Bio

Clinical Focus


  • Stroke
  • Cerebrovascular Disease
  • Neurology

Academic Appointments


Professional Education


  • Fellowship:Stanford Hospital and Clinics-Room HC 435 (2004) CA
  • Residency:Univ of California San Francisco (2003) CA
  • Medical Education:University of Utrecht (1997) Netherlands
  • Board Certification, American Board of Psychiatry and Neurology, Vascular Neurology (2012)
  • Board Certification: Neurology, American Board of Psychiatry and Neurology (2004)
  • Internship:Greater Baltimore Medical Ctr (2000) MD
  • MS, Stanford University, Epidemiology (2008)
  • Ph.D., Univ of Utrecht, The Netherlands, Diffusion-Weighted MRI in Stroke (2002)
  • M.D., Univ of Utrecht, The Netherlands (1997)

Research & Scholarship

Current Research and Scholarly Interests


1. Imaging of Cerebral Perfusion with MRI and Xenon CT
2. Determining selection criteria that identify stroke patients who are most likely to benefit from iv tPA
3. Combining iv tPA with intraarterial mechanical thrombectomy for acute stroke
4. Detection of Atrial Fibrillation in patients with stroke and TIA using long term ambulatory cardiac monitoring
5. Prognosis of critically ill neurological patients

Clinical Trials


  • Efficacy and Safety Study of Desmoteplase to Treat Acute Ischemic Stroke (DIAS-4) Recruiting

    The purpose of the study is to determine whether desmoteplase is effective and safe in the treatment of patients with acute ischaemic stroke when given within 3 to 9 hours from onset of stroke symptoms.

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  • 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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  • 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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  • 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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  • Efficacy and Safety Trial of Transcranial Laser Therapy Within 24 Hours From Stroke Onset (NEST-3) Recruiting

    The purpose of this pivotal study is to demonstrate safety and efficacy of transcranial laser therapy (TLT) with the NeuroThera® Laser System in the treatment of subjects diagnosed with acute ischemic stroke. The initiation of the TLT procedure must be feasible for each subject between 4.5 and 24 hours of stroke onset.

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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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Teaching

2013-14 Courses


Postdoctoral Advisees


Publications

Journal Articles


  • 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

  • Interaction between time to treatment and reperfusion therapy in patients with acute ischemic stroke. Journal of neurointerventional surgery Lansberg, M. G., Dabus, G. 2013; 5: i48-51

    View details for DOI 10.1136/neurintsurg-2013-010728

    View details for PubMedID 23572462

  • 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

  • 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

  • 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

  • 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

  • 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

  • Cost comparison between the atraumatic and cutting lumbar puncture needles NEUROLOGY Tung, C. E., So, Y. T., Lansberg, M. G. 2012; 78 (2): 109-113

    Abstract

    The aim of this study was to determine which type of spinal needle is preferred from a cost perspective, taking into account costs of the spinal needle and treatment of postlumbar puncture headache.A decision-analytic model was created to determine the cost of diagnostic lumbar punctures using atraumatic and cutting needles. We assumed a health care system perspective and based the analysis on the treatment of a patient facing event probabilities derived from prior studies. The economic outcome measure was the difference in estimated costs between the 2 needles. One-way and probabilistic sensitivity analyses tested the robustness of the model.Lumbar puncture performed with the atraumatic needle is associated with an average cost savings of $26.07 per patient. Average total health care costs are $166.08 with the atraumatic needle, compared to $192.15 with the cutting needle. There is 94% certainty that the atraumatic needle is cost-saving compared to the cutting needle based on probabilistic sensitivity analysis. Use of the atraumatic needle over the cutting needle by neurologists alone may result in $10.4 million in cost savings to the US health care system per year.The atraumatic spinal needle is associated with an overall cost savings to the US health care system. The balance of costs and benefits favors the use of the atraumatic needle over the cutting needle for diagnostic lumbar puncture.

