About

Steven R. Messe, MD, is the Ruth M and Tristram C Colket, Jr President's Distinguished Professor and Director of the vascular neurology fellowship at the Hospital of the University of Pennsylvania within the Department of Neurology. He specializes in caring for inpatients with acute stroke and neurologic illnesses requiring critical care, and is a member of the intraoperative monitoring team providing neurophysiologic testing to surgical patients at risk of brain, spinal cord, or nerve injury. His outpatient practice primarily involves patients with stroke and cerebrovascular disease. Dr. Messe has performed research on various topics including the risk of carotid endarterectomy, tPA dosing errors, management of patients with stroke and patent foramen ovale (PFO), and neurologic outcomes from surgical and interventional procedures. His research expertise encompasses stroke management, neurocritical care, and the development of standardized neurological endpoints for cardiovascular clinical trials. He has contributed to the understanding of stroke outcomes, neuroprotection strategies in aortic surgery, and the implications of patent foramen ovale in stroke, among other areas.

Research topics

• Cardiology
• Medicine
• Internal medicine
• Surgery

Selected publications

• 26-A-13780-ACC THROMBOEMBOLIC RISK AND THE RISK OF STROKE AND ACUTE BRAIN INJURY AFTER TAVR: A PATIENT-LEVEL POOLED ANALYSIS

  Journal of the American College of Cardiology · 2026-03-27

  article
  PublisherDOI

• Intracerebral Hemorrhage Outcomes After Reversal of Subtherapeutic Warfarin: Analysis of Data From GWTG-Stroke

  Stroke · 2025-09-17

  article

  BACKGROUND: Current guidelines recommend reversal of warfarin anticoagulation in intracranial hemorrhages. The benefit of reversing subtherapeutic warfarin anticoagulation in acute spontaneous intracerebral hemorrhage is uncertain. METHODS: An observational cohort from the entire Get With The Guidelines Stroke registry between January 2015 and January 2022 was used to determine the association of reversal with outcomes for subtherapeutic anticoagulation (international normalized ratio, 1.5-1.9). Inclusion required current warfarin use. Exclusions included thrombolytics, direct oral anticoagulants, transferring out, or leaving against medical advice. The prespecified primary outcome was the modified Rankin Scale (mRS) score of 0 to 3 at discharge. Logistic regression was used to assess the association between reversal and the mRS score of 0 to 3. Propensity scores with overlap weighting were used to control treatment selection bias. Information on the dose and timing of reversal agents was unknown. RESULTS: Initial cohort 239 681 patients, 18 419 on warfarin. Excluded were 15 712 with an international normalized ratio ≤1.5, ≥1.9, or missing, and 701 missing mRS. Final cohort 1868 (mean age 73, 42% female). Reversal occurred in 894 (47.9%). Primary outcome occurred in 188/894 (21.0%) versus 225/974 (23.1%) with reversal versus without (adjusted odds ratio, 0.80 [95% CI, 0.63-1.005]). Ordinal analysis showed higher odds of mRS score of 0 to 4 versus 5 to 6 (52.7% versus 42.5% [adjusted odds ratio, 1.21 [1.001-1.48]). Outcomes not requiring mRS were analyzed among 2569 patients. Mortality or discharge to hospice was lower 30.6% versus 41.5% (adjusted odds ratio, 0.75 [95% CI, 0.63-0.89]). Hospital length of stay was longer (median, 6 versus 4 days; adjusted risk ratio, 1.25 [95% CI, 1.13-1.37]). There was no difference in venous thromboembolism (2.9% versus 2.3%; adjusted odds ratio, 1.47 [0.88-2.46]). CONCLUSIONS: Reversal of subtherapeutic warfarin with acute spontaneous intracerebral hemorrhage and international normalized ratio 1.5 to 1.9 was not associated with improvement in functional outcome based on discharge mRS score of 0 to 3 versus 4 to 6. Patients receiving reversal agents had 25% lower odds of dying in hospital or being discharged to hospice, but had a longer hospital stay. This exploratory data has limitations inherent to not being a randomized controlled trial.

