Bio

Clinical Focus


  • Neurology

Academic Appointments


Administrative Appointments


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

Professional Education


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

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 diffusion- and perfusion-weighted MRI 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


  • Transient Ischemic Attack (TIA) Triage and Evaluation of Stroke Risk 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.

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  • Insulin Resistance Intervention After Stroke Trial 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.

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

    This is a randomized, multi-center, prospective, double blind, two-stage, adaptive 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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  • Clot Lysis: Evaluating Accelerated Resolution of Intraventricular Hemorrhage Phase III 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 and Boehringer Ingelheim, Inc., Ingelheim, Germany) 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).

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  • Computed Tomography Perfusion (CTP) to Predict Response to Recanalization in Ischemic Stroke Project (CRISP) 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.

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  • 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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Teaching

2013-14 Courses


Publications

Journal Articles


  • 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

  • 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

  • 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

  • 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

  • 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

  • Impact of recanalization, reperfusion, and collateral flow on clinical efficacy. Stroke; a journal of cerebral circulation Albers, G. W. 2013; 44 (6 Suppl 1): S11-2

    View details for PubMedID 23709700

  • 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

  • MR RESCUE: Is the Glass Half-Full or Half-Empty? Stroke; a journal of cerebral circulation Parsons, M. W., Albers, G. W. 2013

    View details for PubMedID 23760218

  • Apparent diffusion coefficient threshold for delineation of ischemic core. International journal of stroke : official journal of the International Stroke Society Purushotham, A., Campbell, B. C., Straka, M., Mlynash, M., Olivot, J. M., Bammer, R., Kemp, S. M., Albers, G. W., Lansberg, M. G. 2013

    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?

    View details for PubMedID 23802548

  • 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 Web of Science ID 000309634300011

    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??g/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??g/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

  • 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 (?=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

  • 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 (?=0.73, 0.72, and 0.74, respectively) and fair for MTT (?=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

  • 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

  • Yield of CT perfusion for the evaluation of transient ischaemic attack. International journal of stroke : official journal of the International Stroke Society 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. M. 2012

    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 PubMedID 23228203

  • 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

  • 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 (?) statistics were used to assess agreement, and the ?(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 [? = 0.69 (95% CI 0.53-0.86) and ? = 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

  • 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

  • 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

  • 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 ?B-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

  • 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 Web of Science ID 000291032700038

    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

  • 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

  • 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% (? = 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

  • 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 Web of Science ID 000283443500058

    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

  • 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 Web of Science ID 000281272300022

    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 Web of Science ID 000278164400015

    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

  • 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
  • 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 Web of Science ID 000270522900007

    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 Web of Science ID 000270229800016

    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

  • Hyperfibrinogenemia and Functional Outcome From Acute Ischemic Stroke STROKE 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. 2009; 40 (5): 1687-1691

    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

  • 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 Web of Science ID 000265579800027

    View details for PubMedID 19299632

  • 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

  • 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

  • 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

  • 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 Web of Science ID 000262784900021

    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

  • 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

  • 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 Web of Science ID 000260215400027

    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 Web of Science ID 000257993400011

    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 CHEST Hirsh, J., Guyatt, G., Albers, G. W., Harrington, R., Schunemann, H. J. 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 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
  • 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

  • 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

  • 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

  • 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

  • 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

  • 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 Web of Science ID 000248455100016

    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 STROKE Akins, P. T., Feldman, H. A., Zoble, R. G., Newman, D., Spitzer, S. G., Diener, H., Albers, G. W. 2007; 38 (3): 874-880

    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

  • 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 Web of Science ID 000242545100006

    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

  • 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 Web of Science ID 000233250900017

    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 Web of Science ID 000228273400036

    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 Web of Science ID 000227628500016

    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

  • 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 AMERICAN JOURNAL OF MANAGED CARE Albers, G. W. 2004; 10 (14): 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 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 Web of Science ID 000224298900014

  • 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 Web of Science ID 000224110000006

    View details for PubMedID 15466327

  • 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

  • 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 Web of Science ID 000220212400001

    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

  • 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

  • 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

  • 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; a journal of cerebral circulation 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

  • 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

  • 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 Web of Science ID 000171119500028

    View details for PubMedID 11559514

  • 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 Web of Science ID 000168156800009

    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

  • 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 Web of Science ID 000165107100009

    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 Web of Science ID 000086277200001

    View details for PubMedID 10753980

  • 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

  • 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

  • Addendum to the supplement to the guidelines for the management of transient ischemic attacks Stroke; a journal of cerebral circulation Albers, G. W., Hart, R. G., Lutsep, H. L., Newell, D. W., Sacco, R. L. 2000; 31 (4): 1001

    View details for PubMedID 10754016

  • 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

  • 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

  • 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 Web of Science ID 000083908700021

    View details for PubMedID 10591384

  • 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
  • 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 Web of Science ID 000082914500004

    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

  • 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

  • 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 Web of Science ID 000080091700026

    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

  • 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

  • Acute Ischemic Stroke. Current treatment options in neurology Chan, B. P., Albers, G. W. 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

  • 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

  • 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 Web of Science ID 000075151800037

    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

  • 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

  • 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

  • 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

  • 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 Web of Science ID A1996UG01100018

    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; and 1 with a corpus callosum lesion consistent with calcium or air. These new ischemic lesions seen on MR images were associated with a focal neurologic deficit in only 4 (27%) of the 15 patients. Neuron-specific enolase and lactic dehydrogenase were abnormally elevated after surgery in 5 (28%) of 18 patients. Adenylate kinase and creatine phosphokinase (brain isozymes) were elevated in one (67%) of the patients. Two (40%) of the five patients with abnormally high neuron-specific enolase or lactic dehydrogenase after surgery also showed a new focal neurologic deficit.MR imaging is a sensitive measure of subclinical cerebral ischemia after cardiac valve replacement under cardiopulmonary bypass. Cerebrospinal fluid neuron-specific enolase and lactic dehydrogenase are less sensitive than MR imaging for detecting subclinical cerebral ischemia, but these values were elevated after surgery more frequently than was adenylate kinase in our patients.