    View details for Web of Science ID 000299159700010

    View details for PubMedID 22205758

  • 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

  • Cost-Effectiveness of Tissue-Type Plasminogen Activator in the 3-to 4.5-Hour Time Window for Acute Ischemic Stroke STROKE Tung, C. E., Win, S. S., Lansberg, M. G. 2011; 42 (8): 2257-2262

    Abstract

    The aim of this study was to determine the cost-effectiveness of tissue-type plasminogen activator (tPA) treatment in the 3- to 4.5-hour time window after ischemic stroke.Decision-analytic and Markov state-transition models were created to determine the cost-effectiveness of treatment of ischemic stroke patients with intravenous tPA administered in the 3- to 4.5-hour time window compared with medical therapy without tPA. Health benefits were measured in quality-adjusted life-years (QALYs). The economic outcome measure of the model was the difference in estimated healthcare costs between the 2 treatment alternatives. The incremental cost-effectiveness ratio was calculated by dividing the cost difference by the difference in QALYs. One-way sensitivity and probabilistic analyses were performed to test the robustness of the model.The administration of tPA compared with standard medical therapy resulted in a lifetime gain of 0.28 QALYs for an additional cost of $6050, yielding an incremental cost-effectiveness ratio of $21 978 per QALY. One-way sensitivity analyses demonstrated that the incremental cost-effectiveness ratio was most sensitive to the cost of hospitalization for patients who received tPA. Based on probabilistic analysis, there is an 88% probability that tPA is the preferred treatment at a willingness-to-pay threshold of $50 000 per QALY.The balance of costs and benefits favors treatment with intravenous tPA in the 3- to 4.5-hour time window. This supports, from a societal perspective, the use of tPA therapy in this treatment time window for acute ischemic stroke.

    View details for DOI 10.1161/STROKEAHA.111.615682

    View details for Web of Science ID 000293077400034

    View details for PubMedID 21719767

  • 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

  • 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

  • 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

  • A comparison of cooling techniques to treat cardiac arrest patients with hypothermia. Stroke research and treatment Finley Caulfield, A., Rachabattula, S., Eyngorn, I., Hamilton, S. A., Kalimuthu, R., Hsia, A. W., Lansberg, M. G., Venkatasubramanian, C., BAUMANN, J. J., Buckwalter, M. S., Kumar, M. A., Castle, J. S., Wijman, C. A. 2011; 2011: 690506-?

    Abstract

    Introduction. We sought to compare the performance of endovascular cooling to conventional surface cooling after cardiac arrest. Methods. Patients in coma following cardiopulmonary resuscitation were cooled with an endovascular cooling catheter or with ice bags and cold-water-circulating cooling blankets to a target temperature of 32.0-34.0°C for 24 hours. Performance of cooling techniques was compared by (1) number of hourly recordings in target temperature range, (2) time elapsed from the written order to initiate cooling and target temperature, and (3) adverse events during the first week. Results. Median time in target temperature range was 19 hours (interquartile range (IQR), 16-20) in the endovascular group versus. 10 hours (IQR, 7-15) in the surface group (P = .001). Median time to target temperature was 4 (IQR, 2.8-6.2) and 4.5 (IQR, 3-6.5) hours, respectively (P = .67). Adverse events were similar. Conclusion. Endovascular cooling maintains target temperatures better than conventional surface cooling.

    View details for DOI 10.4061/2011/690506

    View details for PubMedID 21822470

  • Utility of the anesthetic test dose to avoid catastrophic injury during cervical transforaminal epidural injections SPINE JOURNAL Smuck, M., Maxwell, M. D., Kennedy, D., Rittenberg, J. D., Lansberg, M. G., Plastaras, C. T. 2010; 10 (10): 857-864