  PublisherDOI

• Racial Disparities in Mental Health Among Stroke Survivors in the REDUCE Study (P1-13.014)

  Neurology · 2025-04-07

  article

  To compare mental health status between Black and Non-Black patients recovering from stroke.

  PublisherDOI

• Abstract WMP4: Intravenous Thrombolysis in Patients on Direct Oral Anticoagulants: Analysis of the Get With Guidelines Stroke Registry

  Stroke · 2025-01-30

  article

  Background and Purpose: Intravenous thrombolysis for acute ischemic stroke (AIS) is a proven effective treatment. Whether thrombolysis in AIS patients with recent direct oral anticoagulant (DOAC) use is safe and efficacious is not well established. We aimed to compare outcomes of patients with AIS and recent DOAC use who received thrombolysis to those otherwise eligible but excluded from thrombolysis due to recent DOAC use. Methods: This study included patients entered into the Get with the Guidelines (GWTG) registry with a diagnosis of AIS who presented to an acute care facility within 4.5 hours from last known normal, used a DOAC within 7 days before hospital arrival, and either: 1) received intravenous thrombolysis, OR 2) were excluded from thrombolysis with coagulopathy being the only reason for exclusion. We used univariate and adjusted binary logistic regression models with clustering by site to compare the two groups’ functional status (ambulation on discharge and discharge disposition) and reported rates of safety outcomes in the thrombolysis group (symptomatic intracranial hemorrhage, extracranial hemorrhage, and death). Results: The study sample included 48,907 AIS patients using a DOAC; 4,702 received thrombolysis and 44,205 did not. The mean age was 75.1 years and 50.5% were men. In adjusted logistic regression models, patients with recent DOAC use receiving thrombolysis were more likely to ambulate independently at discharge (OR 1.35, 95% CI 1.21-1.50) and to be discharged home (OR 1.33 95% CI 1.22-1.46). The rate of symptomatic intracranial hemorrhage with intravenous thrombolysis in patients with recent DOAC use was 3.5% (95% CI 3.0%-4.1%). Conclusions: In this analysis of the GWTG registry, intravenous thrombolysis was associated with improved functional outcomes in patients with recent DOAC use and appeared safe. Given the limitations of our real-world registry analysis, these findings require validation by prospective trials.

  PublisherDOI

• Expected Surgical Risk and the Risk of Stroke and Brain Injury After Transcatheter Aortic Valve Replacement: A Patient-Level Pooled Analysis

  Journal of the Society for Cardiovascular Angiography & Interventions · 2025-08-12

  articleOpen access1st authorCorresponding

  Background: The 30-day Society of Thoracic Surgeons Predicted Risk of Mortality (STS-PROM) has been used to risk-stratify patients undergoing transcatheter aortic valve replacement (TAVR). Whether surgical mortality risk predicts stroke and neurocognitive outcomes following TAVR is unknown. We evaluated the association between STS-PROM and clinical outcomes, including stroke, acute brain injury on diffusion-weighted magnetic resonance imaging (DW-MRI), and cognitive decline in patients undergoing TAVR. Methods: Patient-level data were pooled from 4 prospective trials: (1) DEFLECT III (N = 87), (2) NeuroTAVR (N = 44), (3) REFLECT I (N = 214), and (4) REFLECT II (N = 258). All studies included patients undergoing TAVR with a protocol-mandated predischarge DW-MRI and serial cognitive and neurologic assessments. All patients were evaluated by a board-certified neurologist at baseline, postprocedure, and 30 days. Clinical outcomes, including stroke, cognitive decline (Montreal Cognitive Assessment score), death, myocardial infarction, vascular, and bleeding complications were adjudicated by the same clinical events committee. Imaging analysis was performed by a single core laboratory using identical methods. The DW-MRI measures included total lesion number, individual lesion volume, and total lesion volume. Outcomes were compared between low (STS <4), intermediate (STS 4-8), and high (STS >8) risk groups. Results: In total, 537 of 603 patients with DW-MRI and complete STS assessment undergoing transfemoral TAVR were included in this pooled analysis, of which 253 (47%) were low risk, 198 (37%) intermediate risk, and 86 (16%) high risk patients. At 30 days, high risk patients had higher rates of all-cause and cardiovascular mortality, myocardial infarction, acute kidney injury, bleeding, and vascular complications. Rates of stroke, disabling stroke, DW-MRI measures of brain injury, and cognitive decline were similar across risk categories. Conclusions: This pooled analysis demonstrates that the STS score does not predict stroke, cognitive decline, or acute brain injury after TAVR.

