Bio

Clinical Focus


  • Vascular Neurology
  • Neurology

Academic Appointments


Administrative Appointments


  • Program Director, Neurology Residency Program, Dept of Neurology & Neurological Sciences (2010 - Present)
  • Medical Director, F3, Stanford Hospital & Clinics (2010 - Present)
  • Course Director, HHD 223 'Brain Block', Stanford Medical School (2011 - Present)

Professional Education


  • Medical Education:Northwestern University Feinberg School of Medicine (2000) IL
  • Fellowship:Stanford University Medical Center (2005) CA
  • Board Certification: Neurology, American Board of Psychiatry and Neurology (2006)
  • Board Certification: Vascular Neurology, American Board of Psychiatry and Neurology (2008)
  • Residency:Stanford University Medical Center (2004) CA
  • Internship:California Pacific Medical Center (2001) CA
  • MD, Northwestern University (2000)
  • PhD, Northwestern University, Neurophysiology Neuropharmacology (1998)

Research & Scholarship

Current Research and Scholarly Interests


My clinical interests involve inpatient and outpatient care of patients with neurovascular diseases, mostly ischemic and hemorrhagic stroke. I have a particular interest in cervical artery dissection, non-atherosclerotic vasculopathies, and stroke in the young.

Clinical Trials


  • Protected Carotid Artery Stenting in Subjects at High Risk for Carotid Endarterectomy (CEA) (PROTECT) Not Recruiting

    The purpose of this study is to evaluate the long-term safety and efficacy of the Xact? Rapid Exchange Carotid Stent System used in conjunction with the Emboshield® Pro Rapid Exchange Embolic Protection System (Generation 5) and the Emboshield® BareWire? Rapid Exchange Embolic Protection System (Generation 3), in the treatment of atherosclerotic carotid artery disease in high-surgical risk subjects.

    Stanford is currently not accepting patients for this trial. For more information, please contact Ronald Dalman, (650) 725 - 5227.

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

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

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  • Diagnostic Utility of MRI in Intracerebral Hemorrhage Recruiting

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

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  • 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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  • A Study of Modified Stem Cells in Stable Ischemic Stroke Recruiting

    The primary purpose of the clinical study is to determine the safety of a modified stem cell SB623 when administered to chronic, stable ischemic stroke patients. A second purpose is to determine whether SB623 might improve stroke symptoms. Chronic, stable ischemic stroke patients must be between 6 and 60 months after their stroke, and with only this one prior stroke, and and with no further improvement from physical therapy.

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Teaching

2013-14 Courses


Publications

Journal Articles


  • 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

  • Predicting outcome after acute basilar artery occlusion based on admission characteristics NEUROLOGY Greving, J. P., Schonewille, W. J., Wijman, C. A., Michel, P., Kappelle, L. J., Algra, A. 2012; 78 (14): 1058-1063

    Abstract

    To develop a simple prognostic model to predict outcome at 1 month after acute basilar artery occlusion (BAO) with readily available predictors.The Basilar Artery International Cooperation Study (BASICS) is a prospective, observational, international registry of consecutive patients who presented with an acute symptomatic and radiologically confirmed BAO. We considered predictors available at hospital admission in multivariable logistic regression models to predict poor outcome (modified Rankin Scale [mRS] score 4-5 or death) at 1 month. We used receiver operator characteristic curves to assess the discriminatory performance of the models.Of the 619 patients, 429 (69%) had a poor outcome at 1 month: 74 (12%) had a mRS score of 4, 115 (19%) had a mRS score of 5, and 240 (39%) had died. The main predictors of poor outcome were older age, absence of hyperlipidemia, presence of prodromal minor stroke, higher NIH Stroke Scale (NIHSS) score, and longer time to treatment. A prognostic model that combined demographic data and stroke risk factors had an area under the receiver operating characteristic curve (AUC) of 0.64. This performance improved by including findings from the neurologic examination (AUC 0.79) and CT imaging (AUC 0.80). A risk chart showed predictions of poor outcome at 1 month varying from 25 to 96%.Poor outcome after BAO can be reliably predicted by a simple model that includes older age, absence of hyperlipidemia, presence of prodromal minor stroke, higher NIHSS score, and longer time to treatment.