    Abstract

    Reports of serious complications from cervical transforaminal epidural corticosteroid injections often consider accidental intra-arterial injection the most likely mechanism of injury. As a result, many physicians have instituted methods to prevent intravascular injections. Routine use of the anesthetic test dose is one such method. The utility of the anesthetic test dose in this function has not been characterized in the current literature.The aim of this study was to determine the utility of injecting an anesthetic test dose before cervical transforaminal epidural corticosteroid injection and estimate the rate of false-negative intravascular contrast injection using live fluoroscopy and digital subtraction angiography (DSA).Two-center retrospective study.A consecutive cohort of men and women, ages of 23 to 83, who underwent cervical transforaminal epidural injection and received the anesthetic test dose after contrast injection was negative for vascular uptake, observed using live fluoroscopy or DSA.Response to the anesthetic test dose was documented in each procedure note and recorded as either positive or negative.Records of three physiatrists at two academic spine centers (Center A and Center B) were reviewed to identify all patients who received a cervical transforaminal epidural injection during the preceding 5 years, resulting in a cohort of consecutively treated patients at each center. Each patient record was reviewed for demographics, indication for injection, procedure level and side, needle gauge, use of DSA, volume and type of anesthetic test dose used, and result of test dose injection. The test dose was considered positive if the following occurred: agitation or other sudden central nervous system change; gross motor deficits and/or paresthesias in the trunk, legs, or contralateral arm; systemic symptoms of anesthetic toxicity including cardiac arrhythmia, perioral numbness, metallic taste, dizziness, and/or ringing in the ear. For analysis, injections were separated into groups to compare results at Center A to Center B and to compare injections that used DSA to those that did not. The incidence of a positive response was calculated as a percentage from the total number of injections in the group. Differences between groups were analyzed for statistical significance using the Fisher exact test.Six hundred seventy-eight injections were included. Of these, 349 were performed at Center A with test doses given after contrast injection under live fluoroscopy. The remaining 329 were performed at Center B, 183 also using live fluoroscopy, and 146 using DSA. The overall incidence of a positive anesthetic test dose was 0.59% (4/678). There was no significant difference between the incidence at each of the two centers (0.86% [3/349] vs. 0.30% [1/329]; p=.63). The overall incidence after live fluoroscopy was 0.75% (4/532) and after DSA was 0% (0/146), but this difference was not statistically significant (p=.58). Positive symptoms elicited by test dose administration included midneck and contralateral arm pain, metallic taste, dizziness, tachycardia, full body paresthesias, auditory changes, slurred speech, and motor ataxia. In all four cases with a positive response, the procedure was immediately terminated, symptoms resolved, and no lasting complications were observed.The routine use of an anesthetic test dose appears to be safe and capable of detecting potentially dangerous intravascular injections undetected by conventional techniques. Positive responses occur in a small portion of those who receive the test dose injection. Further studies are required to determine the optimal dose and concentration of anesthetic to be used and the time required for observation after test dose administration.

    View details for DOI 10.1016/j.spinee.2010.07.003

    View details for Web of Science ID 000283190400002

    View details for PubMedID 20692210

  • 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

  • STROKE Taking stock-patient selection for acute stroke therapy NATURE REVIEWS NEUROLOGY Lansberg, M. 2010; 6 (7): 358-359

    View details for DOI 10.1038/nrneurol.2010.75

    View details for Web of Science ID 000279624100002

    View details for PubMedID 20639911

  • Outcome prediction in mechanically ventilated neurologic patients by junior neurointensivists NEUROLOGY Caulfield, A. F., GABLER, L., Lansberg, M. G., Eyngorn, I., Mlynash, M., Buckwalter, M. S., Venkatasubramanian, C., Wijman, C. A. 2010; 74 (14): 1096-1101