    View details for Web of Science ID A1996TW23400001

    View details for PubMedID 8938287

  • Safety of heparin in acute ischemic stroke NEUROLOGY Hart, R. G., Boop, B. S., Tong, D. C., Yenari, M. A., Albers, G. W. 1996; 46 (2): 589-589

    View details for Web of Science ID A1996TZ71200067

    View details for PubMedID 8614549

  • MELAS: Clinical and pathologic correlations with MRI, xenon/CT, and MR spectroscopy NEUROLOGY Clark, J. M., Marks, M. P., Adalsteinsson, E., Spielman, D. M., Shuster, D., Horoupian, D., Albers, G. W. 1996; 46 (1): 223-227

    Abstract

    We describe the clinical, imaging, and pathologic findings in a patient with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS). The patient experienced her first stroke-like episode at age forty-four. Brain MRI, obtained at symptom onset, at 3 weeks, and at 1 year, revealed migrating T2-weighted hyperintensities in the temporal/parietal and occipital cortices and later revealed atrophy. Abnormal cerebrovascular reserve was evident on xenon/CT four days after the first MRI. MR spectroscopy at 1 year revealed increased lactate in both the occipital and temporal lobes. Histologic sections demonstrated spongy degeneration of the cortex that was most prominent at the crests of the gyri. Electron microscopy of the blood vessels showed increased numbers of abnormal mitochondria within the vascular smooth muscle and in endothelial cells. We hypothesize that the stroke-like episodes in MELAS may be due to impaired autoregulation secondary to the impaired metabolic activity of mitochondria in the endothelial and smooth muscle cells of blood vessels.

    View details for Web of Science ID A1996TR67100045

    View details for PubMedID 8559380

  • COST-EFFECTIVENESS OF WARFARIN AND ASPIRIN FOR PROPHYLAXIS OF STROKE IN PATIENTS WITH NONVALVULAR ATRIAL-FIBRILLATION JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Gage, B. F., Cardinalli, A. B., Albers, G. W., Owens, D. K. 1995; 274 (23): 1839-1845

    Abstract

    To examine the cost-effectiveness of prescribing warfarin sodium in patients who have nonvalvular atrial fibrillation (NVAF) with or without additional stroke risk factors (a prior stroke or transient ischemic attack, diabetes, hypertension, or heart disease).Decision and cost-effectiveness analyses. The probabilities for stroke, hemorrhage, and death were obtained from published randomized controlled trials. The quality-of-life estimates were obtained by interviewing 74 patients with atrial fibrillation. Costs were estimated from literature review, phone survey, and Medicare reimbursement.In the base case, the patients were 65 years of age and good candidates for warfarin therapy.Treatment with warfarin, aspirin, or no therapy in the decision analytic model.Quality-adjusted survival and marginal cost-effectiveness of warfarin as compared with aspirin or no therapy.For patients with NVAF and additional risk factors for stroke, warfarin therapy led to a greater quality-adjusted survival and to cost savings. For patients with NVAF and one additional risk factor, warfarin therapy cost $8000 per quality-adjusted life-year saved. For 65-year-old patients with NVAF alone, warfarin cost about $370,000 per quality-adjusted life-year saved, as compared with aspirin therapy. However, for 75-year-old patients with NVAF alone, prescribing warfarin cost $110,000 per quality-adjusted life-year saved. For patients who were not prescribed warfarin, aspirin was preferred to no therapy on the basis of both quality-adjusted survival and cost in all patients, regardless of the number of risk factors present.Treatment with warfarin is cost-effective in patients with NVAF and one or more additional risk factors for stroke. In 65-year-old patients with NVAF but no other risk factors for stroke, prescribing warfarin instead of aspirin would affect quality-adjusted survival minimally but increase costs significantly.

    View details for Web of Science ID A1995TK14700024

    View details for PubMedID 7500532

  • Antithrombotic therapy in atrial fibrillation. Chest Laupacis, A., Albers, G., Dalen, J., Dunn, M., Feinberg, W., Jacobson, A. 1995; 108 (4): 352S-359S

    View details for PubMedID 7555188

  • TRANSCRANIAL DOPPLER-DETECTED MICROEMBOLI IN PATIENTS WITH ACUTE STROKE STROKE Tong, D. C., Albers, G. W. 1995; 26 (9): 1588-1592

    Abstract

    Transcranial Doppler sonography (TCD) has been used to detect microembolic signals in a variety of clinical situations. We studied the prevalence of TCD-detected microemboli in 38 acute stroke patients.Consecutive patients with acute anterior circulation stroke were stratified into high-risk (group 1), medium-risk (group 2), and low-risk (group 3) groups based on their risk factors for cerebral embolism.Microemboli were detected in 11% of patients. They were present in 17% of group 1, 10% of group 2, and 0% of group 3 patients. Emboli were present in patients with mechanical prosthetic valves, carotid stenosis (> 70%), and mitral valve strands with a patent foramen ovale. Patients with microemboli more frequently had a history of cerebral ischemia compared with patients without microemboli (P < .05). They also more frequently had recent (< 3 months) symptoms compared with patients without microemboli (P < .05). In patients with a cardiac source of embolization, the number of microemboli detected was directly proportional to the acuity of previous symptoms.These data suggest that TCD-detected microemboli are associated with an increased prevalence of prior cerebrovascular ischemia. The presence of TCD-detected microemboli could be a risk factor for cerebrovascular ischemia.

    View details for Web of Science ID A1995RR82600014

    View details for PubMedID 7660403

  • VERTICAL GAZE PALSIES FROM MEDIAL THALAMIC INFARCTIONS WITHOUT MIDBRAIN INVOLVEMENT STROKE Clark, J. M., Albers, G. W. 1995; 26 (8): 1467-1470

    Abstract

    Although the supranuclear pathways for vertical gaze control are not well defined, lesions of the mesencephalic reticular formation including the nucleus of Darkschewitsch, the rostral interstitial medial longitudinal fasciculus, the interstitial nucleus of Cajal, and the posterior commissure are known to produce vertical gaze palsies. MRI studies have not previously reported isolated thalamic lesions as the cause of vertical gaze palsies.Three patients with acute paralysis of vertical gaze were imaged with MRI. Sagittal T1 and axial T1, T2, and proton-weighted images were obtained. All three patients had repeated scans performed from 3 days to 6 weeks after the original study. Two patients exhibited unilateral right thalamic infarcts (polar and paramedial territory), and one patient had a bilateral paramedian thalamic infarction. There was no evidence of midbrain involvement on any of the images.Vertical gaze palsies are known to be produced by lesions of the rostral interstitial medial longitudinal fasciculus. This MRI study reveals thalamic infarctions without associated midbrain infarctions in three patients with vertical gaze palsies. This may be explained by interruption of supranuclear inputs.

