TL;DR: This community hospital case series reveals a spectrum of vertebral artery compression in posterior circulation stroke, highlighting the underdiagnosis of Bow Hunter's Syndrome and the utility of dynamic DSA in identifying pseudoaneurysms and dynamic occlusions.
Abstract: Background: Posterior circulation strokes without findings on conventional non-dynamic vascular imaging (CTA or MRA) are often presumed cardioembolic or hypercoagulable. This may lead to under-recognition of dynamic vascular pathologies such as Bow Hunter’s Syndrome (BHS)—a spectrum of vertebrobasilar insufficiency from subtle compression to occlusion—that can precipitate recurrent strokes. Our prior investigation suggested that vertebral artery pseudoaneurysm may serve as an indicator of BHS and a prompt for dynamic vascular imaging. Over the course of one year, we encountered three such cases at a community hospital, highlighting the diagnostic utility of dynamic digital subtraction angiography (DSA). Methods: We retrospectively reviewed patients with posterior circulation infarcts and inconclusive workups, including negative CTA, hypercoagulable testing, and cardioembolic evaluation, with no findings to explain the stroke pattern. Results: Case 1: A 41-year-old man with bilateral cerebellar and thalamic infarcts. Dynamic DSA revealed a left V3 pseudoaneurysm with partial compression during head rotation, without occlusion (Figure 1) Case 2: A 45-year-old man with recurrent bilateral cerebellar infarcts and severe dizziness. Imaging showed a hypoplastic, occluded left vertebral artery; dynamic DSA demonstrated kinking of the dominant right vertebral artery with rightward head turn, reproducing his dizziness. (Figure 2) Case 3: A 61-year-old woman with a history of recurrent posterior circulation strokes over three months, despite maximal medical therapy with dual antiplatelet therapy, statin, and closure of a large PFO. Dynamic DSA identified a right V2 pseudoaneurysm abutting a cervical osteophyte, with progressive narrowing culminating in complete occlusion at 60° contralateral head rotation and collateral reconstitution. (Figure 3) Conclusions: The identification of three cases within a single year at a 455-bed community hospital highlights that BHS may be more common than currently appreciated and often remains underdiagnosed. These cases demonstrate a continuum of vascular compromise, from partial compression to complete dynamic occlusion with pseudoaneurysm formation, causing recurrent posterior circulation strokes even when conventional workups are negative. Our findings suggest that vertebral artery pseudoaneurysm on conventional imaging may serve as a valuable marker of underlying BHS, warranting dynamic vascular evaluation.
Annabelle Shanks, Ian Johnson, Hailey Brigger, Steph Maynez, Alison Champagne, Gordon Sze, S. Payabvash, Matthew Rosen, Annabel Sorby-Adams, W. Taylor Kimberly, Kevin Sheth, Adam de Havenon
TL;DR: Portable MRI (pMRI) accurately measures white matter hyperintensity (WMH) volumes in intracranial hemorrhage (ICH) patients, with greater WMH volumes in ICH patients compared to controls, suggesting pMRI as a practical tool for stroke risk and prognostication.
Abstract: Introduction: White matter hyperintensities (WMH) on conventional MRI (cMRI) are linked to stroke risk, mortality, and functional outcome. WMH volume may help guide prognosis and stroke prevention but the cost and logistics of cMRI limit use. Portable MRI (pMRI), a 0.064T mobile scanner, offers a low-cost bedside alternative. Our objective was to determine whether WMH volume can be segmented from pMRI in ICH patients. Methods: In this exploratory retrospective study of pMRI scans from 2019-2023, we included patients with spontaneous ICH who had FLAIR imaging with pMRI during hospitalization. Paired cMRI scans performed during the hospital stay were used for validation. pMRI scans were obtained from age-matched patients, without stroke, scanned due to vascular risk factors. Images were automatically segmented with WMH-SynthSeg. WMH volume was segmented from the contralateral hemisphere to the bleed in ICH patients. In controls, total WMH was halved, yielding average WMH per hemisphere. Analyses were performed using Python 3.9.6. Results: pMRI scans were obtained from 24 ICH patients (mean age 64.4 ± 15.1, 48% male, 68% White, median NIHSS 13), 21 of whom had paired cMRI. They were age-matched within 4 years to 15 controls (mean age 64.4 ± 14.9, 56% male, 76% white). WMH volumes from pMRI correlated with those from cMRI (r=0.776,95% CI [0.518, 0.905], p <0.0001) but showed a median difference (z=52, p=0.026). Bland-Altman analysis of log-transformed WMH volumes showed pMRI measurements averaged 11.6% lower than cMRI (95% CI -57, +81, p=0.86), indicating variability despite correlation. pMRI WMH volume was greater in ICH patients than controls (z=57, p=0.0065; median [IQR] WMH volume 5.33 mL [3.44-7.36 mL] vs. 3.34 mL [2.49-4.44 mL]) with a Hodges–Lehmann median difference of 2.65 mL (95% CI 0.036-3.62 mL). Among ICH patients, 54.2% (95% CI 35.1%–72.1%) had moderate/severe hemispheric WMH (>5mL), compared to 12.0% of controls (95% CI 4.2%–30.0%), corresponding to an odds ratio of 8.67 (95% CI 2.04–36.91, p = 0.0023). The agreement between pMRI and cMRI in identifying moderate/severe WMH was moderate (κ=0.52, CI 0.17-0.84) with a concordance of 76%. Conclusion: Portable MRI produced accurate WMH measurements in ICH patients, who had greater WMH volumes than controls. pMRI is a practical tool for WMH quantification, potentially informing stroke risk and prognostication, though variability and sample size warrant further validation prior to clinical implementation.
Aaron Rodriguez Calienes, Leonardo Cruz-Criollo, Eric Kontowicz, Marta Gadea, Francesco Diana, Johannes Kaesmacher, Adnan Mujanovic, serdar geyik, Songul Senadim, Amedeo Cervo, M Piano, Manuel Moreu, Alfonso López-Frías, Ameer E Hassan, Samantha Miller, Elena Zapata-Arriaza, Asier de Albóniga-Chindurza, Mauro Bergui, Stefano Molinaro, João André Sousa, Fábio Gomes, Andrea M. Alexandre, Alessandro Pedicelli, Jérémy Hofmeister, Paolo Machi, Luca Scarcia, Jose Amorim, N. Abdelhakim, Anderson Brito, Jorge Cespedes Segura, Leonardo Renieri, Francesco Capasso, Eduardo Barcena, David Seoane, Mohamad AbdalKader, Thanh N. Nguyen, Isabel Fragata, D Yavagal, Adnan Siddiqui, Joao Pedro Marto, Michele Romoli, Mohammad AlMajali, José Rodríguez Castro, Pedro Vega, Atilla Ozcan Ozdemir, Sadiq Al Salman, Daniele G. Romano, Francesco Biraschi, Pedro Castro, Pedro Navia, Nikolaos Ntoulias, Mariano Velo, J. Zamorro Parra, Juan Arenillas, Shadi Yaghi, A Tomasello, Tudor G. Jovin, Marc Ribo, Manuel Requena, S Ortega-Gutierrez
TL;DR: This study examines the interaction between periprocedural antiplatelet therapy and intravenous thrombolysis in intracranial stenting for acute ischemic stroke, finding that aggressive antiplatelet therapy and prior thrombolysis increase hemorrhagic risk, with the combination showing the worst outcomes.
Abstract: Introduction: Intracranial stenting during endovascular thrombectomy (EVT) is a common practice in the setting of failed reperfusion or severe stenosis. Immediate stent patency requires periprocedural antiplatelet therapy (APT). How APT intensity interacts with prior intravenous thrombolysis (IVT) to influence hemorrhagic risk remains uncertain. We aimed to assess whether the APT regimen modifies the association of IVT with early intracranial hemorrhage after intracranial stenting during EVT. Methods: This was a subanalysis of the RESISTANT registry, a multicenter, international, retrospective cohort (2016 to 2023) of adults with acute ischemic stroke who underwent intracranial stenting during EVT. APT regimens were categorized as conservative (intravenous or oral aspirin alone, or aspirin plus an oral P2Y12 inhibitor) and aggressive (any regimen including intravenous GPIIb/IIIa inhibitor or intravenous cangrelor). Four main groups were compared according to the APT regimen (conservative/aggressive) and the use of IVT (+/-). The primary outcome was a composite of sICH and parenchymal hematoma types 1 and 2 (sICH-PH2-PH1). Multivariable logistic regression models were used to evaluate the interaction between IVT and APT, adjusting for clinically relevant covariates. Results: Among the 823 included patients, 44 (5.3%) received conservative APT with IVT, 130 (15.8%) received conservative APT without IVT, 145 (17.6%) received aggressive APT with IVT, and 504 (61.2%) received aggressive APT without IVT. Among patients who received IVT, sICH-PH2-PH1 rates were 9.3% with conservative APT and 10.7% with aggressive APT; among those without IVT, rates were 3.2% and 9.9%, respectively. Administration of IVT (adjusted odds ratio [aOR] 5.84, 95%CI 1.07 to 43.92; p=0.05) and aggressive APT (aOR 4.81, 95% CI 1.41 to 30.22; p=0.03) were each associated with higher odds of hemorrhagic complications, with a significant IVT by APT interaction (P interaction =0.05; Figures 1 and 2 ). Within the aggressive APT plus IVT subgroup, sICH-PH2-PH1 occurred in 20% of patients treated with cangrelor and 6.1% treated with a glycoprotein IIb/IIIa inhibitor ( Figure 3 ). Conclusion: Among patients requiring intracranial stenting, aggressive periprocedural APT and prior IVT are each associated with higher hemorrhagic risk, with the combination showing the worst observed crude outcome. Prospective evaluation of protocolized APT pathways in the IVT setting is warranted.