    Abstract

    Physician prediction of outcome in critically ill neurologic patients impacts treatment decisions and goals of care. In this observational study, we prospectively compared predictions by neurointensivists to patient outcomes at 6 months.Consecutive neurologic patients requiring mechanical ventilation for 72 hours or more were enrolled. The attending neurointensivist was asked to predict 6-month 1) functional outcome (modified Rankin scale [mRS]), 2) quality of life (QOL), and 3) whether supportive care should be withdrawn. Six-month functional outcome was determined by telephone interviews and dichotomized to good (mRS 0-3) and poor outcome (mRS 4-6).Of 187 eligible patients, 144 were enrolled. Neurointensivists correctly predicted 6-month functional outcome in 80% (95% confidence interval [CI], 72%-86%) of patients. Accuracy for a predicted good outcome was 63% (95% CI, 50%-74%) and for poor outcome 94% (95% CI, 85%-98%). Excluding patients who had life support withdrawn, accuracy for good outcome was 73% (95% CI, 60%-84%) and for poor outcome 87% (95% CI, 74%-94%). Accuracy for exact agreement between neurointensivists' mRS predictions and actual 6-month mRS was only 43% (95% CI, 35%-52%). Predicted accuracy for QOL was 58% (95% CI, 39%-74%) for good/excellent and 67% (95% CI, 46%-83%) for poor/fair. Of 27 patients for whom withdrawal of care was recommended, 1 patient survived in a vegetative state.Prediction of long-term functional outcomes in critically ill neurologic patients is challenging. Our neurointensivists were more accurate in predicting poor outcome than good outcome in patients requiring mechanical ventilation >or=72 hours.

    View details for Web of Science ID 000276354400005

    View details for PubMedID 20368630

  • Favorable Outcome From A Locked-In State Despite Extensive Pontine Infarction By MRI NEUROCRITICAL CARE Samaniego, E. A., Lansberg, M. G., DeGeorgia, M., Venkatasubramanian, C., Wijman, C. A. 2009; 11 (3): 369-371

    Abstract

    Outcome prediction of patients who are in a locked-in state is challenging. Extensive pontine infarction on diffusion weighted imaging MRI (DWI) has been proposed as a poor prognosticator. We report on three patients with a locked-in state with unexpected favorable recoveries despite DWI evidence of widespread pontine ischemia.Report of three cases.Three young patients (32-, 30-, and 16-years-old) presented with a locked-in state caused by pontine infarction. The first patient did not receive any acute stroke therapies, the second patient underwent endovascular therapy 20 h after symptom onset resulting in partial recanalization of the basilar artery, and the third patient progressed to a locked-in state despite having received intravenous tissue plasminogen activator. The DWI of all three patients demonstrated acute and widespread pontine infarction involving more than two-thirds of the pons. Two patients regained full independence in their activities of daily living. The third patient remained wheelchair bound, but lives with her family, eats independently, uses a typewriter and wrote a book.Patients who are in a locked-in state may have substantial functional recovery despite DWI evidence of extensive pontine infarction.

    View details for DOI 10.1007/s12028-009-9268-y

    View details for Web of Science ID 000271943800011

    View details for PubMedID 19707888

  • 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

  • Efficacy and Safety of Tissue Plasminogen Activator 3 to 4.5 Hours After Acute Ischemic Stroke A Metaanalysis STROKE Lansberg, M. G., Bluhmki, E., Thijs, V. N. 2009; 40 (7): 2438-2441

    Abstract

    The Third European Cooperative Acute Stroke Study (ECASS-3) demonstrated a benefit of treatment with intravenous tissue plasminogen activator (tPA) for acute stroke in the 3- to 4.5-hour time-window. Prior studies, however, have failed to demonstrate a significant benefit of tPA for patients treated beyond 3 hours. The purpose of this study was to produce reliable and precise estimates of the treatment effect of tPA by pooling data from all relevant studies.A metaanalysis was undertaken to determine the efficacy of tPA in the 3- to 4.5-hour time-window. The effect of tPA on favorable outcome and mortality was assessed.The metaanalysis included data from patients treated in the 3- to 4.5-hour time-window in ECASS-1 (n=234), ECASS-2 (n=265), ECASS-3 (n=821) and The Alteplase Thrombolysis for Acute Noninterventional Therapy in Ischemic Stroke (ATLANTIS) (n=302). tPA treatment was associated with an increased chance of favorable outcome (odds ratio 1.31; 95% CI: 1.10 to 1.56; P=0.002) and no significant difference in mortality (odds ratio 1.04; 95% CI: 0.75 to 1.43; P=0.83) compared to placebo treated patients.Treatment with tPA in the 3- to 4.5-hour time-window is beneficial. It results in an increased rate of favorable outcome without adversely affecting mortality.

