, J. C., Sherman, D., Funakoshi, Y. LIPPINCOTT WILLIAMS & WILKINS. 2004: 293–93

    View details for Web of Science ID 000187630500343

  • Stroke prevention with the oral direct thrombin inhibitor ximelagatran compared with warfarin in patients with non-valvular atrial fibrillation (SPORTIF III): randomised controlled trial LANCET Albers, G. W., Diener, H. C., Grind, M., Halperin, J. L., Horrow, J., Olsson, S. B., Petersen, P., Vahanian, A., Frison, L., Nevinson, M., Partridge, S. 2003; 362 (9397): 1691-1698

    Abstract

    Warfarin prevents ischaemic stroke in patients with non-valvular atrial fibrillation, but dose adjustment, coagulation monitoring, and bleeding risk limit its use. The oral direct thrombin inhibitor ximelagatran represents a potential alternative. We aimed to establish whether ximelagatran is non-inferior to warfarin, within a margin of 2% per year, for prevention of stroke and systemic embolism.We randomised 3410 patients with atrial fibrillation and one or more stroke risk factors to open-label warfarin (adjusted-dose, international normalised ratio [INR] 2.0-3.0) or ximelagatran (fixed-dose, 36 mg twice daily); patients were recruited from 259 hospitals, doctor's offices, or health-care clinics. Primary analysis was based on masked event assessment and was by intention to treat. Primary endpoint was stroke or systemic embolism.During 4941 patient-years of exposure (mean 17.4 months, SD 4.1), 96 patients had primary events (56 in the warfarin group vs 40 in the ximelagatran group). The primary event rate by intention to treat was 2.3% per year with warfarin and 1.6% per year with ximelagatran (absolute risk reduction 0.7% [95% CI -0.1 to 1.4], p=0.10; relative risk reduction 29% [95% CI -6.5 to 52]). Rates of disabling or fatal stroke, mortality, and major bleeding were similar between groups, but combined minor and major haemorrhages were lower with ximelagatran than with warfarin (29.8% vs 25.8% per year; relative risk reduction 14% [4 to 22]; p=0.007). Raised serum alanine aminotransferase was more common with ximelagatran.In high-risk patients with atrial fibrillation, fixed-dose oral ximelagatran was at least as effective as well-controlled warfarin for prevention of stroke and systemic embolism.

    View details for Web of Science ID 000186767700006

    View details for PubMedID 14643116

  • Spinal manipulative therapy is an independent risk factor for vertebral artery dissection NEUROLOGY Smith, W. S., Johnston, S. C., Skalabrin, E. J., Weaver, M., Azari, P., Albers, G. W., Gress, D. R. 2003; 60 (9): 1424-1428

    Abstract

    To determine whether spinal manipulative therapy (SMT) is an independent risk factor for cervical artery dissection.Using a nested case-control design, the authors reviewed all patients under age 60 with cervical arterial dissection (n = 151) and ischemic stroke or TIA from between 1995 and 2000 at two academic stroke centers. Controls (n = 306) were selected to match cases by sex and within age strata. Cases and controls were solicited by mail, and respondents were interviewed using a structured questionnaire. The medical records of interviewed patients were reviewed by two blinded neurologists to confirm that the patient had stroke or TIA and to determine whether there was evidence of arterial dissection.After interview and blinded chart review, 51 patients with dissection (mean age 41 +/- 10 years; 59% female) and 100 control patients (44 +/- 9 years; 58% female) were studied. In univariate analysis, patients with dissection were more likely to have had SMT within 30 days (14% vs 3%, p = 0.032), to have had neck or head pain preceding stroke or TIA (76% vs 40%, p < 0.001), and to be current consumers of alcohol (76% vs 57%, p = 0.021). In multivariate analysis, vertebral artery dissections were independently associated with SMT within 30 days (OR 6.62, 95% CI 1.4 to 30) and pain before stroke/TIA (OR 3.76, 95% CI 1.3 to 11).This case-controlled study of the influence of SMT and cervical arterial dissection shows that SMT is independently associated with vertebral arterial dissection, even after controlling for neck pain. Patients undergoing SMT should be consented for risk of stroke or vascular injury from the procedure. A significant increase in neck pain following spinal manipulative therapy warrants immediate medical evaluation.

    View details for Web of Science ID 000182754100007

    View details for PubMedID 12743225

  • Spinal manipulative therapy is an independent risk factor for vertebral artery dissection 28th International Stroke Conference Smith, W. S., Johnston, S. C., Skalabrin, E. J., Weaver, M., Albers, G. W., Gress, D. R. LIPPINCOTT WILLIAMS & WILKINS. 2003: 296–96

    View details for Web of Science ID 000180251100368

  • Transient ischemic attack - Proposal for a new definition. NEW ENGLAND JOURNAL OF MEDICINE Albers, G. W., Caplan, L. R., Easton, J. D., Fayad, P. B., Mohr, J. P., Saver, J. L., Sherman, D. G. 2002; 347 (21): 1713-1716

    View details for Web of Science ID 000179339900015

    View details for PubMedID 12444191

  • Telephone assessment of functioning and well-being following stroke: is it feasible? Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association Goldstein, L. B., Lyden, P., Mathias, S. D., Colman, S. S., Pasta, D. J., Albers, G., Atkinson, R., Kelley, G., Ng, K., Rylander, A. 2002; 11 (2): 80-87

    Abstract

    Stroke can affect the physical, emotional, and social aspects of patients' lives. The purpose of this study was to assess the feasibility and psychometric properties of a telephone-administered version of the Health Utilities Index Mark 2 and 3 (HUI2/3). Subjects included patients who had had an ischemic stroke within the prior 12 months and their unpaid caregivers (n = 76 pairs) and an additional 33 unpaid caregivers of patients who were generally aphasic or severely affected. Complete response rates, test-retest reliability, and convergent, divergent, and known-groups validity were determined. For patient-caregiver pairs, 27% had no complete Health Utilities Index Mark 2 (HUI2) responses (i.e., had missing responses for at least 1 item of each assessment), 51% had partial responses (i.e., had complete responses for at least 1, but not all of the assessments), and 22% had complete responses. For the Health Utilities Mark 3 (HUI3), the percentages were 19%, 52%, and 29%. Test-retest reliability for patients intraclass correlation coefficient (ICC = 0.76 for HUI2; 0.75 for HUI3) and caregivers (ICC = 0.91 and 0.89, respectively) were excellent. There were generally high levels of both convergent and divergent validity. There was limited known-groups validity (mild v moderately and mild v severely affected patients reported different overall HUI2 and HUI3 scores; there was no difference between those with moderate and severe disabilities). The same pattern was found for caregivers. We conclude that the telephone-administered HUI2/3 appears to be reliable and have at least limited validity. However, the proportions of missing data for patient/caregivers administered the HUI2/3 were surprisingly high. This high proportion of missing data would limit the use of the telephone-administered HUI2/3 in the context of stroke trials.

    View details for PubMedID 17903861

  • Patient safety in trials of therapy for acute ischemic stroke JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Goldstein, L. B., Albers, G. W. 2002; 287 (8): 987-987

    View details for Web of Science ID 000174052100020

    View details for PubMedID 11866641

  • ATLANTIS trial: results for patients treated within 3 hours of stroke onset. Alteplase Thrombolysis for Acute Noninterventional Therapy in Ischemic Stroke. Stroke Albers, G. W., Clark, W. M., Madden, K. P., Hamilton, S. A. 2002; 33 (2): 493-495

    Abstract

    Only a single study has demonstrated beneficial effects of intravenous tissue plasminogen activator (tPA) in stroke patients.We evaluated the clinical outcomes of the 61 patients enrolled in the Alteplase Thrombolysis for Acute Noninterventional Therapy in Ischemic Stroke (ATLANTIS) study who were randomized to receive intravenous tPA or placebo within 3 hours of symptom onset.Despite a significant increase in the rate of symptomatic intracranial hemorrhage, tPA-treated patients were more likely to have a very favorable outcome (score of < or = 1) on the National Institutes of Health Stroke Scale at 90 days (P=0.01).These data support current recommendations to administer intravenous tPA to eligible ischemic stroke patients who can be treated within 3 hours of symptom onset.

    View details for PubMedID 11823658

  • ATLANTIS trial - Results for patients treated within 3 hours of stroke onset STROKE Albers, G. W., Clark, W. M., Madden, K. P., Hamilton, S. A. 2002; 33 (2): 493-495

    View details for Web of Science ID 000173644900013

  • Clinical and radiological correlates of reduced cerebral blood flow measured using magnetic resonance Imaging ARCHIVES OF NEUROLOGY Thijs, V. N., Adami, A., Neumann-Haefelin, T., Moseley, M. E., Albers, G. W. 2002; 59 (2): 233-238

    Abstract

    Methods for determining cerebral blood flow (CBF) using bolus-tracking magnetic resonance imaging (MRI) have recently become available. Reduced apparent diffusion coefficient (ADC) values of brain tissue are associated with reductions in regional CBF in animal stroke models.To determine the clinical and radiological features of patients with severe reductions in CBF on MRI and to analyze the relationship between reduced CBF and ADCs in acute ischemic stroke.Case series.Referral center.We studied 17 patients with nonlacunar acute ischemic stroke in whom perfusion-weighted imaging (PWI) and diffusion-weighted imaging (DWI) were performed within 7 hours of symptom onset. A PWI-DWI mismatch of more than 20% was required. We compared patients with ischemic lesions that had CBF of less than 50% relative to the contralateral hemisphere with patients with lesions that had relative CBF greater than 50%. Characteristics analyzed included age, time to MRI, baseline National Institutes of Health Stroke Scale score, mean ADC, DWI and PWI lesion volumes, and 1-month Barthel Index score.Patients with low CBF (n = 5) had lower ADC values (median, 430 x 10 (-6) mm(2)/s vs. 506 x 10 (-6) mm(2)/s; P =.04), larger DWI volumes (median, 41.8 cm(3) vs. 14.5 cm(3); P =.001) and larger PWI lesions as defined by the mean transit time volume (median, 194.6 cm(3) vs. 69.3 cm(3); P =.01), and more severe baseline National Institutes of Health Stroke Scale scores (median, 15 vs. 9; P =.02).Ischemic lesions with severe CBF reductions, measured using bolus-tracking MRI, are associated with lower mean ADCs, larger DWI and PWI volumes, and higher National Institutes of Health Stroke Scale scores.

    View details for Web of Science ID 000173799900008

    View details for PubMedID 11843694

  • Aptiganel hydrochloride in acute ischemic stroke - A randomized controlled trial JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Albers, G. V., Goldstein, L. B., Hall, D., Lesko, L. M. 2001; 286 (21): 2673-2682

    Abstract

    Tissue plasminogen activator is the only thrombolytic agent approved in the United States for treatment of acute ischemic stroke, and has limitations. Aptiganel hydrochloride is a novel and selective ligand for the ion-channel site of the N-methyl-D-aspartate receptor-channel complex and a promising neuroprotective agent in animal models of focal brain ischemia.To determine whether aptiganel improves the clinical outcome for acute ischemic stroke patients.Nested phase 2/phase 3 randomized controlled trial conducted between July 1996 and September 1997.One hundred fifty-six medical centers in the United States, Canada, Australia, South Africa, England, and Scotland.A total of 628 patients with hemispheric ischemic stroke (50.3% male; mean age, 71.5 years).Patients were randomly assigned within 6 hours of stroke to receive 1 of 3 treatment regimens: high-dose aptiganel (5-mg bolus followed by 0.75 mg/h for 12 hours; n = 214); low-dose aptiganel (3-mg bolus followed by 0.5 mg/h for 12 hours; n = 200); or placebo (n = 214).The primary efficacy end point was the Modified Rankin Scale score at 90 days after stroke onset. Secondary end points included mortality and change in National Institutes of Health (NIH) Stroke Scale score at 7 days after stroke.The trial was suspended by the sponsor and the independent data and safety monitoring board because of both a lack of efficacy and a potential imbalance in mortality. There was no improvement in outcome for either aptiganel (low-dose or high-dose) group compared with the placebo group at 90 days (median Modified Rankin Scale score for all 3 treatment groups = 3; P =.31). At 7 days, placebo-treated patients exhibited slightly greater neurological improvement on the NIH Stroke Scale than high-dose aptiganel patients (mean improvement for placebo group, -0.8 points vs for high-dose aptiganel, 0.9 points; P =.04). The mortality rate at 120 days in patients treated with high-dose aptiganel was higher than that in patients who received placebo (26.3% vs 19.2%; P =.06). Mortality in the low-dose aptiganel group was 22.5% (P =.39 vs placebo).Aptiganel was not efficacious in patients with acute ischemic stroke at either of the tested doses, and m ay be harmful. The larger proportion of patients with favorable outcomes and lower mortality rate in the placebo group suggest that glutamate blockade with aptiganel may have detrimental effects in an undifferentiated population of stroke patients.

    View details for Web of Science ID 000172488300026

    View details for PubMedID 11730442

  • Combination therapy with clopidogrel and aspirin - Can the CURE results be extrapolated to cerebrovascular patients? STROKE Albers, G. W., Amarenco, P. 2001; 32 (12): 2948-2949

    View details for Web of Science ID 000172599500046

    View details for PubMedID 11740003

  • A comparison of warfarin and aspirin for the prevention of recurrent ischemic stroke NEW ENGLAND JOURNAL OF MEDICINE Mohr, J. P., Thompson, J. L., Lazar, R. M., Levin, B., Sacco, R. L., Furie, K. L., Kistler, J. P., Albers, G. W., Pettigrew, L. C., Adams, H. P., Jackson, C. M., Pullicino, P. 2001; 345 (20): 1444-1451

    Abstract

    Despite the use of antiplatelet agents, usually aspirin, in patients who have had an ischemic stroke, there is still a substantial rate of recurrence. Therefore, we investigated whether warfarin, which is effective and superior to aspirin in the prevention of cardiogenic embolism, would also prove superior in the prevention of recurrent ischemic stroke in patients with a prior noncardioembolic ischemic stroke.In a multicenter, double-blind, randomized trial, we compared the effect of warfarin (at a dose adjusted to produce an international normalized ratio of 1.4 to 2.8) and that of aspirin (325 mg per day) on the combined primary end point of recurrent ischemic stroke or death from any cause within two years.The two randomized study groups were similar with respect to base-line risk factors. In the intention-to-treat analysis, no significant differences were found between the treatment groups in any of the outcomes measured. The primary end point of death or recurrent ischemic stroke was reached by 196 of 1103 patients assigned to warfarin (17.8 percent) and 176 of 1103 assigned to aspirin (16.0 percent; P=0.25; hazard ratio comparing warfarin with aspirin, 1.13; 95 percent confidence interval, 0.92 to 1.38). The rates of major hemorrhage were low (2.22 per 100 patient-years in the warfarin group and 1.49 per 100 patient-years in the aspirin group). Also, there were no significant treatment-related differences in the frequency of or time to the primary end point or major hemorrhage according to the cause of the initial stroke (1237 patients had had previous small-vessel or lacunar infarcts, 576 had had cryptogenic infarcts, and 259 had had infarcts designated as due to severe stenosis or occlusion of a large artery).Over two years, we found no difference between aspirin and warfarin in the prevention of recurrent ischemic stroke or death or in the rate of major hemorrhage. Consequently, we regard both warfarin and aspirin as reasonable therapeutic alternatives.