  PublisherDOI

• Validation of a Novel Magnetic Resonance Imaging Biomarker of Infarct Severity to Predict Functional Outcome After Endovascular Thrombectomy

  Stroke · 2025-01-30 · 4 citations

  articleSenior author

  BACKGROUND: Endovascular thrombectomy (EVT) dramatically improves clinical outcomes, but the final infarct volume (FIV) on magnetic resonance imaging only accounts for a minority of the treatment effect. An imaging biomarker that more strongly correlates with post-EVT functional outcome would be helpful for clinical prognosis and serve as a surrogate outcome measure in trials of EVT-adjuvant therapies. Here, we aimed to validate a novel magnetic resonance imaging–based metric, infarct density, which leverages post-EVT apparent diffusion coefficient as a marker of infarct severity. METHODS: A retrospective cohort was derived from a single-center prospective EVT registry. Consecutive patients treated with EVT for anterior circulation large vessel occlusion were included from 2018 to 2019 who achieved successful reperfusion (modified Thrombolysis in Cerebral Infarction ≥2b). Magnetic resonance imaging was performed 12 to 48 hours post-EVT and processed via RAPID to quantify FIV using the apparent diffusion coefficient &lt;620 threshold. Lesion volume was also collected using an apparent diffusion coefficient &lt;470 threshold, and infarct density was calculated as: (volume &lt;470/volume &lt;620)×100%. Good outcome was defined as ≤2 on the 90-day modified Rankin Scale. Multivariable logistic regression models quantified the association between clinical/imaging variables and outcome. Receiver operating characteristic analysis quantified model classification performance. RESULTS: Of 319 patients treated with EVT, 272 met inclusion criteria. The mean age was 69±13 years, 41% were female, and 62% achieved a good outcome. After adjusting for clinical and radiographic factors, FIV (adjusted odds ratio, 0.99 per 1 mL [95% CI, 0.98–1.00]; P =0.03) and infarct density (adjusted odds ratio, 0.95 per 1% [95% CI, 0.94–0.97]; P &lt;0.001) were both independently inversely associated with good outcome. The final model incorporating both FIV and infarct density achieved excellent classification performance (area under the curve, 0.87 [95% CI, 0.83–0.91]). Removing infarct density from the model diminished its performance (area under the curve, 0.83 [95% CI, 0.78–0.88]; P =0.01). CONCLUSIONS: Apparent diffusion coefficient–based infarct density after EVT is independently associated with long‐term outcome and provides greater prognostic information than FIV alone. Post-EVT infarct density may be useful in clinical care and as a surrogate outcome measure in trials of EVT-adjuvant therapies.

  PublisherDOI

• Long‐term Cognitive Impact of COVID‐19 Infection in Acute Ischemic Stroke Patients

