About

Lawrence R. Wechsler, MD, is an Adjunct Professor of Neurology in the Department of Neurology at the University of Pennsylvania's Perelman School of Medicine. His contact information includes an office at Pennsylvania Hospital and an email address Lawrence.Wechsler@Pennmedicine.upenn.edu. His educational background includes a Bachelor of Arts in Biology from Harvard College in 1974 and an MD from the University of Pennsylvania in 1978. His professional focus is on neurology, with a particular emphasis on stroke and cerebrovascular diseases, as evidenced by his numerous publications on neuroimaging, stroke recovery, and neurovascular plasticity. His contributions include research on the neuroimaging of acute stroke, the molecular and cellular mechanisms underlying stroke recovery, and the clinical management of stroke patients.

Research topics

• Internal medicine
• Medicine
• Cardiology
• Surgery

Selected publications

• Cerebral Edema in Patients With Large Ischemic Core After Thrombectomy: A Secondary Analysis of SELECT2 Randomized Trial

  Stroke · 2026-03-30 · 1 citations

  article

  BACKGROUND: Cerebral edema is a life-threatening complication of ischemic stroke that disproportionally affects patients with large established infarction. We assessed whether endovascular thrombectomy (EVT) reduces or exacerbates edema development, and the association between edema with short-term and long-term outcomes in this high-risk population. METHODS: In this prespecified secondary analysis of the SELECT2 randomized clinical trial (Randomized Controlled Trial to Optimize Patient’s Selection for Endovascular Treatment in Acute Ischemic Stroke), which tested the efficacy and safety of EVT versus medical management in adult patients with acute anterior circulation large vessel occlusion presenting with large ischemic core (defined as Alberta Stroke Program Early Computed Tomography Score of 3–5 or core volume ≥50 mL on computed tomography perfusion or diffusion magnetic resonance imaging), we assessed maximum midline shift (MLS) within 7 days of randomization between treatment groups using a probabilistic index model. RESULTS: After exclusion of 10 patients who underwent hemicraniectomy before follow-up imaging, 342 patients were analyzed. The median MLS on follow-up magnetic resonance imaging or computed tomography was 6.39 mm (interquartile range, 0–12.0) in the EVT and 4.18 mm (interquartile range, 0–9.66) in medical management patients ( P =0.021). EVT was independently associated with greater MLS (adjusted odds ratio, 1.63 [95% CI, 1.25–2.12]; P =0.0027) after adjusting for age and core volume. There was no interaction between EVT and core volume at presentation on the association with MLS ( P >0.79). MLS was associated with the development of early neurological worsening (adjusted odds ratio, 1.15 [95% CI, 1.07–1.23]; P <0.001), and a lower likelihood of long-term functional improvement assessed on modified Rankin Scale score at 90 days (adjusted odds ratio, 0.96 [95% CI, 0.93–0.98]; P =0.0029). On mediation analysis, cerebral edema reduced the effect of EVT on functional outcome by 10.6%. CONCLUSIONS: Despite overall clinical benefit, EVT in patients presenting with a large ischemic core was associated with increased cerebral edema, which, in turn, was associated with early neurological worsening and worse functional outcome at 90 days. Early recognition and individualized treatment to prevent secondary injury from cerebral edema in this population are warranted. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03876457.

  PublisherDOI

• Association of Ischemic Core Hypodensity With Thrombectomy Treatment Effect in Large Core Stroke: A Secondary Analysis of the SELECT2 Randomized Controlled Trial