    View details for DOI 10.1212/WNL.0b013e31824e8f40

    View details for Web of Science ID 000302618700009

    View details for PubMedID 22442438

  • Antithrombotic and Thrombolytic Therapy for Ischemic Stroke Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines CHEST Lansberg, M. G., O'Donnell, M. J., Khatri, P., Lang, E. S., Nguyen-Huynh, M. N., Schwartz, N. E., Sonnenberg, F. A., Schulman, S., Vandvik, P. O., Spencer, F. A., Alonso-Coello, P., Guyatt, G. H., Akl, E. A. 2012; 141 (2): E601S-E636S
  • Antithrombotic and thrombolytic therapy for ischemic stroke: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest Lansberg, M. G., O'Donnell, M. J., Khatri, P., Lang, E. S., Nguyen-Huynh, M. N., Schwartz, N. E., Sonnenberg, F. A., Schulman, S., Vandvik, P. O., Spencer, F. A., Alonso-Coello, P., Guyatt, G. H., Akl, E. A. 2012; 141 (2): e601S-36S

    Abstract

    This article provides recommendations on the use of antithrombotic therapy in patients with stroke or transient ischemic attack (TIA).We generated treatment recommendations (Grade 1) and suggestions (Grade 2) based on high (A), moderate (B), and low (C) quality evidence.In patients with acute ischemic stroke, we recommend IV recombinant tissue plasminogen activator (r-tPA) if treatment can be initiated within 3 h (Grade 1A) or 4.5 h (Grade 2C) of symptom onset; we suggest intraarterial r-tPA in patients ineligible for IV tPA if treatment can be initiated within 6 h (Grade 2C); we suggest against the use of mechanical thrombectomy (Grade 2C) although carefully selected patients may choose this intervention; and we recommend early aspirin therapy at a dose of 160 to 325 mg (Grade 1A). In patients with acute stroke and restricted mobility, we suggest the use of prophylactic-dose heparin or intermittent pneumatic compression devices (Grade 2B) and suggest against the use of elastic compression stockings (Grade 2B). In patients with a history of noncardioembolic ischemic stroke or TIA, we recommend long-term treatment with aspirin (75-100 mg once daily), clopidogrel (75 mg once daily), aspirin/extended release dipyridamole (25 mg/200 mg bid), or cilostazol (100 mg bid) over no antiplatelet therapy (Grade 1A), oral anticoagulants (Grade 1B), the combination of clopidogrel plus aspirin (Grade 1B), or triflusal (Grade 2B). Of the recommended antiplatelet regimens, we suggest clopidogrel or aspirin/extended-release dipyridamole over aspirin (Grade 2B) or cilostazol (Grade 2C). In patients with a history of stroke or TIA and atrial fibrillation we recommend oral anticoagulation over no antithrombotic therapy, aspirin, and combination therapy with aspirin and clopidogrel (Grade 1B).These recommendations can help clinicians make evidence-based treatment decisions with their patients who have had strokes.

    View details for DOI 10.1378/chest.11-2302

    View details for PubMedID 22315273

  • Concurrent stenoocclusive disease of intracranial and extracranial arteries in a patient with polycythemia vera. Case reports in medicine Hua, L. H., Dodd, R. L., Schwartz, N. E. 2012; 2012: 151767-?

    Abstract

    Moyamoya disease is a stenoocclusive disease involving the intracranial carotid and proximal middle cerebral arteries. There are rarely any additional extracranial stenoses occurring concurrently with moyamoya. The pathophysiology of moyamoya remains obscure, but hematologic disorders, notably sickle-cell anemia, have been associated in some cases. We describe the novel case of polycythemia vera associated with severe steno-occlusive disease of both intracranial and extracranial large arteries. A 47-year-old woman with polycythemia vera had multiple transient ischemic attacks, and noninvasive vessel imaging revealed steno-occlusive disease of bilateral supraclinoid internal carotid arteries with moyamoya-type collaterals, proximal left subclavian artery, right vertebral artery origin, bilateral renal arteries, superior mesenteric artery, and right common iliac artery. Laboratory workup for systemic vasculitis was negative. She required bilateral direct external carotid to internal carotid bypass procedures and percutaneous balloon angioplasty of her right VA origin stenosis. This case suggests that hematologic disorders can lead to vessel stenoses and occlusion. The pathophysiology may be due to a prothrombotic state leading to repeated endothelial injury, resultant intimal hyperplasia, and progressive steno-occlusion.

    View details for DOI 10.1155/2012/151767

    View details for PubMedID 22690222

  • 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

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

    Abstract

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

    View details for DOI 10.1002/ana.22444

    View details for Web of Science ID 000296396700013

    View details for PubMedID 22028220

  • 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

  • The Albumin in Acute Stroke Part 1 Trial An Exploratory Efficacy Analysis STROKE Hill, M. D., Martin, R. H., Palesch, Y. Y., Tamariz, D., Waldman, B. D., Ryckborst, K. J., Moy, C. S., Barsan, W. G., Ginsberg, M. D. 2011; 42 (6): 1621-1625