    View details for Web of Science ID A1995RM16400036

    View details for PubMedID 7631355

  • DETECTION OF CAROTID STENOSIS - FROM NASCET RESULTS TO CLINICAL-PRACTICE STROKE Chang, Y. J., Golby, A. J., Albers, G. W. 1995; 26 (8): 1325-1328

    Abstract

    Results from large multicenter studies have shown that carotid endarterectomy, performed with low perioperative morbidity and mortality, is beneficial for patients with symptomatic carotid stenosis > or = 70% as calculated according to strict angiographic criteria. To apply these results in clinical practice, individual institutions should determine whether locally implemented duplex ultrasonography adequately identifies patients with > or = 70% stenosis and whether the degree of stenosis reported by local angiographers correlates with strict angiographic measurements.We compared estimates of carotid stenosis obtained by duplex ultrasonography and the radiologists' reports from conventional cerebral angiography with each other and with results obtained using North American Symptomatic Carotid Endarterectomy Trial (NASCET) criteria.One hundred seventy-one vessels were available for review. In 155 (91%) of the cases, the reports from the ultrasound and angiogram were in agreement with regard to whether the stenosis was > or = 70% or < 70%. In 11 of the 16 cases where there was a disparity between the studies, the ultrasound was in closer agreement with measurements obtained using NASCET criteria. Nine of the angiography reports overestimated the degree of stenosis compared with NASCET measurements; twice angiography underestimated the stenosis. Twice the ultrasound underestimated the stenosis, and three times it overestimated the stenosis.Duplex ultrasonography was highly sensitive for detecting significant carotid stenosis at our institution; however, angiography reports often graded the degree of stenosis to be more severe than measurements obtained using NASCET criteria. Institutions that evaluate patients for carotid endarterectomy should investigate the correlation between their ultrasound and angiographic studies so that the results of carotid endarterectomy trials can be accurately applied.

    View details for Web of Science ID A1995RM16400002

    View details for PubMedID 7631330

  • NEUROLOGIC COMPLICATIONS FOLLOWING CHIROPRACTIC MANIPULATION - A SURVEY OF CALIFORNIA NEUROLOGISTS NEUROLOGY Lee, K. P., CARLINI, W. G., MCCORMICK, G. F., Albers, G. W. 1995; 45 (6): 1213-1215

    Abstract

    To obtain an estimate of how often practicing neurologists in California encounter unexpected strokes, myelopathies, or radiculopathies following chiropractic manipulation, we surveyed each member of the American Academy of Neurology in California and inquired about the number of patients evaluated over the preceding 2 years who suffered a neurologic complication within 24 hours of chiropractic manipulation. Four hundred eighty-six neurologists were surveyed, 177 responded; 55 strokes, 16 myelopathies, and 30 radiculopathies were reported. Patients were between the ages of 21 and 60, and the majority experienced complications following cervical manipulation. Most of the patients continued to have persistent neurologic deficits 3 months after the onset, and about one-half had marked or severe deficits. Nearly all of the strokes involved the posterior circulation and almost one-half were angiographically proven. Patients, physicians, and chiropractors should be aware of the risk of neurologic complications associated with chiropractic manipulation.

    View details for Web of Science ID A1995RC99300032

    View details for PubMedID 7783892

  • Antithrombotic agents in cerebral ischemia. American journal of cardiology Albers, G. W. 1995; 75 (6): 34B-38B

    Abstract

    The choice of antithrombotic agent in cerebral ischemia depends on the pathogenesis: thrombosis, embolism, or hemorrhage. Antiplatelet agents are considered most beneficial in thrombotic stroke, anticoagulants are most effective in cardioembolic stroke; antithrombotic agents are generally contraindicated in hemorrhagic stroke. A meta-analysis of 18 trials documented a 23% reduction in stroke risk with antiplatelet agents; aspirin is typically the antiplatelet agent of choice for stroke prevention. There are no definitive data regarding the optimal aspirin dose for stroke prevention and this issue remains controversial. Ticlopidine is the most effective antiplatelet agent, but its adverse effect profile restricts its use. Anticoagulants are highly effective for preventing cardioembolic stroke, but their effectiveness in non-cardioembolic stroke is uncertain because of lack of trial data. Results of the ongoing Warfarin/Aspirin Recurrent Stroke Study (warfarin [INR 1.8-2.8] vs aspirin [325 mg/day]) may clarify this issue. There is renewed interest in thrombolytics because recent data indicate that reperfusion within a few hours of stroke onset appears to be effective in preventing neuronal damage. In addition, when given within 6 hours of stroke onset, thrombolytics appear to be relatively safe. Several direct thrombin inhibitors are being evaluated. Experimentally, hirudin, hirulog, D-Phe-L-Pro-L-Arg-CH2Cl (PPACK), and argatroban are clearly more effective than heparin in inhibiting platelet deposition and thrombus formation, and also show promise in preventing reocclusion after thrombolysis for both experimental thrombotic and embolic stroke. However, the risk of hemorrhage in patients with cerebrovascular disease is unknown for these agents.(ABSTRACT TRUNCATED AT 250 WORDS)

    View details for PubMedID 7863971

  • SAFETY, TOLERABILITY, AND PHARMACOKINETICS OF THE N-METHYL-D-ASPARTATE ANTAGONIST DEXTRORPHAN IN PATIENTS WITH ACUTE STROKE STROKE Albers, G. W., Atkinson, R. P., Kelley, R. E., Rosenbaum, D. M. 1995; 26 (2): 254-258

    Abstract

    Dextrorphan hydrochloride is a noncompetitive N-methyl-D-aspartate antagonist that is neuroprotective in experimental models of focal brain ischemia. The purpose of this study was to determine the maximum loading dose and maintenance infusion of dextrorphan hydrochloride that are well tolerated in patients with an acute stroke.An intravenous infusion of dextrorphan or placebo was begun within 48 hours of onset of a mild-to-moderate hemispheric stroke. Initially, patients were treated with either placebo (n = 15) or dextrorphan (n = 22) using a 1-hour loading dose (60 to 150 mg) followed by a 23-hour ascending-dose maintenance infusion (maximum total dose, 3310 mg). Subsequently, 29 patients were treated with dextrorphan in an open trial using a 1-hour loading dose (145 to 260 mg) followed by an 11-hour constant rate (30 to 70 mg/h) infusion.Transient and reversible adverse effects, including nystagmus, nausea, vomiting, somnolence, hallucinations, and agitation, commonly occurred in dextrorphan-treated patients. Loading-dose escalation was stopped because of rapid-onset, reversible, symptomatic hypotension in 7 of 21 patients treated with doses of 200 to 260 mg/h. At the highest rates of maintenance infusion (> 90 mg/h), 3 patients developed deep stupor or apnea. The maximum tolerated loading dose was 180 mg/h, and the maximum tolerated maintenance infusion was 70 mg/h. Maximum plasma levels of 750 to 1000 ng/mL were obtained in 9 patients. There was no difference in neurological outcome at 48 hours between the dextrorphan-treated and placebo-treated patients.The highest doses of dextrorphan administered were associated with serious adverse experiences in some patients. Lower doses (loading doses of 145 to 180 mg, maintenance infusions of 50 to 70 mg/h) were better tolerated and rapidly produced potentially neuroprotective plasma concentrations of dextrorphan. These doses were associated with well-defined pharmacological effects compatible with N-methyl-D-aspartate receptor antagonism.