  Stroke · 2025-03-28 · 17 citations

  article

  BACKGROUND: We aimed to determine whether extensive severe computed tomography (CT) hypodensity, representing blood-brain barrier injury, would be associated with a reduced benefit of endovascular therapy (EVT) in patients presenting with large core stroke. METHODS: This study is an exploratory analysis of SELECT2 (Randomized Controlled Trial to Optimize Patient’s Selection for Endovascular Treatment in Acute Ischemic Stroke), a randomized controlled trial of EVT versus medical management in patients with large ischemic core who presented to 31 comprehensive stroke centers across the United States, Canada, Europe, Australia, and New Zealand. Visible CT hypodensity was outlined, and a threshold of severe CT hypodensity was defined as the lower 99% CI of contralateral thalamic gray matter in Hounsfield units (HU). The association between the volume of severe CT hypodensity and modified Rankin Scale (mRS) score of 0 to 3 was evaluated using logistic regression models, with adjustment for age, National Institutes of Health Stroke Scale, total noncontrast CT core volume, and a volume-by-treatment interaction. The relationship between severe CT hypodensity volume and the probability of an mRS score of 0 to 3 was used to select clinically relevant volume cut points for further evaluation. The treatment effect of EVT versus medical management on independent ambulation and hemicraniectomy was assessed in 2 subgroups based on these volume cut points. RESULTS: In 322 patients, the median CT density was 31 HU (interquartile range, 28–34). The selected threshold of severe CT hypodensity was 26 HU. The volume of ischemic core ≤26 HU (per 1 mL increase) was associated with lower odds of mRS score of 0 to 3 after EVT (adjusted odds ratio [aOR], 0.96 [95% CI, 0.94–0.99]), but not medical management (aOR, 1.01 [95% CI, 0.98–1.03]; P interaction<0.01). In 101 patients with ≥26 mL of severe CT hypodensity, EVT, compared with medical management, was not associated with mRS score of 0 to 3 (aOR, 0.98 [95% CI, 0.33–2.88]) and was associated with hemicraniectomy (≥26 mL: aOR, 3.45 [95% CI, 1.09–10.86] versus <26 mL: aOR, 0.74 [95% CI, 0.31–1.75]; P interaction=0.03), whereas among 221 patients with <26 mL of severe hypodensity EVT was associated with mRS score of 0 to 3 (aOR, 7.20 [95% CI, 3.55–15.47]; P interaction<0.01). CONCLUSIONS: Severe hypodensity within large ischemic regions modifies the thrombectomy treatment effect and increases the likelihood of hemicraniectomy, independent of lesion volume. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03876457.

  PublisherDOI

• General vs Nongeneral Anesthesia for Endovascular Thrombectomy in Patients With Large Core Strokes

  Neurology · 2025-06-26 · 3 citations

  article

  BACKGROUND AND OBJECTIVES: The association of anesthesia approach during endovascular thrombectomy (EVT) with clinical outcomes in large strokes is unexplored. We aimed to evaluate whether general anesthesia (GA), compared with non-GA, was associated with better functional outcomes in the SELECT2 trial. METHODS: In a prespecified secondary analysis of the SELECT2 trial that enrolled patients with large strokes on noncontrast CT (Alberta Stroke Program Early CT Score [ASPECTS] 3-5), CT perfusion/MRI (core volume ≥50 mL), or both, functional outcomes were compared in EVT-treated patients who received GA or non-GA and whether this association was modified by stroke severity (NIH Stroke Scale score), ischemic injury estimates, and collateral status was evaluated. The primary outcome was 90-day functional status (ordinal modified Rankin Scale [mRS]). Secondary outcomes were functional independence (mRS scores 0-2), independent ambulation (mRS scores 0-3), complete dependence or death (mRS scores 5-6), and mortality. RESULTS: -interaction = 0.77 and 0.89, respectively). DISCUSSION: In patients with large core strokes randomized in SELECT2, EVT outcomes did not differ significantly based on anesthesia approach (GA or non-GA) without heterogeneity across stroke severity and size. While GA was associated with higher SBP variability and lower minimum SBP, this did not modify GA association with functional outcomes. While allocation to anesthesia approach was nonrandomized, our findings suggest that optimizing institutional protocols for preferred anesthesia technique, whether GA or non-GA, may enhance EVT procedural outcomes. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov ID: NCT03876457. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that in patients presenting within 24 hours with large vessel occlusion strokes undergoing EVT, the 90-day mRS score is comparable in those with or without GA.

  PublisherDOI

• Endovascular thrombectomy plus medical care versus medical care alone for large ischaemic stroke: 1-year outcomes of the SELECT2 trial