    View details for Web of Science ID 000172132700002

    View details for PubMedID 11794192

  • Use of anti-ICAM-1 therapy in ischemic stroke - Results of the Enlimomab Acute Stroke Trial NEUROLOGY Sherman, D. G., Bes, A., Easton, J. D., Hacke, W., Kaste, M., Polmar, S. H., Zivin, J. A., Fieschi, C., Miller, P., Schoenfeld, D., Street, J., Albers, G., Atkinson, R., Biller, J., Bruno, A., Carpenter, D., Clark, W., DeGraba, T., Driscoll, P., Ellis, J., Greenlee, R., Hess, D., Horowitz, D. R., Davenport, J., Hsu, C., Starkman, S., Madden, K., Pettigrew, C., Rosenbaum, D., Schim, J., Tietjen, G., Mansbach, H., Edwards, K., Webb, R., Crisostomo, E., Wilterdink, J., Rothrock, J., Zweifler, R., Dexter, J., Horowitz, S., Futrell, N., Alter, M., Schneider, D., Ferbert, A., Hacke, W., Prange, H., Wiersbitzky, M., Buttner, T., Schwartz, A., Busse, O., Klingelhofer, J., Kaste, M., Erila, T., Sivenius, J., Sotaniemi, K., Liukkonen, J., Hedman, C., Muuronen, A., Rissanen, A., Bes, A., Feve, J. R., Mahagne, M. H., Rancurel, G., Trouillas, P., Weber, M., Thomassen, L., Johnsen, H. J., Kjallman, L., Petersson, J., Ferrari, G., Lagi, A., Mamoli, A., Re, G. 2001; 57 (8): 1428-1434

    Abstract

    There has been recent interest in the possible role of reperfusion-induced inflammation with neuronal injury after stroke. Enlimomab, a murine intercellular adhesion molecule-1 (ICAM-1) antibody, reduces leukocyte adhesion and infarct size in experimental stroke studies. The purpose of the current clinical trial was to evaluate the use of enlimomab after ischemic stroke.A total of 625 patients with ischemic stroke were randomized to receive either enlimomab (n = 317) or placebo (n = 308) within 6 hours of stroke onset. Treatment was given over 5 days. Patients were evaluated at baseline and on days 5 and 90 after initiation of treatment; long-term assessments were carried out after 6 and 12 months. The primary efficacy endpoint was the response to therapy at 90 days on the Modified Rankin Scale; other endpoints included Barthel Index (BI) and NIH Stroke Scale and survival.At day 90, the Modified Rankin Scale score was worse in patients treated with enlimomab than with placebo (p = 0.004). Fewer patients had symptom-free recovery on enlimomab than placebo (p = 0.004), and more died (22.2 versus 16.2%). The negative effect of enlimomab was apparent on days 5, 30, and 90 of treatment (p = 0.005). There were significantly more adverse events with enlimomab treatment than placebo, primarily infections and fever. Patients experiencing fever were more likely to have a poor outcome or die.The authors conclude that anti-ICAM therapy with enlimomab is not an effective treatment for ischemic stroke in the model studied and, indeed, may significantly worsen stroke outcome.

    View details for Web of Science ID 000171681500015

    View details for PubMedID 11673584

  • Relationship between severity of MR perfusion deficit and DWI lesion evolution NEUROLOGY Thijs, V. N., Adami, A., Neumann-Haefelin, T., Moseley, M. E., Marks, M. P., Albers, G. W. 2001; 57 (7): 1205-1211

    Abstract

    To assess whether a quantitative analysis of the severity of the early perfusion deficit on MRI in acute ischemic stroke predicts the evolution of the perfusion/diffusion mismatch and to determine thresholds of hypoperfusion that can distinguish between critical and noncritical hypoperfusion.Patients with acute ischemic stroke were studied in whom perfusion-weighted imaging (PWI) and diffusion-weighted imaging (DWI MRI) were performed within 7 hours of symptom onset and again after 4 to 7 days. Patients with early important decreases in points on the NIH Stroke Scale were excluded. Maps of cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT) were created. These hemodynamic parameters were correlated with the degree of recruitment of the baseline PWI lesion by the DWI lesion.Twelve patients had an initial PWI > DWI mismatch of >20%. A linear relationship was observed between the initial MTT and the degree of recruitment of the baseline PWI lesion by the DWI lesion at follow-up (R(2) = 0.9, p < 0.001). Higher CBV values were associated with higher degrees of recruitment (rho = 0.732, p < 0.007). The volume of MTT of >4 (R(2) = 0.86, p < 0.001) or >6 seconds (R(2) = 0.85, p < 0.001) predicted final infarct size.Among patients who have had an acute stroke with PWI > DWI, who do not have dramatic early clinical improvement, the degree of expansion of the initial DWI lesion correlates with the severity of the initial perfusion deficit as measured by the mean transit time and the cerebral blood volume.

    View details for Web of Science ID 000171415400010

    View details for PubMedID 11591836

  • Potential utility of diffusion-weighted imaging in venous infarction ARCHIVES OF NEUROLOGY Bernstein, R., Albers, G. W. 2001; 58 (10): 1538-1539

    View details for Web of Science ID 000171444400001

    View details for PubMedID 11594909

  • Advances in intravenous thrombolytic therapy for treatment of acute stroke NEUROLOGY Albers, G. W. 2001; 57 (5): S77-S81

    Abstract

    Intravenous tissue plasminogen activator (tPA) is an effective therapy for treatment of acute ischemic stroke when administered within 3 hours of symptom onset. Three large randomized clinical trials that have attempted to extend the time window for tPA treatment beyond 3 hours have failed to demonstrate convincing evidence of efficacy. A recently published prospective, monitored, multicenter study of 389 patients, who were treated with tPA for ischemic stroke at 57 medical centers (24 academic, 33 community) across the United States, demonstrated favorable outcomes and low rates of symptomatic intracerebral hemorrhage. Recent advances in neuroimaging, including diffusion-weighted MRI (DWI) and perfusion-weighted MRI (PWI), have the potential to differentiate salvageable ischemic brain tissue from irreversibly injured tissue. Preliminary data suggest that acute stroke patients who present with a PWI lesion that is considerably larger than the initial DWI lesion may be good candidates for intravenous thrombolysis, even beyond 3 hours after symptom onset. Additional research is required to clarify the optimal use of these diagnostic techniques and their cost-effectiveness.

    View details for Web of Science ID 000170938000015

    View details for PubMedID 11552060

  • Hyperperfusion syndrome with hemorrhage after angioplasty for middle cerebral artery stenosis AMERICAN JOURNAL OF NEURORADIOLOGY Liu, A. Y., Do, H. M., Albers, G. W., Lopez, J. R., Steinberg, G. K., Marks, M. P. 2001; 22 (8): 1597-1601

    Abstract

    Hyperperfusion syndrome is a well-documented complication of carotid endarterectomy, as well as internal carotid artery angioplasty and stent placement. We report a similar complication after distal intracranial (middle cerebral artery [MCA] M2 segment) angioplasty. To our knowledge, this is the first report of hyperperfusion syndrome after intracranial angioplasty of a distal MCA branch.

    View details for PubMedID 11559514

  • Antithrombotic therapy for prevention and treatment of ischemic stroke 6th National Conference on Anticoagulant Therapy Albers, G. W. SPRINGER. 2001: 19–22

    Abstract

    Atherosclerosis involving the cervical vessels, intracranial vessels, or the aorta is the most common cause of ischemic stroke. Occlusive lesions of small penetrating brain arteries cause small "lacunar" strokes, which account for about 20% of ischemic strokes. Emboli from a variety of cardiac sources, particularly atrial fibrillation, account for about 25%. Efforts to prevent and treat ischemic stroke are complicated by the variety of etiologies underlying it and the selection of antithrombotic or thrombolytic therapy appropriate to the particular etiology.

    View details for Web of Science ID 000172168500003

    View details for PubMedID 11711684

  • Recommendations for clinical trial evaluation of acute stroke therapies - Stroke Therapy Academic Industry Roundtable II (STAIR-II) STROKE Albers, G. W., Bogousslavsky, J., Bozik, M. A., Brass, L. M., Broderick, J. P., Fisher, M., Goldstein, L. B., Salazar-Grueso, E., Akitsuki, S., Aranko, K., Ashwood, T., Atkinson, R. P., Bell, R. D., Brott, T. G., Cady, W. J., Caplan, L. R., Coggins, S., Cramer, S., Cyrus, P., Dayno, J., Easton, J. D., Elliott, P. J., Finklestein, S. P., Furlan, A. J., Gamzu, E., Glasky, M. S., Gordon, K., Gorelick, P. B., Greenwood, D. T., Grotta, J. C., Gunn, K., Hachinski, V., Hacke, W., Hall, E. D., Hsu, C. Y., Humphreys, D. M., Ishikawa, H., Jacobs, A. J., Kaste, M., Koroshetz, W. J., Krams, M., Lauritano, A. A., Leclerc, J., Lees, K. R., Lesko, L., Levine, S. R., Levy, D. E., Li, F. H., Lyden, P. D., Masayasu, H., McDermott, J., Meibach, R. C., Meya, U., Miyairi, K., Niidome, T., Oeda, J., Poole, R. M., Ron, E. S., Sacco, R. L., Saltarelli, M. D., Shimizu, K., Shook, B. J., Soehngen, M., Soehngen, W., Stamler, D. A., Styren, S. D., Teal, P. A., Tilley, B. C., Traystman, R. J., Walker, M. D., Wallin, B. A., Warach, S., Ward, D. P., Wessel, T. C., Wettstein, J. 2001; 32 (7): 1598-1606

    View details for Web of Science ID 000169724900022

  • Evolution of cerebral infarct volume assessed by diffusion-weighted magnetic resonance imaging ARCHIVES OF NEUROLOGY Lansberg, M. G., O'Brien, M. W., Tong, D. C., Moseley, M. E., Albers, G. W. 2001; 58 (4): 613-617

    Abstract

    Knowledge of the natural evolution of ischemic brain lesions may be a crucial aspect in the assessment of future stroke therapies.To establish daily changes of ischemic cerebral lesion volume using diffusion-weighted magnetic resonance imaging.Prospective cohort study.Referral center.Serial magnetic resonance imaging scans were performed in consecutive untreated stroke patients. The baseline scan was obtained within 48 hours after symptom onset; subsequent scans, 12 to 48 hours, 3 to 4 days, 5 to 7 days, and 30 days after baseline. Lesion volumes were measured on each scan by 2 independent observers.Daily change in lesion volume.A total of 112 magnetic resonance imaging scans were obtained in 24 patients. An early increase in lesion volume was seen in all patients. Maximum lesion volume was reached at a mean of 74 hours. Lesion volumes increased by a mean (+/- SEM) of 21% +/- 12% during day 2 and 10% +/- 12% during day 3. No significant change occurred during day 4. During days 5, 6, and 7, statistically significant mean (+/- SEM) decreases of 6% +/- 8%, 3% +/- 4%, and 4% +/- 5%, respectively, were observed.Ischemic lesions follow a relatively consistent pattern of growth during the first 3 days and subsequent decrease in size. These data in conjunction with data regarding the evolution of lesion volume during the first 24 hours after symptom onset may be useful in the design of pilot studies of therapies for acute stroke.

    View details for Web of Science ID 000167935900011

    View details for PubMedID 11295992

  • Evolution of apparent diffusion coefficient, diffusion-weighted, and T2-weighted signal intensity of acute stroke AMERICAN JOURNAL OF NEURORADIOLOGY Lansberg, M. G., Thijs, V. N., O'Brien, M. W., Ali, J. O., de Crespigny, A. J., Tong, D. C., Moseley, M. E., Albers, G. W. 2001; 22 (4): 637-644

    Abstract

    Serial study of such MR parameters as diffusion-weighted imaging (DWI), apparent diffusion coefficient (ADC), ADC with fluid-attenuated inversion recovery (ADC(FLAIR)), and T2-weighted imaging may provide information on the pathophysiological mechanisms of acute ischemic stroke. Our goals were to establish the natural evolution of MR signal intensity characteristics of acute ischemic lesions and to assess the potential of using specific MR parameters to estimate lesion age.Five serial echo-planar DWI studies with and without an inversion recovery pulse were performed in 27 patients with acute stroke. The following lesion characteristics were studied: 1) conventional ADC (ADC(CONV)); 2) ADC(FLAIR); 3) DWI signal intensity (SI(DWI)); 4) T2-weighted signal intensity (SI(T2)), and 5) FLAIR signal intensity (SI(FLAIR)).The lesion ADC(CONV) gradually increased from low values during the first week to pseudonormal during the second week to supranormal thereafter. The lesion ADC(FLAIR) showed the same pattern of evolution but with lower absolute values. A low ADC value indicated, with good sensitivity (88%) and specificity (90%), that a lesion was less than 10 days old. All signal intensities remained high throughout follow-up. SI(DWI) showed no significant change during the first week but decreased thereafter. SI(T2) initially increased, decreased slightly during week 2, and again increased after 14 days. SI(FLAIR) showed the same initial increase as the SI(T2) but remained relatively stable thereafter.Our findings further clarify the time course of stroke evolution on MR parameters and indicate that the ADC map may be useful for estimating lesion age. Application of an inversion recovery pulse results in lower, potentially more accurate, absolute ADC values.

    View details for PubMedID 11290470

  • Antithrombotic therapy in atrial fibrillation CHEST Albers, G. W., Dalen, J. E., Laupacis, A., Manning, W. J., Petersen, P., Singer, D. E. 2001; 119 (1): 194S-206S

    View details for Web of Science ID 000166812000012

    View details for PubMedID 11157649

  • Recent clinical trials of neuroprotective agents and thrombolytic therapy for acute stroke 21st Princeton Conference on Cerebrovascular Disease Albers, G. W. FUTURA PUBL CO INC. 2001: 419–428

    View details for Web of Science ID 000172045100029

  • Antithrombotic and thrombolytic therapy for ischemic stroke CHEST Albers, C. W., Amarenco, P., Easton, J. D., Sacco, R. L., Teal, P. 2001; 119 (1): 300S-320S

    View details for Web of Science ID 000166812000019

    View details for PubMedID 11157656

  • Is early ischemic lesion volume on diffusion-weighted imaging an independent predictor of stroke outcome? A multivariable analysis STROKE Thijs, V. N., Lansberg, M. G., Beaulieu, C., Marks, M. P., Moseley, M. E., Albers, G. W. 2000; 31 (11): 2597-2602

    Abstract

    The heterogeneity of stroke makes outcome prediction difficult. Neuroimaging parameters may improve the predictive value of clinical measures such as the National Institutes of Health Stroke Scale (NIHSS). We investigated whether the volume of early ischemic brain lesions assessed with diffusion-weighted imaging (DWI) was an independent predictor of functional outcome.We retrospectively selected patients with nonlacunar ischemic stroke in the anterior circulation from 4 prospective Stanford Stroke Center studies evaluating early MRI. The baseline NIHSS score and ischemic stroke risk factors were assessed. A DWI MRI was performed within 48 hours of symptom onset. Clinical characteristics and early lesion volume on DWI were compared between patients with an independent outcome (Barthel Index score >/=85) and a dependent outcome (Barthel Index score <85) at 1 month. A logistic regression model was performed with factors that were significantly different between the 2 groups in univariate analysis.Sixty-three patients fulfilled the entry criteria. One month after symptom onset, 24 patients had a Barthel Index score <85 and 39 had a Barthel Index score >/=85. In univariate analysis, patients with independent outcome were younger, had lower baseline NIHSS scores, and had smaller lesion volumes on DWI. In a logistic regression model, DWI volume was an independent predictor of outcome, together with age and NIHSS score, after correction for imbalances in the delay between symptom onset and MRI.DWI lesion volume measured within 48 hours of symptom onset is an independent risk factor for functional independence. This finding could have implications for the design of acute stroke trials.