    View details for Web of Science ID A1995QE11000011

    View details for PubMedID 7831698

  • ANTICOAGULATION/PLATELET INHIBITION FOR ATRIAL-FIBRILLATION CORONARY ARTERY DISEASE Albers, G. W., Hirsh, J. 1995; 6 (2): 129-135

    View details for Web of Science ID A1995QR28600007

    View details for PubMedID 7780618

  • INCIDENCE OF TRANSCRANIAL DOPPLER-DETECTED CEREBRAL MICROEMBOLI IN PATIENTS REFERRED FOR ECHOCARDIOGRAPHY STROKE Tong, D. C., Bolger, A., Albers, G. W. 1994; 25 (11): 2138-2141

    Abstract

    Transcranial Doppler can detect cerebral microemboli. These emboli may be a risk factor for embolic stroke. We studied the prevalence of microemboli in patients referred for echocardiography.Forty-two patients were evaluated. Patients were studied with continuous monitoring over one middle cerebral artery for 30 minutes, and the number of microemboli was recorded. Patients were divided into three groups, those with prosthetic heart valves (group A, n = 15), atrial fibrillation (group B, n = 14), and no major cardiac risk factor (group C, n = 14).Seventeen percent (7 of 42) of all patients had microemboli. In group A, 5 of 15 (33%) had microemboli. In group B, 2 of 13 (15%) patients had microemboli. Twenty-five percent (7 of 28) of patients in groups A and B combined (A+B) had microemboli. No patients (0 of 14) in group C had microemboli. Groups A and A+B had significantly more emboli than group C (P < .05). Prosthetic heart valve patients with emboli more commonly had a history of prior stroke than valve patients without emboli (3 of 5 versus 2 of 10). The number of emboli seen per 30-minute monitoring session was greater in patients with a prior history of stroke than in patients without (10 microemboli versus 3).Microemboli can be found in a significant percentage of selected patients referred for echocardiography. The prevalence of microembolism is greater in patients with a known high risk of embolization (eg, prosthetic valves) and less in patients with a lower risk of embolization (eg, atrial fibrillation). These microemboli may be associated with an increased prevalence of previous stroke in patients with prosthetic valves.

    View details for Web of Science ID A1994PN94200005

    View details for PubMedID 7974534

  • ATRIAL-FIBRILLATION AND STROKE - 3 NEW STUDIES, 3 REMAINING QUESTIONS ARCHIVES OF INTERNAL MEDICINE Albers, G. W. 1994; 154 (13): 1443-1448

    Abstract

    Three new studies help clarify important clinical issues regarding antithrombotic therapy for stroke prevention in patients with atrial fibrillation. The European Atrial Fibrillation Trial compared the efficacy of oral anticoagulation, aspirin, and placebo for stroke prevention in patients with atrial fibrillation with a recent stroke or transient ischemic attack. The results of the Stroke Prevention in Atrial Fibrillation II trial, which compared the efficacy of warfarin and aspirin, provide new information regarding the risk of intracranial hemorrhage in elderly patients with atrial fibrillation. Finally, an analysis of pooled data from the first five randomized trials identified clinical features that are predictive of stroke risk in individual patients with atrial fibrillation. These studies address unanswered questions regarding atrial fibrillation and stroke and have significant implications for patient management.

    View details for Web of Science ID A1994NW09000004

    View details for PubMedID 8017999

  • TRANSESOPHAGEAL ECHOCARDIOGRAPHY AND CAROTID ULTRASOUND IN PATIENTS WITH CEREBRAL-ISCHEMIA - PREVALENCE OF FINDINGS AND RECURRENT STROKE RISK JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Comess, K. A., DeRook, F. A., Beach, K. W., LYTLE, N. J., Golby, A. J., Albers, G. W. 1994; 23 (7): 1598-1603

    Abstract

    This study was conducted to determine the yield of transesophageal echocardiographic findings in a consecutive series of patients with stroke and transient ischemic attack, with and without carotid stenosis, and to estimate the recurrent stroke risk associated with specific echocardiographic findings.Transesophageal echocardiography has a high yield for identification of potential sources of cardiac embolism in patients with cerebral ischemia; however, the clinical significance of the most commonly detected abnormalities is uncertain.We evaluated 145 consecutively admitted patients with stroke or transient ischemic attack with both transesophageal echocardiography and carotid ultrasound. Patients were followed up prospectively for a mean duration of 18 months to document the rate of recurrent cerebral ischemia.Transesophageal echocardiography detected at least one potential cardiac source of embolism in 45% of the patients. Atrial septal aneurysm and interatrial shunt were detected more frequently in patients who did not have a significant carotid stenosis that could account for their ischemic event. During follow-up, a higher rate of recurrent stroke or transient ischemic attack occurred in patients with positive transesophageal echocardiographic findings, particularly atrial septal aneurysm, interatrial shunt and left atrial thrombus.These data support recent studies that suggest that atrial septal aneurysm and interatrial shunts may be a significant source of cardioembolic stroke. Further studies are needed to clarify the optimal management of patients with these abnormalities.

    View details for Web of Science ID A1994PH37400013

    View details for PubMedID 8195520

  • GUIDELINES FOR THE MANAGEMENT OF TRANSIENT ISCHEMIC ATTACKS - FROM THE AD-HOC COMMITTEE ON GUIDELINES FOR THE MANAGEMENT OF TRANSIENT ISCHEMIC ATTACKS OF THE STROKE COUNCIL OF THE AMERICAN-HEART-ASSOCIATION STROKE Feinberg, W. M., Albers, G. W., Barnett, H. J., Biller, J., Caplan, L. R., Carter, L. P., Hart, R. G., Hobson, R. W., Kronmal, R. A., Moore, W. S., ROBERTSON, J. T., Adams, H. P., Mayberg, M. 1994; 25 (6): 1320-1335

