Mandel, Daniel M

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: Patients with cervical artery dissection (CAD) have a higher prevalence of cerebral aneurysms, likely due to underlying vasculopathies. Understanding risk factors and outcomes in this population may inform screening and management strategies. Methods: We conducted a post-hoc analysis of the STOP-CAD study, a multicenter international registry of patients with non-major trauma-related CAD across 63 centers. Cerebral aneurysms were identified based on medical history and intracranial vascular imaging obtained for dissection diagnosis. We compared demographic, clinical, laboratory, and imaging characteristics between patients with and without aneurysms. Variables with p<0.05 in univariate analysis were entered into a multivariable binary logistic regression to identify independent predictors. Clinical outcomes including ischemic stroke and symptomatic intracranial hemorrhage at follow-up were compared between both groups. Results: Out of 4023 patients included in the STOP-CAD study, 116 (2.9%) had at least one incidental cerebral aneurysm. In adjusted binary logistic regression, patients with cerebral aneurysm were more likely to have a history of migraine (aOR 1.78 95% CI 1.15-2.75, p=0.009), history of hypertension (aOR 1.65 95% CI 1.12-2.43, p = 0.010), known connective tissue disorder (aOR 3.47 95% CI 1.71-7.03), history of dissection (aOR 2.63 95% CI 1.31-5.28, p = 0.007), and a dissecting aneurysm at the site of the dissection (aOR 1.94 95% CI 1.25-3.01, p = 0.003). At follow-up, the presence of a cerebral aneurysm was not associated with ischemic stroke (7.8% vs. 5.6% p>0.1), but with a trend towards increased odds of symptomatic intracranial hemorrhage (3.4% vs. 1.2%, p = 0.062). Conclusions: Patients with CAD and concurrent incidental cerebral aneurysm were more likely to have a history of migraine headaches and markers of underlying vasculopathy and had a non-significantly increased risk of intracranial hemorrhage at follow-up. Further studies are needed to identify best practices for surveillance and risk stratification in this subgroup.

Background: Cervical artery dissection (CeAD) accounts for nearly 25% of all ischemic strokes in young adults. CeAD can lead to the development of dissecting aneurysms (DA). However, the incidence, risk factors and outcomes of CeAD patients with DA is not well established. This study aims to identify risk factors for developing DA, subsequent growth, and impact on patient outcomes. Methods: This is a secondary analysis of the Antithrombotics for Stroke Prevention in Cervical Artery Dissection (STOP-CAD), a multicenter cross-sectional international retrospective study. CeAD patients were stratified for the presence of DA. We used multivariable regression to identify factors associated with DA. Patients with DA were further analyzed for DA growth. The primary outcome was ischemic stroke after CeAD+DA diagnosis. Secondary outcomes included ischemic stroke after CeAD+DA with DA growth. Multivariable logistic regression analysis was used to assess the association between DA and risk factors. We also performed univariate Cox regression and generated Kaplan-Meier survival curves comparing study outcomes based on presence of DA and subsequent growth. Results: Of the 4023 patients included in the STOP-CAD study, 4008 were included in this analysis and 767 (19%) patients had DA (546 with DA on initial presentation). Patients with DA had a mean age of 46 [IQR 37-55] years and 50% (383) were women. In combined adjusted analyses, DA patients were more often non-Hispanic (aOR 0.63, 95% CI 0.41-0.94, p<0.02), more commonly had a history of migraine (aOR 1.27, 95% CI 1.01-1.59, p=0.037), connective tissue disorder (aOR 2.02, 95% CI 1.22-3.36, p=0.007), minor neck trauma (aOR 1.70, 95% CI 1.29-2.26, p<0.001) and were more likely to present with ischemic stroke (aOR 1.73, 95% CI 1.05-2.87, p=0.031). DA growth was noted in 55 out of 546 (10%) patients with DA on presentation. There was no significant difference in the risk of ischemic stroke by day 180 in patients with DA (hazard ratio [HR] 0.92 [95% CI, 0.65-1.30]; P =0.63) or DA growth (HR 2.40, [95% CI, 0.79-7.24]; P =0.12). Conclusion: In this subanalysis of STOP-CAD, nearly one in five patients with CeAD developed a DA. Factors associated with a higher likelihood of DA included non-Hispanic ethnicity, history of migraine, connective tissue disorder, minor neck trauma, and ischemic stroke at presentation. DA diagnosis and DA growth did not impact the risk of subsequent ischemic stroke at 6 months.