TL;DR: Researchers develop a hospital-wide protocol to evaluate patients with stroke-like symptoms receiving anti-amyloid monoclonal antibodies, addressing diagnostic and therapeutic challenges due to amyloid-related imaging abnormalities and thrombolysis risks.
Abstract: Objective: To develop a hospital-wide protocol for emergent evaluation of patients with stroke-like symptoms who are receiving anti-amyloid monoclonal antibodies (Aβ immunotherapy). Background: Aβ immunotherapy is now FDA-approved as disease modifying therapy for patients with mild cognitive impairment or mild dementia attributable to Alzheimer Disease (AD). A known adverse event associated with this class of therapy is amyloid-related imaging abnormalities (ARIA), which are often asymptomatic but a small percentage present with stroke-like symptoms. This creates diagnostic and therapeutic challenges when considering thrombolysis for stroke. While data is limited, there have been two reported cases of intracerebral hemorrhages following thrombolysis in patients on Aβ immunotherapy. Until there is further data to show the safety of thrombolysis, the FDA advises caution in this population. With the growing use of Aβ immunotherapy, hospitals must be prepared to rapidly and safely evaluate these complex cases. Methods: We are developing a protocol to identify patients receiving Aβ immunotherapy and evaluate whether focal symptoms are due to ARIA or ischemia. We are updating the electronic medical record to display a banner best practice advisory (BPA) to alert providers that a patient is on Aβ immunotherapy. If CT and CTA are not revealing, patients receiving Aβ immunotherapy will undergo a rapid sequence MRI stroke protocol to evaluate for ischemia or ARIA-related changes. We are revising our institutional and statewide relative and absolute contraindication list for thrombolysis to include Aβ immunotherapy. We will provide targeted education for health care providers at our hospital as well as emergency providers throughout the state to ensure awareness of ARIA causing stroke-like symptoms and caution with thrombolysis in this population. Results: This protocol is currently in development at our institution with plans to disseminate the information throughout the state. Implementation steps, lessons learned, and results will be presented at the International Stroke Conference. Conclusion: As Aβ immunotherapy becomes more widespread, structured protocols are essential for safely managing stroke-like presentations. The goal is to ensure that the increased risk and implications for stroke therapies in patients being treated with Aβ immunotherapy are recognized so the clinician can include them in clinical decision-making.
TL;DR: A multidisciplinary CAA clinic integrating vascular and cognitive neurology provides coordinated care, biomarker analysis, and clinical trial access, enabling comprehensive characterization of a diverse patient population with cerebral amyloid angiopathy.
Abstract: Background: Cerebral amyloid angiopathy (CAA) is a heterogeneous small vessel disease with presentations including intracerebral hemorrhage, transient focal neurological episodes and cognitive decline, often with overlapping Alzheimer’s Disease-related pathology. In June 2024, we established a multidisciplinary CAA clinic integrating Vascular and Cognitive Neurology to provide individualized risk assessment, diagnostic precision, and longitudinal management. Services include psychometric testing, advanced imaging, biomarker analysis, structured patient–caregiver education, and support from a clinic coordinator and social worker. We also aimed to increase institutional awareness and access to available clinical trials. This report summarizes the first year of clinic operations. Methods: We analyzed all patients seen from June 2024 to July 2025. Referrals came via standard in-network pathways, with out-of-network or out-of-state via clinic email. Data were prospectively captured at the point of care using an EMR-integrated tool. A subset of patients participated in an integrative, same-day visit with Vascular Neurology, Cognitive Neurology, psychometric testing, and a structured family/caregiver debrief. Advanced diagnostics—including serum or CSF amyloid (A), tau (T), neurodegeneration (N) biomarkers, APOE genotyping, and amyloid PET—were obtained when indicated. Results: During the 12-month period, 200 unique patients were evaluated in the CAA Clinic. A total of 48%(N=96) of visits followed the integrative same-day model, and 8% (N=16) of patients were enrolled in clinical trials during the study period. Overall, 17% (N=34) of patients completed APOE genotyping, 77.5% (N=155) completed ATN biomarker testing, 32.5 % (N=65) received amyloid PET imaging, and 67% (N=133) received full psychometric analysis. Detailed demographics, diagnostic distributions, biomarker completion rates, imaging characteristics, and cognitive outcomes are presented in Tables 1–3. Conclusions: A multidisciplinary CAA clinic is feasible in a tertiary setting and enables comprehensive characterization of a diverse patient population. Integration of Vascular and Cognitive Neurology expertise with advanced diagnostics and prospective EMR capture supports individualized, longitudinal management while also facilitating clinical trial participation.
TL;DR: Geospatial analysis in Texas identifies 14 optimal Mobile Stroke Unit locations, increasing stroke treatment accessibility by 16.6% and rural coverage by 279%, particularly for socially vulnerable and minority populations, with a scalable approach to optimizing MSU placement.
Abstract: Background: Mobile Stroke Units (MSUs) can significantly improve the outcomes of stroke treatment by enabling faster intravenous thrombolysis. However, they are costly and the optimal deployment strategies remain unclear, particularly for rural and underserved populations. Objective: To use geospatial analysis to determine the optimal geographic distribution of MSUs in Texas, with the aim of maximizing coverage of stroke patients and targeting rural, socially vulnerable and minority populations. Methods: We conducted a statewide geospatial analysis in Texas using publicly available data, including CDC PLACES, Social Vulnerability Index, Rural-Urban Commuting Area (codes, and the Texas Department of State Health Services stroke facility database. Level-I and II stroke centers were geocoded, and drive-time buffers (30, 60, 120, and 180 minutes) around these centers were modeled using ArcGIS Pro. MSU rendezvous points with Emergency Medical Services (EMS) units were assumed to be located halfway between rural stroke locations and stroke centers. Coverage was compared against a baseline 30-minute EMS transport to all stroke centers. Results: We identified fourteen optimal MSU locations (11 Level I and 3 Level II centers) in Texas. Using an 180-minute drive time radius (with a 90-minute rendezvous time), it was estimated that approximately 741,852 stroke patients (99.1% of all stroke patients in Texas) could receive treatment within three hours. This represented a 16.6% increase compared to the baseline EMS scenario. Notably, coverage for rural stroke patients increased by 279%. Using a 120-minute buffer increased treatment availability by 12.3% overall, and by 232% for rural patients. While the 60-minute buffer showed no net increase in patients treated, it enabled 600,101 individuals already covered by EMS to receive care more quickly. Conclusions: Geospatial modelling shows that the strategic deployment of mobile stroke units (MSUs) could greatly improve stroke treatment accessibility and outcomes across Texas, particularly for rural and underserved populations. These findings provide health policymakers with a scalable approach to optimizing MSU placement and reducing disparities in stroke care delivery.
TL;DR: This multicenter study found that antithrombotic therapy, particularly anticoagulants, increased the risk of intracranial hemorrhage (ICH) and other adverse outcomes in patients with cerebral cavernous malformations without prior ICH.
Abstract: Background: The safety of antithrombotic therapy in patients with cerebral cavernous malformations (CCMs) without prior intracranial hemorrhage (ICH) remains uncertain. Methods: We conducted a retrospective, multicenter, propensity score-matched cohort study using the TriNetX Analytics Platform. Adult patients with CCMs and no prior ICH were included. Patients receiving antithrombotic therapy (antiplatelet or anticoagulant) were compared with those receiving no antithrombotic therapy. The primary outcome was ICH; secondary outcomes included seizures, inpatient readmission, and emergency department (ED) visits. Subgroup analyses evaluated outcomes by antithrombotic class. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. Results: Among 19,222 eligible patients, 4,347 in each group were matched. ICH occurred more frequently in the antithrombotic group (5.0%) than in the no-therapy group (4.0%) (OR, 1.27; 95% CI, 1.04–1.56; P=0.020). Seizures (17.1% vs. 10.3%; OR, 1.80; 95% CI, 1.58–2.04), inpatient readmission (42.6% vs. 18.2%; OR, 3.34; 95% CI, 3.03–3.68), and ED visits (37.0% vs. 17.7%; OR, 2.73; 95% CI, 2.48–3.02) were more common. In subgroup analyses, anticoagulant use increased ICH risk (5.6% vs. 4.1%; OR, 1.40; 95% CI, 1.03–1.92), whereas antiplatelet use did not (3.9% vs. 4.1%; OR, 0.96; 95% CI, 0.70–1.32). Conclusions: In CCM patients without prior ICH, antithrombotic therapy was associated with increased risk of ICH and other adverse outcomes, primarily driven by anticoagulants.
TL;DR: Midlife obesity, but not late-life obesity, is associated with increased odds of amyloid positivity in late-life, highlighting the importance of midlife as a critical period influencing future brain health in adults without dementia.