    View details for Web of Science ID A1994NP14200052

    View details for PubMedID 8203003

  • GUIDELINES FOR THE MANAGEMENT OF TRANSIENT ISCHEMIC ATTACKS - FROM THE AD-HOC-COMMITTEE-ON-GUIDELINES-FOR-THE-MANAGEMENT-OF-TRANSIENT-ISCHEMIC-ATTACKS OF THE STROKE-COUNCIL OF THE AMERICAN-HEART-ASSOCIATION CIRCULATION Feinberg, W. M., Albers, G. W., Barnett, H. J., Biller, J., Caplan, L. R., Carter, L. P., Hart, R. G., Hobson, R. W., Kronmal, R. A., Moore, W. S., ROBERTSON, J. T., Adams, H. P., Mayberg, M. 1994; 89 (6): 2950-2965

    View details for Web of Science ID A1994NQ83000080

    View details for PubMedID 8205721

  • TRANSESOPHAGEAL ECHOCARDIOGRAPHIC FINDINGS IN STROKE SUBTYPES STROKE Albers, G. W., Comess, K. A., DeRook, F. A., Bracci, P., Atwood, J. E., Bolger, A., Hotson, J. 1994; 25 (1): 23-28

    Abstract

    Transesophageal echocardiography has a high yield for detecting potential cardiac sources of embolism in patients with clinical risk factors for cardioembolism or unexplained stroke. The yield in other stroke subtypes is unknown.We classified 145 consecutively admitted patients into stroke subtypes based on clinical findings, brain imaging, and carotid ultrasound. Both transesophageal and transthoracic echocardiography were performed to detect left atrial thrombi, spontaneous echo contrast, atrial septal aneurysm, interatrial shunts, ventricular thrombus or aneurysm, and myxomatous mitral valve.Transesophageal echocardiography documented at least one of these findings in 46% of the patients compared with an 8% yield on the transthoracic study (P = .002). The yield of transesophageal echocardiography was substantial in all stroke subgroups. Patients with clinical risk factors for cardiac embolism had the highest frequency of spontaneous echo contrast (P = .001). Atrial septal aneurysms were most frequent in patients with lacunar syndromes (P = .012), and interatrial shunts were common in all stroke subtypes.Transesophageal echocardiographic findings vary considerably between stroke subgroups.

    View details for Web of Science ID A1994MP10600005

    View details for PubMedID 8266377

  • LABORATORY MONITORING OF ORAL ANTICOAGULANT-THERAPY - ARE WE BEING MISLED NEUROLOGY Albers, G. W. 1993; 43 (3): 468-470

    View details for Web of Science ID A1993KT21500002

    View details for PubMedID 8450985

  • ANTICOAGULATION AND ATRIAL-FIBRILLATION HERZ Atwood, J. E., Albers, G. W. 1993; 18 (1): 27-38

    Abstract

    The decision to anticoagulate patients with atrial fibrillation (AF) involves weighting the risk of an embolic event without therapy versus the risk of a hemorrhagic event on therapy. Improved methods of monitoring anticoagulation with the International Normalized Ratio (INR), and recent evidence of the efficacy and safety of low-dose warfarin (INR range 2.0 to 3.0) have clarified the role of anticoagulation in AF. Over the past four years, five large prospective randomized trials in patients with nonvalvular atrial fibrillation (NVAF) have reported substantial reductions in stroke in patients treated with low-dose warfarin therapy. The results of these trials, combined with previous studies, suggest that anticoagulation is the treatment of choice for patients with atrial fibrillation associated with rheumatic valvular disease, prosthetic valve disease, and now NVAF. Although the results of the prospective atrial fibrillation trials are very consistent in regard to the efficacy and safety of anticoagulation, there continues to be uncertainty regarding which subgroups of patients are at highest risk for embolic events. Subgroups that appear to be at high risk include patients with hypertension, previous embolic events, structural heart disease (enlarged left atrial size, previous myocardial infarction, left ventricular dysfunction), and older age. Young patients with no evidence of structural heart disease or hypertension (lone atrial fibrillation) have a low embolic rate and do not warrant anticoagulation. Recent studies suggest that there is little difference in the risk of stroke in patients with paroxysmal or chronic AF, therefore this factor should not have a major impact on therapeutic decisions. Anticoagulation is also recommended for patients undergoing elective cardioversion (recent onset of atrial fibrillation greater than two days in duration), and patients with atrial fibrillation and hyperthyroidism because of studies suggesting a higher rate of embolism if these patients are not anticoagulated. The role of aspirin in AF is less clear as only two of the five prospective trials randomized patients to aspirin therapy and only one documented aspirin benefit. Therefore, aspirin appears to offer less benefit but is a satisfactory alternative to warfarin therapy. Aspirin is currently recommend for patients who are poor candidates for anticoagulation or individuals with AF who are considered to be at low risk for stroke.

    View details for Web of Science ID A1993KP28300004

    View details for PubMedID 8454250

  • TOLERABILITY OF ORAL DEXTROMETHORPHAN IN PATIENTS WITH A HISTORY OF BRAIN ISCHEMIA CLINICAL NEUROPHARMACOLOGY Albers, G. W., Saenz, R. E., Moses, J. A. 1992; 15 (6): 509-514

    Abstract

    Twelve patients with a history of cerebral ischemia were randomized to treatment with the N-methyl-D-aspartate antagonist dextromethorphan (60 or 90 mg p.o. q.i.d.) or placebo for 2 weeks in a randomized, safety study. Neuropsychological testing did not detect evidence of cognitive dysfunction; however, side effects including lightheadedness, drowsiness, nausea, decreased coordination, and unsteady gait were reported by several patients while taking dextromethorphan.

    View details for Web of Science ID A1992JY06700009

    View details for PubMedID 1477851

  • TRANSESOPHAGEAL ECHOCARDIOGRAPHY IN THE EVALUATION OF STROKE ANNALS OF INTERNAL MEDICINE DeRook, F. A., Comess, K. A., Albers, G. W., Popp, R. L. 1992; 117 (11): 922-932

    Abstract

    To review the current role of transesophageal echocardiography in the evaluation of stroke.Articles examining the role of transesophageal echocardiography for evaluation of patients with stroke were identified using computer and bibliography searches.All English-language articles that provided full details on patient selection criteria, methods, and study design were reviewed.Cardiogenic embolism is frequently an uncertain diagnosis merely inferred by finding a potential cardiac source. Transthoracic echocardiography has had a low yield in screening unselected patients with stroke. Several series of patients with stroke have been reported comparing transthoracic and transesophageal echocardiography. Potential cardiac sources of embolism were consistently identified in many more patients by transesophageal echocardiography. Many findings are, however, of uncertain significance; these include spontaneous echo contrast, patent foramen ovale, filamentous strands on the mitral valve, and atrial septal aneurysm.Transesophageal echocardiography is most helpful in patients with stroke who are less than 45 years of age and in those without clinical evidence of heart disease. The indications for its use in the evaluation of stroke remain controversial. Further studies are needed using transesophageal echocardiography in patients with stroke and in control groups, not only to determine the natural history of transesophageal, echocardiographically detected abnormalities but also to evaluate treatment options.