    Abstract

    The Albumin in Acute Stroke (ALIAS) Part 2 Trial is directly testing whether 2 g/kg of 25% human albumin (ALB) administered intravenously within 5 hours of ischemic stroke onset results in improved clinical outcome. Recruitment into Part 1 of the ALIAS Trial was halted for safety reasons. ALIAS Part 2 is a new, reformulated trial with more-stringent exclusion criteria. Our aim was to explore the efficacy of ALB in the ALIAS Part 1 data and to assess the statistical assumptions underlying the ALIAS Part 2 Trial.ALIAS is a multicenter, blinded, randomized controlled trial. Data on 434 subjects, comprising the ALIAS Part 1 subjects, were analyzed. We examined both the thrombolysis and nonthrombolysis cohorts combined and separately in a "target population" by excluding subjects who would not have been eligible for the ALIAS Part 2 Trial; the latter comprised patients >83 years of age, those with elevated baseline troponin values, and those with in-hospital stroke. We examined the differences in the primary composite outcome, defined as a modified Rankin Scale score of 0 to 1 and/or a National Institutes of Health Stroke Scale score of 0 to 1 at 90 days after randomization.In the combined thrombolysis plus nonthrombolysis cohorts of the target population, 44.7% of subjects in the ALB group had a favorable outcome compared with 36.0% in the saline group (absolute effect size=8.7%; 95% CI, -2.2% to 19.5%). Among thrombolyzed subjects of the target population, 46.7% had a favorable outcome in the ALB group compared with 36.6% in the saline group (absolute effect size=10.1%; 95% CI, -2.0% to 20.0%).Preliminary results from the ALIAS Part 1 suggest a trend toward a favorable primary outcome in subjects treated with ALB and support the validity of the statistical assumptions that underlie the ALIAS Part 2 Trial. The ALIAS Part 2 Trial will confirm or refute these results.URL: http://www.clinicaltrials.gov/ALIAS. Unique identifier: NCT00235495.

    View details for DOI 10.1161/STROKEAHA.110.610980

    View details for Web of Science ID 000291032700040

    View details for PubMedID 21546491

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

    Abstract

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

    View details for DOI 10.1161/STROKEAHA.110.590638

    View details for Web of Science ID 000283443500058

    View details for PubMedID 20947849

  • Acute Basilar Artery Occlusion in the Basilar Artery International Cooperation Study Does Gender Matter? STROKE Arnold, M., Fischer, U., Compter, A., Gralla, J., Findling, O., Mattle, H. P., Kappelle, L. J., Tanne, D., Algra, A., Schonewille, W. J. 2010; 41 (11): 2693-2696

    Abstract

    Randomized trials suggested a different benefit of intravenous thrombolysis (IVT) and intra-arterial thrombolysis (IAT) between men and women with anterior circulation stroke because of a worse outcome of women in the control group.We compared outcome and recanalization in men and women with basilar artery occlusion treated with antithrombotic treatment alone, IVT or combined IVT-IAT, or IAT in the Basilar Artery International Cooperation Study.Overall, 389 male and 226 female patients were analyzed. In the antithrombotic treatment group, 68 of 111 (61%) men and 47 of 70 (67%) women had a poor outcome defined as a modified Rankin Scale score of 4 to 6 (adjusted risk ratio [aRR], 0.96; 95% CI, 0.75 to 1.24), in the IVT/combined IVT-IAT group, 47 of 77 (61%) men and 24 of 43 (56%) women (aRR, 1.19; 95% CI, 0.89 to 1.60), and in the IAT group, 142 of 185 (77%) men and 71 of 102 (70%) women (aRR, 1.01; 95% CI, 0.88 to 1.17). Mortality was not different between men and women in the antithrombotic treatment group (aRR, 0.80; 95% CI, 0.55 to 1.16), the IVT/combined IVT-IAT group (aRR, 1.11; 95% CI, 0.72 to 1.73), or in the IAT group (aRR, 1.01; 95% CI, 0.75 to 1.36). Insufficient recanalization after combined IVT-IAT or IAT was similar in men and women (23% versus 22%; aRR, 0.92; 95% CI, 0.58 to 1.46).In patients with acute basilar artery occlusion, no significant gender differences for outcome and recanalization were observed, regardless of treatment modality.

    View details for DOI 10.1161/STROKEAHA.110.594036

    View details for Web of Science ID 000283443500062

    View details for PubMedID 20947845

  • Intravenous Thrombolysis Plus Hypothermia for Acute Treatment of Ischemic Stroke (ICTuS-L) Final Results STROKE Hemmen, T. M., Raman, R., Guluma, K. Z., Meyer, B. C., Gomes, J. A., Cruz-Flores, S., Wijman, C. A., Rapp, K. S., Grotta, J. C., Lyden, P. D. 2010; 41 (10): 2265-2270