    View details for DOI 10.1161/STROKEAHA.109.552547

    View details for Web of Science ID 000267467900026

    View details for PubMedID 19478213

  • Treatment Time-Specific Number Needed to Treat Estimates for Tissue Plasminogen Activator Therapy in Acute Stroke Based on Shifts Over the Entire Range of the Modified Rankin Scale STROKE Lansberg, M. G., Schrooten, M., Bluhmki, E., Thijs, V. N., Saver, J. L. 2009; 40 (6): 2079-2084

    Abstract

    To make informed treatment decisions, patients and physicians need to be aware of the benefits and risks of a proposed treatment. The number needed to treat (NNT) for benefit and harm are intuitive and statistically valid measures to describe a treatment effect. The aim of this study is to calculate treatment time-specific NNT estimates based on shifts over the entire spectrum of clinically relevant functional outcomes.The pooled data set of the first 6 major randomized acute stroke trials of intravenous tissue plasminogen activator was used for this study. The data were stratified by 90-minute treatment time windows. NNT for benefit and NNT for harm estimates were determined based on expert generation of joint outcome distribution tables. NNT for benefit estimates were also calculated based on joint outcome distribution tables generated by a computer model.NNT for benefit estimates based on the expert panel were 3.6 for patients treated between 0 and 90 minutes, 4.3 with treatment between 91 and 180 minutes, 5.9 with treatment between 181 and 270 minutes, and 19.3 with treatment between 271 and 360 minutes. The computer simulation yielded very similar results. The NNT for harm estimates for the corresponding time intervals are 65, 38, 30, and 14.Up to 4(1/2) hours after symptom onset, tissue plasminogen activator therapy is associated with more benefit than harm, whereas there is no evidence of a net benefit in the 4(1/2)- to 6-hour time window. The NNT estimates for each 90-minute epoch provide useful and intuitive information based on which patients may be able to make better informed treatment decisions.

    View details for DOI 10.1161/STROKEAHA.108.540708

    View details for Web of Science ID 000266302200025

    View details for PubMedID 19372447

  • 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

  • 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

  • Cost-effectiveness analysis of mechanical thrombectomy in acute ischemic stroke Clinical article JOURNAL OF NEUROSURGERY Patil, C. G., Long, E. F., Lansberg, M. G. 2009; 110 (3): 508-513

    Abstract

    Mechanical thrombectomy is increasingly being used for the treatment of large-vessel ischemic stroke in patients who arrive outside of the 3-hour tissue plasminogen activator time window. In this study, the authors evaluated the cost and effectiveness of mechanical thrombectomy compared with standard medical therapy in patients who are ineligible to receive tissue plasminogen activator.Clinical outcomes of an open-label study of mechanical thrombectomy were compared with a hypothetical control group with a lower recanalization rate (18 vs 60%) and a lower rate of symptomatic intracranial hemorrhage (0.6 vs 7.8%) than the active treatment group. A Markov cost-effectiveness model was built to compare the health benefits and costs associated with mechanical thrombectomy compared with standard medical therapy. All probabilities, quality-of-life factors, and costs were estimated from the published literature. Univariate sensitivity analyses were performed to assess how variations in model parameters affect health and economic outcomes.Treatment of acute ischemic stroke with mechanical thrombectomy increased survival time by 0.54 quality-adjusted life years (QALYs), compared with standard medical therapy (2.37 vs 1.83 QALYs), at an increased cost of $6600. This yielded an incremental cost-effectiveness ratio (ICER) of $12,120 per QALY gained, a value generally considered cost-effective. Sensitivity analysis showed that mechanical thrombectomy remained cost-effective (ICER < $50,000 per QALY gained) for all model inputs varied over a reasonable range, except for age at stroke treatment. For patients older than 82 years of age, the treatment was only borderline cost-effective (ICER of $50,000-100,000 per QALY gained).The treatment of large-vessel ischemic stroke with mechanical thrombectomy appears to be costeffective. These results require validation when data from a randomized, controlled trial of mechanical thrombectomy become available.