Abstract: Introduction: In many people with Alzheimer’s disease (AD), vascular and metabolic disease are common and may contribute to disease pathogenesis. Obesity, defined as a body mass index (BMI) >= 30, has differential associations with brain health depending on when in the life course it is measured. It appears to be a risk factor when measured in midlife but not in late-life. Most current studies only use BMI to measure obesity, which does not differentiate fat distribution, a factor that can influence disease risk. In the Atherosclerosis Risk in Communities (ARIC) study, we investigated the association of obesity (measured using BMI, waist circumference (WC), and waist-to-hip ratio (WHR)) in midlife and late-life with late-life brain amyloid deposition on florbetapir PET as a marker of AD pathogenesis in adults without dementia. Methods: Participants were followed from 1987-1989 (visit 1; midlife, ages 45-64) and received a PET scan at a late-life visit (between visit 5 (2011-2013) and visit 11 (2025); ages 67-95). Our analysis included all participants with a PET scan who were dementia-free at time of scan. The measures of obesity were categorical BMI, sex-specific WC, and sex-specific WHR measured at midlife and late-life. Logistic regressions assessed the relationship between obesity measures and amyloid positivity (standardized uptake value ratio >1.2) in separate models. Models were adjusted for demographics and vascular risk factors. Results: In 803 participants meeting inclusion criteria, 438 were amyloid negative and 365 were amyloid positive. In midlife, those with obese, but not overweight, BMI had a 70% increase in odds of amyloid positivity compared to those with normal BMI (Table 1). In late life, neither overweight nor obese BMI was associated with amyloid positivity (Table 2). No relationship between categorical WC or WHR and amyloid positivity was seen at visit 1 or 5. Conclusion: Midlife obesity is significantly associated with increased odds of amyloid positivity in late-life in adults without dementia, but no association is seen with late-life obesity, overweight BMI at midlife or late-life, or WC or WHR. These findings highlight the importance of midlife as a critical period influencing future brain health and suggest BMI may be a more useful clinical marker than WC or WHR when evaluating the role of obesity in the development of dementia and perhaps AD in particular.
TL;DR: This study of 160 patients found that distal left M1 segment thrombectomy resulted in greater early language improvement compared to proximal left MCA occlusions, with female sex and lower baseline language severity associated with better outcomes.
Abstract: Background: The impact of arterial segment location on post-thrombectomy language improvement has not been well characterized. We evaluated trends in language function after thrombectomy and hypothesized that patients with proximal left MCA occlusions would show greater language improvement when compared to distal M1 occlusions post thrombectomy. Methods: A retrospective analysis of 160 patients who underwent thrombectomy of proximal left MCA vs. distal M1 occlusions was conducted. Baseline demographics, stroke severity, and language function were extracted. Language outcomes were assessed using NIHSS language sub-score (Question 9) before thrombectomy and 24-hour post. Multiple logistic regression was utilized to compare outcomes between proximal MCA trunk and distal M1 groups, adjusting for age, baseline NIHSS and language score. Patients with baseline aphasia (Item-9 > 0) and a defined endpoint of ≥1 point improvement in Item-9 at 24-hour post-thrombectomy were analyzed. We conducted a multivariable logistic regression, adjusting for age, sex, baseline Item-9 severity, thrombolytic use, and reperfusion success. Results: 160 patients with baseline aphasia were included (53.12% female, mean age [71.09 ± 13.78]) in the study. In this cohort, the left MCA main trunk vs. distal M1 was associated with lower odds of ≥1 point language improvement at 24 h (adjusted OR 0.48, 95% CI 0.24–0.95, p= 0.0362). Female sex showed higher odds of improvement (OR 2.05, 1.01–4.26, p= 0.0469). Greater baseline Item-9 severity trended toward lower odds (OR 0.67, 0.42–1.05). Thrombolytic use was not associated with improvement (OR 1.05, 0.48–2.40). Model discrimination: AUC 0.65 (95% CI 0.56–0.74). Conclusion: After thrombectomy, patients with distal left M1 demonstrated significantly greater early (24-hour) language improvement compared to patient with proximal left MCA occlusions following thrombectomy independent of age, baseline language severity, thrombolytic use, and reperfusion success. These findings support thrombus location as a practical predictor for early language recovery and may assist bedside prognostication after thrombectomy.
TL;DR: This study found that impaired cerebral autoregulation and increased hypoperfusion burden below the lower limit of cerebral autoregulation are associated with postoperative acute kidney injury in non-cardiac surgery patients, highlighting the need for personalized hemodynamic management.
Abstract: Introduction: Interindividual variation in the lower limit of cerebral autoregulation (LLA) challenges fixed mean arterial pressure (MAP) targets. We assessed whether impaired cerebral autoregulation and hypoperfusion burden below the LLA are associated with acute kidney injury (AKI) after noncardiac surgery. Methods: Adults undergoing major noncardiac surgery had continuous intraarterial pressure and bifrontal nearinfrared spectroscopy monitoring. Bilateral frontoparietal near infrared spectroscopy monitoring of regional cerebral oxygen saturations (rSO2) and invasive MAP were captured intraoperatively and analysed using wavelet semblance. The LLA was defined as the MAP corresponding to the inflection point on semblance vs MAP plots, with semblance values >0.3 indicating impaired autoregulation. Hypoperfusion burden was quantified as the area under the curve for pressure values below the LLA (mmHg.min). The primary outcome was AKI (Kidney Disease: Improving Global Outcomes). Between group comparisons used t-tests or Wilcoxon rank–sum for continuous data and χ 2 /Fisher’s exact tests for categorical data; covariate adjusted associations were explored using multivariable logistic regression. Relevant ethics approvals were prospectively obtained (PAABLo: HREC/18/QPCH/48043, ACTRN12617001365358; Wavelet HREC/17/QPCH/33, ACTRN12617000834392) and all participants provided written informed consent. Results: One hundred and four patients contributed 19,416 monitored minutes. An LLA was identifiable in 85% (88/104). In those with a detectable LLA, the median LLA was 70 mmHg (IQR 56.3–77.5, Figure 1). Across all patients, 15% of monitored time occurred with mean arterial pressure below the LLA. AKI occurred in 16/101 (15.8%). Compared with patients without AKI, those with AKI had higher mean semblance consistent with impaired autoregulation (0.3 [IQR 0.2–0.4] vs 0.2 [0.1–0.3]; p=0.005), larger hypoperfusion burdens(AUC<LLA 235.7 mmHg.min [IQR 24.2–520.1] vs 42.0 mmHg.min [IQR 0.3–248.9]; p=0.033), and longer durations with pressure below the LLA (40.1 min [IQR 2.3–53.1] vs 9.8 min [IQR 0.5–39.2]; p=0.031). Conclusions: Impaired cerebral autoregulation and greater hypoperfusion burden below the patient specific LLA are associated with postoperative AKI. Marked interindividual LLA variability undermines one size fits all pressure targets and justifies randomised trials of personalised, autoregulation guided haemodynamic management.
TL;DR: This retrospective study of 65 ICH patients found that follow-up MRI rarely changed clinical management, with only 1 patient's management altered, and no significant association between clinical factors and alternative etiology identification.
Abstract: Introduction: Intracerebral hemorrhage (ICH) is a common neurologic diagnosis characterized by the accumulation of blood within the brain parenchyma. While the most common etiology of nontraumatic ICH is hypertension, Magnetic Resonance Imaging (MRI) is often performed to identify alternative ICH etiologies. Sometimes additional follow-up MRI is performed to assess brain parenchyma for etiologic lesions after time is given for blood products to clear. Research is limited in evaluating the utility of such follow-up imaging. This retrospective chart review study was conducted to quantify the frequency of and risk factors associated with a change in ICH etiology on follow-up MRI. Methods: ICH cases at an academic, public, comprehensive stroke center from April 2017 to December 2024 were identified using, SlicerDicer, an Epic integrated informatics tool. Information on patient demographics, medical history, social history, initial and follow-up imaging results, and follow-up visits were collected by chart review. Patients were included if they received MRI inpatient and were recommended to receive follow-up MRI 2-3 months later as an outpatient. Correlational analysis between odds of change in etiology and clinical or demographic variables was analyzed using Firth’s logistic regression. Results: This study included 65 patients with a mean age of 61.5 (SD=14.4). 28 (43%) were female assigned at birth. 36 (55%) patients with ICH received both an inpatient and follow-up MRI leaving 29 (45%) lost to follow-up after discharge. Of those who completed follow-up MRI, the underlying etiology of ICH was identified in 4 (11%) cases. Repeat imaging changed management for only 1 (3%) patient. Correlational analysis showed no significant association with changes in etiology on repeat MRI. Conclusions: In conclusion, follow-up MRI rarely changed clinical management in this sample, and no clinical or demographic factors were associated with a statistically significant increased odds of finding an alternative etiology of ICH. Additionally, nearly half of the patients recommended to receive outpatient MRI were lost to follow-up. Future work will aim to further characterize individuals who are most likely to benefit from follow-up MRI by predictive modeling to reduce healthcare expenditure and unnecessary imaging. Additionally, future work should aim to evaluate barriers to outpatient follow-up MRI when indicated.