    View details for PubMedID 11062281

  • Advantages of adding diffusion-weighted magnetic resonance imaging to conventional magnetic resonance imaging for evaluating acute stroke ARCHIVES OF NEUROLOGY Lansberg, M. G., Norbash, A. M., Marks, M. P., Tong, D. C., Moseley, M. E., Albers, G. W. 2000; 57 (9): 1311-1316

    Abstract

    Accurate localization of acute ischemic lesions in patients with an acute stroke may aid in understanding the etiology of their stroke and may improve the management of these patients.To determine the yield of adding diffusion-weighted magnetic resonance imaging (DWI) to a conventional magnetic resonance imaging (MRI) protocol for acute stroke.A prospective cohort study.A referral center.Fifty-two patients with a clinical diagnosis of acute stroke who presented within 48 hours after symptom onset were included. An MRI scan was obtained within 48 hours after symptom onset. A neuroradiologist (A.M.N.) and a stroke neurologist (G.W.A.) independently identified suspected acute ischemic lesions on MRI sequences in the following order: (1) T2-weighted and proton density-weighted images, (2) fluid-attenuated inversion recovery images, and (3) diffusion-weighted images and apparent diffusion coefficient maps.Diagnostic yield and interrater reliability for the identification of acute lesions, and confidence and conspicuity ratings of acute lesions for different MRI sequences.Conventional MRI correctly identified at least one acute lesion in 71% (34/48) to 80% (39/49) of patients who had an acute stroke; with the addition of DWI, this percentage increased to 94% (46/49) (P<.001). Conventional MRI showed only moderate sensitivity (50%-60%) and specificity (49%-69%) compared with a "criterion standard." Based on the diffusion-weighted sequence, interrater reliability for identifying acute lesions was moderate for conventional MRI (kappa = 0.5-0.6) and good for DWI (kappa = 0.8). The observers' confidence with which lesions were rated as acute and the lesion conspicuity was significantly (P<.01) higher for DWI than for conventional MRI.During the first 48 hours after symptom onset, the addition of DWI to conventional MRI improves the accuracy of identifying acute ischemic brain lesions in patients who experienced a stroke.

    View details for Web of Science ID 000089283000010

    View details for PubMedID 10987898

  • Symptomatic intracranial atherosclerosis - Outcome of patients who fail antithrombotic therapy NEUROLOGY Thijs, V. N., Albers, G. W. 2000; 55 (4): 490-497

    Abstract

    To determine the prognosis of patients with symptomatic intracranial atherosclerosis who fail antithrombotic therapy.The outcome of patients with symptomatic intracranial atherosclerosis who fail antithrombotic therapy is unknown. These patients may represent the target group for investigation of more aggressive therapies such as intracranial angioplasty.The authors performed a chart review and telephone interview of patients with symptomatic intracranial atherosclerosis identified in the Stanford Stroke Center clinical database. A Cox regression model was created to identify factors predictive of failure of antithrombotic therapy. The authors generated Kaplan-Meier survival curves to determine the timing of recurrent TIA, stroke, or death after failure of antithrombotic therapy.Fifty-two patients had symptomatic intracranial atherosclerosis and fulfilled entry criteria. Twenty-nine of the 52 patients (55.8%) had cerebral ischemic events while receiving an antithrombotic agent (antiplatelet agents [55%], warfarin [31%], or heparin [14%]). In a Cox regression model, older age was an independent predictor of failure of antithrombotic therapy, and warfarin use was associated with a decrease in risk. Recurrent TIA (n = 7), nonfatal/fatal stroke (n = 6/1), or death (n = 1) occurred in 15 of 29 (51.7%) of the patients who failed antithrombotic therapy. The median time to recurrent TIA, stroke, or death was 36 days (95% CI 13 to 59).Patients with symptomatic intracranial atherosclerosis who fail antithrombotic therapy have extremely high rates of recurrent TIA/stroke or death. Recurrent ischemic events typically occur within a few months after failure of standard medical therapy. The high recurrence risk observed warrants testing of alternative treatment strategies such as intracranial angioplasty.

    View details for Web of Science ID 000088855000007

    View details for PubMedID 10953179

  • Clinical problem-solving. Eyes wide open. New England journal of medicine Morton-Bours, E. C., Jacobs, M. B., Albers, G. W. 2000; 343 (1): 50-55

    View details for PubMedID 10882769

  • New magnetic resonance imaging methods for cerebrovascular disease: Emerging clinical applications ANNALS OF NEUROLOGY Neumann-Haefelin, T., Moseley, M. E., Albers, G. W. 2000; 47 (5): 559-570

    Abstract

    During the 1990s, novel magnetic resonance imaging (MRI) techniques have emerged that allow the noninvasive and rapid assessment of normal brain functioning and cerebral pathophysiology. Some of these techniques, including diffusion-weighted imaging and perfusion-weighted imaging, have already been used extensively in specialized centers for the evaluation of patients with cerebrovascular disease. Evidence is now rapidly accumulating that both diffusion- and perfusion-weighted imaging, particularly when used in combination with high-speed MR angiography, will lead to improvements in the clinical management of acute stroke patients. Other novel MR techniques, such as spectroscopic imaging, diffusion tensor imaging, and blood oxygenation level-dependent functional MRI, have not yet assumed a definitive role in the diagnostic evaluation of cerebrovascular disease. However, they are promising research tools that provide noninvasive data about infarct evolution as well as mechanisms of stroke recovery. In this article, we review the basic principles underlying these novel MRI techniques and outline their current and anticipated future impact on the diagnosis and management of patients with cerebrovascular disease.

    View details for Web of Science ID 000086731000002

    View details for PubMedID 10805325

  • Recent advances in stroke management. Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association Albers, G. W., Alberts, M. J., Broderick, J. P., Lyden, P. D., Sacco, R. L. 2000; 9 (3): 95-105

    Abstract

    Major advances in stroke treatment and prevention have, occurred over the last several years. Recent studies have documented that appropriate modification of stroke risk factors can lead to, a substantial reduction in stroke incidence. In addition, a variety of new risk factors, such as elevated plasma homocysteine levels, antiphospholipid antibodies, and specific genetic factors, are being recognized. The most significant advance in acute stroke therapy is the use of intravenous tissue plasminogen activator, (t-PA) for treatment of patients with ischemic stroke within 3 hours of symptom onset. T-PA is currently the only stroke treatment approved by the Federal Drug Administration. There continues to be uncertainty and misunder-standing regarding the risks and benefits of this therapy. A variety of neuroprotective agents have been highly successful for reducing ischemic brain injury in animal stroke models. Recent clinical trials with these agents, however, have not produced beneficial effects in humans. Newer neuroprotective agents with more favorable safety profiles and improvements in clinical trial design may lead to therapeutic successes in the near future. It is apparent that both thrombolytic and neuroprotective treatments for acute stroke must be administered very rapidly, after stroke onset. Therefore, acute stroke teams are being developed to facilitate rapid diagnostic evaluation and treatment of stroke patients.

    View details for PubMedID 17895205

  • Comparison of diffusion-weighted MRI and CT in acute stroke NEUROLOGY Lansberg, M. G., Albers, G. W., Beaulieu, C., Marks, M. P. 2000; 54 (8): 1557-1561

    Abstract

    To compare diffusion-weighted MRI (DWI) and CT with respect to accuracy of localizing acute cerebral infarction; sensitivity, specificity, and interrater reliability for identifying more than one-third middle cerebral artery (MCA) territory involvement; and correlation of acute lesion volume with final infarct volume.Nineteen consecutive stroke patients underwent CT and DWI within 7 hours of stroke onset and a follow-up DWI examination 36 hours after symptom onset, which served as the "gold standard" for lesion location and extent of MCA involvement. Each scan was evaluated for acute ischemic lesions by two experienced observers. After 30 days, T2-weighted MRI was obtained for assessment of the final infarct volume.The acute CT and DWI scans were obtained on average 2.6 and 5.1 hours after symptom onset. On DWI the acute lesion was identified correctly in all instances and on CT it was identified correctly in 42 to 63% of patients. Sensitivity for detection of more than 33% MCA involvement was better for DWI (57 to 86%) than for CT (14 to 43%), whereas specificity was excellent for both. Interrater reliability was moderately good for both (kappa, 0.6 for DWI; 0.5 for CT). A positive correlation (r = 0.79; p = 0.001) existed between lesion volume on acute DWI and final infarct volume, whereas no correlation was found between CT volume and final infarct volume.When compared with CT, DWI was more accurate for identifying acute infarction and more sensitive for detection of more than 33% MCA involvement. In addition, lesion volume on acute DWI, but not on acute CT, correlated strongly with final infarct volume. Additional studies are required to demonstrate whether these advantages of DWI are clinically relevant in the management of patients with acute stroke.

    View details for Web of Science ID 000086642000006

    View details for PubMedID 10762493

  • Yield of diffusion-weighted MRI for detection of potentially relevant findings in stroke patients NEUROLOGY Albers, G. W., Lansberg, M. G., Norbash, A. M., Tong, D. C., O'Brien, M. W., Woolfenden, A. R., Marks, M. P., Moseley, M. E. 2000; 54 (8): 1562-1567

    Abstract

    To determine whether diffusion-weighted imaging (DWI) could identify potentially clinically relevant findings in patients presenting more than 6 hours after stroke onset when compared with conventional MRI.MRI with both conventional (T2 and proton density images) and echoplanar imaging (DWI and apparent diffusion coefficient maps) was performed 6 to 48 hours after symptom onset (mean, 27 hours) in 40 consecutive patients with acute stroke. All acute lesions were identified first on conventional images, then on DWI, by a neuroradiologist who was provided with the suspected lesion location, based on a neurologist's examination before imaging. Abnormalities were rated as potentially clinically relevant if they were detected only on DWI and 1) confirmed the acute symptomatic lesion to be in a different vascular territory than suspected clinically, 2) revealed multiple lesions in different vascular territories suggestive of a proximal source of embolism, or 3) clarified that a lesion, thought to be acute on conventional imaging, was not acute.The initial clinical impression of lesion localization was incorrect in 12 patients (30%). Clinically significant findings were detected by DWI alone in 19 patients (48%). DWI demonstrated the symptomatic lesion in a different vascular territory than suspected clinically or by conventional MRI in 7 patients (18%) and showed acute lesions in multiple vascular distributions in 5 patients (13%). In 8 patients (20%), DWI clarified that lesions thought to be acute on conventional MRI were actually old.In patients imaged 6 to 48 hours after stroke onset, DWI frequently provided potentially clinically relevant findings that were not apparent on conventional MRI.

    View details for Web of Science ID 000086642000007

    View details for PubMedID 10762494

  • The rtPA (Alteplase) 0-to 6-hour acute stroke trial, part A (A0276g) - Results of a double-blind, placebo-controlled, multicenter study STROKE Clark, W. M., Albers, G. W., Madden, K. P., Hamilton, S. 2000; 31 (4): 811-816

    Abstract

    The Thrombolytic Therapy in Acute Ischemic Stroke Study, which started in August of 1991, was designed to assess the efficacy and safety of intravenous rtPA (alteplase) in patients with acute (0 to 6 hours) ischemic stroke. In October 1993 enrollment was halted because of Safety Committee (DMSB) concerns. In December 1993 the time window was changed to 0 to 5 hours, and it was decided to restart enrollment as a separate study (part B). We report here the results of the original study (part A), focusing on evaluating the safety and efficacy of rtPA given between 0 and 6 hours after stroke onset.This investigation was a phase II, placebo-controlled, double-blind, randomized study utilizing 0.9 mg/kg IV rtPA or placebo over 1 hour, which was conducted at university and community sites in North America. Except for time to treatment, enrollment criteria were very similar to those of the NINDS rtPA stroke study. Primary efficacy end points were the number of patients with a decrease of 4 or more points on the National Institutes of Health Stroke Scale (NIHSS) at 24 hours and day 30, along with infarct volume at day 30. Secondary end points included mortality and functional recoveries on the Barthel Index and Modified Rankin scale at days 30 and 90.A total of 142 patients were enrolled at 42 sites in North America, including 22 <3 hours (15%) and 46 between 5 and 6 hours (32%). The groups were well matched on baseline characteristics, including NIHSS (mean of 13 for both). For the primary end points, a higher percentage of rtPA patients had a 4-point improvement at 24 hours (placebo 21%, rtPA 40%; P=0.02); however, this early effect was reversed by 30 days, with more placebo patients having a 4-point improvement (75%) than patients treated with rtPA (60%, P=0.05). Treatment with rtPA significantly increased the rate of symptomatic intracerebral hemorrhage within 10 days (11% versus 0%, P<0.01) and mortality at 90 days (23% versus 7%, P<0.01).This study found no significant rtPA benefit on any of the planned efficacy end points at 30 and 90 days in patients treated between 0 and 6 hours after stroke onset. These negative results apply to patients treated after 3 hours, because only 15% of the patients were enrolled before 3 hours. The risk of symptomatic intracerebral hemorrhage was increased with rtPA treatment, particularly in patients treated between 5 and 6 hours after onset. These results do not support the use of intravenous rtPA for stroke treatment >3 hours after onset.

    View details for PubMedID 10753980

  • Addendum to the supplement to the guidelines for the management of transient ischemic attacks Stroke Albers, Hart, Lutsep, NEWELL, Sacco 2000; 31 (4): 1001-?

    View details for PubMedID 10754016

  • Choice of endpoints in antiplatelet trials - Which outcomes are most relevant to stroke patients? NEUROLOGY Albers, G. W. 2000; 54 (5): 1022-1028

    Abstract

    The relative efficacies of different antiplatelet agents for stroke prevention are unclear because of differences in clinical trial design, a lack of direct comparisons between individual agents, and differences in the choice of primary endpoints. Individual endpoints in a clinical trial are often combined into a single primary endpoint cluster. Theoretically, a combined endpoint may reduce the sample size required to demonstrate significant benefits of an effective therapy. However, unless all components of a composite endpoint are affected in the same direction and to a similar degree, their inclusion may not provide the anticipated increase in statistical power. In fact, the use of a combined endpoint may lead to an underestimate of therapeutic benefits when patients at high risk for one particular endpoint are studied. For patients with stroke or TIA, the single outcome of stroke is particularly important because these patients have a higher risk of recurrent stroke than any other vascular outcome during the initial years after a stroke. Because of the low incidence of myocardial infarction (MI) in stroke trials, the inclusion of MI in the primary endpoint will usually have minimal influence on trial outcome, and antiplatelet therapy has not been shown to be beneficial in preventing nonvascular death. Chance variations in the incidence of MI or death may detract from the benefit of the agent for stroke prevention when it is included in a combined endpoint. The benefit of antiplatelet therapies for patients with recent cerebrovascular events is determined most accurately if stroke alone is chosen as the primary endpoint.