  The Lancet · 2024-02-01 · 68 citations

  article
  PublisherDOI

• Provider Impressions of Inpatient Teleneurology Consultation

  Neurology Clinical Practice · 2024-04-18 · 3 citations

  articleOpen access

  Background and Objectives: Teleneurology usage has increased during the severe acute respiratory syndrome coronavirus 2 pandemic. However, studies evaluating physician impressions of inpatient teleneurology are limited. We implemented a quality improvement initiative to evaluate neurologists' impression following individual inpatient teleneurology consultation at a satellite hospital of a large academic center with no in-person neurology coverage. Methods: A REDCap survey link was embedded within templates used by neurologists for documentation of inpatient consultations to be completed immediately after encounters. All teleneurology encounters with completed surveys at a single satellite hospital of the University of Pennsylvania Health System Neurology Department between May 10, 2021, and August 14, 2022, were included. Individual patient-level and encounter-level data were extracted from the medical record. Results: A total of 374 surveys (response rate of 54.05%) were completed by 19 neurologists; 341 questionnaires were included in the analysis. Seven neurologists who specialized as neurohospitalists completed 231 surveys (67.74% of total surveys completed), while 12 non-neurohospitalists completed 110 (32.36%). The history obtained was rated as worse (14%) or the same (86%) as an in-person consult; none reported the history as better than nonteleneurology encounters. The physician-patient relationship was poor or fair in 25% of the encounters and good or excellent in 75% of visits. The overall experience was judged to be worse than in-person consultation in 32% of encounters, the same in 66%, and better in 2%. Fifty-one percent of providers responded that there were elements of the neurologic examination that might have changed their assessment and plan of care if performed in-person. Encounters with peripheral or neuromuscular-related chief complaints had the most inadequate examinations and worse overall experiences, while the most positive impressions of these clinical experiences were observed among seizure-related chief complaints. Discussion: Determining best practices for inpatient teleneurology should consider the patient chief complaint to use teleneurology in scenarios with the highest likelihood of a positive experience. Further efforts should be made to the patient experience and to improve the remote examination to enhance the applicability of teleneurology to the full spectrum of inpatient neurologic consultations.

  PublisherOA PDFDOI

• Clinical relevance of intracranial hemorrhage after thrombectomy versus medical management for large core infarct: a secondary analysis of the SELECT2 randomized trial

  Journal of NeuroInterventional Surgery · 2024-03-12 · 8 citations

  article

  Background The incidence of intracerebral hemorrhage (ICH) and its effect on the outcomes after endovascular thrombectomy (EVT) for patients with large core infarcts have not been well-characterized. Methods SELECT2 trial follow-up imaging was evaluated using the Heidelberg Bleeding Classification (HBC) to define hemorrhage grade. The association of ICH with clinical outcomes and treatment effect was examined. Results Of 351 included patients, 194 (55%) and 189 (54%) demonstrated intracranial and intracerebral hemorrhage, respectively, with a higher incidence in EVT (134 (75%) and 130 (73%)) versus medical management (MM) (60 (35%) and 59 (34%), both P<0.001). Hemorrhagic infarction type 1 (HBC=1a) and type 2 (HBC=1b) accounted for 93% of all hemorrhages. Parenchymal hematoma (PH) type 1 (HBC=1c) and type 2 (HBC=2) were observed in 1 (0.6%) EVT-treated and 4 (2.2%) MM patients. Symptomatic ICH (sICH) (SITS-MOST definition) was seen in 0.6% EVT patients and 1.2% MM patients. No trend for ICH with core volumes (P=0.10) or Alberta Stroke Program Early CT Score (ASPECTS) (P=0.74) was observed. Among EVT patients, the presence of any ICH did not worsen clinical outcome (modified Rankin Scale (mRS) at 90 days: 4 (3–6) vs 4 (3–6); adjusted generalized OR 1.00, 95% CI 0.68 to 1.47, P>0.99) or modify EVT treatment effect (P interaction =0.77). Conclusions ICH was present in 75% of the EVT population, but PH or sICH were infrequent. The presence of any ICH did not worsen functional outcomes or modify EVT treatment effect at 90-day follow-up. The high rate of hemorrhages overall still represents an opportunity for adjunctive therapies in EVT patients with a large ischemic core.