TL;DR: This study evaluates the effectiveness of an Integrated Chinese-Western Medicine (ICWM) program in stroke rehabilitation, finding significant improvements in mobility, daily living activities, and swallowing function compared to conventional rehabilitation, with TCM syndromes associated with better recovery.
Abstract: Background: Post-stroke permanent disability posed a huge socio-economic burden. It was unclear whether adjunctive traditional Chinese medicine (TCM) consisting of acupuncture and herbal therapy in an Integrated Chinese-Western Medicine (ICWM) rehabilitation programme might improve stroke outcomes. Objective: We aimed to evaluate the safety and efficacy of an ICWM Programme implemented in public hospitals in Hong Kong since 2014. Methods: In this retrospective cohort study, we compared the outcome of all patients who received ICWM treatment during acute-to-subacute phase of strokes between September 2014 and December 2022 with that of control patients who underwent conventional stroke rehabilitation in the same period selected by propensity score matching in a 1:1 ratio. We measured and compared 3 functional outcomes between ICWM and control groups by multivariable generalized linear models: 1) Ambulation as measured by the Modified Functional Ambulatory Category (MFAC); 2) Activities of daily living by the Modified Barthel Index (MBI); and 3) Swallowing function by the Royal Brisbane Hospital Outcome Measure for Swallowing (RBHOMS). We conducted a secondary analysis to determine the association between functional recovery and TCM syndromes. Results: Of the 917 patients who received ICWM and the 21,342 patients with conventional stroke rehabilitation, 666 pairs were matched. Baseline characteristics, including MFAC, MBI and RBHOMS scores at stroke onset were balanced. The magnitude of improvement in MFAC (ICWM vs control: 1.3±1.2 vs 0.9±1.3, P <0.001), MBI (16.9±15.3 vs 9.2±14.9, P <0.001) and RHOMBS (1.1±1.4 vs 0.4±1.4, P <0.001) was significantly higher in the ICWM group compared to the control group. On discharge, MFAC (5[4, 6] vs 4[3, 6], P =0.03) and RBHOMS (8 [7, 9] vs 8 [6, 9], P <0.001) were significantly higher in the ICWM group. Among patients participating in the ICWM program, Phlegm-Heat Syndrome and Wind-Phlegm Syndrome were associated with better functional recovery. Conclusion: Compared to conventional stroke rehabilitation, the ICWM program was associated with a greater magnitude of stroke recovery in terms of mobility, activities of daily living, and swallowing function. Furthermore, TCM syndrome categorization may inform stroke prognosis.
TL;DR: This study reveals significant scanner-dependent variability in CT clot radiomics, with 54 of 107 texture features differing between two clinical CT systems, highlighting a critical bottleneck for clinical translation and emphasizing the need for harmonization approaches to ensure trustworthy biomarkers.
Abstract: Introduction: Radiomics enables quantitative analysis of clot texture, which serves as a proxy for clot biology and may guide thrombectomy and thrombolysis outcomes. However, radiomic features are highly sensitive to scanner and protocol variability, a barrier that has not been systematically evaluated in clot radiomics. We experimentally tested scanner-dependent effects using standardized clot models. Methods: Synthetic clots (40% red blood cells), with and without neutrophil extracellular traps (NETs), were fabricated (n=8) and imaged on two clinical CT systems: GE LightSpeed VCT and Canon Aquilion One (4D CT), using stroke protocols. Clots were segmented, and paired comparisons of volume, mean Hounsfield Units (HU), and 107 radiomic features (RFs) were performed with Wilcoxon tests, FDR correction, log-fold change, and Cohen’s d. Results: Volumes and mean HU were comparable across scanners (GE 405.5±71.2 mm3 vs. Canon 407.6±80.2 mm3, p=0.74; GE 11.3±6.7 HU vs. Canon 9.2±7.5 HU, p=0.35). In contrast, texture RFs diverged sharply: 64 of 107 RFs differed at p<0.05, 54 remained significant after FDR correction, 13 showed |log-fold change|>1, and 11 demonstrated |Cohen’s d|>1.2. Features most affected included First-order variance and 10th percentile; GLCM cluster tendency, cluster prominence, cluster shade; GLDM gray-level variance, large-dependence low-gray-level emphasis; GLSZM gray-level variance, large-area low-gray-level emphasis; NGTDM complexity and strength. Histogram PDFs confirmed scanner-specific distributions: GE images showed broader, diffuse intensity patterns, while Canon images appeared more condensed near the mean. Qualitatively, GE scans exhibited higher GLCM cluster tendency, reflecting more homogeneous appearance. Conclusions: Gross clot measures (volume, HU) are scanner-robust, but radiomic texture features vary substantially, exposing a critical bottleneck for translation. This is the first study to empirically demonstrate scanner-dependence in clot RFs. Impact: Recognizing and correcting scanner-dependent biases is essential. Solving this problem through harmonization approaches such as ComBat will enable trustworthy, reproducible clot biomarkers across sites. Addressing this bottleneck opens the door for radiomics to reach its full potential as a powerful adjunct to vessel morphometrics, demographics, and comorbidity data in predicting thrombectomy and tPA outcomes, ultimately paving the way for personalized stroke management at scale.
TL;DR: Regular dental flossing is independently associated with a 12% reduced risk of incident dementia, translating to an absolute risk reduction of 7% and a number needed to floss of 14, after adjusting for various covariates in a cohort of 9,766 participants.
Abstract: Background: Periodontitis is a potential modifiable factor influencing dementia risk. We examined whether improving periodontal health via regular flossing is associated with lower dementia risk. Methods: A total of 9,766 Atherosclerosis Risk in Communities (ARIC) study participants with teeth were followed from visit 4 (1996-1998) through 2021. Cox proportional hazards regression was used to estimate associations between regular dental flossing (≥1/week) and incident dementia. Covariates included age, race, gender, hypertension, diabetes, alcohol use, smoking status, obesity, physical activity, education level, income, insurance status, brushing frequency, regular dental care use and apolipoprotein E4 (APOE4) allele status . Cumulative incidence functions were estimated using death as a competing event. Results: Participants had mean age 62.6 years (SD = 5.6), 56% female, 79% white, 21% black, 63% reported regular flossing and 29.2% participants carry at least one APOE4 allele. The cumulative incidence of dementia was 52.6 % overall over 25 years. Regular flossing was independently and significantly associated with a lower hazard of developing dementia (HR = 0.90, 95% CI: 0.82–0.98, p = 0.02) after adjustment for all the covariates. In contrast, tooth brushing frequency (p=0.55) and regular dental care visit (p=0.22) were not significantly associated with dementia risk. By 25 years of follow-up, the cumulative incidence of dementia was 50% among flossers compared with 57% among non-flossers (Gray’s test p<0.0001, Figure). This translated to an Absolute Risk Reduction of 7%, Relative Risk Reduction of 12%, Number Needed to Floss 14. Conclusion: Flossing, but not tooth brushing or regular dental care, is independently associated with a reduced hazard of incident dementia. Dental flossing may be an additional strategy to reduce dementia risk. For every 14 individuals who floss ≥1/week, one fewer person will develop dementia.
TL;DR: A 60-day dual antiplatelet therapy (DAPT) followed by lifelong aspirin monotherapy is safe and effective for patients with intracranial aneurysms treated with the Pipeline Flex-Shield Embolization Device, with promising results for early DAPT cessation.
Abstract: Introduction: Flow-diverting stents traditionally require dual antiplatelet therapy (DAPT) to prevent thromboembolic complications, though DAPT is associated with high hemorrhagic risk (up to 27%). The Pipeline™ Flex Embolization Device with Shield Technology™ incorporates a phosphorylcholine polymer (<3 nm) to reduce thrombogenicity, with in vitro data demonstrating lower thrombin generation and platelet activation. Early clinical experience, including 15 ruptured aneurysms treated with aspirin alone, suggests PED Shield may allow safe use with reduced or single antiplatelet therapy. Methods: A prospective, single arm, open label EFS was conducted to evaluate the safety and preliminary effectiveness of PED Shield with reduced duration of DAPT (60 days). Ten patients were enrolled and monitored by a DSMB for safety. All received 60 days of DAPT with aspirin (325 mg) and clopidogrel (75 mg); clopidogrel non-responders (P2Y12 > 200) received ticagrelor (90 mg BID) instead. After 60 days, DAPT will transition to lifelong aspirin monotherapy. Results: Ten patients (median age 60.5 years; 8 female, 9 White) with baseline mRS 0 underwent endovascular treatment of intracranial aneurysms. Locations included superior hypophyseal (n=3), posterior communicating (n=3), ophthalmic (n=2), cavernous ICA (n=1), and dorsal ICA (n=1); median dome and neck diameters were 4.2 mm and 3.1 mm. Four aneurysms had blebs, and three showed dome-branch incorporation. Procedures were performed under conscious sedation with balloon guide catheter (n=3) or triaxial system (n=4); median groin-to-deployment and total procedural times were 36 and 48 minutes. Immediate post-deployment angiography showed complete occlusion in all cases. Post-procedural MRI revealed new clinically silent DWI lesions in 2 patients. During follow-up (median 377 days), two ischemic events occurred: one transient ischemic attack and one minor stroke; no in-stent thrombosis or alternative etiology was found. Remaining patients maintained mRS 0. At median angiographic follow-up of 367 days, seven aneurysms were fully occluded, two had neck remnants, and one remained unoccluded. Among seven patients with 12-month DSA, six showed complete occlusion. Conclusion: Preliminary results suggest early promise for discontinuing DAPT at 60 days following PED Shield placement. The study is now accelerating enrollment to expand the cohort and strengthen evidence supporting early DAPT cessation.