    View details for Web of Science ID A1992JZ27600009

    View details for PubMedID 1443955

  • FAILURE OF HIGH-DOSE HEPARIN TO PREVENT RECURRENT CARDIOEMBOLIC STROKES IN A PREGNANT PATIENT WITH A MECHANICAL HEART-VALVE NEUROLOGY Golby, A. J., Bush, E. C., DeRook, F. A., Albers, G. W. 1992; 42 (11): 2204-2206

    Abstract

    A 27-year-old woman with a mechanical heart valve suffered multiple thromboembolic events while pregnant despite anticoagulation with high-dose heparin. Warfarin, the anti-coagulant of choice for patients with prosthetic heart valves, is teratogenic and can cause hemorrhagic complications at delivery. Heparin reduces thromboembolic complications, but is of uncertain efficacy. We discuss alternatives for the prevention of thromboembolic complications in pregnant women with mechanical heart valves.

    View details for Web of Science ID A1992JY62700028

    View details for PubMedID 1436538

  • ANTITHROMBOTIC THERAPY IN ATRIAL-FIBRILLATION CHEST Laupacis, A., Albers, G., Dunn, M., Feinberg, W. 1992; 102 (4): S426-S444
  • RECURRENT TRANSVERSE MYELITIS, MYASTHENIA-GRAVIS, AND AUTOANTIBODIES ANNALS OF NEUROLOGY Lindsey, J. W., Albers, G. W., Steinman, L. 1992; 32 (3): 407-409

    Abstract

    A 45-year-old man with a longstanding diagnosis of myasthenia gravis presented with four episodes of transverse myelitis in 5 years. Each episode improved after treatment with steroids. Laboratory studies revealed no evidence of multiple sclerosis or a structural spinal lesion. He had antinuclear and anti-DNA antibodies and the HLA-A1, B8, DR3 haplotype known to be associated with certain autoimmune diseases. We propose an autoimmune cause for the recurrent episodes of myelitis.

    View details for Web of Science ID A1992JN14500018

    View details for PubMedID 1416813

  • ROLE OF TICLOPIDINE FOR PREVENTION OF STROKE STROKE Albers, G. W. 1992; 23 (6): 912-916

    Abstract

    Ticlopidine, an antiplatelet agent with a unique mechanism of action, is now available for clinical use in the United States and Canada.Recently two large randomized trials demonstrated that ticlopidine can reduce the risk of subsequent stroke in patients presenting with a transient ischemic attack or stroke. One study found that ticlopidine was more effective than aspirin for stroke prevention; however, it was less well tolerated than aspirin and was associated with severe but reversible neutropenia in almost 1% of patients.Ticlopidine is effective for both primary and secondary stroke prevention. It has a favorable risk/benefit ratio and is a particularly attractive option for patients who are unable to take aspirin.

    View details for Web of Science ID A1992HW86000023

    View details for PubMedID 1595115

  • DO NMDA ANTAGONISTS PREVENT NEURONAL INJURY - YES ARCHIVES OF NEUROLOGY Albers, G. W., Goldberg, M. P., Choi, D. W. 1992; 49 (4): 418-420

    View details for Web of Science ID A1992HM46300024

    View details for PubMedID 1558524

  • LACUNAR STROKE - RELATIONSHIP BETWEEN ATYPICAL ETIOLOGY AND INFARCT SIZE ARCHIVES OF NEUROLOGY Albers, G. W. 1991; 48 (12): 1215-1215

    View details for Web of Science ID A1991GZ42000001

    View details for PubMedID 1845020

  • STROKE PREVENTION IN NONVALVULAR ATRIAL-FIBRILLATION ANNALS OF INTERNAL MEDICINE Albers, G. W., Atwood, J. E., Hirsh, J., Sherman, D. G., Hughes, R. A., Connolly, S. J. 1991; 115 (9): 727-736

    Abstract

    There has been considerable uncertainty about the best way to prevent stroke in patients with nonvalvular atrial fibrillation. Recent studies have suggested that low-dose warfarin therapy, in addition to producing fewer bleeding complications, may be as effective as higher-dose therapy in preventing thromboembolic events. Four large, prospective, randomized trials have examined the risks and benefits of warfarin therapy for stroke prophylaxis in patients with nonvalvular atrial fibrillation. All four studies showed a substantially reduced incidence of stroke and a low incidence of significant bleeding in patients treated with warfarin. One of these studies also showed that aspirin reduced the incidence of stroke. The benefits associated with long-term low-dose warfarin therapy appear to exceed the risks for serious bleeding in most patients with atrial fibrillation. Aspirin may be a viable therapeutic option for patients who are unable to take warfarin or for those in subgroups at a low risk for stroke.

    View details for Web of Science ID A1991GL69700012

    View details for PubMedID 1834004

  • STROKE PREVENTION IN NONVALVULAR ATRIAL-FIBRILLATION - A REVIEW OF PROSPECTIVE RANDOMIZED TRIALS ANNALS OF NEUROLOGY Albers, G. W., Sherman, D. G., Gress, D. R., Paulseth, J. E., Petersen, P. 1991; 30 (4): 511-518

    Abstract

    Patients with atrial fibrillation are at risk for cerebral embolism; however, the roles of chronic anticoagulation or antiplatelet therapy for stroke prevention in patients with nonvalvular atrial fibrillation have been controversial. Recently, the results of three large prospective randomized trials that examined the risks and benefits of warfarin or aspirin for stroke prophylaxis in patients with nonvalvular atrial fibrillation were reported. All three studies revealed a reduction in the stroke rate for patients treated with warfarin and a small incidence of major bleeding. One of the studies also reported a reduced stroke rate in aspirin-treated patients. The reduction of thromboembolic events associated with chronic warfarin therapy appears to outweigh the risks of significant bleeding for most patients with nonvalvular atrial fibrillation. Aspirin may offer an alternative for subgroups of patients who are at low risk for stroke or those who are not good candidates for anticoagulation.