  PublisherDOI

• Abstract 40: Relationship of Collateral Status With Clinical Outcomes in Endovascular Thrombectomy for Large Core Stroke: <i>A SELECT2 Subanalysis</i>

  Stroke · 2024-02-01

  article

  Background: Previous studies demonstrating association of collateral status with clinical outcomes after endovascular thrombectomy (EVT) excluded patients with large core infarcts. We analyzed the association of collateral status with clinical outcomes and EVT treatment effect in SELECT2. Methods: In SELECT2, a central core lab adjudicated CT-angiographic collateral status using collateral scores (CS) by Tan et al. Patients were stratified based on CS into poor (CS 0-1) vs good (CS 2-3) collaterals. The primary outcome was the distribution of modified Rankin Scale score at 90-day follow-up. Models were adjusted for core volume, ASPECTS in addition to age, stroke severity and time to randomization. Results: Of 352 patients, 180 received EVT. Median collateral status was 2(IQR 1-2). Patients presenting &lt;6h after last known well (LKW) (n=100) had poorer collaterals than those presenting at 6-24 hours (n=252), median 1 (1-2) vs 2 (1-2), p&lt;0.001. Collateral status inversely correlated with CTP core volume (Rho=-0.32, p&lt;0.0001), but not with CT ASPECTS (Rho=0.07, p=0.16). Overall, point estimates favored EVT in patients with poor (CS 0-1) [aGenOR: 1.32, 95% CI: 0.98-1.79, p=0.068] and good (CS 2-3) collaterals [aGenOR: 1.97, 95% CI: 1.43-2.72, p&lt;0.001] without significant heterogeneity [p-interaction=0.094]. However, in the earlier 0-6h time window, there was evidence of treatment effect hetermogeneity with a larger treatment effect when good collaterals were present [aGenOR: 4.10, 95% CI: 1.81-9.29] and an absent treatment effect when only poor collaterals were observed [aGenOR: 1.26, 95% CI: 0.79-1.99], p-interaction=0.023. In the late time window, (6-12h), the EVT treatment effect did not differ significantly between poor collaterals (aGenOR: 1.35, 95% CI: 0.91-2.01) and good collaterals (aGenOR: 1.78, 95% CI: 1.24-2.56, p-interaction=0.50). Conclusion: Collateral status was worse in large core patients presenting in early (&lt;6 hours) window; and correlated with ischemic core volume but not ASPECTS. Collaterals status modified EVT treatment effect in the early but not the late time window, in which both good and poor collaterals still benefited from EVT. Clinicaltrials.gov registration: NCT03876457

  PublisherDOI

• Abstract WMP91: Ischemic Injury Extent on Different Imaging Modalities and Its Association With Endovascular Thrombectomy Outcomes for Large Core Stroke: <i>A SELECT2 Imaging Analysis</i>

  Stroke · 2024-02-01

  article

  Introduction: The association of extent of ischemic injury on various imaging modalities and EVT efficacy and safety in patients with large ischemic core remains unexplored. We analyzed ischemic injury estimates on structural and perfusion imaging modalities and their association with time and EVT treatment effect. Methods: In SELECT2, all patients received non contrast CT and CT perfusion/MR diffusion. Baseline ischemic injury was estimated using ASPECTS, CTP/MRI with RAPID processing, manual delineation of CT hypodensity and composite core [the larger of the CT hypodensity and CTP/MRI core volumes], Figure 1A. We assessed how these estimates compared to one another, which correlated best with the outcomes and described EVT treatment effect across their strata. Results: Of 352 patients, 16 were excluded for missing mRS/imaging data. 170/336 (51%) received EVT. The median (IQR) CT-ASPECTS was 4 (3-5), CT-hypodensity 86 (49-114) mL, CTP/MRI core 73 mL (46-107). 60% had CT hypodensity &gt; CTP/MRI core volume. CTP core was larger in 81% within 0-3 hours that inverted to 86% patients with larger CT hypodensity in 21-24 hours of LKW [Figure 1B]. Composite core (101 [72-138] ml) had best fit for mRS (Bayesian Information Criteria for mRS shift: ASPECTS - 448, CT hypodensity - 443, CTP core - 434, Composite core - 429 with lower the better). Treatment effect estimates favored EVT across strata (≥70 ml, ≥100ml &amp; ≥150 ml) for CT hypodensity, CTP/MRI core and composite core as well as ASPECTS 3,4 and 5. For a given volume probability of independent ambulation with EVT decreased with age and time to reperfusion. Conclusions: CT perfusion and CT hypodensity were complementary and most prognostic when used together, in conjunction with age and time to reperfusion. Thrombectomy benefit was preserved across ischemic volumes and ASPECTS. These findings can assist clinicians in assessing the likely outcome of thrombectomy for individual patients. Trial Registration: NCT03876457

  PublisherDOI

• Abstract 156: Cerebral Edema in Patients Presenting With Large Ischemic Core Undergoing Thrombectomy versus Medical Therapy: Secondary Analysis of SELECT 2 Trial