TL;DR: This study identifies three distinct brain imaging subtypes in 5,732 adults, linked to vascular risk profiles, with varying patterns of gray matter volume loss and white matter hyperintensity accumulation, highlighting the complexity of brain changes with age and vascular risk.
Abstract: Background: Age and vascular risk factors (VRFs) contribute to changes in brain structure which include accumulation of white matter hyperintensities (WMH), gray matter (GM) atrophy. However, data from simultaneous examination of GM and WMH volumes in relation to VRFs and aging are sparce. Therefore, we used an advanced multi-modal deep learning approach to identify synergistic brain structural changes in relation to VRFs. Methods: We used clinical brain MRIs acquired in 5,732 community-dwelling adults (age 50–76; n=3,088 women). Anyone with known neurological diagnosis or evidence of structural lesions resulting from a neurological diagnosis, was excluded. Deep Non-Negative Matrix Factorization Neural Network was jointly applied to GM volumes and total WMH burden, followed by unsupervised consensus clustering. Cluster assignments were linked to demographics and vascular risk factors (VRFs: hypertension, diabetes, dyslipidemia, coronary artery disease, smoking, BMI) by ANOVA and Chi-square testing. Results: Our analysis revealed three robust imaging subtypes (clusters). The overall difference between the clusters is shown as a heatmap which highlights GM regions and WMH volume that differentiated the clusters (Figure 1). Cluster 1 had the highest WMH burden and pronounced GM loss across multiple regions. Clusters 2 and 3 had similar WMH burden (less than cluster 1), but they differed in GM structures. Frontal and subcortical GM volumes were relatively preserved in cluster 2, while cingulate, parahippocampal, and precuneus volumes were relatively preserved in cluster 3 (Figure 2). Table 1 summarizes the VRF profile of clusters. Cluster 1 individuals were older and had a higher VRF burden than the other two clusters. Cluster 2 and 3 had similar VRF profile. Conclusion: Our findings highlight distinct patterns of GM volume loss and WMH accumulation associated with age and VRFs. While the cluster with greatest VRF burden exhibited global GM loss and highest WMH burden, other two, which had similar WMH and VRF profiles had distinct patterns of GM atrophy. Whether these GM atrophy profiles translate to distinct cognitive profiles is unknown, but the expectation is that cluster 2 would exhibit preserved executive function while and cluster 3 would exhibit better memory function. Ongoing work is targeting analyses to further phenotype these clusters and advance our understanding of underlying mechanisms selecting different patterns of GM atrophy in relation to VRFs.
Aliza Brown, Lori Berry, R. E. BANKS, Brandi Alred, Journey Woods, Julia Weatherford, Joanne Sullivan, Jennifer McCurry, B Simon, T. Glenn Pait, Rohit Dhall, Krishna Nalleballe, Sanjeeva Onteddu
TL;DR: The UAMS IDHI Telestroke Program in Arkansas significantly improved acute stroke treatment access, efficiency, and outcomes, increasing consult volume 164%, lytic-treated patients 3-fold, and median door-to-needle times from 120 to 50 minutes from 2015 to 2024.
Abstract: Background: Arkansas has one of the highest stroke mortality rates in the United States, driven by rural–urban disparities in access to timely interventions. The UAMS Institute for Digital Health&Innovation (IDHI) Telestroke Program was developed to provide 24/7 Vascular Neurology and Neurosurgery expertise via a hub-and-spoke network. Integration of spoke-site nursing facilitators, hub-site stroke coordinator teams and formal program evaluation enables continuous performance monitoring and targeted quality improvement. Methods: We retrospectively analyzed prospectively collected telestroke consult data from 2015–2024. Key measures included consult volume, intravenous thrombolytic (lytic) use, door-to-needle (DTN) times, and patient outcomes. Linear trend projections estimated metrics through 2027. Results: From 2015 to 2024, consult volume increased 164% (809 to 2,140), lytic-treated patients rose from 238 to 775 (>3-fold), and those receiving lytics within 60 minutes increased from 59 to 526. Median DTN times improved from 120 minutes at program inception to 50 minutes in 2024. The proportion of lytic-treated patients achieving DTN ≤60 minutes improved from 25% to 68%, with projections approaching 95% by 2027. Mortality remains low at 3.4%, with 62% of patients discharged home. Conclusions: The UAMS IDHI Telestroke Program has significantly improved acute stroke treatment access, efficiency, and outcomes in a high-burden rural state. Analytics-driven program evaluation has enabled sustained performance gains and equitable care delivery, offering a scalable model for other underserved regions.
TL;DR: This study examines the relationship between vascular calcification burden and outcomes in acute ischemic stroke patients undergoing endovascular therapy, finding associations between calcification in the cervical ICA and aortic arch with worse functional outcomes and longer procedural times.
Abstract: Background: Vascular calcification has been linked to poor outcomes in ischemic stroke, but most prior studies have focused on intracranial arteries alone. The prognostic impact of combined calcification burden across multiple vessel beds in patients undergoing endovascular therapy (EVT) remains unclear. Objective: To determine whether automated, quantitative calcification measurement in the aortic arch, cervical internal carotid artery (ICA), and intracranial ICA predicts EVT outcomes. Methods: We retrospectively analyzed patients with acute ischemic stroke treated with EVT from 2018–2022. CT angiography (CTA) studies underwent automated calcification quantification using a deep learning U-net model. Calcification burden was calculated separately for each vessel bed and combined. High burden was defined as ≥75th percentile of the cohort. Clinical, imaging, and procedural data were collected. Primary outcomes were favorable recanalization (TICI 2b–3) and favorable functional outcome (mRS 0–2) at 90 days. Multivariable logistic regression adjusted for clinical and procedural covariates. Results: A total of 384 patients were included (mean age 64.4 ± 15.9 years, 48.2% female). Median admission National Institute of Health stroke scale (NIHSS) was 14, median baseline modified Rankin Scale (mRS) was 0, 67% had middle cerebral artery occlusion, and 34% received IV thrombolysis. There was no association between calcification burden and favorable recanalization rate (Figure 1). Higher cervical ICA burden was associated with longer time from groin stick to first pass (p=0.014), but no difference observed in number of passes. Greater cervical ICA and aortic arch calcification were associated with lower likelihood of favorable functional outcomes at 90-days (p = 0.007 and p = 0.009, respectively; Figure 2). In multivariable models, baseline NIHSS and pre-stroke mRS but not vascular calcification remained independent predictors of functional outcome. Conclusion: High calcification burden in the cervical ICA and aortic arch is associated with worse unadjusted functional outcomes after EVT, but NIHSS and mRS remain independent factors. Higher cervical ICA calcification is associated with longer procedural time but does not affect the outcome.
TL;DR: Early dispatch of Mobile Stroke Treatment Units (MSTUs) to large vessel occlusion stroke patients via prehospital Emergency Medical Services (EMS) diagnostics improves arrival time and CT scan completion, potentially leading to better outcomes, but further studies are needed to optimize dispatching accuracy.
Abstract: Introduction: Stroke requires early recognition and dispatch of adequate Emergency Medical Services (EMS). Traditional EMS dispatch systems are not geared toward the utilization of Mobile Stroke Treatment Units (MSTUs). We evaluated the initial dispatched complaint for patients with large vessel occlusion (LVO) strokes and evaluated if the time of MSTU dispatch impact stroke patient outcomes. Methods: We reviewed all patients with LVO ischemic strokes evaluated in the MSTU between 7/25/23 to 6/30/25. All patients who initiated their 911 calls in Alachua County were included in the study. We reviewed EMS dispatch records to determine the time of call, initial complaint, and whether the MSTU was dispatched at the time of the call (early dispatch) or at a later time (late dispatch). Stroke metrics such as time to CT and time to needle, and time to puncture were calculated from the initial 911 call. We also evaluated discharge NIHSS and modified Rankin Score (mRS). Univariate and multivariate logistic regression analyses were performed to evaluate differences between patients with early vs late MSTU dispatch. Results: In this study, 48 patients with LVO were treated on the MSTU (mean age of 72 years and 50% male); in 24 cases the MSTU was dispatched early. The most common reasons for late dispatch were unconscious/fainting (29%), fall (29%) and other (34%). Initial NIHSS was higher for late-dispatch patients. The early MSTU dispatch group arrived faster to scene (15.5 vs. 26.3 min., p<0.001) and had CT scan completed faster (29.5 vs. 36.8 min., p=0.003). Time to thrombolytics and time to groin puncture were also faster but not statistically significant (Discharge NIHSS was significantly lower in the early MSTU dispatch group (mean 2.25 vs. 8.46, p=0.045), but there were no differences in mRS when dichotomized to good (mRS 0-2) vs. poor outcomes (3-5). On logistic regression analysis adjusting for age, gender, initial NIHSS, and TNK treatment, there were no differences in discharge NIHSS (OR 0.96 (CI 0.68-1.01), p=0.014) or discharge mRS (OR 1.06 (CI 0.15-8.12), p=0.95). Conclusion: Early MSTU dispatch results in faster arrival on scene and faster CT. Late dispatch was more likely to occur for calls that did not specifically report “stroke” or in the setting of higher NIHSS, which could affect the caller and dispatch ability to assess for stroke. Further studies are warranted to optimize the accuracy of the current dispatching system.