    Abstract

    Induced hypothermia is a promising neuroprotective therapy. We studied the feasibility and safety of hypothermia and thrombolysis after acute ischemic stroke.Intravenous Thrombolysis Plus Hypothermia for Acute Treatment of Ischemic Stroke (ICTuS-L) was a randomized, multicenter trial of hypothermia and intravenous tissue plasminogen activator in patients treated within 6 hours after ischemic stroke. Enrollment was stratified to the treatment time windows 0 to 3 and 3 to 6 hours. Patients presenting within 3 hours of symptom onset received standard dose intravenous alteplase and were randomized to undergo 24 hours of endovascular cooling to 33°C followed by 12 hours of controlled rewarming or normothermia treatment. Patients presenting between 3 and 6 hours were randomized twice: to receive tissue plasminogen activator or not and to receive hypothermia or not. Results- In total, 59 patients were enrolled. One patient was enrolled but not treated when pneumonia was discovered just before treatment. All 44 patients enrolled within 3 hours and 4 of 14 patients enrolled between 3 to 6 hours received tissue plasminogen activator. Overall, 28 patients randomized to receive hypothermia (HY) and 30 to normothermia (NT). Baseline demographics and risk factors were similar between groups. Mean age was 65.5±12.1 years and baseline National Institutes of Health Stroke Scale score was 14.0±5.0; 32 (55%) were male. Cooling was achieved in all patients except 2 in whom there were technical difficulties. The median time to target temperature after catheter placement was 67 minutes (Quartile 1 57.3 to Quartile 3 99.4). At 3 months, 18% of patients treated with hypothermia had a modified Rankin Scale score of 0 or 1 versus 24% in the normothermia groups (nonsignificant). Symptomatic intracranial hemorrhage occurred in 4 patients (68); all were treated with tissue plasminogen activator <3 hours (1 received hypothermia). Six patients in the hypothermia and 5 in the normothermia groups died within 90 days (nonsignificant). Pneumonia occurred in 14 patients in the hypothermia and in 3 of the normothermia groups (P=0.001). The pneumonia rate did not significantly adversely affect 3 month modified Rankin Scale score (P=0.32).This study demonstrates the feasibility and preliminary safety of combining endovascular hypothermia after stroke with intravenous thrombolysis. Pneumonia was more frequent after hypothermia, but further studies are needed to determine its effect on patient outcome and whether it can be prevented. A definitive efficacy trial is necessary to evaluate the efficacy of therapeutic hypothermia for acute stroke.

    View details for DOI 10.1161/STROKEAHA.110.592295

    View details for Web of Science ID 000282221700036

    View details for PubMedID 20724711

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

    View details for DOI 10.1161/STROKEAHA.110.584557

    View details for Web of Science ID 000278019400041

    View details for PubMedID 20395603

  • Endovascular Thrombectomy for Acute Ischemic Stroke in Failed Intravenous Tissue Plasminogen Activator Versus Non-Intravenous Tissue Plasminogen Activator Patients Revascularization and Outcomes Stratified by the Site of Arterial Occlusions STROKE Shi, Z., Loh, Y., Walker, G., Duckwiler, G. R. 2010; 41 (6): 1185-1192

    Abstract

    Intracranial mechanical thrombectomy is a therapeutic option for acute ischemic stroke patients failing intravenous tissue plasminogen activator (IV tPA). We compared patients treated by mechanical embolus removal in cerebral ischemia (MERCI) thrombectomy after failed IV tPA with those treated with thrombectomy alone.We pooled MERCI and Multi MERCI study patients, grouped them either as failed IV tPA or non-IV tPA, and assessed revascularization rates, procedural complications, symptomatic hemorrhage rates, clinical outcomes, and mortality. We also evaluated outcomes stratified by the occlusion site and final revascularization.Among 305 patients, 48 failed, and 257 were ineligible for IV tPA. Nonresponders to IV tPA trended toward a higher revascularization rate (73% versus 63%) and less mortality (27.7% versus 40.1%) and had similar rates of symptomatic hemorrhage and procedural complications. Favorable 90-day outcomes were similar in failed and non-IV tPA patients (38% versus 31%), with no difference according to occlusion site. Among patients failing IV tPA, good outcomes tended to occur more frequently in revascularized patients (47.1% versus 15.4%), although this relationship was attributable solely to middle cerebral artery and not internal carotid artery occlusions, with no difference in mortality. Among IV tPA-ineligible patients, revascularization correlated with good outcome (47.4% versus 4.4%) and less mortality (28.5% versus 59.6%).The risks of hemorrhage and procedure-related complications after mechanical thrombectomy do not differ with respect to previous IV tPA administration. Thrombectomy after IV tPA achieves similar rates of good outcomes, a tendency toward lower mortality, and similar revascularization rates when stratified by clot location. Good outcomes correlate with successful revascularization except with internal carotid artery occlusions in tPA-nonresponders.

