Yedavalli, Vivek

BACKGROUND AND OBJECTIVES: Medical management options for nontraumatic subdural hematoma (SDH) remain limited, with only atorvastatin demonstrating benefit in a single phase 2 randomized clinical trial and mixed evidence for dexamethasone. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) may benefit SDH outcomes. The objective of this study was to evaluate the association between GLP-1 RA use and rescue surgery rates and mortality in patients with medically managed nontraumatic SDH. METHODS: We conducted a retrospective cohort study using the TriNetX database from 2016 to 2025, including adults with SDH who were managed conservatively without surgical evacuation or middle meningeal artery embolization. Patients prescribed GLP-1 RAs were compared with nonusers. After propensity matching, rescue surgical evacuation, all-cause mortality at 1 year, and GLP-1 RA–associated adverse events were analyzed. RESULTS: A total of 134 901 patients with conservatively managed nontraumatic SDH were identified, of whom 1470 (1.1%) were GLP-1 RA users. After propensity score matching, 2922 patients remained, with 1461 in each group. At 1 year, GLP-1 RA users experienced significantly lower rates of rescue surgery (2.23% vs 3.51%; P = .046), culminating in an overall 38% reduction in relative hazard. All-cause mortality was also significantly lower for GLP-1 RA users at 1 year (16.1% vs 23.7%, P < .001), reflecting a 33% reduction in hazards. GLP-1 RA users did not experience different rates of adverse events, such as pancreatitis, gallbladder disease, or ileus/bowel obstruction (all P > .05). CONCLUSION: Among patients with medically managed nontraumatic SDH, GLP-1 RA use was associated with significantly lower rates of rescue surgery and all-cause mortality without significantly increased risk of common GLP-1 RA–related complications.

Background: Asymptomatic intracranial atherosclerotic arterial stenosis (ICAS) is an underrecognized entity for which vascular risk-factor optimization is the primary management strategy, with no current indication for routine antiplatelet therapy or endovascular intervention for primary stroke prevention. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) reduce major adverse cardiovascular events, including stroke, in high-risk cardiometabolic populations, but their association with outcomes in asymptomatic ICAS is yet to be evaluated. The present study aims to evaluate the association between GLP-1RA use and cerebrovascular outcomes in adults with asymptomatic ICAS. Materials and Methods: We used the TriNetX US Collaborative Network (71 healthcare organizations) to identify adults (≥18 years) with ICAS between 1 January 2016 and 31 December 2025, and excluded patients with prior cerebral infarction, intracranial hemorrhage, or cerebrovascular ischemic syndromes. Exposure was defined as initiation of any GLP-1 receptor agonist (lixisenatide, semaglutide, liraglutide, tirzepatide, dulaglutide) during the 6 months before or on the date of index ICAS diagnosis. Outcomes were assessed at 1 year, and included ischemic stroke, all-cause mortality, and a composite of ischemic stroke or mortality. Propensity-score matching (1:1) was performed, including demographics, vascular risk factors, comorbidities, antithrombotics, lipid/diabetes therapies, and cardiometabolic laboratory/physiologic measures. Results: Before matching, 1746 GLP-1RA users and 71,792 non-users met inclusion criteria; after matching, 1728 patients remained in each cohort. GLP-1RA use was associated with lower 1-year risk of ischemic stroke (4.40% vs. 6.10%; hazard ratio [HR] 0.70, 95% CI 0.52–0.95; p = 0.044), lower all-cause mortality (3.40% vs. 9.40%; HR 0.35, 95% CI 0.26–0.47; p < 0.001), and lower composite outcome risk (7.50% vs. 15.00%; HR 0.48, 95% CI 0.39–0.59; p < 0.001). Notably, these associations were observed despite matching for HbA1c, LDL cholesterol, BMI, and systolic blood pressure, suggesting potential effects beyond measured cardiometabolic risk profiles. Conclusions: In this large, propensity-matched cohort of adults with a-ICAS, GLP-1RA use was associated with lower ischemic stroke, all-cause mortality, and composite outcome at 1 year. These findings are hypothesis-generating and require further prospective studies to confirm this observation.