    View details for DOI 10.3171/2008.8.JNS08133

    View details for Web of Science ID 000263868000017

    View details for PubMedID 19025358

  • 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

  • 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

  • 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

  • Concurrent presentation of perimesencephalic subarachnoid hemorrhage and ischemic stroke. Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association Lansberg, M. G. 2008; 17 (4): 248-250

    Abstract

    Perimesencephalic subarachnoid hemorrhage (SAH) is a relatively benign form of SAH. The etiology of this condition is unknown but venous leakage has been believed to be the most likely cause. This report describes a patient with perimesencephalic SAH who presented with a concurrent acute pontine infarct demonstrated on diffusion-weighted magnetic resonance imaging. These findings suggest that in some instances perimesencephalic SAH is caused by rupture of a perforating artery.

    View details for DOI 10.1016/j.jstrokecerebrovasdis.2008.03.005

    View details for PubMedID 18589349

  • Delirium following abrupt discontinuation of fluoxetine CLINICAL NEUROLOGY AND NEUROSURGERY Blum, D., Maldonado, J., Meyer, E., Lansberg, M. 2008; 110 (1): 69-70

    Abstract

    Sudden discontinuation of serotonin reuptake inhibitors (SRI) can lead to a number of psychological (e.g., nervousness, anxiety, crying spells, psychomotor agitation, irritability, depersonalization, decreased mood, memory disturbances, confusion, decreased concentration, and/or slowed thinking) and somatic (e.g., nausea, dizziness, headache) symptoms. Recent studies have shown that withdrawal symptoms are common with paroxetine, venlafaxine and fluvoxamine, but relatively rare and mild with fluoxetine cessation, likely as a result of its longer half-life. We report an unusual case of a patient who developed delirium after abrupt discontinuation of fluoxetine.

    View details for DOI 10.1016/j.clineuro.2007.08.016

    View details for Web of Science ID 000252799500013

    View details for PubMedID 17913343

  • 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

  • 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

  • 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

  • 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

  • "Paradoxical" transtentorial herniation due to CSF drainage in the presence of a hemicraniectomy NEUROLOGY Fields, J. D., Lansberg, M. G., Skirboll, S. L., Kurien, P. A., Wijman, C. A. 2006; 67 (8): 1513-1514

    View details for Web of Science ID 000241494800046

    View details for PubMedID 17060591

  • 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

  • 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

  • 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

  • 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

  • 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

  • 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

  • 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

  • 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

  • Intra-arterial rtPA treatment of stroke assessed by diffusion- and perfusion-weighted MRI STROKE Lansberg, M. G., Tong, D. C., Norbash, A. M., Yenari, M. A., Moseley, M. E. 1999; 30 (3): 678-680

    Abstract

    Diffusion-weighted MRI (DWI) and perfusion-weighted MRI (PWI) are new techniques that can be used for the evaluation of acute ischemic stroke. However, their potential role in the management of patients treated with recombinant tissue plasminogen activator (rtPA) has yet to be determined.The authors present the case of a 73-year-old man who was treated with intra-arterial rtPA, and they compare findings on DWI and PWI scans with angiography. PWI revealed decreased cerebral perfusion corresponding to an area that was not successfully recanalized, but revealed no abnormality in regions in which blood flow was restored. DWI was unremarkable in the region that was reperfused early (3 hours) but revealed hyperintensity in an area that was reperfused 3. 5 hours after symptom onset and in the area that was not reperfused.Findings on PWI correlated well with angiography, and DWI detected injured tissue in the hyperacute stage, whereas conventional MRI findings were negative. This suggests that these techniques may be useful to noninvasively evaluate the success of thrombolytic therapy.

    View details for Web of Science ID 000078913700040

    View details for PubMedID 10066870

  • 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

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