    View details for Web of Science ID A1991GJ81500001

    View details for PubMedID 1789680

  • SAFETY AND TOLERANCE OF ORAL DEXTROMETHORPHAN IN PATIENTS AT RISK FOR BRAIN ISCHEMIA STROKE Albers, G. W., Saenz, R. E., Moses, J. A., Choi, D. W. 1991; 22 (8): 1075-1077

    Abstract

    Experimental ischemia models have shown the antitussive dextromethorphan to be an N-methyl-D-aspartate antagonist with neuroprotective properties. We treated 10 patients with a history of recent stroke or transient ischemic attack with oral dextromethorphan (60 mg q.i.d.) for 3 weeks in a placebo-controlled, double-blind, crossover tolerance study. We documented no clinical evidence of toxicity attributable to dextromethorphan in this preliminary study.

    View details for Web of Science ID A1991GB31200018

    View details for PubMedID 1866755

  • INTENSITY OF ANTICOAGULANT TREATMENT AND RISK OF INTRACEREBRAL HEMATOMA STROKE Albers, G. W. 1990; 21 (12): 1758-1758

    View details for Web of Science ID A1990EN83400019

    View details for PubMedID 2264086

  • POTENTIAL THERAPEUTIC USES OF N-METHYL-D-ASPARTATE ANTAGONISTS IN CEREBRAL-ISCHEMIA CLINICAL NEUROPHARMACOLOGY Albers, G. W. 1990; 13 (3): 177-197

    View details for Web of Science ID A1990DF11400001

    View details for PubMedID 1972652

  • NIFEDIPINE VERSUS PROPRANOLOL FOR THE INITIAL PROPHYLAXIS OF MIGRAINE HEADACHE Albers, G. W., SIMON, L. T., Hamik, A., Peroutka, S. J. 1989; 29 (4): 215-218

    Abstract

    We conducted a randomized open-labeled study of nifedipine versus propranolol for the initial prophylaxis of migraine. Propranolol was effective in 67% of patients (12/18) and well tolerated. Nifedipine was effective in only 30% of patients (6/20). The lack of overall efficacy of nifedipine was attributable to a high incidence of side effects, including an unusual symptom complex resembling erythromelalgia. These side effects led 45% (9/20) of the nifedipine patients to withdraw from the study within two weeks. By contrast, no patient (0/18) withdrew from the study within the first 2 weeks of propranolol therapy. We conclude that nifedipine is not an agent of first choice for the prophylaxis of migraine.

    View details for Web of Science ID A1989U492600001

    View details for PubMedID 2654067

  • N-METHYL-D-ASPARTATE ANTAGONISTS - READY FOR CLINICAL-TRIAL IN BRAIN ISCHEMIA ANNALS OF NEUROLOGY Albers, G. W., Goldberg, M. P., Choi, D. W. 1989; 25 (4): 398-403

    Abstract

    Antagonists of the N-methyl-D-aspartate (NMDA) subclass of glutamate receptors may offer a new approach for the treatment of ischemic brain injury. This strategy is supported by a well-developed scientific foundation and encouraging results in a variety of in vivo and in vitro experimental models. Several specific antagonists, including MK-801, dextrorphan, dextromethorphan, and ketamine, have already been used at low doses in humans for other indications and are potential candidates for Phase I clinical trials.

    View details for Web of Science ID A1989U068400011

    View details for PubMedID 2565699

  • TREATMENT RESPONSE IN MALIGNANT OPTIC GLIOMA OF ADULTHOOD NEUROLOGY Albers, G. W., Hoyt, W. F., Forno, L. S., Shratter, L. A. 1988; 38 (7): 1071-1074

    Abstract

    Two adults with malignant optic gliomas displayed dramatic tumor shrinkage and prolonged survival after radiation therapy alone in one case and combined radiation and chemotherapy in the other. Although malignant optic gliomas have been reported to be radiation resistant, marked treatment response may occur and aggressive treatment protocols should be considered.

    View details for Web of Science ID A1988P183900013

    View details for PubMedID 3386825

  • LEFT-VENTRICULAR TUMOR MASQUERADING AS MULTIPLE-SCLEROSIS ARCHIVES OF NEUROLOGY Albers, G. W., AVALOS, S. M., Weinrich, M. 1987; 44 (7): 779-780

    Abstract

    A 30-year-old man had relapsing and remitting neurologic symptoms, which had been diagnosed as multiple sclerosis for nine years. Eventually, an unusual left ventricular tumor was discovered. The pathologic diagnosis was cavernous angiectasia, which, to our knowledge, is a previously undescribed histologic entity. Embolization from cardiac tumors can mimic multiple sclerosis and multiple echocardiograms may be required for diagnosis.

    View details for Web of Science ID A1987H920700020

    View details for PubMedID 3593066

  • CALCIUM-CHLORIDE FOR TREATMENT OF SUBCUTANEOUS LIPOMAS IN DOGS JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION Albers, G. W., THEILEN, G. H. 1985; 186 (5): 492-494

    Abstract

    Ten dogs were selected for treatment of SC lipomas (n = 18) with intratumor injection of 10% calcium chloride. At 6-month follow-up, 4 tumors had regressed completely and 14 were less than 50% of their original size. Skin necrosis overlying treated tumors developed in 3 dogs.

    View details for Web of Science ID A1985ACT5800009

    View details for PubMedID 3972710

Conference Proceedings


  • Hemisphere Volume Is Associated with Neurological Deterioration and Outcome after Malignant Infarction 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
  • The Acute Diffusion Lesion Reliably Represents Infarct Core: Clinically Relevant Reversibility Is Rare 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
  • TIA Clinic Triage Strategy Reduces the Cost of TIA Evaluation 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
  • Worse Stroke Outcome In Atrial Fibrillation Links To More Severe Hypoperfusion 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
  • The Combination Of Reperfusion And Recanalization Predicts Favorable Outcome Better Than Reperfusion Or Recanalization Alone In Target Mismatch Patients 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
  • Higher rCBV Values In The PWI/DWI Mismatch Area Predict Favorable Clinical Outcome In Acute Ischemic Stroke Lee, J., Lansberg, M. G., Mlynash, M., Straka, M., Bammer, R., Olivot, J., Kemp, S., Albers, G. W. LIPPINCOTT WILLIAMS & WILKINS. 2011: E112-E112
  • Mri Based Tia Triage Study Wolford, C., Mlynash, M., Schwartz, N. E., Purushotham, A., Lansberg, M., Kemp, S., Albers, G. W., Olivot, J. LIPPINCOTT WILLIAMS & WILKINS. 2011: E210-E210
  • Validation of the Malignant Profile in the DEFUSE-EPITHET Pooled Database 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
  • Factors Predicting the Presence of Acute Ischemic Lesions on Diffusion Weighted in the Stanford TIA Study (Two Aces) Olivot, J. M., Wolford, C., Mlynash, M., Castle, J., Lansberg, M., Schwartz, N., Kemp, S., Albers, G. W. LIPPINCOTT WILLIAMS & WILKINS. 2010: E273-E273
  • Diagnostic Accuracy of MRI in Spontaneous Intra-cerebral Hemorrhage (DASH): Initial Results 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
  • Large and Severe Baseline PWI Volumes Predict Poor Response to Intravenous tPA vs. Placebo in the Pooled DEFUSE-EPITHET Database 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
  • Symptomatic Intracranial Hemorrhage Rates With IV tPA Treatment by Stroke Subtype 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
  • DEFUSE and EPITHET: Two Different Studies With One Consistent Message 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
  • Optimal Perfusion Thresholds for Prediction of Tissue Destined for Infarction in the Combined EPITHET and DEFUSE Dataset 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
  • Optimal Definition of the Malignant Profile in the DEFUSE-EPITHET Pooled Database 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
  • Does Presence of Arterial Obstruction Influence the Treatment Effect of Intravenous tPA Over Placebo in the 3-6 Hour Time Window? 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
  • SENSE Diffusion-weighted Imaging Improves Diagnostic Sensitivity in Acute Ischemic Stroke 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
  • Acute stroke imaging research roadmap. 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: 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