BACKGROUND: Unruptured intracranial aneurysms (UIAs) affect up to 5% of the population, and rupture can lead to devastating subarachnoid hemorrhage. GLP-1RAs (glucagon-like peptide-1 receptor agonists) have anti-inflammatory and vasculoprotective effects, but their impact on aneurysm stability and subarachnoid hemorrhage outcomes is unexplored. This study evaluated whether GLP-1RA use is associated with reduced rupture risk and attenuated severity in the event of a rupture. METHODS: We conducted a retrospective cohort study using the TriNetX US Collaborative Network (2016–2024). Cohort 1 included patients with newly diagnosed, untreated UIA; cohort 2 included those who suffered aneurysm rupture. GLP-1RA exposure was defined as use before or within 3 months of UIA diagnosis (cohort 1) or before rupture (cohort 2). The primary outcome was aneurysm rupture risk in cohort 1. Secondary outcomes include presentation severity, vasospasm, and mortality in cohort 2. Propensity score matching balanced demographics, comorbidities, and medications. RESULTS: After propensity score match, cohort 1 of patients with untreated UIA included 8088 GLP-1RA users and 8088 nonusers. GLP-1RA use was associated with significantly lower probabilities of aneurysm rupture at 1-year (0.65% versus 1.51%; P <0.001), 3-year (1.18% versus 1.85%; P <0.001), and 5-year (1.49% versus 2.10%; P <0.001) timepoints, representing a 48% decrease in hazards (hazard ratio, 0.52 [95% CI, 0.38–0.69]). Among patients who suffered aneurysm rupture (cohort 2, N=298 after propensity score match), prerupture GLP-1RA use (n=149) was associated with lower rates of intraparenchymal hemorrhage (17.4% versus 33.6%; P <0.001), intraventricular hemorrhage (10.1% versus 23.5%; P <0.001), and clinically significant vasospasm (10.7% versus 24.2%; P =0.002), as well as numerically lower rates of 30-day mortality (9.4% versus 14.1%; P =0.21). CONCLUSIONS: For patients with untreated UIA, GLP-1RA use was associated with a 48% reduction in aneurysm rupture risk and, among those who suffered aneurysm rupture, milder clinical and radiographic severity. These findings suggest possible neuroprotective and vascular stabilizing effects of GLP-1RAs for patients with UIA.

Abstract This work presents a first-of-its-kind artificial intelligence (AI-)integrated MR pulse sequence that detects out-of-voxel (OOV) artifacts in real-time (within-TR) and responds prospectively by updating the crusher gradient scheme. Per Excitation Real-time Execution & Guided Responses with Integrated Neural-network Evaluation (PEREGRINE), allows for deployment of deep learning models and pulse sequence updates. In this study, PEREGRINE operated a time-domain (TD) and frequency-domain (FD) convolutional autoencoder that detect OOV artifacts. Scans without (AI-off) and with (AI-on) updates were collected from the medial prefrontal cortex of healthy volunteers using a MEGA-edited MRS experiment. The degree of OOV contamination (OOV Score) was quantified per transient based upon the prevalence of OOV signals in the TD and FD data. OOV Scores above a user-defined threshold triggered an update of the crusher gradient scheme, iterating through 48 permutations (6 axis transpositions × 8 polarity flips). Within each 2-second TR, PEREGRINE successfully provided single-transient OOV Scores and updated gradients accordingly. No difference was observed between the OOV Scores from the full (“Full” condition) AI-on and AI-off sessions due to the AI-on scan cycling over better and worse gradient permutations relative to the AI-off scan. However, the AI-on scan had significantly lower OOV Scores than the AI-off scan when selecting the transients where PEREGRINE persisted (“Dwell” condition) on a given gradient permutation. Ultimately, Fit Quality Number (FQN) from linear combination modeling improved significantly for the AI-on compared to the AI-off scan. PEREGRINE enabled an adaptive and AI-integrated sequence allowing for real-time evaluation and response to OOV artifacts, identifying gradient modifications that produced less OOV contamination. Graphical Abstract Graphical Abstract Summary PEREGRINE, Per Excitation Real-time Execution & Guided Responses with Integrated Neural-network Evaluation, allows for pulse sequence updates using on-scanner deployed neural networks. To demonstrate the utility, PEREGRINE was used to operate two neural networks (time/frequency domain), trained to detect out-of-voxel artifacts, during a MEGA-edited MRS experiment in the prefrontal cortex. When artifacts were detected, PEREGRINE updated the crusher gradients within the same TR. Real-time, adaptive, and AI-driven MR will provide a long-awaited solution for combatting artifacts and poor data quality. Graphical Abstract Figure