Vincent Brissette, Zoe Tsai, Timothy Ramsay, Elham Sabri, Brian Dewar, Risa Shorr, Robert Fahed, Michel Shamy, Mayank Goyal, Michael Hill, D Dowlatshahi
TL;DR: This meta-analysis of 1,182 patients found that a lower Alberta Stroke Program Early CT Score (ASPECTS) was significantly associated with higher odds of any intracerebral hemorrhage (ICH) after endovascular therapy for anterior circulation stroke, but not symptomatic ICH.
Abstract: Introduction: Despite the success of endovascular thrombectomy (EVT) for ischemic stroke, complications such as intracerebral hemorrhage (ICH) occur. In individual studies, the Alberta Stroke Program Early CT Score (ASPECTS) predicts ICH risk, but comprehensive data are lacking. We conducted a systematic review and pooled patient meta-analysis to evaluate the association between ASPECTS and ICH after EVT. Methods: We searched MEDLINE, EMBASE, CINAHL, PsycINFO, Web of Science, and Cochrane from January 1, 2012, to July 1, 2024. We included randomized controlled trials and prospective observational studies of patients ≥18 years old with anterior circulation ischemic stroke on CT, CTP, or DWI-MRI who underwent EVT within 24h of symptoms onset. The primary outcome was the association between ASPECTS and symptomatic ICH; the secondary outcome was ASPECTS and any ICH. For the meta-analysis, we conducted an exploratory analysis to identify covariates for the multivariable model. Odds ratios (OR) with 95% CI were calculated, adjusting for hypertension, diabetes, National Institutes of Health Stroke Scale (NIHSS) score, time from symptoms onset to randomization, and modified Thrombolysis in Cerebral Infarction (mTICI) score. Results: A total of 3,290 studies were screened, with 31 selected for full-text review. Thirteen met inclusion criteria: 11 randomized controlled trials and 2 prospective observational studies. Symptomatic ICH rates ranged from 0–11.7%, and any ICH from 2.8–91.5%. Data from DEFUSE3, ESCAPE, ESCAPE-NA1, and IMS3 were included in the patient-level meta-analysis, comprising a total of 1,182 patients. A 1-point lower ASPECT score was not associated with higher odds of symptomatic ICH (OR 1.01; 95% CI 0.90, 1.14; p=0.84) but was associated with higher odds of any ICH (OR 1.19; 95% CI 1.12, 1.27; p<0.0001). Compared with ASPECT score 9–10, categories 6–8, 3–5, and 0–2 were all associated with increased odds of any ICH (Table 1). Conclusion: In this patient-level meta-analysis, a lower ASPECT score was significantly associated with higher odds of any ICH, but not symptomatic ICH. These findings provide important information on complications in patients with larger stroke burden treated with EVT.
TL;DR: This study introduces the Optimizing Post-Stroke Intervention Methods for Recovery (OPTIM-R) trial, a prospective superiority trial comparing individualized upper extremity rehabilitation with conventional standardized therapy in post-stroke patients, addressing methodological limitations of a previous study.
Abstract: Introduction: The Critical Periods After Stroke Study (CPASS; n=72) was a Phase II RCT testing 20 additional hours of individualized upper extremity (UE) therapy within 1-year post-stroke at acute (<30d), subacute (2–3mo), and chronic (6–9mo) timepoints. Compared with controls, subacute participants achieved Action Research Arm Test (ARAT) gains exceeding the minimal clinically important difference (p=0.009), while acute participants showed smaller but significant improvement (p=0.043). The chronic group showed no significant gains, suggesting a critical recovery period. CPASS used a usual care control. An intensity-matched active control is needed to clarify whether recovery reflects timing, therapy content, or both. This study outlines the methodological decisions guiding the Optimizing Post-Stroke Intervention Methods for Recovery (OPTIM-R) trial, which introduces a standardized, equal-intensity active control (figure 1) . Hypothesis: Individualized UE rehabilitation will produce superior 1-year ARAT outcomes relative to conventional standardized therapy. Methods: OPTIM-R is a prospective superiority trial comparing the CPASS subacute cohort with a newly recruited active control group. Key design features include aligning assessments and outcomes with CPASS to ensure comparability while reducing participant burden, initiating therapy within 0–3 months to capture acute and subacute participants, and excluding CPASS’s individualized elements to isolate treatment effects. Strategic design choices ensured fidelity to CPASS while making the intervention reproducible and distinct from the experimental arms. The primary outcome is 1-year ARAT scores, analyzed with generalized estimating equations consistent with CPASS. 24 participants meeting CPASS inclusion/exclusion criteria will be enrolled using stratified methods to balance the new cohort, chosen instead of adaptive randomization since the active control does not include multiple groups. Conclusion: By establishing an intensity-matched active control, OPTIM-R addresses the methodological question raised by CPASS, enabling direct comparison of individualized therapy with equal-intensity conventional care. This design clarifies whether personalization of UE therapy provides added benefit when delivered at the same post-stroke time point. By emphasizing fidelity, feasibility, and reproducibility, OPTIM-R advances methodological rigor and offers a replicable framework for future stroke rehabilitation trials.
TL;DR: This study investigates the association between idiopathic intracranial hypertension (IIH) and ischemic stroke (IS) in a large US cohort, finding no significant link after adjusting for cardiovascular risk factors, despite similar IS rates in IIH and migraine patients.
Abstract: Introduction: Idiopathic intracranial hypertension (IIH) is a rare cause of headache that is associated with several adverse health outcomes. A recent study demonstrated an association between IIH and ischemic stroke (IS) in a large European cohort, after accounting for obesity and other cardiovascular risk factors. Given the well-established relationship between migraine and stroke, we sought to use US population-level data to further explore the association between hospitalization for IS and IIH as well as with migraine with and without aura. Methods: We conducted a retrospective cohort study using statewide administrative claims data encompassing emergency department presentations and inpatient hospitalizations from the Healthcare Cost and Utilization Project across 11 states between 2016 and 2021. Patients with IIH (primary cohort) or migraine (comparison cohort) were identified using validated ICD-10-CM codes. The primary study endpoint was hospitalization for IS, also defined using validated codes, after an initial headache diagnosis. Cox regression models assessed the association between IIH and IS after adjustment for demographics and cardiovascular risk factors (including obesity). Results: We identified 11,861 patients with diagnoses of IIH and 862,209 patients with diagnoses of migraine. In comparison to patients with migraine, patients with IIH were younger, more often female and of a non-White race, and had higher rates of comorbid hypertension, diabetes, atrial fibrillation, coronary artery disease, congestive heart failure, obstructive sleep apnea, and obesity. During a median follow-up time of 3.3 years, 11 patients (0.09%) with IIH were hospitalized for IS, compared to 534 patients (0.06%) with migraine. Multivariable Cox regression analysis did not demonstrate a significant association between IIH and incident IS (adjusted HR 1.43, 95% CI, 0.79–2.61). Conclusion: Although IIH and migraine had similar rates of incident IS in a large nationally representative US cohort, we found no association between IIH and IS after adjustment for cardiovascular risk factors. The relationship between IIH and incident stroke requires further exploration.
TL;DR: Endothelial protease-activated receptor 1 deletion preserves blood-brain barrier integrity, reduces lesion volume, and enhances functional recovery after ischemic stroke, suggesting a critical role in mediating BBB disruption and potential therapeutic target for stroke treatment.
Abstract: Introduction: Ischemic stroke remains a leading cause of adult disability worldwide, with limited treatment options. Blood-brain barrier (BBB) breakdown is a key pathological event after stroke, as it promotes vasogenic edema and hemorrhagic transformation, leading to worse neurological outcomes. Understanding how different components of the neurovascular unit contribute to BBB breakdown is essential for developing new treatments. Hypothesis: We hypothesized that the activation of protease-activated receptor 1 (PAR1) in endothelial cells exacerbates BBB breakdown after ischemic stroke, and targeted endothelial PAR1 deletion would improve outcomes. Methods: We used a novel endothelial cell-specific, tamoxifen-inducible PAR1 knockout (KO) mouse line (TIE2Cre ERT2 PAR1 f/f ) in the current study. Age matched male and female mice (n = 11/sex/group) were randomized to receive daily intraperitoneal injections of vehicle or tamoxifen (150 mg/kg) for 3 days. Ten days after the final vehicle/tamoxifen injection, transient left middle cerebral artery occlusion (MCAo) was performed for 60 min followed by reperfusion. BBB permeability was assessed 2 days after stroke using dynamic contrast-enhanced (DCE) MRI to calculate the plasma-to-tissue transfer constant (K trans ) of gadolinium. Lesion volume was measured 2- and 30-days poststroke with T2-weighted MRI. Neurological recovery was evaluated using neurological deficit scoring (NDS), corner test and Barnes maze. Results: Endothelial PAR1 deletion significantly reduced BBB disruption 2 days after stroke (relative K trans 2.95 vs 1.76, P < 0.05). Lesion volume was also decreased in the endothelial PAR1 KO group at both days 2 (29.88 ± 16.49 mm 3 vs 19.69 ± 7.304 mm 3 , P < 0.05) and 30 poststroke (10.51 ± 4.464 mm 3 vs 6.725 ± 3.708 mm 3 , P < 0.01). In addition, endothelial PAR1 deletion significantly improved functional outcome in NDS on day 2 (P < 0.05) and mean reversal test in Barnes maze on day 30 (P < 0.01). However, no significant difference was observed in the corner index on day 7 after stroke. Conclusion: In conclusion, our results demonstrate a critical role of endothelial PAR1 in mediating BBB disruption after ischemic stroke. Specific deletion of endothelial PAR1 using TIE2 Cre preserves BBB integrity, reduces lesion volume and promotes functional recovery. Further studies are required to investigate the role of endothelial PAR1 on the regulation of tight junction integrity and neuroinflammation after stroke.