    View details for Web of Science ID 000085785700005

    View details for PubMedID 10720269

  • Intravenous tissue-type plasminogen activator for treatment of acute stroke - The standard treatment with alteplase to reverse stroke (STARS) study JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Albers, G. W., Bates, V. E., Clark, W. M., Bell, R., Verro, P., Hamilton, S. A. 2000; 283 (9): 1145-1150

    Abstract

    Tissue-type plasminogen activator (tPA) is the only therapy for acute ischemic stroke approved by the Food and Drug Administration.To assess the safety profile and to document clinical outcomes and adverse events in patients treated with intravenous tPA for acute stroke in clinical practice.Prospective, multicenter study of consecutive patients enrolled between February 1997 and December 1998 at 57 medical centers in the United States (24 academic and 33 community).Intravenous tPA (recombinant alteplase).Three hundred eighty-nine patients with a mean age of 69 years (range, 28-100 years); 55% were men.Time intervals between stroke symptom onset, hospital arrival, and treatment with tPA; pretreatment computed tomographic scan results, intracerebral hemorrhage, and major systemic bleeding. The modified Rankin Scale score was used to assess clinical outcomes at 30 days.Median time from stroke onset to treatment was 2 hours 44 minutes, and the median baseline National Institutes of Health Stroke Scale score was 13. The 30-day mortality rate was 13%. At 30 days after treatment, 35% of patients had very favorable outcomes (modified Rankin score, 0-1) and 43% were functionally independent (modified Rankin score, 0-2). Thirteen patients (3.3%) experienced symptomatic intracerebral hemorrhage, including 7 who died. Twenty-eight patients (8.2%) had asymptomatic intracerebral hemorrhage within 3 days of treatment with tPA. Protocol violations were reported for 127 patients (32.6%), and included treatment with tPA more than 3 hours after symptom onset in 13.4%, treatment with anticoagulants within 24 hours of tPA administration in 9.3%, and tPA administration despite systolic blood pressure exceeding 185 mm Hg in 6.7%. A multivariate analysis found predictors of favorable outcome to be a less severe baseline National Institutes of Health Stroke Scale score, absence of specific abnormalities (effacement or hypodensity of >33% of the middle cerebral artery territory or a hyperdense middle cerebral artery) on the baseline computed tomographic scan, an age of 85 years or younger, and a lower mean arterial pressure at baseline.This study, conducted at multiple institutions throughout the United States, suggests that favorable clinical outcomes and low rates of symptomatic intracerebral hemorrhage can be achieved using tPA for stroke treatment.

    View details for Web of Science ID 000085424100023

    View details for PubMedID 10703776

  • Basilar artery stenosis: clinical and neuroradiographic features. Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association Woolfenden, A. R., Tong, D. C., Norbash, A. M., Ali, A. O., Marks, M. P., O'Brien, M. W., Albers, G. W. 2000; 9 (2): 57-63

    Abstract

    Although basilar artery stenosis (BAS) is an important cause of posterior circulation stroke, few reports detail the clinical and neuroradiological features of patients with BAS.A retrospective review of symptomatic BAS patients who were evaluated by our Stroke Center.Twenty-eight patients were followed-up for a median of 16 months. Transient ischemic attacks (TIAs) specific for posterior circulation involvement were common (12/19 patients with TIA), were often multiple, and frequently preceded a posterior circulation stroke. The proximal (13/28) and mid (10/28) basilar arteries were the most common sites of stenosis. Brain infarction most often affected the pons, but also frequently involved the cerebellum and thalamus. Concomitant vertebral artery disease was prevalent (12/18 patients who underwent conventional cerebral angiography). Stroke mechanisms included artery to artery embolus, basilar branch disease, and hypoperfusion. The same-territory recurrent stroke rate was 8.2% per year. Most patients in the series were treated with warfarin. No patients suffered a recurrent stroke while on a therapeutic dose of warfarin (international normalized ratio [INR], 2.0 to 3.0). Angioplasty was performed in 6 patients.The same-territory stroke recurrence rate was 8.2% per year. Warfarin (INR, 2.0 to 3.0) appeared to be effective in preventing recurrent strokes. Angioplasty of the basilar artery was technically feasible. Symptomatic BAS typically affected the proximal and mid-basilar artery and most often caused infarction in the pons. The mechanisms for stroke were heterogeneous. TIAs frequently preceded a posterior circulation stroke.

    View details for PubMedID 17895197

  • Selfotel in acute ischemic stroke - Possible neurotoxic effects of an NMDA antagonist STROKE Davis, S. M., Lees, K. R., Albers, G. W., Diener, H. C., Markabi, S., Karlsson, G., Norris, J. 2000; 31 (2): 347-354

    Abstract

    Based on neuroprotective efficacy in animal models, we evaluated the N-methyl D-aspartate antagonist Selfotel in patients with ischemic stroke, after doses up to 1.5 mg/kg were shown to be safe in phase 1 and phase 2a studies.Two pivotal phase 3 ischemic stroke trials tested the hypothesis, by double-blind, randomized, placebo-controlled parallel design, that a single intravenous 1.5 mg/kg dose of Selfotel, administered within 6 hours of stroke onset, would improve functional outcome at 90 days, defined as the proportion of patients achieving a Barthel Index score of >/=60. The trials were performed in patients aged 40 to 85 years with acute ischemic hemispheric stroke and a motor deficit.The 2 trials were suspended on advice of the independent Data Safety Monitoring Board because of an imbalance in mortality after a total enrollment of 567 patients. The groups were well matched for initial stroke severity and time from stroke onset to therapy. There was no difference in the 90-day mortality rate, with 62 deaths (22%) in the Selfotel group and 49 (17%) in the placebo-treated group (RR=1.3; 95% CI 0.92 to 1.83; P=0.15). However, early mortality was higher in the Selfotel-treated patients (day 30: 54 of 280 versus 37 of 286; P=0.05). In patients with severe stroke, mortality imbalance was significant throughout the trial (P=0.05).Selfotel was not an effective treatment for acute ischemic stroke. Furthermore, a trend toward increased mortality, particularly within the first 30 days and in patients with severe stroke, suggests that the drug might have a neurotoxic effect in brain ischemia.

    View details for Web of Science ID 000085039900001

    View details for PubMedID 10657404

  • Phase II studies of the glycine antagonist GV150526 in acute stroke - The North American experience 23rd International Joint Conference on Stroke and Cerebral Circulation Babikian, V., Licata-Gehr, E., Joseph, L. N., Bailey, P., Boyle, R., MacDougall, A., MacLean, G., Wheelock, W. B., Kolyvas, G., Banas, T., Wissman, M. A., Heckaman, J. D., Porter, M. A., Bhat, M. H., Later, P. E., Wissmann, S. D., Ottinger, C. J., Stevens, J. C., Plant, R., CHANG, F. L., Beatty, J., Beatty, T. W., Cohen, S. B., Vasquez, A. B., Schmidt, D. W., Allen, T., Bellavance, A., Hebert, L., Berger, L., Filatrault, R., Nasredding, Z., Trottier, A. G., Duplessis, M., Maison, F. G., Ninkovic, S., Berman, B., Yipelkonen, M., Miskin, B. M., Shaivitz, S. A., Benavente, O., Bruce, G., Solomen, D., Sherman, D., Hart, R., Kanter-Carolin, M., Lalonde, D. R., Rogers, D., Bruce, G., Leonard, A., Brott, T., Spilker, J., Broderick, J., Kothari, R., Panicoli, A., Sauerbeck, L., Miller, R., Clark, W. M., Deely, S. M., Fisher, S., Lutsep, H., Quinn, J., Crawford, J., EGAN, R., Nesbit, G., Al-Azzaz, A., Earley, C., Herr, M., Michel, H., Dike, G., Maragakis, N., Polydefkis, M., Wagner, K., Wang, M., Rusa, R., Jones, C., Kerr, D., Moo, L., Pardo, C., Silverman, I., Hoffman, J., Diebert, E., Jinnah, H., York, J., Hoke, A., Vega-Bermudez, F., Comi, A., HILLIS, A., Rich, J., Ervin, J., Bryan, C., Allen, A. A., Kelley, G. B., Perll, M. F., Box, M. S., Robles, L. H., Zwibelman, J. S., Hopewell, D. K., Ryan, M. E., Wendland, R. T., Feinberg, W., Coull, B., Rose-Taylor, D., Ahern, G., Anderson, L. R., Keim, S., Sherman, S., Rose-Taylor, D., Haley, E. C., Morris, A., Ahern, K., Johnston, K., Solenski, N., Nathan, B., Bleck, T., Worrall, B., Leszczyszyn, D., Hemstreet, M., Kiely, J., Burns, T., Klein, C., Cail, W., Huff, S., Quinn, J., Armstrong, R., Provencio, J., Snider, R., Van Gerpen, J., Hsu, C., Duke, L., Banet, G., Choi, J., Lee, J. M., Lowenkopf, T., Innes, G., Metcalf, C., Huang, P., Rumball, C., Miller, B., Haegert, J., Holmes, A., Oldring, B., Macnab, J., Grosch, R., Deady, B., Street, R., O'Brien, R., Vertesi, L., Erhardt, G., Finkler, J., Tessler, C., Glazer, S., Noseworthy, R., Knazen, M., Macdonald, P., Smyth, A., Karp, J., Phillips, B., Spiegel, A., Bowman, S. C., Hampsey, J. P., Habib, M. W., Schroeder, T., Stopnytsky, K., Kertecz, A., Piotrowski, S., Cooper, P., Lyden, P., Rapp, K., Jackson, C., Ellis, R., Noack, H., Sabbagh, M., Galasko, D., Rapp, K., Kelly, N., WERNER, J., Chang, C. L., Morris, D. T., Pusek, S., Hinn, A., Ma, J., Bernard, E., Phillips, S., Reidy, Y., Gubitz, G., Tanha, F., Leckey, R., Ansell, J., Darvesh, S., Aguilar, E., Pullicino, P., Starr, S., Munschauer, F. E., Ross, D. B., Norris, D., Steinberg, J., Zaret, B., Maniar, M., Sacco, R. L., Boden-Albala, B., Jimenez, M., Mohr, J. P., Kargman, D., Marshall, R., Elkind, M. S., Roberts, K., Gan, R., Shipley, N., Aboumatar, S., Greene, R., Shuaib, A., Kadribasic, E., Keegan, M., Stewart, B., Khaan, K., Shuaib, A., Dean, T. R., Richardson, P., Moussavian, M., Faloriji, W., Johnson, M., Levin, Z., Silliman, S., Fuqua, P. S., Berger, A., Najjar, S., Schwartz, R., Solomon, D. H., Limon, L., Hart, R. G., Sherman, D. G., Carolin, M. C., Lalonde, D. R., Benavente, O., Starkman, S., Schubert, G. B., Dobkin, B., Saver, J., Vespa, P., Alger, J., Teitelbaum, J., Lachance, N., Robillard, A., Lachapelle, J., Boileau, J., Rousseau, S., Roy, L., Laplante, P., Thurston, S., McGee, J. R., Lutz, M. A., McGee, F. E., Harris, J. K., White, R. J., O'Bannon, J. M., Brush, J. J., Cohen, R. J., SMITH, T. A., Mathe, S. A., Karner, S. F., Worthington, A. K., Deel, J. G., Tong, D., Hock, N., Albers, G., O'Brien, M., Woofenden, A., Yenari, M., Freyberg, S., Guro, G., Hock, N., Tuhrim, S., Augustine, S., Weinberger, J., Horowitz, D., Sheinart, K., Schonewille, W., Atlas, S., Veloso, F., REID, M., Adaikari, K., Gebhardt, V., Nair, C. P., Wang, D., Vrabel, D., McLean, J., Kumar, J., Garwacki, D., Roda, M., Hui, E., Coyner, J., Vrabel, D., Honings, D., Rose, J., Sladana, R., Wechsler, L., Yasko, L., Knepper, L., Massaro, L., Graham, S., Larkin, G., Ulicny, T., Yonas, H., Barch, C., Lin, H., Brader, E., Berkey, K., Ludovici, J., Kaufmann, A., De Cesare, S., Hodgdon, A., MacLeod, B., Thompson, D., Piatkowski, S., O'Toole, K., Yasko, L., Ilkhanipour, K., Maenza, R., Mathias, S., Thulborn, K., Jungreis, C., Cockley, P., Corsello, G., Ammon, C., Rasheed, A., Weston, L., Bourque, G., Silverberg, D., Harper, B., Robinson, D., MacEachern, M., Williams, A. D., Roth, R., Rice, M., Hogan, J., Pellegrino, T. R., Holland, M. T., Lanoue, R. J., Redding, A., Handler, J., Haley, E. C., Alves, W. M., Elder, L., Davenport, K., McClure, K., Knowlton, S., Cuccia, E., Maupin, K., Lotts, M., Hund, M., Shelleck, K., Szewc, T., Cail, W., Wagner, G., Gates, K., Earley, C., Haley, E. C., Johnston, K. C., Sacco, R. L., Schuaib, A., Snipes, R., Wang, D. Z., Brass, L. M., Clark, W. R., Grotta, J. C., Harrison, M., McIntyre, N., Zimmerman, H., Wellcome, G., Snipes, R., Watson, D., Ordronneau, P., Hoke, F., Ko, W. J., Clayton, L., EnneyO' Mara, L., Johnson, J., Orander, C., Card, B., Green, S. LIPPINCOTT WILLIAMS & WILKINS. 2000: 358–65

    View details for Web of Science ID 000085039900003

  • Diffusion and perfusion magnetic resonance imaging for the evaluation of acute stroke: potential use in guiding thrombolytic therapy CURRENT OPINION IN NEUROLOGY Tong, D. C., Albers, G. W. 2000; 13 (1): 45-50

    Abstract

    Recent data indicate that diffusion/perfusion weighted imaging could eventually play a significant role in acute stroke management, particularly in determining the suitability of acute stroke patients for thrombolytic therapy. The evidence supporting these uses is reviewed, and the future role of diffusion and perfusion weighted imaging in acute stroke management is discussed.