  Alzheimer s & Dementia · 2025-12-01

  articleOpen access

  BACKGROUND: About one in three COVID-19 patients experience neurological problems; and acute ischemic stroke (AIS) is one of the common comorbidities of COVID-19. As stroke doubles the risk of dementia, AIS patients with COVID-19 infection may experience even higher risk of developing poststroke dementia. Still, little is known about the incidence of poststroke dementia in AIS patient with COVID-19 infection. METHOD: Using data from the Get With The Guidelines-Stroke linked Medicare claims, we conducted a retrospective cohort study to estimate the incidence of poststroke dementia in AIS patients (1) with COVID-19 with or without bacterial infection, (2) with bacterial infection only, and (3) with no infection. AIS Patients aged 66+ without pre-stroke dementia from January 1, 2020, to June 30, 2021 were included and followed up for 12 months post discharge. Primary outcome-incident poststroke dementia-was obtained based on the International Classification of Diseases, Tenth Revision, from Medicare claims. Secondary outcomes include incident vascular dementia, poststroke mild cognitive impairment, and composite of poststroke mild cognitive impairment and dementia. Poisson regression was used to model the incidence of poststroke dementia accounting for age and stroke severity. RESULT: Of 103,378 patients (median [interquartile range] age, 79 [73-86], 56,769 [54.9%] female; 84.074 [81.3.9%] white), 1,438 (1.4%) had COVID-19 infection during stroke onset, and 6,084 (5.9%) had bacterial infection only. A total of 12,925 incident dementia cases developed during 1,310,658 person-days after stroke onset. Poststroke dementia incidence rate was 0.011 in patients with COVID-19 infection, 0.011 in patients with bacterial infection only, and 0.010 in patients with no infection. Compared to patients with no infection, the rates of poststroke dementia were significantly higher in patients with only bacterial infection (adjusted rate ratio[aRR]: 1.13 [95% CI, 1.06-1.22]). Similar trends were observed in patients with COVID-19 infection, although not statistically significant (aRR: 1.14 [95% CI, 0.96-1.36]). Similar results were seen in the incidence of vascular dementia and composite cognitive outcome. CONCLUSION: We observed a higher incidence of poststroke dementia in AIS patients with bacterial infection only and those with COVID-19 infection. COVID-19 infection may be associated with higher risk of dementia post stroke.

  PublisherOA PDFDOI

• Abstract WP97: Derivation and Validation of the Get with the Guidelines®-Stroke Endovascular Thrombectomy Risk Scores

  Stroke · 2025-01-30

  article

  Introduction: Prior attempts to assess risk of symptomatic intracranial hemorrhage (sICH) after endovascular thrombectomy have been limited by reliance on information obtained after thrombectomy (such as TICI reperfusion) and lack of generalizability to routine clinical practice. Methods: Patients presenting to GWTG-Stroke participating hospitals between July 2021 and June 2023 with last known well within six hours prior to presentation, who received endovascular thrombectomy were included. The primary outcome was sICH; secondary outcomes included in-hospital mortality, mRS at discharge, and length of stay. The study population was divided into a derivation and validation cohort with 70:30 partition. According to a pre-specified statistical analysis plan, a full model of 31 candidate variables and subsequently a highly parsimonious model including only variables measured before EVT deployment was fit for each endpoint, with variable retention guided by multiple factor analysis (MFA). Models were then externally validated in the HERMES clinical trial population. Results: 31,668 patients (median age 71 [Q1: 61, Q3: 81]) were included, of whom 1,799 (5.7%) developed sICH. In the validation cohort, the area under the receiver operating characteristics curve (AUC) for the full model was 0.649 (Table 1), and the AUC for the simplified points score was 0.589 (Table 2). At the conference, we will present results of external validation and secondary endpoints, details of model calibration, and direct comparisons to existing risk scores. Conclusions: A risk score for sICH after thrombectomy for acute stroke devised using routinely collected data known prior to intervention had good performance compared to existing approaches.

  PublisherDOI

• Perioperative Stroke: Mechanisms, Risk Stratification, and Management

  Stroke · 2025-05-30 · 11 citations

  review

  Perioperative stroke, defined as a cerebrovascular event occurring during surgery or within 30 days postoperatively, remains a devastating complication associated with substantial morbidity, disability, mortality, and increased healthcare utilization. Although overall incidence is relatively low-up to 1% in most surgical populations-it is significantly elevated in cardiac, major vascular, and neurosurgical procedures, often exceeding 5%. The rising prevalence of perioperative stroke, primarily driven by an aging surgical population burdened by multiple chronic vascular conditions and increasingly eligible for high-risk surgical interventions, underscores the urgency of optimizing preventive and management strategies. This review synthesizes insights into patient- and procedure-related risk factors, highlighting the intricate interplay of embolic, thrombotic, and hypoperfusion mechanisms underpinning perioperative ischemic strokes. Key patient-specific risks include advanced age, recent cerebrovascular events, atrial fibrillation, carotid stenosis, and chronic cardiovascular comorbidities. Procedural factors, such as the type and complexity of surgery, intraoperative hypotension, and vascular manipulations, further modulate stroke risk. Emphasizing an evidence-based approach to risk mitigation, this review examines preoperative risk stratification, intraoperative techniques designed to minimize cerebral embolization and preserve adequate perfusion, and structured postoperative protocols aimed at rapid stroke detection. Acute management complexities are also discussed, with careful consideration of intravenous thrombolysis and mechanical thrombectomy in the postoperative setting. Finally, gaps in current guidelines and promising areas for future research are identified, advocating a multidisciplinary approach involving neurology, surgery, anesthesiology, and allied specialties to enhance patient outcomes and reduce the perioperative stroke burden.