    View details for DOI 10.1161/STROKEAHA.109.568451

    View details for Web of Science ID 000278019400021

    View details for PubMedID 20431084

  • Clinical Outcomes in Middle Cerebral Artery Trunk Occlusions Versus Secondary Division Occlusions After Mechanical Thrombectomy Pooled Analysis of the Mechanical Embolus Removal in Cerebral Ischemia (MERCI) and Multi MERCI Trials STROKE Shi, Z., Loh, Y., Walker, G., Duckwiler, G. R. 2010; 41 (5): 953-960

    Abstract

    The benefit of endovascular revascularization of patients with acute ischemic stroke with middle cerebral artery (MCA) secondary division (M2) occlusions as compared with MCA trunk (M1) occlusions is not known. In this analysis, we compared revascularization status and clinical outcomes in patients with angiographically confirmed MCA M1 versus isolated M2 occlusions treated with mechanical thrombectomy using the Merci Retriever devices.We retrospectively analyzed the pooled data of patients with MCA strokes from the Mechanical Embolus Removal in Cerebral Ischemia (MERCI) and Multi MERCI trials. Patient data were dichotomized into 2 groups: MCA M1 occlusions and isolated M2 occlusions. Baseline characteristics, revascularization rates, hemorrhage rates, complications, outcomes, and mortality were evaluated for both groups.Of 178 patients with MCA occlusion treated in the MERCI and Multi MERCI trials, 84.3% had M1 lesions and 15.7% had isolated M2 lesions. Patients with isolated M2 occlusions were revascularized at a higher rate, required a lower mean number of passes, and were associated with a trend toward shorter mean procedure time than patients with M1 occlusions. No statistically significant differences were found between M2 and M1 groups for symptomatic hemorrhage, clinically significant procedural adverse events, favorable 90-day outcome, or 90-day mortality, although in all instances, the M2 outcomes were numerically better than those in M1 subjects. In multivariate analysis, final revascularization was the strongest independent predictor of good outcome at 90 days.Patients with both MCA M1 occlusions and isolated M2 occlusions can achieve a relatively high rate of revascularization and favorable clinical outcomes after mechanical thrombectomy. In fact, patients with isolated M2 occlusions had a higher rate of revascularization, required fewer passes, and had no increased complications compared with patients with M1 occlusions.

    View details for DOI 10.1161/STROKEAHA.109.571943

    View details for Web of Science ID 000277064300021

    View details for PubMedID 20378867

  • Utility of Early MRI in the Diagnosis and Management of Acute Spontaneous Intracerebral Hemorrhage CEREBROVASCULAR DISEASES Wijman, C. A., Venkatasubramanian, C., Bruins, S., Fischbein, N., Schwartz, N. 2010; 30 (5): 456-463

    Abstract

    The optimal diagnostic evaluation for spontaneous intracerebral hemorrhage (ICH) remains controversial. In this retrospective study, we assessed the utility of early magnetic resonance imaging (MRI) in ICH diagnosis and management.Eighty-nine (72%) of 123 patients with spontaneous ICH underwent a brain CT and MRI within 30 days of ICH onset. Seventy patients with a mean age of 62 ± 15 years were included. A stroke neurologist and a general neurologist, each blinded to the final diagnosis, independently reviewed the admission data and the initial head CT and then assigned a presumed ICH cause under 1 of 9 categories. ICH cause was potentially modified after subsequent MRI review. The final 'gold standard' ICH etiology was determined after review of the complete medical record by an independent investigator. Change in diagnostic category and confidence and the potential impact on patient management were systematically recorded.Mean time to MRI was 3 ± 5 days. Final ICH diagnosis was hypertension or cerebral amyloid angiopathy (CAA) in 50% of patients. After MRI review the stroke neurologist changed diagnostic category in 14%, diagnostic confidence in an additional 23% and management in 20%, and the general neurologist did so in 19, 21 and 21% of patients, respectively. MRI yield was highest in ICH secondary to ischemic stroke, CAA, vascular malformations and neoplasms, and did not differ by age, history of hypertension, hematoma location or the presence of intraventricular hemorrhage.The results of this study suggest potential additive clinical benefit of early MRI in patients with spontaneous ICH.

    View details for DOI 10.1159/000316892

    View details for Web of Science ID 000282752200004

    View details for PubMedID 20733299

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

    Abstract

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

    View details for DOI 10.1016/j.jstrokecerebrovasdis.2008.11.016

    View details for Web of Science ID 000272114400002

    View details for PubMedID 19900642

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

    Abstract

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

    View details for DOI 10.1002/jmri.21908

    View details for Web of Science ID 000270522900007

    View details for PubMedID 19787719

  • Treatment and outcomes of acute basilar artery occlusion in the Basilar Artery International Cooperation Study (BASICS): a prospective registry study LANCET NEUROLOGY Schonewille, W. J., Wijman, C. A., Michel, P., Rueckert, C. M., Weimar, C., Mattle, H. P., Engelter, S. T., Tanne, D., Muir, K. W., Molina, C. A., Thijs, V., Audebert, H., Pfefferkorn, T., Szabo, K., Lindsberg, P. J., de Freitas, G., Kappelle, L. J., Algra, A. 2009; 8 (8): 724-730