TL;DR: This study evaluates portable low-field MRI (Hyperfine) against CT for subdural hematoma thickness measurement, demonstrating good agreement and no significant differences, with potential benefits of radiation-free and bedside imaging.
Abstract: Background: Accurate assessment of subdural hematoma (SDH) thickness is critical for clinical decision-making. While non-contrast computed tomography (CT) remains the gold standard, Hyperfine portable low-field MRI offers key advantages by eliminating radiation exposure and can be performed at the bedside in both inpatient and outpatient settings. Methods: At our community based, university medical center, we retrospectively analyzed 15 patients with acute, subacute, and chronic convexity SDHs who underwent both non-contrast CT and Hyperfine MRI within a 3 day period. Maximum SDH thickness was measured in both the axial and coronal planes. Agreement between modalities was assessed using Bland–Altman analysis, and paired t-tests were performed to evaluate systematic differences. Results: A Bland–Altman analysis demonstrated good overall agreement between Hyperfine MRI and CT in measuring convexity SDH thickness. In the axial plane, Hyperfine measurements were on average 0.35 mm greater than CT (bias = +0.35 mm), with 95% limits of agreement ranging from –3.20 to +3.90 mm. In the coronal plane, Hyperfine measurements were on average 0.71 mm less than CT (bias = –0.71 mm), with wider 95% limits of agreement (–6.61 to +5.20 mm). Paired t-tests showed no statistically significant difference between modalities in either the axial (p = 0.47) or coronal (p = 0.38) views. Discussion: These findings indicate that portable low-field MRI provides comparable estimates of SDH thickness relative to non-contrast CT. The small mean differences suggest no systematic bias, and the lack of statistical significance reinforces that Hyperfine measurements are not meaningfully different from CT. Agreement was tighter in the axial plane, where differences generally remained within ±4 mm, whereas coronal measurements showed greater variability, extending to ±6 mm. From a clinical perspective, these differences are unlikely to alter decision-making in most cases, particularly for monitoring hematoma progression or stability. Importantly, Hyperfine MRI offers the advantages of avoiding radiation exposure and enabling bedside imaging, which may expand access to neuroimaging in settings where CT is less practical or safe.
TL;DR: This study compares outcomes of aneurysmal subarachnoid hemorrhage patients directly admitted to a Comprehensive Stroke Center versus those transferred from other hospitals, finding no significant differences in discharge disposition, length of stay, or modified Rankin Scale change.
Abstract: Introduction: Aneurysmal Subarachnoid hemorrhage (SAH) is a neuroemergency requiring early intervention, advanced neurocritical care, and multidisciplinary expertise. The American Heart Association (AHA) recommends transferring SAH patients to Comprehensive Stroke Centers (CSCs) for definitive management. The impact of interhospital transfer (IHT) on outcomes has not been well studied. We compared outcomes among SAH patients transferred through the Neuroemergencies Management and Transfers (NEMAT) program versus those admitted directly via the Emergency department (ED) to our CSC. Methods: Data were collected from Get With the Guidelines (GTWG) and NEMAT QA databases within the Mount Sinai Health System (1/1/2021-5/30/2025). Primary outcomes were discharge disposition, length of stay (LOS), and change in modified Rankin Scale (mRS) from admission to discharge, with transfer status as the primary predictor. Covariates included sex, age, Hunt-Hess score, pre-stroke mRS, and mortality. Associations between transfer status and outcomes were assessed with bivariate analyses (Fisher’s exact for discharge, Wilcoxon rank-sum test for LOS, and t-test for mRS change). Multivariable regression models were constructed for each outcome (multinomial for discharge, gamma for LOS, linear regression for mRS change), adjusting for covariates. Results: Of 385 SAH patients, 343 were transfers, 61.6% female, median age 58 (IQR: 20), median Hunt-Hess score 2 (IQR: 2), and12.2% deceased. At discharge, 196 patients went home, 120 to rehabilitation, 47 expired, 13 to acute care, 7 left against medical advice, and 2 to hospice. Median LOS was 16.4 days (IQR 17.1) and mean change in mRS was 2.35 (SD 1.94). Transfer status was not associated with discharge disposition (p>0.999) or adjusted models, except for hospice (RR: 901.63, p=0.001), though only 2 patients went to hospice. Transfer status was linked to longer LOS in unadjusted analysis (median difference: 6.66 days, p=0.004), but not significant after adjustment (10% decrease, median adjusted decrease of 1.66 days, p=0.562). Transfer status was not associated with change in mRS, unadjusted (mean difference: 0.73, p=0.171) or adjusted (β=0.12, p=0.789). Conclusion: In a large urban health system with centralized triage and transfer, aSAH patients undergoing IHT had outcomes comparable to direct ED admits. Larger multicenter studies are needed to confirm these findings and evaluate transfer-related effects across diverse settings.
TL;DR: This study investigates the effect of graded body-weight and incline training on plantar flexor activation in stroke survivors, finding significant increases in activation with increased body-weight loading, particularly at 75% and 90% of body weight.
Abstract: Introduction: The plantar flexors (PFs) are crucial for ankle push-off during gait, providing forward propulsion and controlling foot movement during the stance phase. In stroke survivors, reduced activation of the PFs leads to difficulty with propulsion and toe clearance, contributing to abnormal gait patterns known as hemiplegic gait. This issue is often exacerbated by decreased weight bearing (WB) on the paretic limb and adaptive shortening on the paretic PFs, as PF activation is highly dependent on loading input for balance and gait. Purpose and Hypothesis: This study investigates whether simultaneously increasing paretic WB and PF muscle length can enhance paretic PF muscle activation during a dynamic skateboarding task. We hypothesize that this combination will significantly increase paretic PF activation. Methods: This study was a single-session, randomized controlled trial. We recruited 15 individuals with chronic stroke and measured the activations of their paretic plantar flexors using surface electromyography (EMG). Measurements were taken under six randomized conditions: three paretic limb loadings (50%, 75%, and 90% of BW) paired with two surface configurations (level and incline). During each condition, participants were instructed to roll a skateboard forward and backward for three cycles using their unaffected limbs, all while maintaining the targeted WB level on their paretic limbs. A high-speed camera system recorded foot trajectories to define the onsets of the forward and backward cycles during the skateboarding motions.PF muscle activation was calculated by integrating the EMG signal within a cycle and then normalized to 50% BW on the level condition. Results: The results showed increasing paretic BW loading resulted in significant increases in paretic PF activation. The normalized paretic PF activation was significantly higher during 75% BW and 90% BW loading compared to 50% (p =0.04 and 0.01 respectively). There was a trend of increasing PF activation on the incline surface compared to the level surface, however, this difference was not statistically different. Discussion and Conclusion: These findings suggest greater paretic PF activation is associated with increasing paretic WB. Locomotor exercises should aim to increase WB on the paretic limb to enhance paretic PF activation, which may improve gait and standing balance. Further studies with subacute stroke populations and a larger sample size are needed to generalize these results.
Seong Hwa Jang, Jeong-Ho Hong, Hee-joon BAE, Sung-Il Sohn, H. I. Park, Kyusik Kang, Soo Joo Lee, Jae Guk Kim, Soo Joo Lee, Min Hwan Lee, Jae-kwan Cha, Dae-hyun Kim, Jung Hwa Seo, Jinheon Jeong, Han Moon-Ku, Beom Joon Kim, Jun Yup Kim, Jonguk Kim, Han-gil Jeong, T. J. Park, S H Park, Kyungbok Lee, J. H. Lee, Doo Hyuk Kwon, Keun-sik Hong, Yong-jin Cho, H. I. Park, Byung‐Chul Lee, Kyung-Ho Yu, Mi-Sun Oh, M. G. LEE, Chulho Kim, Dong‐Eog Kim, Joon-Tae Kim, Kangho Choi, H. S. Kim, Joonggoo Kim, Wook-Joo Kim, Dong-Ick Shin, Kyu Sun Yum, Sanghwa Lee, Chulho Kim, Chan-Young Park, 찬영 박, J. H. Lee, J. H. Lee
TL;DR: A nationwide cohort study found high early recurrence of ischemic stroke after cranio-cervical artery dissection, with 27.9% of patients experiencing recurrence within 1 year, predominantly within the first week, and vascular morphologic features strongly predicting recurrence timing and risk.