    View details for Web of Science ID 000168284400009

    View details for PubMedID 10719649

  • Cardioembolic vs. noncardioembolic strokes in atrial fibrillation: Frequency and effect of antithrombotic agents in the stroke prevention in atrial fibrillation studies CEREBROVASCULAR DISEASES Hart, R. G., Pearce, L. A., Miller, V. T., Anderson, D. C., Rothrock, J. F., Albers, G. W., Nasco, E. 2000; 10 (1): 39-43

    Abstract

    While atrial fibrillation (AF) increases the risk of cardioembolic stroke, some ischemic strokes in AF patients are noncardioembolic.To assess ischemic stroke mechanisms in AF and to compare their responses to antithrombotic therapies.On-therapy analyses of ischemic strokes occurring in 3,950 participants in the Stroke Prevention in Atrial Fibrillation I-III clinical trials. Strokes were classified by presumed mechanism according to specified neurologic features by neurologists unaware of antithrombotic therapy.Of 217 ischemic strokes, 52% were classified as probably cardioembolic, 24% as noncardioembolic, and 24% as of uncertain cause (i.e., 68% of classifiable infarcts were deemed cardioembolic). Compared to those receiving placebo or no antithrombotic therapy, the proportion of cardioembolic stroke was lower in patients taking adjusted-dose warfarin (p = 0.02), while the proportion of noncardioembolic stroke was lower in those taking aspirin (p = 0.06). Most (56%) ischemic strokes occurring in AF patients taking adjusted-dose warfarin were noncardioembolic vs. 16% of strokes in those taking aspirin. Adjusted-dose warfarin reduced cardioembolic strokes by 83% (p < 0.001) relative to aspirin. Cardioembolic strokes were particularly disabling (p = 0.05).Most ischemic strokes in AF patients are probably cardioembolic, and these are sharply reduced by adjusted-dose warfarin. Aspirin in AF patients appears to primarily reduce noncardioembolic strokes. AF patients at highest risk for stroke have the highest rates of cardioembolic stroke and have the greatest reduction in stroke by warfarin.

    View details for Web of Science ID 000085008100007

    View details for PubMedID 10629345

  • Impact of diffusion weighted MRI (DWI) on patient management: Is it of practical value? Tong, D. C., Skalabrin, E., Chan, B. P., Moseley, M. E., Kemp, S., Albers, G. W. LIPPINCOTT WILLIAMS & WILKINS. 2000: 286–86

    View details for Web of Science ID 000084589100113

  • Recanalization rates in cervical carotid and vertebral dissection Skalabrin, E. J., Smith, W. S., Albers, G. W. LIPPINCOTT WILLIAMS & WILKINS. 2000: 335–35

    View details for Web of Science ID 000084589100354

  • The ATLANTIS T-PA acute stroke trial: Results for patients treated within three hours of stroke onset Albers, G. W., Clark, W. M., Madden, K. P., Hamilton, S. A. LIPPINCOTT WILLIAMS & WILKINS. 2000: 307–

    View details for Web of Science ID 000084589100221

  • Supplement to the AHA guidelines for the management of transient ischemic attacks Stroke; a journal of cerebral circulation Hughes, R. L., Albers, G. W., Hart, R. G., Lutsep, H. L., Newell, D. W., Sacco, R. L. 2000; 31 (4): 983–91

    View details for PubMedID 10754011

  • Recombinant tissue-type plasminogen activator (alteplase) for ischemic stroke 3 to 5 hours after symptom onset - The ATLANTIS study: A randomized controlled trial JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Clark, W. M., Wissman, S., Albers, G. W., Jhamandas, J. H., Madden, K. P., Hamilton, S. 1999; 282 (21): 2019-2026

    Abstract

    Recombinant tissue-type plasminogen activator (rt-PA) improves outcomes for patients with acute ischemic stroke, but current approved use is limited to within 3 hours of symptom onset. This restricts the number of patients who can be treated, since most stroke patients present more than 3 hours after symptom onset.To test the efficacy and safety of rt-PA in patients with acute ischemic stroke when administered between 3 and 5 hours after symptom onset.The Alteplase ThromboLysis for Acute Noninterventional Therapy in Ischemic Stroke (ATLANTIS) study is a phase 3, placebo-controlled, double-blind randomized study conducted between December 1993 and July 1998, with up to 90 days of follow-up.One hundred forty university and community hospitals in North America.An intent-to-treat population of 613 acute ischemic stroke patients was enrolled, with 547 of these treated as assigned within 3 to 5 hours of symptom onset. A total of 39 others were treated within 3 hours of symptom onset, 24 were treated more than 5 hours after symptom onset, and 3 never received any study drug.Administration of 0.9 mg/kg of rt-PA (n = 272) or placebo (n = 275) intravenously over 1 hour.Primary efficacy was an excellent neurologic recovery at day 90 (National Institutes of Health Stroke Scale [NIHSS] score of < or =1); secondary end points included excellent recovery on functional outcome measures (Barthel index, modified Rankin scale, and Glasgow Outcome Scale) at days 30 and 90. Serious adverse events were also assessed.In the target population, 32% of the placebo and 34% of rt-PA patients had an excellent recovery at 90 days (P = .65). There were no differences on any of the secondary functional outcome measures. In the first 10 days treatment with rt-PA significantly increased the rate of symptomatic intracerebral hemorrhage (ICH) (1.1% vs 7.0% [P<.001]), a symptomatic ICH (4.7% vs 11.4% [P = .004]), and fatal ICH (0.3% vs 3.0% [P<.001]). Mortality at 90 days was 6.9% with placebo and 11.0% with rt-PA (P = .09). Results in the intent-to-treat population were similar.This study found no significant rt-PA benefit on the 90-day efficacy end points in patients treated between 3 and 5 hours. The risk of symptomatic ICH increased with rt-PA treatment. These results do not support the use of intravenous rt-PA for stroke treatment beyond 3 hours.

    View details for PubMedID 10591384

  • Recommendations for standards regarding preclinical neuroprotective and restorative drug development STROKE Feinklestein, S. P., Fisher, M., Furland, A. J., Goldstein, L. B., Gorelick, P. B., Kaste, M., Lees, K. R., Traystman, R. J., Albers, G. W., Anwer, U. E., Ashwood, T., Barone, F. C., Basta, S. L., Bogousslavsky, J., Buchan, A. M., Cady, W. J., Chan, P. H., Clemens, J. A., Cox, B. F., Craddock, R. E., Cramer, S. C., Del Zoppo, G. J., Dielrich, W. D., Elliott, P., Faden, A. I., Feuerstein, G. Z., Ginsberg, M. D., Gold, M., Greene, W. L., Hall, E. D., Hsu, C. Y., Hunter, A. J., Lai, M., Lesko, L. M., Levy, D. E., Li, F. H., Locke, K. W., LODGE, D., Lowe, D., Marcoux, F. W., McCulloch, J., McDermott, J., Meibach, R., Messersmith, E. K., Moseley, M., Moskowitz, M. A., Mueller, A. L., Munro, F., Nudo, R. J., Oeda, J., Ohlstein, E. H., Parsons, A., Patmore, L., Poole, R. M., Pschorn, U., Pulsinelli, W. A., Sacco, R. L., Saeki, S., Salazar-Grueso, E., Sandage, B. W., Schallert, T., Schielke, G. P., Sharkey, J., Sotak, C. H., Steiger, B., Storall, S., Takahashi, Y., Tumas, D., Van Bruggen, N., Versavel, M., Vornov, J., Walker, M. D., Wallin, B., Wang, J., Warach, S., Wells, D. S., Witcher, J. A. 1999; 30 (12): 2752-2758

    Abstract

    The plethora of failed clinical trials with neuroprotective drugs for acute ischemic stroke have raised justifiable concerns about how best to proceed for the future development of such interventions. Preclinical testing of neuroprotective drugs is an important aspect of assessing their therapeutic potential, but guidelines concerning how to perform preclinical development of purported neuroprotective drugs for acute ischemic stroke are lacking. This conference of academicians and industry representatives was convened to suggest such guidelines for the preclinical evaluation of neuroprotective drugs and to recommend to potential clinical investigators the data they should review to reassure themselves that a particular neuroprotective drug has a reasonable chance to succeed in an appropriately designed clinical trial. Without rigorous, robust, and detailed preclinical evaluation, it is unlikely that novel neuroprotective drugs will prove to be effective when tested in large, time-consuming, and expensive clinical trials. Additionally, similar recommendations are provided for drugs with the potential to enhance recovery after acute ischemic stroke, a burgeoning new field with great potential but little currently available data. The suggestions contained in this document are meant to serve as overall guidelines that must be adapted to the individual characteristics related to particular drugs and their preclinical and clinical development needs.

    View details for Web of Science ID 000083890700044

    View details for PubMedID 10583007

  • Antithrombotic management of atrial fibrillation for stroke prevention in older people CLINICS IN GERIATRIC MEDICINE Tong, D. C., Albers, G. W. 1999; 15 (4): 645-?

    Abstract

    Atrial fibrillation (AF) is a common cardiac condition in the elderly population. The primary concern in individuals with AF is the risk of stroke. The management of AF for stroke prevention requires an understanding of the relative risks and benefits of antithrombotic therapy. Numerous randomized clinical trials have improved tremendously our understanding of the relative merits of anticoagulation and aspirin, and indicate that anticoagulation is the appropriate treatment for the majority of individuals with AF. In patients who have contraindications to anticoagulation, aspirin is recommended.

    View details for Web of Science ID 000083539800002

    View details for PubMedID 10499928

  • Supplement to the guidelines for the management of transient ischemic attacks - A statement from the Ad Hoc Committee on guidelines for the management of transient ischemic attacks, Stroke Council, American Heart Association STROKE Albers, G. W., Hart, R. G., Lutsep, H. L., Newell, D. W., Sacco, R. L. 1999; 30 (11): 2502-2511

    View details for Web of Science ID 000083434100054

  • AHA Scientific Statement. Supplement to the guidelines for the management of transient ischemic attacks: A statement from the Ad Hoc Committee on Guidelines for the Management of Transient Ischemic Attacks, Stroke Council, American Heart Association. Stroke Albers, G. W., Hart, R. G., Lutsep, H. L., Newell, D. W., Sacco, R. L. 1999; 30 (11): 2502-2511

    View details for PubMedID 10548693

  • Expanding the window for thrombolytic therapy in acute stroke - The potential role of acute MRI for patient selection STROKE Albers, G. W. 1999; 30 (10): 2230-2237

    Abstract

    Effective therapy was not available for treatment of acute stroke until 1995, when tissue plasminogen activator (tPA) was shown to improve neurological and functional outcome in stroke patients who were treated within 3 hours of symptom onset.Currently, many patients do not qualify for tPA therapy because they present for evaluation beyond 3 hours after stroke onset. Attempts to expand the treatment window to 6 hours, using CT to select patients, have failed. Use of early MR imaging may provide significant advantages over CT for identification of patients who are likely to benefit from thrombolytic therapy because (1) the early perfusion-weighted imaging (PWI) lesion estimates the region of acute dysfunctional brain tissue, whereas the acute diffusion-weighted imaging (DWI) lesion appears to correspond to the core of the early infarction; (2) the mismatch between the acute PWI lesion and the smaller DWI lesion represents potentially salvageable brain tissue (an estimate of the ischemic penumbra); and (3) in patients with a PWI/DWI mismatch, early reperfusion is often associated with substantial clinical improvement and reversal or reduction of DWI lesion growth.Clinical trials that use new MRI techniques to screen patients may be able to identify a subset of acute stroke patients who are ideal candidates for thrombolytic therapy even beyond 3 hours after stroke onset.

    View details for Web of Science ID 000082983200042

    View details for PubMedID 10512933

  • Antiplatelet therapy: New foundations for optimal treatment decisions NEUROLOGY Albers, G. W., Tijssen, J. G. 1999; 53 (7): S25-S31

    Abstract

    Individuals who experience a stroke or a transient ischemic attack require long-term treatment to prevent a subsequent stroke. According to the current guidelines, patients with a first cerebrovascular event due to cardioembolism should be treated with oral anticoagulants, barring any contraindications. Individuals with ischemic cerebral events due to atherothrombosis should typically receive antiplatelet agents. Aspirin is the best-studied antiplatelet agent and has been used in stroke prevention for many years. Trials evaluating aspirin have, over time, enrolled more patients and tested lower aspirin doses. No individual trial conducted in cerebrovascular patients has established the optimal aspirin dose for prevention of vascular events, but meta-analyses of trials at different dose ranges and the two single trials that directly compared different doses strongly suggest that the benefit of aspirin is independent of dose in this patient population. Lower doses (50-325 mg daily) are now recommended because of their more favorable side-effect profiles. Because its value is established, aspirin has been used as a control to evaluate other antiplatelet agents. On the basis of large clinical trials versus aspirin, three other antiplatelet agents (ticlopidine, clopidogrel, and the combination of aspirin plus extended-release dipyridamole) have all been shown to be effective for stroke prevention. Physician opinions regarding the efficacy of these agents in indirect comparisons and the differences in their safety profiles, availability, and cost will influence the choice of agent for the individual patient.

    View details for Web of Science ID 000083207300004

    View details for PubMedID 10532645

  • Longitudinal magnetic resonance imaging study of perfusion and diffusion in stroke: Evolution of lesion volume and correlation with clinical outcome ANNALS OF NEUROLOGY Beaulieu, C., de Crespigny, A., Tong, D. C., Moseley, M. E., Albers, G. W., Marks, M. P. 1999; 46 (4): 568-578

    Abstract

    A prospective longitudinal diffusion-weighted and perfusion-weighted magnetic resonance imaging (DWI/PWI) study of stroke patients (n = 21) at five distinct time points was performed to evaluate lesion evolution and to assess whether DWI and PWI can accurately and objectively demonstrate the degree of ischemia-induced deficits within hours after stroke onset. Patients were scanned first within 7 hours of symptom onset and then subsequently at 3 to 6 hours, 24 to 36 hours, 5 to 7 days, and 30 days after the initial scan. Lesion evolution was dynamic during the first month after stroke. Most patients (18 of 19, 95%) showed increased lesion volume over the first week and then decreased at 1 month relative to 1 week (12 of 14, 86%). Overall, lesion growth appeared to depend on the degree of mismatch between diffusion and perfusion at the initial scan. Abnormal volumes on the acute DWI and PWI (<7 hours) correlated well with initial National Institutes of Health (NIH) stroke scale scores, outcome NIH stroke scale scores, and final lesion volume. DWI and PWI can provide an early measure of metabolic and hemodynamic insufficiency, and thus can improve our understanding of the evolution and outcome after acute ischemic stroke.

    View details for PubMedID 10514093

  • A standardized MRI stroke protocol: Comparison with CT in hyperacute intracerebral hemorrhage STROKE Tong, D. C., Albers, G. W., Yenari, M. A., Marks, M. P. 1999; 30 (9): 1974-1975

    View details for Web of Science ID 000082278400047

    View details for PubMedID 10471453

  • Emerging evidence for inflammation in conditions frequently affecting older adults: Report of a symposium Annual American-College-of-Physicians Meeting Hamerman, D., Berman, J. W., Albers, G. W., Brown, D. L., Silver, D. WILEY-BLACKWELL PUBLISHING, INC. 1999: 1016–25

    View details for Web of Science ID 000081880800015

    View details for PubMedID 10443865

  • Cerebral amyloid angiopathy with unilateral hemorrhages, mass effect, and meningeal enhancement NEUROLOGY Morton-Bours, E. C., Skalabrin, E. J., Albers, G. W. 1999; 53 (1): 233-234

    View details for Web of Science ID 000081354000049

    View details for PubMedID 10408572

  • Applications of diffusion-perfusion magnetic resonance imaging in acute ischemic stroke NEUROLOGY Fisher, M., Albers, G. W. 1999; 52 (9): 1750-1756

    Abstract

    Diffusion-weighted imaging (DWI) and perfusion imaging (PI) are two new magnetic resonance technologies that are becoming increasingly available for evaluation of acute ischemic stroke patients. DWI provides information about the location of acute focal ischemic brain injury at early time points and PI can document the presence of disturbances in microcirculatory perfusion. DWI and PI are now being used in clinical practice and in clinical trials of potential acute stroke therapies to assess their utility. In the future, DWI and PI may aid in the development of effective acute stroke therapies and help identify which stroke patients are most likely to benefit from specific agents.