    Abstract

    Treatment strategies for acute basilar artery occlusion (BAO) are based on case series and data that have been extrapolated from stroke intervention trials in other cerebrovascular territories, and information on the efficacy of different treatments in unselected patients with BAO is scarce. We therefore assessed outcomes and differences in treatment response after BAO.The Basilar Artery International Cooperation Study (BASICS) is a prospective, observational registry of consecutive patients who presented with an acute symptomatic and radiologically confirmed BAO between November 1, 2002, and October 1, 2007. Stroke severity at time of treatment was dichotomised as severe (coma, locked-in state, or tetraplegia) or mild to moderate (any deficit that was less than severe). Outcome was assessed at 1 month. Poor outcome was defined as a modified Rankin scale score of 4 or 5, or death. Patients were divided into three groups according to the treatment they received: antithrombotic treatment only (AT), which comprised antiplatelet drugs or systemic anticoagulation; primary intravenous thrombolysis (IVT), including subsequent intra-arterial thrombolysis; or intra-arterial therapy (IAT), which comprised thrombolysis, mechanical thrombectomy, stenting, or a combination of these approaches. Risk ratios (RR) for treatment effects were adjusted for age, the severity of neurological deficits at the time of treatment, time to treatment, prodromal minor stroke, location of the occlusion, and diabetes.619 patients were entered in the registry. 27 patients were excluded from the analyses because they did not receive AT, IVT, or IAT, and all had a poor outcome. Of the 592 patients who were analysed, 183 were treated with only AT, 121 with IVT, and 288 with IAT. Overall, 402 (68%) of the analysed patients had a poor outcome. No statistically significant superiority was found for any treatment strategy. Compared with outcome after AT, patients with a mild-to-moderate deficit (n=245) had about the same risk of poor outcome after IVT (adjusted RR 0.94, 95% CI 0.60-1.45) or after IAT (adjusted RR 1.29, 0.97-1.72) but had a worse outcome after IAT compared with IVT (adjusted RR 1.49, 1.00-2.23). Compared with AT, patients with a severe deficit (n=347) had a lower risk of poor outcome after IVT (adjusted RR 0.88, 0.76-1.01) or IAT (adjusted RR 0.94, 0.86-1.02), whereas outcomes were similar after treatment with IAT or IVT (adjusted RR 1.06, 0.91-1.22).Most patients in the BASICS registry received IAT. Our results do not support unequivocal superiority of IAT over IVT, and the efficacy of IAT versus IVT in patients with an acute BAO needs to be assessed in a randomised controlled trial.Department of Neurology, University Medical Center Utrecht.

    View details for DOI 10.1016/S1474-4422(09)70173-5

    View details for Web of Science ID 000268555800014

    View details for PubMedID 19577962

  • Tissue Plasminogen Activator Does Not Benefit Most Eligible Patients With Stroke ARCHIVES OF NEUROLOGY Lansberg, M. G., Schwartz, N. E. 2009; 66 (4): 540-541

    View details for Web of Science ID 000265104400025

    View details for PubMedID 19364946

  • 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

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

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

    View details for PubMedID 18793901

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

    View details for DOI 10.1136/bcr.2006.111773

    View details for PubMedID 21687235

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

    Abstract

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

    View details for DOI 10.1159/000202427

    View details for Web of Science ID 000264862500010

    View details for PubMedID 19218803

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

    Abstract

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

    View details for DOI 10.3174/ajnr.A1189

    View details for Web of Science ID 000260023800029

    View details for PubMedID 18635617

  • Mechanical thrombectomy for acute ischemic stroke - Final results of the multi MERCI trial STROKE Smith, W. S., Sung, G., Saver, J., Budzik, R., Duckwiler, G., Liebeskind, D. S., Lutsep, H. L., Rymer, M. M., Higashida, R. T., Starkman, S., Gobin, Y. P. 2008; 39 (4): 1205-1212

    Abstract

    Endovascular mechanical thrombectomy may be used during acute ischemic stroke due to large vessel intracranial occlusion. First-generation MERCI devices achieved recanalization rates of 48% and, when coupled with intraarterial thrombolytic drugs, recanalization rates of 60% have been reported. Enhancements in embolectomy device design may improve recanalization rates.Multi MERCI was an international, multicenter, prospective, single-arm trial of thrombectomy in patients with large vessel stroke treated within 8 hours of symptom onset. Patients with persistent large vessel occlusion after IV tissue plasminogen activator treatment were included. Once the newer generation (L5 Retriever) device became available, investigators were instructed to use the L5 Retriever to open vessels and could subsequently use older generation devices and/or intraarterial tissue plasminogen activator. Primary outcome was recanalization of the target vessel.One hundred sixty-four patients received thrombectomy and 131 were initially treated with the L5 Retriever. Mean age+/-SD was 68+/-16 years, and baseline median (interquartile range) National Institutes of Health Stroke Scale score was 19 (15 to 23). Treatment with the L5 Retriever resulted in successful recanalization in 75 of 131 (57.3%) treatable vessels and in 91 of 131 (69.5%) after adjunctive therapy (intraarterial tissue plasminogen activator, mechanical). Overall, favorable clinical outcomes (modified Rankin Scale 0 to 2) occurred in 36% and mortality was 34%; both outcomes were significantly related to vascular recanalization. Symptomatic intracerebral hemorrhage occurred in 16 patients (9.8%); 4 (2.4%) of these were parenchymal hematoma type II. Clinically significant procedural complications occurred in 9 (5.5%) patients.Higher rates of recanalization were associated with a newer generation thrombectomy device compared with first-generation devices, but these differences did not achieve statistical significance. Mortality trended lower and the proportion of good clinical outcomes trended higher, consistent with better recanalization.