Abstract: Introduction: Cranio-cervical artery dissection (CAD) is a major cause of ischemic stroke in young and middle-aged adults. Although the overall prognosis is often favorable, a substantial proportion of patients experience recurrent ischemic events, particularly in the early period. The incidence and predictors of ischemic stroke recurrence after CAD remain poorly defined, particularly in patients presenting with acute ischemic stroke or transient ischemic attack (TIA). Methods: We conducted a multicenter, prospective cohort study using data from the Clinical Research Collaboration for Stroke in Korea–National Institute of Health (CRCS-K-NIH), a nationwide web-based stroke registry. The study included consecutive patients aged ≥18 years who were admitted with acute ischemic stroke or TIA to one of 17 participating academic centers between January 2011 and April 2021. CAD was diagnosed within 7 days of symptom onset. Recurrent ischemic stroke events were assessed over a 1-year follow-up. Analyses were stratified by dissection location (intracranial vs. extracranial), and by angiographic patterns (occlusion, stenosis without dilatation, dilatation without stenosis, and the pearl-and-string sign), and other vascular imaging features (intramural hematoma, intimal flap, and double lumen). Results: Among the 711 patients (mean [SD] age, 49.0 [12.5] years; 73.0% men), 541 (76.1%) had intracranial dissections. Recurrent ischemic stroke occurred in 243 patients (27.9%), and 74.5% of events occurred within 7 days of symptom onset. In time-specific analysis, recurrence incidence was highest on day 1 (131.8 per 1,000 person-days) and declined sharply thereafter. Dissection location was not significantly associated with recurrence risk after adjustment. In contrast, vascular morphologic features were strongly associated with recurrence timing and risk: occlusion was linked to recurrence on day 1 (adjusted IRR, 2.18; 95% CI, 1.03–4.61), double lumen to recurrence at 4–7 days (IRR, 2.83; 95% CI, 1.41–5.68), and dilatation without stenosis beyond 7 days (IRR, 2.86; 95% CI, 1.00–8.17). Conclusion: Recurrent ischemic stroke after CAD is common and occurs predominantly within the first week. Vascular morphologic features—not dissection location—are the most powerful and time-sensitive predictors of recurrence. Early identification of high-risk imaging features may facilitate individualized monitoring and secondary prevention strategies during the acute period.
TL;DR: Simulation-based training using the FANG mnemonic significantly reduced door-to-neuro IR activation (12.5 minutes, 35.2%), door-to-arterial puncture (10.5 minutes, 11.9%), and showed a trend toward improved door-to-clot engagement in neurology teams managing large vessel occlusion strokes.
Abstract: Background: In large vessel occlusion (LVO) strokes, approximately 1.9 million neurons and 14 billion synapses are lost per minute of ischemia, underscoring the need for rapid recognition and intervention. It is of paramount importance that LVO is promptly recognized to provide timely and effective acute stroke management. The purpose of this quality improvement project is to improve LVO identification and expedite neurointerventional care. Methods: A simulation-based training program using the FANG mnemonic (Field Cut, Aphasia, Neglect, Gaze Preference) was implemented for neurology residents and advanced practice providers (APPs). A retrospective analysis compared stroke intervention times six months before (Jan–Jun 2024) and after (Jul–Dec 2024) implementation. Data was extracted from the Get With The Guidelines-Stroke database and supplemented by manual data abstraction. Primary outcomes were times for door-to-neuro IR activation, door-to-arterial puncture, and door-to-clot engagement. A one-tailed Student’s t-test for two independent means assessed differences. Statistical significance was defined as p = 0.05. Results: Simulation training significantly improved stroke intervention times. Door-to-neuro IR activation decreased by 12.5 minutes (35.2%, p = 0.015), and door-to-arterial puncture decreased by 10.5 minutes (11.9%, p = 0.04). Door-to-clot engagement decreased by 6.5 minutes (6.2%) and showed a non-significant trend toward improvement (p = 0.07). Conclusion: Simulation-based training enhanced LVO recognition and significantly reduced critical intervention times. These findings support incorporating simulation into stroke training programs to improve outcomes. Future studies should further quantify the long-term impact of such training and explore its integration into accredited stroke programs for APPs and faculty
TL;DR: Pre-reperfusion hypothermia uniquely enables RBM3 accumulation by combining CREB1/GATA3-driven transcription with mitochondrial preservation, averting ROS-mediated suppression and reducing pyroptosis and apoptosis in stroke models, offering a strategic target for stroke therapy.
Abstract: Background: The neuroprotective efficacy of therapeutic hypothermia is highly time-dependent, with pre-reperfusion hypothermia offering superior benefit. The cold shock protein RBM3 is upregulated during hypothermia, while the specific mechanisms on temporal advantage by which pre-reperfusion cooling enhances RBM3 accumulation remain to be determined. Methods: Rat middle cerebral artery occlusion/reperfusion (MCAO/R) and SH-SY5Y cell oxygen-glucose deprivation/reoxygenation (OGD/R) models were treated with pre-reperfusion hypothermia (1-h pre-reperfusion) or during-reperfusion hypothermia. Pharmacological cooling (chlorpromazine+promethazine) was applied in vivo and physical hypothermia (32°C) were applied in vitro . Infarct volume (TTC), apoptosis/pyroptosis (TUNEL, flow cytometry), mitochondrial function (ATP, respiratory complex I/II, ROS)(ELISA), RBM3 expression, inflammasome (NLRP3, TXNIP, GSDMD-N), and ER stress (p-PERK, p-eIF2α, CHOP) were assessed using qPCR and Western Blot (WB). TXNIP-CHOP interaction was verified by co-immunoprecipitation (co-IP) and immunofluorescence. RBM3 was knockdown by AAV in vivo . In vitro, CREB1/GATA3 regulation of RBM3 transcription was examined via siRNA silencing, and by WB, qPCR, Co-IP, and ChIP. Mitochondrial function was monitored (JC-1, MitoSOX, mPTP). Oxidative damage was modeled by hydrogen peroxide exposure. Results: Both cooling regimens activated CREB1/GATA3 and increased RBM3 transcription. Only pre-reperfusion hypothermia preserved mitochondrial function and suppressed the reperfusion ROS bursts ( in vivo and in vitro ), thereby sustaining RBM3 protein levels, as evidenced by direct ROS suppression in hydrogen peroxide-treated cells. Animal experiments proved that elevated RBM3 protein attenuated ER stress and disrupted TXNIP-CHOP binding, inhibited NLRP3 inflammasome activation, and thus reduced pyroptosis and apoptosis. During-reperfusion hypothermia failed to protect mitochondria, resulting in ROS accumulation, RBM3 loss, and thus infarction. Conclusion: Pre-reperfusion hypothermia uniquely enables RBM3 accumulation by combining CREB1/GATA3-driven transcription with mitochondrial preservation to avert ROS-mediated suppression. RBM3 acts as a pivotal determinant of neuroprotection, providing strategic targets for stroke therapy.
TL;DR: This study identifies factors associated with hospital length of stay in non-traumatic subarachnoid hemorrhage patients, finding significant correlations with Hunt-Hess score, Modified Fisher score, and external ventricular drain placement, but not age, sex, or open surgical intervention.
Abstract: Introduction: Patients with non-traumatic subarachnoid hemorrhage (SAH) often have complex hospital courses, due to complications including vasospasm and hydrocephalus. Prolonged length of stay (LOS) in the hospital can be associated with unfavorable outcomes such as hospital-acquired infections, pressure ulcers, and increased burden on the healthcare system. In our cohort of patients with non-traumatic SAH, we sought to identify factors associated with LOS at our tertiary care hospital. Methods: Using ICD-10 codes, we extracted data from all patients discharged with a diagnosis of SAH at our hospital from July 2023-December 2024. Patients were excluded if they deceased in the hospital or had traumatic SAH. We collected information on sex, age, Hunt-Hess score (a clinical scale with higher ratings indicating more severe presentation), Modified Fisher score (a radiographic scale with higher ratings indicating more severe SAH), whether or not patients required open intervention for aneurysm treatment, and whether or not they had an external ventricular drain (EVD) placed. Statistics were performed in Stata software. Unpaired two-tailed t-tests were used for categorical variables. Pearson correlation coefficients were used for continuous variables and Spearman correlation coefficients were used for ordinal variables. Results: Our cohort consisted of 69 patients (Table 1). LOS was not associated with age (Pearson correlation coefficient=0.04, p=0.74), sex (mean 17.9 days in women, 14.9 days in men, p=0.21), or open intervention (mean 17.1 days in open group compared to 16.7, p=0.90). LOS was associated with Hunt-Hess score (Spearman correlation coefficient=0.48, p<0.01), Modified Fisher score (Spearman correlation coefficient=0.51, p<0.01), and EVD (mean 21.3 days compared to 13.1, p<0.01) (Tables 2 and 3). Conclusions: In our cohort of patients with SAH, Hunt-Hess score, Modified Fisher score, and EVD placement were all associated with longer hospital LOS. Age, sex, and open surgical intervention were not associated with longer LOS. Understanding factors that contribute to LOS in our SAH patients can help us set expectations with families at time of admission and can help identify patients that may be at higher risk for hospital-acquired complications. The finding that open surgical intervention did not increase LOS is somewhat unexpected but may reflect faster recovery times with modern surgical techniques.