    View details for Web of Science ID 000080758500008

    View details for PubMedID 10371519

  • Evaluation of early reperfusion and IV tPA therapy using diffusion- and perfusion-weighted MRI NEUROLOGY Marks, M. P., Tong, D. C., Beaulieu, C., Albers, G. W., de Crespigny, A., Moseley, M. E. 1999; 52 (9): 1792-1798

    Abstract

    To characterize the effects of recombinant tissue plasminogen activator (rt-PA) therapy and early reperfusion on diffusion-weighted (DWI) and perfusion-weighted imaging (PWI) changes observed following acute ischemic injury.Twelve patients were evaluated prospectively using echo planar DWI and bolus tracking PWI. Six patients received i.v. rt-PA 0.9 mg/kg and were compared with six patients who did not. Patients receiving rt-PA were initially imaged (T1) 3 to 5 hours postictus (mean, 4 hours 20 minutes) whereas those not treated with tissue plasminogen activator (tPA) were imaged 4 to 7 hours postictus (mean, 5 hours, 25 minutes). Follow-up imaging was performed 3 to 6 hours (T2), 24 to 36 hours (T3), 5 to 7 days (T4), and 30 days (T5) after the first scan in all patients. Lesion volumes were measured on both DWI and time-to-peak maps constructed from PW images.PWI was performed successfully at T1 and T3 in 11 of 12 patients. In the group that received i.v. tPA, initial PWI volumes were less than DWI volumes in five of six patients (83%), whereas only one of five patients (20%) not receiving tPA had PWI < DWI volume (p = 0.08). PWI normalized by 24 to 36 hours (T3) in 6 of 11 patients (early reperfusers), with 5 of 6 of these early reperfusers having received tPA. The aggregate apparent diffusion coefficient (ADC) values for the early reperfusers were consistently higher at T2 (p = 0.04), T3 (p = 0.002), and T4 (p = 0.0005). Five of six patients with early reperfusion demonstrated regions of elevated ADC within the ischemic zone (mean ipsilateral ADC/contralateral ADC, 1.46 +/- 0.19) by 24 to 36 hours, whereas none of the nonearly reperfusers showed these regions of elevated ADC (p = 0.015).Early reperfusion is seen more frequently with i.v. tPA therapy. In addition, the study showed that ADC may undergo early increases that are tied closely to reperfusion, and marked ADC heterogeneity may exist within the same lesion. Early reperfusion is seen more frequently with i.v. tPA therapy.

    View details for Web of Science ID 000080758500014

    View details for PubMedID 10371525

  • Acute Ischemic Stroke. Current treatment options in neurology Chan, Albers 1999; 1 (2): 83-96

    Abstract

    Patients with acute ischemic stroke should be immediately transported to the nearest hospital for rapid evaluation and treatment. Intravenous t-PA within 3 hours of symptom onset is the recommended treatment for patients who meet the National Institute of Neurological Disorders and Stroke (NINDS) study eligibility criteria. Patients should be informed of the risk of symptomatic cerebral hemorrhage, and strict adherence to the NINDS study protocol is strongly recommended to optimize the risk-benefit ratio. Ischemic stroke patients who are not eligible for t-PA therapy should usually be started on aspirin. Intravenous heparin is not recommended as a standard treatment but may be considered for specific patient subgroups. Low-dose subcutaneous heparin is recommended for prophylaxis of deep vein thrombosis in immobilized patients. Management of stroke patients by a designated stroke team is recommended to facilitate prompt diagnosis and treatment and early initiation of rehabilitation therapy. We also recommend that physicians who manage patients with acute stroke maintain contact with local or regional stroke centers to facilitate referral of appropriate patients for intensive care or specialized diagnostic tests or therapies.

    View details for PubMedID 11096699

  • Outcome of angioplasty for atherosclerotic intracranial stenosis STROKE Marks, M. P., Marcellus, M., Norbash, A. M., Steinberg, G. K., Tong, D., Albers, G. W. 1999; 30 (5): 1065-1069

    Abstract

    We sought to assess the long-term outcome and efficacy of percutaneous transluminal angioplasty in the treatment of symptomatic intracranial atherosclerotic stenoses.Twenty-three patients with fixed symptomatic intracranial stenoses were treated over a 5-year period with percutaneous transluminal angioplasty. Patients who underwent successful angioplasty were followed up for 16 to 74 months (mean, 35.4 months).An angioplasty that resulted in decreased stenosis was performed in 21 of 23 patients (91.3%). In 1 case a stenosis could not be safely crossed, and in another balloon dilatation resulted in vessel rupture. This vessel rupture resulted in the 1 periprocedural death in the series. In follow-up there was 1 stroke in the same vascular territory as the angioplasty and 2 strokes in the series overall. This yielded an annual stroke rate of 3.2% for strokes in the territory appropriate to the site of angioplasty.Intracranial angioplasty can be performed with a high degree of technical success. The long-term clinical follow-up available in this series suggests that it may reduce the risk of future stroke in patients with symptomatic intracranial stenoses.

    View details for PubMedID 10229745

  • MRI abnormalities associated with partial status epilepticus NEUROLOGY Lansberg, M. G., O'Brien, M. W., Norbash, A. M., Moseley, M. E., Morrell, M., Albers, G. W. 1999; 52 (5): 1021-1027

    Abstract

    To report neuroimaging findings in patients with complex partial status epilepticus.During status epilepticus, neuroimaging may be used to exclude other neurologic conditions. Therefore, it is important to identify the neuroimaging features that are associated with status epilepticus. In addition, MRI characteristics may provide insight into the pathophysiologic changes during status epilepticus.The history and neuroimaging examination results of three patients with complex partial status epilepticus were reviewed. Studies obtained during status epilepticus included diffusion-weighted MRI (DWI), MR angiography (MRA), postcontrast T1-weighted MRI, T2-weighted MRI, and CT. Follow-up MRI was obtained in two patients, and autopsy results were available for the third.Some of the MRI and CT findings during partial status epilepticus mimicked those of acute ischemic stroke: DWI and T2-weighted MRI showed cortical hyperintensity with a corresponding low apparent diffusion coefficient, and CT showed an area of decreased attenuation with effacement of sulci and loss of gray-white differentiation. However, the lesions did not respect vascular territories, there was increased signal of the ipsilateral middle cerebral artery on MRA, and leptomeningeal enhancement appeared on postcontrast MRI. On follow-up imaging, the abnormalities had resolved, but some cerebral atrophy was present.The radiologic characteristics of status epilepticus resemble those of ischemic stroke but can be differentiated based on lesion location and findings on MRA and postcontrast MRI. The MRI abnormalities indicated the presence of cytotoxic and vasogenic edema, hyperperfusion of the epileptic region, and alteration of the leptomeningeal blood-brain barrier. These changes reversed, but they resulted in some regional brain atrophy.

    View details for Web of Science ID 000079516900022

    View details for PubMedID 10102423

  • Dose escalation study of the NMDA glycine-site antagonist licostinel in acute ischemic stroke STROKE Albers, G. W., Clark, W. M., Atkinson, R. P., Madden, K., Data, J. L., Whitehouse, M. J. 1999; 30 (3): 508-513

    Abstract

    Licostinel (ACEA 1021; 5-nitro-6, 7-dichloro-2,3-quinoxalinedione), a competitive antagonist of glycine at the N-methyl-D-aspartate (NMDA) receptor, is an effective neuroprotective agent in animal models of cerebral ischemia. The purpose of this study was to assess the safety, tolerability, and pharmacokinetics of licostinel in patients with acute stroke.In this 5-center dose escalation trial, patients were enrolled within 48 hours of an ischemic stroke and treated with ascending doses of a short infusion of licostinel or a placebo. Adverse effects were assessed with clinical and laboratory measurements, and patient outcome was determined with the National Institutes of Health Stroke Scale.Sixty-four patients (44 treated with escalating doses of licostinel and 20 who received placebo) were treated. Lower doses of licostinel (0.03 to 0.60 mg/kg) were not associated with any significant adverse effects. Higher doses of licostinel (1.2 to 3.0 mg/kg) were associated with a variety of mild-to-moderate adverse effects including neurological and gastrointestinal complaints. No major psychotomimetic effects or significant safety concerns occurred. At the higher dose levels, peak plasma concentrations of licostinel were substantially higher than those required for neuroprotection in animal stroke models. A similar improvement in National Institutes of Health Stroke Scale scores over time was seen in both the placebo group and the licostinel-treated patients.A short infusion of licostinel in doses up to 3.0 mg/kg is safe and tolerable in acute stroke patients. Licostinel may be a safer and better tolerated neuroprotective agent than many of the previously evaluated NMDA antagonists.

    View details for Web of Science ID 000078913700006

    View details for PubMedID 10066844

  • Moyamoya syndrome in children with Alagille syndrome: Additional evidence of a vasculopathy PEDIATRICS Woolfenden, A. R., Albers, G. W., Steinberg, G. K., Hahn, J. S., Johnston, D. C., Farrell, K. 1999; 103 (2): 505-508

    View details for Web of Science ID 000078437800023

    View details for PubMedID 9925853

  • Risk factors for stroke and primary prevention of stroke in atrial fibrillation JOURNAL OF THROMBOSIS AND THROMBOLYSIS Laupacis, A., Singer, D., Jacobsen, A., Dunn, M., Dalen, J., Albers, G. 1999; 7 (1): 21-26

    View details for Web of Science ID 000079077700004

    View details for PubMedID 10337356

  • Orolingual angioedema complicating Rtpa (Alteplase) for acute ischemic stroke (AIS) Fayad, P. B., Albers, G. W., Frey, J. L., Raps, E. C. LIPPINCOTT WILLIAMS & WILKINS. 1999: 242–42

    View details for Web of Science ID 000077934200116

  • Headache with neurological deficits and CSF lymphocytosis: A transient ischemic attack mimic. Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association Lansberg, M. G., Woolfenden, A. R., Norbash, A. M., Smith, D. B., Albers, G. W. 1999; 8 (1): 42-44

    Abstract

    Headache with neurological deficits and cerebrospinal fluid (CSF) lymphocytosis (HaNDL) is a benign condition with a transient ischemic attack (TIA)-like presentation. It is a disease of young adults that is characterized by headache, transient focal neurological symptoms, and lymphocytic pleocytosis. The onset of neurological symptoms after cerebral angiography in patients with this disease has occasionally been reported. The authors present the case of a 28-year-old man with episodes of left-sided numbness and weakness associated with headache. He underwent cerebral angiography as part of his evaluation, after which he experienced an episode of right hemiplegia and aphasia. A subsequent magnetic resonance image (MRI) revealed two small new infarcts in the left parietal cortex. A diagnosis of HaNDL was made based mainly on clinical symptoms and CSF analysis. The symptoms resolved with conservative therapy. HaNDL is a benign condition that can present with symptoms similar to a TIA. Although HaNDL remains a diagnosis of exclusion, caution is required when considering cerebral angiography in the evaluation of patients with a HaNDL-like syndrome, because these patients seem prone to developing neurological symptoms after angiography.

    View details for PubMedID 17895137

  • Antithrombotic and thrombolytic therapy for ischemic stroke CHEST Albers, G. W., Easton, J. D., Sacco, R. L., Teal, P. 1998; 114 (5): 683S-698S

    View details for Web of Science ID 000077034200018

    View details for PubMedID 9822071

  • Antithrombotic therapy in atrial fibrillation CHEST Laupacis, A., Albers, G., Dalen, J., Dunn, M. I., Jacobson, A. K., Singer, D. E. 1998; 114 (5): 579S-589S

    View details for Web of Science ID 000077034200011

    View details for PubMedID 9822064

  • Diffusion-weighted MRI for evaluation of acute stroke NEUROLOGY Albers, G. W. 1998; 51 (3): S47-S49

    Abstract

    Diffusion-weighted imaging (DWI) is a new magnetic resonance imaging technique that detects the tiny random movements of water molecules (diffusion) in tissues. This technique allows a map of the average apparent diffusion coefficient (ADC) to be calculated. Shortly after the onset of an ischemic stroke, the ADC of brain tissue is significantly reduced because of cytotoxic edema. Over several days, the rapid initial drop in ADC is followed by a return to "pseudonormal" values at approximately 1 week. Subsequently, elevated ADC values are seen at chronic time points. DWI is remarkably sensitive in detecting and localizing acute ischemic brain lesions and allows differentiation of acute regions of ischemia from chronic infarcts. Recent studies have shown a high correlation between the volume of early DWI lesions and clinical neurologic outcome. In addition, the volume of the early DWI lesion correlates well with final infarct volume as measured by T2-weighted imaging. Therefore, this technique may facilitate optimal selection of patients for new medical therapies for stroke and may provide a highly sensitive technique for evaluating the efficacy of new treatments.

    View details for Web of Science ID 000075941900013

    View details for PubMedID 9744834

  • Ethical standards in phase 1 trials of neuroprotective agents for stroke therapy STROKE Albers, G. W., Zivin, J. A., Choi, D. W. 1998; 29 (8): 1493-1494

    View details for Web of Science ID 000075183000004

    View details for PubMedID 9707181

  • Choice of antithrombotic therapy for stroke prevention in atrial fibrillation - Warfarin, aspirin, or both? ARCHIVES OF INTERNAL MEDICINE Albers, G. W. 1998; 158 (14): 1487-1491

    View details for Web of Science ID 000074957200001

    View details for PubMedID 9679788

  • Angiographically defined primary angiitis of the CNS - Is it really benign? NEUROLOGY Woolfenden, A. R., Tong, D. C., Marks, M. P., Ali, A. O., Albers, G. W. 1998; 51 (1): 183-188

    Abstract

    Primary angiitis of the CNS (PACNS) is a diagnostically challenging disorder. In patients whose diagnosis is ascertained solely by cerebral angiography without histologic verification, a benign monophasic clinical course with favorable response to a brief course of immunosuppressive therapy is often reported.We performed a retrospective review of patients with PACNS seen at the Stanford Stroke Center.Patients were followed for a median of 27.5 months. Acute focal deficits (9 of 10) and headache (3 of 10) were the most frequent presenting symptoms. Significant recurrent neurologic symptoms occurred in 5 of 10 patients before the initiation of immunosuppressive treatment. Three of six patients had recurrent symptoms during prednisone therapy alone, whereas only one of seven patients had recurrent symptoms while receiving combination immunosuppressive therapy. None had recurrent stroke during immunosuppressive treatment. Dynamic arterial changes were seen in four of five patients who underwent follow-up angiography that often, but not always, correlated with disease activity.Patients with angiographically defined PACNS frequently did not have a benign outcome or monophasic course. Repeat angiography was useful in supporting the diagnosis of PACNS, but did not always correlate with disease activity. A prospective multicenter collaborative effort is required to better define the clinical course and optimal treatment of PACNS.