Background Dual antiplatelet therapy (DAPT) is recommended around carotid artery stenting (CAS) to reduce periprocedural stroke risk. Clopidogrel is widely used, but response variability related to pharmacokinetics and CYP2C19 polymorphisms may limit its effectiveness. Ticagrelor is a more potent, direct acting P2Y12 inhibitor, but its comparative effectiveness in CAS remains uncertain. Methods We conducted a retrospective cohort study in the TriNetX database, identifying adults with carotid artery stenosis who underwent CAS between January 2016 and August 2025 and received either ticagrelor or clopidogrel. Primary outcomes at 180 days included ischemic stroke, major hemorrhage, intracranial hemorrhage, and all cause mortality. Secondary outcomes included inpatient readmission and emergency department (ED) visits. Propensity score matching (1:1), Kaplan–Meier survival, and Cox proportional hazards analysis were used. Results Among 6996 patients, 378 received ticagrelor and 6618 received clopidogrel; aspirin co-use was similar (89.7% vs 91.7%). After matching, 377 patients remained in each cohort. Ischemic stroke (2.7% vs 4.2%; HR 0.56, 95% CI 0.25 to 1.27; P=0.159) and major hemorrhage (2.9% vs 4.8%; HR 0.61, 95% CI 0.29 to 1.30; P=0.197) were numerically lower with ticagrelor. Rates of intracranial hemorrhage were similar (2.7% vs 2.7%; HR 0.61, 95% CI 0.14 to 2.53; P=0.488). Mortality was numerically higher with ticagrelor (3.4% vs 2.7%; HR 1.64, 95% CI 0.68 to 3.97; P=0.263). ED visits were similar (14.3% vs 14.6%; HR 0.97, 95% CI 0.67 to 1.42; P=0.895). Inpatient readmission was numerically lower with ticagrelor (15.9% vs 19.1%; HR 0.81, 95% CI 0.57 to 1.14; P=0.223). Conclusion Ticagrelor and clopidogrel showed comparable safety and effectiveness following CAS. Future prospective genotype informed trials are warranted to confirm these findings.

Background: Patients with acute ischemic stroke secondary to distal and medium vessel occlusion (AIS-DMVO) and minor strokes present a challenge in determining the most appropriate emergent treatment. Factors leading to early neurological deterioration (END) in this patient population are understudied, but END is known to result in poor functional outcomes. Therefore, we aimed to investigate the factors contributing to END in minor AIS-DMVO cases. Methods: We included patients with AIS-DMVO and minor strokes from 37 sites across North America, Asia, and Europe. Minor stroke was defined as a baseline National Institutes of Health Stroke Scale (NIHSS) score of ⩽5. The primary outcome measure, END, was defined as a shift of ⩾4 points in the NIHSS score at day one after treatment compared to baseline. Univariable and multivariable logistic regression analyses were performed to identify factors associated with END. Results: Among 559 consecutive patients with DMVO and minor strokes, END was reported in 68 patients. In multivariable analysis, mechanical thrombectomy (MT) was independently associated with higher odds of END (adjusted odds ratio [aOR] 2.37, 95% CI 1.12–5.02, p = 0.02), while intravenous thrombolysis (IVT) was associated with lower odds of END (aOR 0.46, 95% CI 0.26–0.81, p = 0.008). However, the association between MT and END was no longer statistically significant in the IPTW-adjusted analysis (OR 1.65, 95% CI 0.69–3.98, p = 0.26). Hypertension and antiplatelet use at baseline were also independently associated with END. Among MT-treated patients, successful and excellent recanalization and first-pass effect were protective against END. Conclusion: MT was associated with END in patients with minor AIS-DMVO, although this association was not significant after IPTW adjustment. IVT was independently associated with reduced risk of END. These findings support careful patient selection and further study in randomized trials.

Objective Cognitive impairment is increasingly recognized in patients with cerebral venous congestion (CVC), yet the cognitive tools used are largely adapted from stroke and dementia research. This review examines current literature on cognitive function in CVC, including conditions such as cerebral venous sinus thrombosis (CVST), idiopathic intracranial hypertension (IIH), and dural arteriovenous fistulas (dAVFs). Special emphasis is placed on the limitations of common screening tools like the Montreal Cognitive Assessment (MoCA) and Mini-Mental State Examination (MMSE). Cognitive dysfunction—primarily affecting executive function, processing speed, and attention—is reported in up to 86% of CVC cases, yet only about 20% of studies use validated cognitive testing tools, most of which may lack sensitivity for CVC-specific deficits. Emerging techniques such as ocular motor testing and physiological markers show promise but require further validation. There is an urgent need for standardized, CVC-specific cognitive assessment protocols that reflect the unique pathophysiology of venous disorders. Future research should prioritize the development of targeted cognitive batteries and integrate objective physiological measures to enhance diagnostic accuracy.