    View details for DOI 10.1161/STROKEAHA.107.497115

    View details for Web of Science ID 000254632900025

    View details for PubMedID 18309168

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

    Abstract

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

    View details for Web of Science ID 000256319000004

    View details for PubMedID 18367036

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

    Abstract

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

    View details for PubMedID 18173943

  • The Basilar Artery International Cooperation Study (BASICS) INTERNATIONAL JOURNAL OF STROKE Schonewille, W. J., Wijman, C. A., Michel, P., Algra, A., Kappelle, L. J. 2007; 2 (3): 220-223

    Abstract

    Basilar artery occlusion is a rare cause of stroke with a high case fatality rate and an often poor clinical outcome among survivors. Our limited knowledge on the outcome in patients with basilar artery occlusion comes from small case series of selected patients.The main purpose of the registry is to collect preliminary data that will help direct the design of a future clinical treatment trial. The target number of patients included is 500.BASICS is a prospective, observational, multi-center, international registry of consecutive patients presenting with a symptomatic and radiologically confirmed basilar artery occlusion.From November 2002 until December 2006 data have been collected on 400 patients, from 42 centers in 12 countries. Most patients were treated with IA therapy (55%), followed by antithrombotics (29%) and IV thrombolysis (6%). The overall mortality was 45%.

    View details for Web of Science ID 000248857700013

    View details for PubMedID 18705948

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

    View details for PubMedID 17575019

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

    View details for Web of Science ID 000247143500018

    View details for PubMedID 17562941

  • Action at a distance: A lumbar spine tumor presenting as trigeminal neuralgia CLINICAL NEUROLOGY AND NEUROSURGERY Schwartz, N. E., Rosenberg, S., So, Y. T. 2006; 108 (8): 806-808

    Abstract

    Trigeminal neuralgia (TN) is often secondary to an underlying structural cause, frequently compression of the fifth nerve root by an ectatic artery. Here we describe a case of a 36-year-old woman with symptoms of TN who was found to have severe communicating hydrocephalus. Further investigation revealed a lumbar myxopapillary ependymoma, which in turn was responsible for the communicating hydrocephalus. An argument connecting these seemingly disparate findings is made. This unusual set of circumstances is an example of "action at a distance" in the nervous system, and reminds clinicians to think broadly about the various pathophysiologic mechanisms that can potentially underlie common disorders.

    View details for DOI 10.1016/j.clineuro.2006.02.001

    View details for Web of Science ID 000242708300019

    View details for PubMedID 16530323

  • Physiological activation of presynaptic metabotropic glutamate receptors increases intracellular calcium and glutamate release JOURNAL OF NEUROPHYSIOLOGY Schwartz, N. E., Alford, S. 2000; 84 (1): 415-427

    Abstract

    Activation of metabotropic glutamate receptors (mGluRs) has diverse effects on the functioning of vertebrate synapses. The cellular mechanisms that underlie these changes, however, are largely unknown. The role of presynaptic mGluRs in modulating Ca(2+) dynamics and regulating neurotransmitter release was investigated at the vestibulospinal-reticulospinal (VS-RS) synapse in the lamprey brain stem. Application of the specific Group I mGluRs antagonist 7-(hydroxyimino) cyclopropa[b]chromen-1a-carboxylate ethyl ester (CPCCOEt) reduced the amplitude of consecutive high-frequency evoked excitatory postsynaptic currents (EPSCs). A series of experiments using techniques of electrophysiology and calcium imaging were carried out to determine the cellular mechanisms by which this phenomenon occurs. Concentration-dependent increases in the pre- and postsynaptic [Ca(2+)](i) were seen with the application of mGluR agonists. Similarly, high-frequency stimulation of axons caused a Group I mGluR-dependent enhancement in presynaptic Ca(2+) transients. Application of mGluR agonist caused a depolarization of the presynaptic elements, while thapsigargin decreased the high-frequency stimulus- and agonist-induced rises in [Ca(2+)](i). These data suggest that both membrane depolarization and the release of Ca(2+) from intracellular stores potentially play a role in mGluR-induced Ca(2+) signaling. To determine the effect of this modulation of Ca(2+) dynamics on spontaneous glutamate release, miniature EPSCs were recorded from postsynaptic reticulospinal neurons. A potent Group I mGluR agonist, (S)-homoquisqualic acid, caused a large increase in the frequency of events. These results demonstrate the presence of presynaptic Group I mGluRs at the VS-RS synapse. Activation of these receptors leads to a rise in [Ca(2+)](i) and enhances the spontaneous and evoked release of glutamate. Taken together, these studies highlight the importance of synaptic activation of these facilitatory autoreceptors in both short-term plasticity and synaptic transmission.