    View details for PubMedID 9674800

  • Progressive facial hemiatrophy: Abnormality of intracranial vasculature NEUROLOGY Woolfenden, A. R., Tong, D. C., Norbash, A. M., Albers, G. W. 1998; 50 (6): 1915-1917

    Abstract

    Progressive facial hemiatrophy (PFH) or Parry-Romberg syndrome is associated with ipsilateral brain lesions and neurologic symptoms. We describe a 35-year-old man with PFH and frequent hemiplegic migraine. On cerebral angiography, reversible vessel caliber changes were seen within the symptomatic hemisphere. An abnormality of the intracranial vasculature may be present in some patients with PFH and neurologic manifestations.

    View details for Web of Science ID 000074226700078

    View details for PubMedID 9633763

  • Thrombolysis with reteplase, an unglycosylated plasminogen activator variant, in experimental embolic stroke. Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association Yenari, M. A., Lee, L. K., Beaulieu, C., Sun, G. H., Kunis, D., Chang, D., Albers, G. W., Moseley, M. E., Steinberg, G. K. 1998; 7 (3): 179-186

    Abstract

    We incorporated diffusion-weighted magnetic resonance imaging (MRI) (DWI) and perfusion-weighted MRI (PWI) to evaluate the efficacy of thrombolysis in experimental embolic stroke using a plasminogen activator, reteplase. Reteplase (rPA) is an unglycosylated plasminogen activator with enhanced fibrinolytic potency. Right internal carotid arteries of 34 rabbits were embolized using aged heterologous thrombi. Baseline DWI and PWI scans 0.5 hours after embolization confirmed successful embolization among 32. Intravenous treatment with rPA (n=11; 1 mg/kg bolus), recombinant tissue plasminogen activator (rt-PA) (n=11; 6 mg/kg bolus over 1 hour), or placebo (n=10) commenced 1 hour after stroke induction. MRIs were performed at 1.75, 3, and 5 hours after embolization. Six hours after embolization, brains were harvested and examined for hemorrhage. Posttreatment areas of diffusion abnormality and perfusion delay were graded using both a semiquantitative scale and percent areas expressed as a ratio of the baseline values. Improved perfusion was seen among the rt-PA, and rPA-treated groups compared with placebo, using a semiquantitative scale (P<.01 rt-PA v controls, P<.05, rPA v controls). DWI scans, however, were not improved with thrombolysis. Cerebral hemorrhage was not increased with thrombolytic treatment, although the incidence of wound site hemorrhage was higher with either rPA or rt-PA. One fatal systemic hemorrhage was observed in each of the thrombolytic-treated groups. Cerebral perfusion was equally improved with either rt-PA or rPA without causing excess cerebral hemorrhage. An advantage of rPA is single-bolus dosing rather than continuous infusion. Use of rPA for stroke treatment should be further explored.

    View details for PubMedID 17895078

  • Correlation of perfusion- and diffusion-weighted MRI with NIHSS score in acute (< 6.5 hour) ischemic stroke NEUROLOGY Tong, D. C., Yenari, M. A., Albers, G. W., O'Brien, M., Marks, M. P., Moseley, M. E. 1998; 50 (4): 864-870

    Abstract

    Diffusion-weighted (DWI) and perfusion-weighted (PWI) MRI are powerful new techniques for the assessment of acute cerebral ischemia. However, quantitative data comparing the severity of clinical neurologic deficit with the results of DWI or PWI in the earliest phases of stroke are scarce. Such information is vital if MRI is potentially to be used as an objective adjunctive measure of stroke severity and outcome.The authors compared initial DWI and PWI lesion volumes with subsequent 24-hour neurologic deficit as determined by National Institutes of Health Stroke Scale (NIHSS) score in acute stroke patients. Initial DWI and PWI volumes were also compared with T2W MRI lesion volume at 1 week to assess the accuracy of these MRI techniques for the detection of acute cerebral ischemia.Patients with stroke underwent MRI scanning within 6.5 hours of symptom onset. Lesion volumes on DWI and PWI were measured and compared with 24-hour NIHSS score. Initial DWI and PWI volumes were also compared with T2W lesion size at 1 week.There was a high correlation between 24-hour NIHSS score and lesion volume as determined by PWI (r = 0.96, p < 0.001) or DWI (r = 0.67, p = 0.03). A similar high correlation was seen between T2W stroke size at 7 days and initial DWI and PWI lesion size (r = 0.99, p < 0.00001).Both DWI and PWI are highly correlated with severity of neurologic deficit by 24-hour NIHSS score. These findings may have substantial implications for the use of MRI scanning in the assessment and management of acute stroke patients.

    View details for Web of Science ID 000073187300010

    View details for PubMedID 9566364

  • Rationale for early intervention in acute stroke. American journal of cardiology Albers, G. W. 1997; 80 (4C): 4D-10D

    Abstract

    Ischemic stroke occurs after an abrupt reduction in cerebral blood flow, usually related to thrombosis of an intracranial or extracranial artery. The presenting symptoms and signs of stroke vary greatly, depending on the region of the brain involved. Most individuals are unaware of the warning signs or symptoms of stroke and do not seek medical care immediately after stroke onset. Recently, thrombolytic therapy with intravenous tissue plasminogen activator (t-PA) has been shown to be effective for treatment of selected stroke patients if administered <3 hours after stroke onset. This therapy is now approved for stroke treatment, but relatively few stroke patients currently receive t-PA. Neuroprotective agents that improve the intrinsic ability of brain parenchyma to withstand ischemia are currently undergoing intensive clinical evaluation. Their development has been facilitated by significant scientific advances in the understanding of the pathophysiology of acute ischemic neuronal injury. Strategies aimed at interfering with these fundamental processes of ischemic neuronal injury have shown encouraging results in several preliminary clinical trials. However, these agents probably must also be administered within a few hours of stroke onset to be beneficial. Eventually, combined neuroprotective and thrombolytic therapy will likely be used for acute stroke treatment. This strategy's success will depend on increased public and professional education efforts dealing with stroke recognition, evaluation, and treatment.

    View details for PubMedID 9284038

  • Etiology of stroke American-Heart-Association Prevention Conference IV: Prevention and Rehabilitation of Stroke Mohr, J. P., Albers, G. W., Amarenco, P., Babikian, V. L., Biller, J., Brey, R. L., Coull, B., Easton, J. D., Gomez, C. R., Helgason, C. M., Kase, C. S., Pullicino, P. M., Turpie, A. G. LIPPINCOTT WILLIAMS & WILKINS. 1997: 1501–6

    View details for Web of Science ID A1997XK48200040

  • Clinical characteristics and management of acute stroke in patients with atrial fibrillation admitted to US university hospitals NEUROLOGY Albers, G. W., Bittar, N., Young, L., Hattemer, C. R., Gandhi, A. J., Kemp, S. M., Hall, E. A., Morton, D. J., Yim, J., Vlasses, P. H. 1997; 48 (6): 1598-1604

    Abstract

    The optimal evaluation and management of patients with atrial fibrillation who suffer an acute ischemic stroke remains controversial.Medical records of 171 consecutive patients with atrial fibrillation and acute stroke at six U.S. university hospitals were reviewed. Data collected included the use of antithrombotic therapy, brain and cardiac imaging, bleeding complications, stroke risk factors, and contraindications to anticoagulation.Mean age was 75.4 years. Cardiovascular risk factors associated with increased stroke risk were present in 87%; 35% had at least one contraindication to anticoagulation. Half of the patients with stroke risk factors and no contraindications to anticoagulation were not receiving any antithrombotic therapy at the time of admission. Of the 22 patients who were treated with warfarin, and had INR values on admission, 16 had levels of < 2.0; only six had INR values between 2.0 and 3.0. Transthoracic echocardiography was performed in 107 patients (63%); intracardiac thrombi were visualized in only 5%. Initial brain imaging revealed hemorrhagic transformation in nine. Heparin was used in 93 patients (54%), usually within 48 hours of stroke onset. Patients who received delayed heparin typically did not have repeat brain imaging prior to starting heparin. One patient had a delayed symptomatic cerebral hemorrhage. Of the survivors, 47% were discharged and treated with warfarin (or warfarin plus aspirin), 28% with ASA, 7% with other antithrombotic therapies, and 18% with no antithrombotic therapy.Antithrombotic therapy was underutilized and inadequately monitored in atrial fibrillation patients prior to stroke onset. After hospital admission, a wide range of diagnostic and management strategies, which often did not follow current recommendations, were employed.

    View details for Web of Science ID A1997XE09100023

    View details for PubMedID 9191773

  • Clinical utility of diffusion-weighted magnetic resonance imaging in the assessment of ischemic stroke ANNALS OF NEUROLOGY Lutsep, H. L., Albers, G. W., deCrespigny, A., Kamat, G. N., Marks, M. P., Moseley, M. E. 1997; 41 (5): 574-580

    Abstract

    Diffusion-weighted imaging (DWI) detects small changes in water diffusion that occur in ischemic brain. This study evaluated the clinical usefulness of a phase-navigated spin-echo DWI sequence compared with T2-weighted magnetic resonance imaging (T2W MRI) in patients with cerebral ischemia and assessed apparent diffusion coefficient (ADC) and T2-weighted imaging (T2WI) changes over time. ADC values and T2 ratios of image intensity were measured from the region of ischemia and from the corresponding contralateral brain region. The clinical histories of patients with DWI scans obtained over the course of 1 year were reviewed to ascertain whether DWI aided in clinical diagnosis or management. Of 103 scans obtained a mean of 10.4 days after symptom onset, DWI detected six lesions not seen on T2WI and discriminated two new infarcts from old lesions. DWI was most useful within 48 hours of the ictus. The evolution of ADC values and T2 ratios was evaluated in 26 cases with known symptom onset times. ADC values were low at less than 1 week after stroke onset and became elevated at chronic time points. T2 ratios were near normal acutely, increasing thereafter. DWI was superior to T2W MRI in detecting acute stroke, whereas both techniques assisted in determining lesion age.

    View details for Web of Science ID A1997WZ80900004

    View details for PubMedID 9153518

  • Improved perfusion with rt-PA and hirulog in a rabbit model of embolic stroke JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM Yenari, M. A., deCrespigny, A., Palmer, J. T., Roberts, S., Schrier, S. L., Albers, G. W., Moseley, M. E., Steinberg, G. K. 1997; 17 (4): 401-411

    Abstract

    We conducted a study using diffusion-weighted (DWI) and perfusion-weighted (PWI) magnetic resonance imaging (MRI) to evaluate the efficacy of thrombolysis in an embolic stroke model with recombinant tissue plasminogen activator (rt-PA) and hirulog, a novel direct-acting antithrombin. DWI can identify areas of ischemia minutes from stroke onset, while PWI identifies regions of impaired blood flow. Right internal carotid arteries of 36 rabbits were embolized using aged heterologous thrombi. Baseline DWI and PWI scans were obtained to confirm successful embolization. Four animals with no observable DWI lesion on the initial scan were excluded; therefore, a total of 32 animals were randomized to one of three treatment groups: rt-PA (n = 11), rt-PA plus hirulog (n = 11), or placebo (n = 10). Treatment was begun 1 h after stroke induction. Intravenous doses were as follows: rt-PA, 5 mg/kg over 0.5 h with 20% of the total dose given as a bolus; hirulog, 1 mg/kg bolus followed by 5 mg/kg over 1 h. MRI was performed at 2, 3, and 5 h following embolization. Six hours after embolization, brains were harvested, examined for hemorrhage, then prepared for histologic analysis. The rt-PA decreased fibrinogen levels by 73%, and hirulog prolonged the aPTT to four times the control value. Posttreatment areas of diffusion abnormality and perfusion delay were expressed as a ratio of baseline values. Significantly improved perfusion was seen in the rt-PA plus hirulog group compared with placebo (normalized ratios of the perfusion delay areas were as follows: placebo, 1.58, 0.47-3.59; rt-PA, 1.12, 0.04-3.95; rt-PA and hirulog, 0.40, 0.02-1.08; p < 0.05). Comparison of diffusion abnormality ratios measured at 5 h showed trends favoring reduced lesion size in both groups given rt-PA (normalized ratios of diffusion abnormality areas were as follows: placebo, 3.69, 0.39-15.71; rt-PA, 2.57, 0.74-5.00; rt-PA and hirulog, 1.95, 0.33-6.80; p = 0.32). Significant cerebral hemorrhage was observed in one placebo, two rt-PA, and three rt-PA plus hirulog treated animals. One fatal systemic hemorrhage was observed in each of the rt-PA groups. We conclude that rt-PA plus hirulog improves cerebral perfusion but does not necessarily reduce cerebral injury. DWI and PWI are useful methods for monitoring thrombolysis.

    View details for Web of Science ID A1997WW73800005

    View details for PubMedID 9143222

  • Management of acute ischemic stroke - An update for primary care physicians WESTERN JOURNAL OF MEDICINE Albers, G. W. 1997; 166 (4): 253-262

    Abstract

    Few areas of medicine have had as many major advances in recent years as the treatment and prevention of ischemic stroke. During the 1990s-"the decade of the brain"-carotid endarterectomy was demonstrated to be effective for preventing stroke in patients with significant carotid stenosis. Large clinical studies have documented the effectiveness of new antiplatelet agents and oral anticoagulant therapy for stroke prevention in specific patients groups, and recently tissue plasminogen activator was approved for the treatment of acute ischemic stroke. Because the use of these new therapies is restricted to specific patient subgroups, the accurate determination of the cause of stroke is now mandatory. Fortunately, advances in diagnostic methods, including cardiac and vascular ultrasonographic techniques and brain imaging, facilitate the determination of the stroke subtype in most patients. Additional advances in stroke treatment and prevention are on the immediate horizon. New therapeutic agents, including neuroprotective medications, and new treatment modalities such as cerebral angioplasty are promising investigational therapies.