  PublisherDOI

• Short-Term Safety and Effectiveness for Tenecteplase and Alteplase in Acute Ischemic Stroke

  JAMA Network Open · 2025-03-12 · 10 citations

  articleOpen access

  Importance: Tenecteplase is an alternative to alteplase for emergency treatment of acute ischemic stroke. However, limited data are available comparing their clinical effectiveness in routine clinical practice. Objective: To compare short-term effectiveness and safety outcomes for patients with ischemic stroke treated with intravenous tenecteplase vs alteplase. Design, Setting, and Participants: This comparative effectiveness study used data prospectively collected from July 1, 2020, through June 30, 2022, from the Get With The Guidelines-Stroke registry. Exposure: Consecutive patients with ischemic stroke treated with either tenecteplase or alteplase within 4.5 hours from last known well time were included. Main Outcomes and Measures: The primary end point was functional independence on discharge (modified Rankin Scale [mRS] score, 0-2). Secondary effectiveness end points included disability free at discharge (mRS score, 0-1), discharge home, and independent ambulation at discharge. Safety end points included symptomatic intracranial hemorrhage (sICH) within 36 hours and combined in-hospital mortality or hospice discharge. Generalized linear mixed models were fit to evaluate associations between exposure to tenecteplase (vs alteplase) and end points after adjustment for demographic, clinical, and hospital-level variables. Adjusted odds ratios (AORs) with 95% CIs were computed. Results: Among 79 550 patients treated with intravenous thrombolysis, the mean (SD) age was 68.6 (14.8) years, 38 596 (48.5%) were female, and the median National Institutes of Health Stroke Scale (NIHSS) score was 7 (IQR, 4-13). Of these patients, 9465 (11.9%) received tenecteplase (mean [SD] age, 69.6 [14.7] years; median NIHSS score, 7 [IQR, 4-14]; 4504 [47.6%] female) and 70 085 (88.1%) received alteplase (mean [SD] age, 68.5 [14.8] years; median NIHSS score, 7 [IQR, 4-13]; 34 092 [48.6%] female). After adjustment for covariates, no significant differences were found between tenecteplase and alteplase in effectiveness or safety outcomes for the overall cohort, including functional independence at discharge (AOR, 1.00; 95% CI, 0.93-1.07), sICH (AOR, 0.96; 95% CI, 0.83-1.11), and in-hospital mortality or hospice discharge (AOR, 0.98; 95% CI, 0.89-1.07), but significant improvement was found in discharge home (AOR, 1.26; 95% CI, 1.03-1.53), in-hospital mortality (AOR, 0.63; 95% CI, 0.47-0.85), and composite in-hospital mortality or hospice discharge (AOR, 0.78; 95% CI, 0.62-0.97) among those who were eligible for but did not undergo endovascular thrombectomy. Conclusions and Relevance: This large, nationwide comparative effectiveness study using data from routine clinical practice demonstrated similar effectiveness and safety outcomes with tenecteplase compared with alteplase in patients with acute ischemic stroke. This study supports tenecteplase as a reasonable alternative to alteplase.

  PublisherOA PDFDOI

Frequent coauthors

• Scott E. Kasner

  Hospital of the University of Pennsylvania

  501 shared

• Lee H. Schwamm

  Yale University

  468 shared

• Eric E. Smith

  University of Calgary

  467 shared

• Gregg C. Fonarow

  University of California, Los Angeles

  388 shared

• Brett Cucchiara

  Hospital of the University of Pennsylvania

  328 shared

• Jeffrey L. Saver

  University of California, Los Angeles

  316 shared

• Eric D. Peterson

  The University of Texas Southwestern Medical Center

  295 shared

• Deepak L. Bhatt

  Cornell University

  273 shared