    View details for Web of Science ID 000088215000038

    View details for PubMedID 10899215

  • Modulation of pre- and postsynaptic calcium dynamics by ionotropic glutamate receptors at a plastic synapse JOURNAL OF NEUROPHYSIOLOGY Schwartz, N. E., Alford, S. 1998; 79 (4): 2191-2203

    Abstract

    This study was conducted to assess the role of ionotropic glutamate receptors in the modulation of calcium dynamics on both sides of a vertebrate plastic synapse. Retrograde labeling of neuronal elements with high-affinity calcium-sensitive dyes was used in conjunction with confocal imaging techniques in an in vitro lamprey brain stem preparation. A prolonged calcium transient was measured both pre- and postsynaptically in response to a period of high-frequency ("tetanic") stimulation to the vestibulospinal-reticulospinal synapse. The ionotropic glutamate receptor antagonists 6-cyano-7-nitroquinoxaline-2,3-dione (10 microM) and D,L-2-amino-5-phosphonopentanoate (D,L-AP5; 100 microM) reduced the calcium signal in both compartments of the synapse. The presynaptic D,L-AP5-sensitive component was enhanced markedly by the removal of Mg2+ from the superfusate. Increasing the extracellular stimulus intensity progressively augmented the presynaptic calcium signal, suggesting the recruitment of excitatory axo-axonic inputs onto these fibers. Further, the presence of an excitatory amino acid-mediated presynaptic potential underlying a component of the Ca2+ signal was demonstrated by electrophysiological recordings from vestibulospinal axons. Bath application of agonist, in the presence of tetrodotoxin (1 microM), confirmed the existence of N-methyl-D-aspartate receptors at the presynaptic element capable of modulating calcium levels. The postsynaptic Ca2+ response, which is known to be necessary for long-term potentiation (LTP) induction at this synapse, was localized to areas of the dendritic tree that correlated with the location of known synaptic inputs; thus the synaptically activated rise in postsynaptic calcium may confer the synapse specificity of LTP induction previously demonstrated. In summary, we have demonstrated the existence of physiologically activated presynaptic ionotropic glutamate receptors that are capable of modulating levels of intracellular calcium and have highlighted the importance of receptor-mediated increases in postsynaptic calcium for neuronal plasticity in the lamprey.

    View details for Web of Science ID 000073273700049

    View details for PubMedID 9535978

Conference Proceedings


  • Mri Based Tia Triage Study Wolford, C., Mlynash, M., Schwartz, N. E., Purushotham, A., Lansberg, M., Kemp, S., Albers, G. W., Olivot, J. LIPPINCOTT WILLIAMS & WILKINS. 2011: E210-E210
  • TIA Clinic Triage Strategy Reduces the Cost of TIA Evaluation Mlynash, M., Castle, J., Olivot, J., Wolford, C., Schwartz, N. E., Lansberg, M. G., Edwards, G., Kemp, S., Albers, G. W. LIPPINCOTT WILLIAMS & WILKINS. 2011: E250-E250
  • Diagnostic Accuracy of MRI in Spontaneous Intra-cerebral Hemorrhage (DASH): Initial Results Wijman, C. A., Snider, R. W., Venkatasubramanian, C., Caulfield, A. F., Buckwalter, M., Eyngorn, I., Fischbein, N., Gean, A., Schwartz, N., Lansberg, M., Mlynash, M., Kemp, S., Thai, D., Narayana, R. K., Marks, M., Bammer, R., Moseley, M., Albers, G. W. LIPPINCOTT WILLIAMS & WILKINS. 2010: E210-E211
  • Factors Predicting the Presence of Acute Ischemic Lesions on Diffusion Weighted in the Stanford TIA Study (Two Aces) Olivot, J. M., Wolford, C., Mlynash, M., Castle, J., Lansberg, M., Schwartz, N., Kemp, S., Albers, G. W. LIPPINCOTT WILLIAMS & WILKINS. 2010: E273-E273
  • SENSE Diffusion-weighted Imaging Improves Diagnostic Sensitivity in Acute Ischemic Stroke Schwartz, N. E., Newbould, R. D., Skare, S., Zaharchuk, G., Mlynash, M., Olivot, J., Lansberg, M. G., Eyngorn, I., Thai, D., Albers, G. W., Bammer, R. LIPPINCOTT WILLIAMS & WILKINS. 2009: E115-E115

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