  • Yield of transesophageal echocardiography in ischemic stroke patients by age and lesion pattern on diffusion-weighted MRI 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: 575-576
  • MRI-based diagnostic evaluation has substantial impact on final stroke diagnosis 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: 569-569
  • A multicenter pooled, patient-level data analysis of diffusion-weighted MRI in TIA patients 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: 463-463
  • Clinical and radiographic history of cervical artery dissections Hirsch, K., Vertinsky, T., Albers, G. W., Schwartz, N. E. LIPPINCOTT WILLIAMS & WILKINS. 2007: 587-587
  • Who is most likely to benefit from tPA? The perfusion-diffusion and clinical-diffusion mismatch models disagree 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: 437-437
  • Proceedings of the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy: evidence-based guidelines. 2004: 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

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

    View details for PubMedID 15111655

  • Safety and tolerability of ONO-2506 in acute ischemic stroke. Pettigrew, L. C., Kasner, S. E., Kwiatkowski, T., Albers, G. W., Gorman, M., Grotta, J. C., Sherman, D., Funakoshi, Y. LIPPINCOTT WILLIAMS & WILKINS. 2004: 293-293
  • Spinal manipulative therapy is an independent risk factor for vertebral artery dissection Smith, W. S., Johnston, S. C., Skalabrin, E. J., Weaver, M., Albers, G. W., Gress, D. R. LIPPINCOTT WILLIAMS & WILKINS. 2003: 296-296
  • Antithrombotic therapy for prevention and treatment of ischemic stroke 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

  • Phase II studies of the glycine antagonist GV150526 in acute stroke - The North American experience 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: 358-365
  • Recanalization rates in cervical carotid and vertebral dissection Skalabrin, E. J., Smith, W. S., Albers, G. W. LIPPINCOTT WILLIAMS & WILKINS. 2000: 335-335
  • 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: 286-286
  • 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: 307-307
  • Emerging evidence for inflammation in conditions frequently affecting older adults: Report of a symposium Hamerman, D., Berman, J. W., Albers, G. W., Brown, D. L., Silver, D. WILEY-BLACKWELL PUBLISHING, INC. 1999: 1016-1025

    View details for Web of Science ID 000081880800015

    View details for PubMedID 10443865

  • 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: 242-242
  • Etiology 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: 1501-1506
  • 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
  • ANTITHROMBOTIC THERAPY IN ATRIAL-FIBRILLATION Laupacis, A., Albers, G., Dalen, J., Dunn, M., Feinberg, W., Jacobson, A. AMER COLL CHEST PHYSICIANS. 1995: S352-S359
  • Safety, tolerability and pharmacokinetics of the N-methyl-D-aspartate antagonist Ro-01-6794/706 in patients with acute ischemic stroke Albers, G. W., Atkinson, R., Kelley, R. E., Rosenbaum, D. M., Katz, P., Lesko, L. M., Paul, K., Rae, J., Modi, M., Yoo, K., Pitman, V., Lehr, L., Magni, G. NEW YORK ACAD SCIENCES. 1995: 249-261
  • Safety, tolerability, and pharmacokinetics of the N-methyl-D-aspartate antagonist dextrorphan in patients with acute stroke Albers, G. W., Atkinson, R., Kelly, R. E., Rosenbaum, D. M., Paul, K. L., Lesko, L., Rae, J., Pitman, V., Modi, M., Yoo, K., Lehr, L., Magni, G. WISSENSCHAFTLICHE verlagsgesellschaft mbh. 1994: 625-634
  • Antithrombotic therapy in atrial fibrillation. Laupacis, A., Albers, G., Dunn, M., Feinberg, W. 1992: 426S-433S

    View details for PubMedID 1395826

  • TREATMENT OF TARDIVE-DYSKINESIA WITH VITAMIN-E Egan, M. F., Hyde, T. M., Albers, G. W., Elkashef, A., Alexander, R. C., Reeve, A., Blum, A., Saenz, R. E., WYATT, R. J. AMER PSYCHIATRIC ASSOCIATION. 1992: 773-777

    Abstract

    Vitamin E (alpha-tocopherol), a free-radical scavenger, has been reported to improve symptoms of tardive dyskinesia. The authors attempted to replicate this finding under more controlled conditions in a larger study group.Fifteen inpatients and six outpatients with tardive dyskinesia received up to 1600 IU/day of vitamin E for 6 weeks in a double-blind, placebo-controlled crossover study. Abnormal Involuntary Movement Scale (AIMS) examinations of these patients were videotaped and rated independently by two trained raters. Levels of neuroleptic medication and vitamin E were measured during both treatment periods. Eighteen patients who demonstrated high blood levels of vitamin E were included in the data analysis.Vitamin E levels were significantly higher while the patients were receiving vitamin E than while they were receiving placebo. For all 18 patients, there were no significant differences between AIMS scores after receiving vitamin E and AIMS scores after receiving placebo. In agreement with previous studies, however, the nine patients who had had tardive dyskinesia for 5 years or less had significantly lower AIMS scores after receiving vitamin E than after receiving placebo. There were no changes in neuroleptic levels during vitamin E treatment.Vitamin E had a minor beneficial effect on tardive dyskinesia ratings in a selected group of patients who had had tardive dyskinesia for 5 years or less. This effect was not due to an increase in blood levels of neuroleptic medications.

    View details for Web of Science ID A1992HW16300006

    View details for PubMedID 1350428

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