  Stroke · 2024-02-01 · 1 citations

  article

  Background: Endovascular thrombectomy (EVT) improves long-term outcome in patients presenting with large ischemic core but is associated with early neurological worsening (ENW), potentially related to cerebral edema post-reperfusion. We investigated whether EVT increases edema development, and the relationship between edema and ENW in a secondary analysis of the SELECT2 trial. Methods: SELECT 2 tested the efficacy and safety of EVT versus medical therapy in patients with large ischemic core (ASPECTS 3-5 or core volume ≥50ml on CT Perfusion[CTP]/MR diffusion). Core volume was defined as the larger of the CTP-CBF relative cerebral blood flow &lt;30% or the visible hypodensity on non-contrast CT. Cerebral edema was measured as the maximum midline shift (MLS) on 24h follow-up MRI or CT. ENW was defined as &gt;=4 point worsening in NIHSS at 24h compared to baseline. Probabilistic index model was used in multivariable analyses to assess ≥1 point improvement on modified Rankin Scale at 90-days. Results: After exclusion of 10 patients with hemicraniectomy, the median MLS in 327 patients was 2.75mm (IQR 0-5.85) in EVT and 0mm (IQR 0-4.02) in control patients (p=0.005). EVT was independently associated with greater MLS (adjusted odds ratio, aOR 1.50, 95%CI 1.17-1.92, p=0.0012) after adjusting for age and core volume. There was no interaction between EVT and core volume on the association with MLS (p&gt;0.79). Patient with ENW had greater MLS (5.05mm [IQR2.06-10.2] vs 0mm [IQR0-3.94, p&lt;0.001]) MLS was associated with development of ENW (aOR 1.22, 95%CI 1.13-1.32, p&lt;0.001), and lower likelihood of long-term functional improvement (adjusted generalized OR 0.96, 95%CI 0.92-0.97, p&lt;0.001, adjusted for core volume, EVT, age and baseline NIHSS). Sensitivity analysis testing alternative definitions of core volume (CTP core volume only and Hypodensity on non-contrast only) showed concordant results. Conclusion: In patients presenting with large ischemic core, EVT was associated with increased cerebral edema at 24h which, in turn, was associated with ENW. Despite overall benefit of EVT, EVT-related edema is independently associated with neurological deterioration and long-term disability and is therefore a potential treatment target to improve EVT outcomes.

  PublisherDOI

• Telemedicine quality and outcomes in stroke: A scientific statement for healthcare professionals from the American Heart Association/American Stroke Association

  UNC Libraries · 2024-04-18 · 1 citations

  articleOpen access

  Purpose - Telestroke is one of the most frequently used and rapidly expanding applications of telemedicine, delivering much-needed stroke expertise to hospitals and patients. This document reviews the current status of telestroke and suggests measures for ongoing quality and outcome monitoring to improve performance and to enhance delivery of care. Methods - A literature search was undertaken to examine the current status of telestroke and relevant quality indicators. The members of the writing committee contributed to the review of specific quality and outcome measures with specific suggestions for metrics in telestroke networks. The drafts were circulated and revised by all committee members, and suggestions were discussed for consensus. Results - Models of telestroke and the role of telestroke in stroke systems of care are reviewed. A brief description of the science of quality monitoring and prior experience in quality measures for stroke is provided. Process measures, outcomes, tissue-type plasminogen activator use, patient and provider satisfaction, and telestroke technology are reviewed, and suggestions are provided for quality metrics. Additional topics include licensing, credentialing, training, and documentation.

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Recent grants

• Network of Excellence in Neuroscience Clinical Trials (University of Pittsburgh CRS)

  NIH · $2.8M · 2018–2028

Frequent coauthors

• Randall T. Higashida

  384 shared

• Gregory W. Albers

  Stanford Medicine

  359 shared

• Helmut Schumacher

  Cooper Medical School of Rowan University

  320 shared

• Anthony J. Furlan

  Cleveland University

  275 shared

• Marc I. Chimowitz

  Medical University of South Carolina

  246 shared

• Colin P. Derdeyn

  243 shared

• Cathy Sila

  Cleveland University

  238 shared

• Seemant Chaturvedi

  University of Maryland, Baltimore

  234 shared

Labs

• Wechsler LaboratoryPI