Objective Mechanical thrombectomy (MT) is well-established for the treatment of acute ischemic stroke (AIS) from large vessel occlusion (LVO), with growing data supporting the expansion to distal and medium vessel occlusions (DMVO). Despite successful recanalization in DMVO, certain patients still experience poor long-term clinical outcomes, prompting our study to comprehensively explore pre-MT factors influencing outcome despite excellent recanalization (final modified Thrombolysis in Cerebral Infarction [mTICI] score ≥2c). Methods We retrospectively examined data from patients who consecutively underwent MT for a primary middle cerebral artery (MCA) DMVO across 37 centers in North America, Asia, and Europe. We identified baseline clinical and imaging factors associated with poor clinical outcome (defined as a modified Rankin Scale [mRS] score of 3–6) at 3 months, despite excellent recanalization using a multivariable model. Results Between September 2017 and July 2021, 623 patients achieved mTICI > 2b and they were included in our study. Among them, 198 (32%) experienced a poor clinical outcome (mRS 3–6). Predictors of poor clinical outcome included higher age (OR 1.05 [1.03–1.07], p < 0.001), higher NIHSS at admission (OR 1.12 [1.08–1.15], p < 0.001), higher baseline mRS (OR 1.77 [0.96–3.26], p = 0.067), and diabetes (OR 1.59 [1.01–2.48], p = 0.044). Higher ASPECTS was associated with a decreased risk of poor clinical outcome (OR 0.82 [0.71–0.94], p = 0.006). Conclusion Older age, diabetes, higher baseline mRS, and NIHSS were associated with poor clinical outcome in MCA DMVO despite excellent recanalization. Conversely, a higher ASPECTS decreased the probability of such an outcome.

OBJECTIVE Mechanical thrombectomy (MT) is well established for large-vessel occlusion (LVO) strokes, but its safety in distal and medium-vessel occlusions (DMVOs) requires further investigation. This study analyzed the relationship between procedural approaches, petechial hemorrhage (PetH), and clinical outcomes in DMVO thrombectomy, with particular attention to technical considerations and the complex interplay between tissue injury and hemorrhagic complications. METHODS A retrospective cohort study was conducted on DMVO stroke patients treated with MT at 37 stroke centers worldwide from 2016 to 2024. Patients were categorized based on follow-up imaging into those with or without PetH. Four logistic regression models analyzed the association of PetH with favorable functional outcomes (modified Rankin Scale score ≤ 2) at 90 days, early neurological improvement (≥ 4-point National Institutes of Health Stroke Scale score decrease at 24 hours), all-cause mortality, and independent determinants of PetH. Adjusted odds ratios (aORs), 95% confidence intervals, and p values were reported. RESULTS Of 1428 patients, 439 (30.7%) developed PetH. Factors independently associated with PetH were multiple thrombectomy passes (aOR 1.58, 95% CI 1.21–2.06; p = 0.001), IV thrombolysis (aOR 1.31, 95% CI 1.01–1.69; p = 0.04), and the combined use of a stent retriever with aspiration as the first-line method compared with aspiration alone (aOR 1.66, 95% CI 1.15–2.38; p = 0.007). Conversely, general anesthesia (aOR 0.55, 95% CI 0.40–0.77; p < 0.001), higher Alberta Stroke Program Early CT Scores (aOR 0.76, 95% CI 0.69–0.83; p < 0.001), and successful recanalization (aOR 0.56, 95% CI 0.39–0.80; p = 0.002) were significantly associated with a lower odds of PetH. PetH was associated with a decreased odds of favorable functional outcomes (aOR 0.51, 95% CI 0.36–0.73; p < 0.001), reduced early neurological improvement (aOR 0.59, 95% CI 0.44–0.79; p < 0.001), and increased all-cause mortality (aOR 1.84, 95% CI 1.23–2.76; p < 0.001). CONCLUSIONS PetH is a frequent sequela following MT in DMVO strokes and is associated with poorer outcomes, likely reflecting underlying ischemic injury rather than direct causation. Procedural factors influence PetH risk, suggesting medical treatment as first-line therapy for DMVOs, with MT reserved for refractory cases using less aggressive approaches.