Background: The clinical characteristics and complications associated with de novo pseudoaneurysm formation beyond the acute phase of cervical artery dissection remain poorly defined. In this study, we examined the incidence, risk factors, and related ischemic and hemorrhagic events of post-acute de novo pseudoaneurysm formation. Methods: We analyzed data from the STOP-CAD study (Antithrombotic Treatment for Stroke Prevention in Cervical Artery Dissection). A de novo pseudoaneurysm was defined as a new (not present on initial imaging) focal enlargement in the diameter of the artery, greater than the native lumen. The incidence of de novo pseudoaneurysm was assessed at 90 days, 180 days, and beyond 180 days of follow-up. Univariate and multivariate regression analyses were conducted to identify risk factors for post-acute de novo pseudoaneurysm formation. Kaplan-Meier survival estimates were used to compare ischemic and hemorrhagic events between patients with and without de novo pseudoaneurysms. Results: Among 4008 patients, 546 were excluded as they had dissecting pseudoaneursyms on initial presentation. Therefore, 3,462 patients were included in this analysis of whom 220 patients (6.35%) developed a de novo pseudoaneurysm over a maximum follow-up of 4.4 years. Of these, 127 (57.72%) were detected within the first 90 days, and 172 (78.18%) within the first 180 days. In multivariate regression analyses, in addition to hypertension, active smoking and Hispanic ethnicity, fibromuscular dysplasia (FMD) was an independent risk factor for post-acute de novo pseudoaneurysm formation (adjusted OR: 2.160; 95% CI: 1.408–3.315; p < 0.001). Notably, the presence of a de novo pseudoaneurysm was not associated with a significant increase in ischemic (hazard ratio [HR] 1.43 [95% CI, 0.89–2.30]; P=0.14) or hemorrhagic events (hazard ratio [HR] 1.42 [95% CI, 0.43–4.69]; P=0.57). Conclusion: De novo pseudoaneurysm formation following a diagnosis of a cervical artery dissection is not uncommon and most frequently occurs within the first 180 days. FMD was independently associated with this complication. The development of a de novo pseudoaneurysm did not significantly increase the risk of subsequent ischemic or hemorrhagic events.

Background: Interfacility transfers, especially in rural settings, present challenges including limited ambulance availability, bed capacity, image sharing and disparities in access. Regional transfer minimizes time to definitive stroke center care, relies less on costly helicopter transport, supports local healthcare economies, and preserves comprehensive stroke center (CSC) resources for those most likely to benefit. Although these advantages are well-established and reflected in the guidelines, transfers within our connected care rural network were not previously accepted at hospitals outside of our central comprehensive stroke center (CSC). Methods: We identified a local primary stroke center to serve as the regional stroke transfer center (rSTC) within our larger telestroke network. Over one year, (2023-2024), stakeholder meetings with representatives from the rSTC, surrounding smaller hospitals and the CSC were conducted to pinpoint potential roadblocks and create workflows that facilitated regional transfer. Regionally appropriate transfers were defined as patients without LVO, low likelihood for any neurosurgical decompression, or critical illness requiring dedicated neuro-intensive care. Education surrounding these criteria occurred quarterly and case logs were maintained and reviewed by the rSTC stroke coordinator. Retrospective chart review one year following the intervention period (2024-2025) was performed. Results: Of the 99 total transferred patients, 73 (73.7%) patients were transferred regionally. Their average LOS was 2.1 days, with 0% mortality rate and 0% requiring a secondary transfer to the CSC. 26 (26.3%) patients went to the CSC; LOS was 10.6 days and mortality 23.1%. Transfer times were shorter for rSTC patients (60 min vs 188 min). Six CSC patients met regional criteria (26.3% overtriage rate). Conclusion: Establishing an effective regional transfer model is possible with broad stakeholder engagement and regular network maintenance. Following our intervention, most eligible patients remained local and were treated appropriately. Although there was a significant reduction of the patients transferred to the CSC, the majority of CSC transfers were also appropriately triaged. This rSTC model facilitates the care of all stroke patients by providing the right level of care for the right patient, avoiding futile transfers with costly admissions far from home while opening beds and reducing transfer times to CSCs.

BACKGROUND: Cervical artery dissection (CeAD) may result in dissecting aneurysm (DA) formation. We aimed to characterize risk factors and clinical outcomes associated with DA in a large, international CeAD cohort. METHODS: We performed a secondary analysis of STOP-CAD (Antithrombotic Treatment for Stroke Prevention in Cervical Artery Dissection), an international, multicenter, retrospective cohort. Patients with spontaneous CeAD were assessed for DA at baseline and de novo DA formation. Significant covariates in univariable analysis were included in multivariable regression models aiming to identify factors associated with DA formation. Logistic regression and Cox proportional hazards models evaluated the association of DA with ischemic and hemorrhagic outcomes. RESULTS: Among 4008 patients with CeAD, 546 (13.6%) had a DA at baseline, and 221/2938 (7.5%) patients developed a de novo DA during follow-up, of which 172/221 (78.2%) were detected in the first 180 days. Patients with DA had a mean age of 47 years, and 383 (49.9%) were women. Baseline or de novo DA was associated with a history of connective tissue disorder (adjusted odds ratio [aOR], 2.02 [95% CI, 1.22–3.36]), fibromuscular dysplasia (aOR, 1.69 [95% CI, 1.28–2.25]), and multiple vessel dissection (aOR, 1.53 [95% CI, 1.19–1.98]). Lower odds of DA were seen in Hispanic ethnicity (aOR, 0.64 [95% CI, 0.43–0.97]) and ischemic stroke presentation (aOR, 0.41 [95% CI, 0.34–0.49]). Fibromuscular dysplasia was associated with de novo DA formation (aOR, 2.30 [95% CI, 1.52–3.49]). DA was not associated with ischemic stroke (hazard ratio, 0.71 [95% CI, 0.44–1.16]; P =0.173) or intracranial hemorrhage (HR, 1.09 [95% CI, 0.42–2.84]; P =0.86) by day 180. CONCLUSIONS: DAs are relatively common manifestations of CeAD, typically occurring within 6 months of CeAD diagnosis. DA was not associated with an increased risk of subsequent ischemic stroke or intracranial hemorrhage.