    View details for Web of Science ID A1997WZ70200003

    View details for PubMedID 9168683

  • The feasibility of a collaborative double-blind study using an anticoagulant CEREBROVASCULAR DISEASES Mohr, J. P., Sacco, R. L., FLEISS, J., Lazar, R. M., Thompson, J. L., Gohs, D., Lynn, L., Burroughs, D., Caputo, A., Coleman, M., Costigan, T., Fields, B., Kann, G., Kim, J. S., King, R., Ma, W., Ruzicka, J. L., Slane, K., Zidel, A., Tilley, B. C., Sciacca, R., Rosner, B., Wende, K., Levin, B., Adams, H. P., Alter, M., Kistler, J. P., Pettigrew, L. C., Pullicino, P., Brey, R. L., Feldmann, E., Kittner, S. J., Babikian, V., Homma, S. H., DiTullio, M., Greenberg, S., Trevisan, M., Fisher, C. M., Barnett, H. J., Wisnant, J. P., Gautier, J. C., Sandercock, P., Karanjia, P., Buonanno, F. S., Albers, G., Nichols, F., Grotta, J., Helgason, C., RAMIREZLASSEPAS, M., Tuhrim, S., Pessin, M., Culebras, A., Sila, C., Chimowitz, M., Weinreb, H., Brass, L., Warach, S., Kase, C., Hamill, R., Rosenbaum, D., Hollander, J., Johnson, C., Gaines, K., Yaseen, M., Mitsias, P., Libman, R., Nafziger, A., Forteza, A., Miller, A., Biller, J., Kirschner, H., Haley, E., Binder, J., Zalewski, M., Jamieson, D., Anderson, D., Dandapani, B., Lennihan, L., Winkelman, M., Hughes, R., Jackson, C., Boop, B., Chaturvedi, S., Rothrock, J., FREY, A. Z., Dyken, M. L., Lowe, A., Marler, J. R., Meissner, I., Sherman, D. G., Taylor, D. W., Walker, M. D. 1997; 7 (2): 100-112

    View details for Web of Science ID A1997WP25900009

  • Use of fluid attenuating inversion recovery, MR angiogram, and diffusion-weighted MRI techniques for assessment of pontine infarction in a patient treated with radiation therapy for pituitary neoplasm NEUROLOGY Graef, L. M., Lutsep, H. L., Norbash, A., Albers, G. W. 1997; 48 (2): 540-542

    View details for Web of Science ID A1997WH53500050

    View details for PubMedID 9040759

  • Termination of acute stroke studies involving selfotel treatment LANCET Davis, S. M., Albers, G. W., Diener, H. C., Lees, K. R., Norris, J. 1997; 349 (9044): 32-32

    View details for Web of Science ID A1997WA72500023

    View details for PubMedID 8999265

  • Intravenous thrombolytic therapy in acute stroke. Vascular medicine Tong, D. C., Yenari, M. A., Albers, G. W. 1997; 2 (1): 51-60

    Abstract

    The article reviews the experimental basis of thrombolytic therapy, and summarizes the results of the recent trials of thrombolysis. Five large clinical trails have evaluated intravenous thrombolytic therapy for the treatment of hyperacute (< 6 h) stroke. Three of these studies were negative, one was equivocal, and one was strongly positive. The failure of demonstrate efficacy definitively in four of these trials may be related to a number of methodological factors, including the type and dose of drug administered, the timing of drug administered, and the method of patient selection for treatment. The NINDS recombinant tissue plasminogen activator (rt-PA) study showed that thrombolytic therapy can be of substantial benefit when administered within 3 h of stroke onset using strict patient selection criteria and rt-PA is now FDA approved for treatment of acute stroke. However, the risk of clinically significant bleeding is elevated. To achieve the favorable risk/benefit ratio demonstrated in the NINDS trial, patients must be screened by experienced clinicians for contraindications to thrombolysis and the acute computerized tomography (CT) brain scan must be carefully evaluated for radiographic features that increase the risk of cerebral hemorrhage. Guidelines for the use of rt-PA are provided, as well as insights into future thrombolytic treatment strategies.

    View details for PubMedID 9546949

  • Dose escalation study of the NMDA glycine-site antagonist ACEA 1021 in acute ischemic stroke Albers, G. W., Clark, W. M., Atkinson, R. P., Madden, K., Barbut, D., LECHTENBERG, R., Whitehouse, M. J. LIPPINCOTT WILLIAMS & WILKINS. 1997: 8–8

    View details for Web of Science ID A1997WB81400059

  • Anticoagulant therapy monitoring with international normalized ratio at us academic health centers ANNALS OF PHARMACOTHERAPY YIM, J. M., Albers, G. W., Vlasses, P. H. 1996; 30 (12): 1390-1395

    Abstract

    To assess the extent of incorporation of international normalized ratio (INR) reporting in US academic hospitals.Survey of academic hospital clinical laboratories in January 1995.Fifty-eight academic hospital clinical laboratories at institutions that are members of the University Health System Consortium.The methods for monitoring oral anticoagulant therapy at the surveyed laboratories were determined. The extent of reporting of prothrombin time (PT), PT ratio, INR, and INR therapeutic range was determined.All 58 of the responding hospital clinical laboratories reported INR in patients receiving oral anticoagulation. The median length of time that hospitals had been reporting INR was 24 months (range 3-108). A majority of hospitals continued to report PT values (95%) and PT reference ranges (93%) in addition to INR. Therapeutic INR ranges were reported by only 25 of the laboratories (43%). Of those that report INR ranges, many follow the published recommendations by the American College of Chest Physicians and the Food and Drug Administration. A majority of the hospitals (79%) do not confirm the accuracy of the international sensitivity index (ISI) for their own analyzers.Contrary to previous reports, academic hospital clinical laboratories have now adopted the more accurate system of reporting INR values in addition to PT values in patients receiving oral anticoagulation. However, better reporting of INR ranges, use of more sensitive thromboplastins, and confirmation of the accuracy of the ISI for local analyses would further improve the monitoring of oral anticoagulation.

    View details for Web of Science ID A1996VX90400005

    View details for PubMedID 8968449

  • Status of antithrombotic therapy for patients with atrial fibrillation in university hospitals ARCHIVES OF INTERNAL MEDICINE Albers, G. W., YIM, J. M., Belew, K. M., Bittar, N., Hattemer, C. R., Phillips, B. G., Kemp, S., Hall, E. A., Morton, D. J., Vlasses, P. H. 1996; 156 (20): 2311-2316

    Abstract

    The risk of stroke in patients with atrial fibrillation can be significantly reduced with antithrombotic therapy. Despite this, many physicians remain hesitant to prescribe warfarin sodium or aspirin therapy for patients with atrial fibrillation.To assess the use of antithrombotic therapy in patients with atrial fibrillation at 6 academic hospitals in the United States.Records were reviewed from consecutive hospital admissions of 309 patients with atrial fibrillation at 6 members of the University Health System Consortium, Oak Brook, III, which is a member driven alliance of 70 academic health centers in the United States. Risk factors for stroke, contraindications to anticoagulant therapy, and use of antithrombotic therapy at admission and discharge were recorded.The mean age of patients was 71.6 years, 54% had chronic, 22% paroxysmal, and 24% new-onset atrial fibrillation. Eighty-two percent of the patients had cardiovascular risk factors that have been associated with increased risk of stroke. At least 1 relative contraindication to anticoagulant therapy was present in 44%. At the time of admission. 32% of the patients with previously diagnosed atrial fibrillation (n = 235) were receiving warfarin (or warfarin plus aspirin), 31% were receiving aspirin alone, and 36% were receiving no antithrombotic therapy. At discharge (n = 230), 41% of these patients were taking warfarin (or warfarin plus aspirin) and 36% were taking aspirin. Forty-four percent of the patients with risk factors for stroke and no contraindications to anticoagulation (n = 134) were discharged on a regimen of warfarin (or warfarin plus aspirin), 34% were discharged on a regimen of aspirin, and 22% received no antithrombotic therapy.About half of the patients with atrial fibrillation admitted to these academic hospitals had clinical risk factors that are associated with increased risk of stroke and no contraindications to anticoagulation. Antithrombotic therapy was underused in these patients.

    View details for Web of Science ID A1996VR60300004

    View details for PubMedID 8911237

  • Adjusted-dose warfarin versus low-intensity, fixed-dose warfarin plus aspirin for high-risk patients with atrial fibrillation: Stroke prevention in atrial fibrillation III randomised clinical trial LANCET Blackshear, J. L., Baker, V. S., Rubino, F., Safford, R., Lane, G., Flipse, T., Malouf, J., Thompson, R., Webel, R., Flaker, G. C., Young, L., Hess, D., Friedman, G., Burger, R., McAnulty, J. H., Coull, B. M., Marchant, C., Timberg, J., Janzik, C., Giraud, G., Halperin, B., Kron, J., Wynn, M., Raitt, M., Anderson, D. C., Asinger, R. W., Newburg, S. M., Fifield, J., Bundlie, S. R., Koller, R. L., Tarrel, R. D., Dick, C., Haugland, J. M., Jorgensen, C. R., Leonard, A. D., KANTER, M. C., Solomon, D. H., Zabalgoitia, M., Mego, D., Carter, J. E., Boyd, S. Y., Boop, B. S., Lalonde, D., Modlin, R., LOGAN, W. R., Green, B. J., Hamilton, W. P., Mezei, L., RIGGIO, S., Feldman, G., Hayward, A., Strauss, R., ANDERSON, W., Grover, J., McKenzie, M., HartMcArthur, P., Gramberg, M., Houston, H., Halperin, J. L., Rothauf, E. B., Weinberger, J. M., Goldman, M. E., Laupacis, A., Chan, K. L., Bourque, P., Biggs, J., Ives, A., Feinberg, W. M., Kern, K. B., Pennock, G. D., Fenster, P. E., Huerta, B. J., Ohm, J., Dittrich, H. C., Kerridge, C., Keen, W., Swenson, M., Kopecky, S. L., Litin, S. C., Wiebers, D. O., Holland, A. E., Brown, R. D., Khandheria, B. K., Meissner, I., Tucker, K. R., Rothbart, R., Torelli, J., Schmidt, J., Murray, D., RUZICH, R. S., Loutfi, H., Appleton, C., Ingall, T., Carlson, L., Wilson, D., Dunn, M., Nolte, B., Edwards, C., Dick, A., Price, L. A., Janosik, D. L., Bjerregaard, P., Quattromani, A., Schiller, L., Labovitz, A., Burch, C., Parks, B. J., Thompson, D., BERARDUCCI, L., Carey, S., Vigil, A., Falk, R., Battinelli, N., McNeil, M., Davidoff, R., Bernard, S., Bergethon, P., Fiori, L., Albers, G., Atwood, E., Clark, J., Tong, D., Yenari, M., Froelicker, V., Lutsep, H., Hock, N. H., Quaglietti, S., Kemp, S., Alpert, M. A., Rothrock, J. F., Hupp, C. H., Massey, C. V., Hamilton, W. J., Miller, V. T., Fox, J. 1996; 348 (9028): 633-638

    Abstract

    Adjusted-dose warfarin is highly efficacious for prevention of ischaemic stroke in patients with atrial fibrillation (AF). However, this treatment carries a risk of bleeding and the need for frequent medical monitoring. We sought an alternative that would be safer and easier to administer to patients with AF who are at high-risk of thromboembolism.1044 patients with AF and with at least one thromboembolic risk factor (congestive heart failure or left ventricular fractional shortening < or = 25%, previous thromboembolism, systolic blood pressure of more than 160 mm Hg at study enrollment, or being a woman aged over 75 years) were randomly assigned either a combination of low-intensity, fixed-dose warfarin (international normalised ratio [INR] 1.2-1.5 for initial dose adjustment) and aspirin (325 mg/day) or adjusted-dose warfarin (INR 2.0-3.0). Drugs were given open-labelled.The mean INR during follow-up of patients taking combination therapy (n = 521) was 1.3, compared with 2.4 for those taking adjusted-dose warfarin (n = 523). During follow-up, 54% of INRs in patients taking combination therapy were 1.2-1.5 and 34% were less than 1.2. The trial was stopped after a mean, follow-up of 1.1 years when the rate of ischaemic stroke and systemic embolism (primary events) in patients given combination therapy (7.9% per year) was significantly higher than in those given adjusted-dose warfarin (1.9% per year) at an interim analysis (p < 0.0001), an absolute reduction of 6.0% per year (95% Cl 3.4, 8.6) by adjusted-dose warfarin. The annual rates of disabling stroke (5.6% vs 1.7%, p = 0.0007) and of primary event or vascular death (11.8% vs 6.4%, p = 0.002), were also higher with combination therapy. The rates of major bleeding were similar in both treatment groups.Low-intensity, fixed-dose warfarin plus aspirin in this regimen is insufficient for stroke prevention in patients with non-valvular AF at high-risk for thromboembolism; adjusted-dose warfarin (target INR 2.0-3.0) importantly reduces stroke for high-risk patients.

    View details for Web of Science ID A1996VF60900007

    View details for PubMedID 8782752

  • Acute and chronic stroke: Navigated spin-echo diffusion-weighted MR imaging RADIOLOGY Marks, M. P., deCrespigny, A., Lentz, D., Enzmann, D. R., Albers, G. W., Moseley, M. E. 1996; 199 (2): 403-408

    Abstract

    The authors evaluated a phase-navigated spin-echo (SE) motion-correction sequence for use at diffusion-weighted (DW) magnetic resonance (MR) imaging after cerebral infarction.Twenty-nine patients underwent 32 conventional T2-weighted fast SE and SE DW imaging after stroke (n=25), transient ischemic attack (n=3), or reversible ischemic neurologic deficit (n=1). Imaging was performed in a standard head holder with standard padding. Apparent diffusion coefficient (ADC) maps were constructed.DW images depicted high signal intensity compatible with localization of the ischemic symptoms in all cases. Lesions were depicted more clearly on DW than on T2-weighted images. On DW images, acute infarct ADC values were uniformly low (mean, 0.401x10(-5) cm2/sec =+/- 0.143 [standard deviation]) compared with control ADC values (mean, 0.754x10(-5) cm2/sec +/- 0.201). ADC values of chronic infarcts were supranormal (mean, 1.591x10(-5) cm2/sec +/- 0.840) compared with control values (mean, 0.788x10(-5) cm2/sec +/- 0.166). DW imaging did not show a change after transient ischemic attack. with reversible ischemic neurologic deficit, however, hyperintensity on DW images and low ADC resolved after symptoms abated.Clinical phase-navigated SE DW imaging improved early diagnosis of stroke and helped differentiate acute from chronic stroke. Changes on DW images are reversed after symptoms resolve.

    View details for PubMedID 8668785

  • MR and cerebrospinal fluid enzymes as sensitive indicators of subclinical cerebral injury after open-heart valve replacement surgery AMERICAN JOURNAL OF NEURORADIOLOGY Steinberg, G. K., Delapaz, R., Mitchell, R. S., Bell, T. E., Albers, G. W. 1996; 17 (2): 205-212

    Abstract

    To evaluate MR imaging and lumbar cerebrospinal fluid enzymes as potential sensitive indicators of cerebral injury after open-heart valve replacement surgery.Thirty-four patients with cardiac valvular disease were prospectively entered into this study and then underwent valve replacement or repair under cardiopulmonary bypass using a membrane oxygenator. In 26 patients, MR head images were obtained 12 to 24 hours before surgery; repeat MR images were obtained between 1 and 2 weeks after surgery. In 18 patients, lumbar puncture cerebrospinal fluid was analyzed 24 to 48 hours after surgery; the analyses included measurement of lactic dehydrogenase, creatine phosphokinase, adenylate kinase, and neuron-specific enolase.After surgery, MR imaging showed new ischemic lesions in 15 (58%) of 26 patients: 7 with deep white matter hyperintense lesions; 5 with brain stem, caudate, cerebellar, or thalamic/basal ganglia infarcts; 1 with intraparenchymal hemorrhage; 1 with a subdural hematoma and cortical infarct; a