Citations

Background: Cardiac CT acquired during the acute stroke imaging protocol is an emerging diagnostic modality to detect cardiac thrombi. We aimed to determine its diagnostic yield in a large, international, multicenter study. Methods: We performed an individual patient data meta-analysis by pooling prospective and retrospective observational data of patients with acute ischemic stroke (AIS) who underwent cardiac CT (ECG-gated or non-ECG-gated) as part of the acute imaging protocol between May 2018 and June 2024. We excluded patients with a TIA or stroke mimic. The primary outcome was the proportion of patients with a cardiac thrombus detected on cardiac CT. Secondary outcomes were additional scan time and radiation dose, comparison of yield with echocardiography, and 90-day mortality and recurrent ischemic stroke rates. Results: We included 3940 patients from 4 hospitals (median age 74 [IQR 63-82], 58.0% male, median NIHSS 6 [IQR 3-12], median time onset to hospital arrival 100 minutes [IQR 62-185]). Atrial fibrillation at baseline was present in 23.1% patients, and 29.6% had a large vessel occlusion. Cardiac CT was non-diagnostic in 17 (0.4%) patients. In total, cardiac CT detected 254 cardiac thrombi in 243/3923 (6.2%) patients. Thrombi were located in the left atrial appendage (n=193), left atrium (n=19), and left ventricle (n=42). Of 95/243 (39.1%) patients with a cardiac thrombus that underwent echocardiography (median interval cardiac CT-echocardiography: 2 days), transthoracic echocardiography detected a thrombus in 18/92 (19.6%) patients and transesophageal echocardiography in 2/5 (40.0%) patients. The diagnostic yield in patients that underwent both modalities was higher for cardiac CT (OR 7.5 [CI 4.0-15.3], p<0.001). Median additional scan time was 6 minutes (IQR 5-7) for ECG-gated and 17 seconds (IQR 15-63) for non-ECG-gated cardiac CT. Median additional radiation dose was 5.4mSv (IQR 3.0-7.6). Patients with a cardiac thrombus on cardiac CT had higher 90-day mortality than those without a thrombus (33.3% vs 14.6%, p<0.001). We found no difference in 90-day recurrent stroke rate (5.4% vs 4.4%, p=0.50). Conclusion: Routine cardiac CT performed during the acute stroke imaging protocol detects a cardiac thrombus in 1 out of 16 patients with AIS, with a 7-times higher yield than routine echocardiography. Mortality rate was doubled in patients with a cardiac thrombus, but 90-day stroke recurrence risk did not differ.

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.

Introduction: Spinal cord infarction (SCI) is a rare but serious neurological condition that accounts for 1-2% of all ischemic strokes and can lead to significant disability. Despite its clinical importance, existing studies are limited by small sample sizes that lack national generalizability, and little is known about post-discharge events such as hospital readmissions. We aimed to evaluate factors associated with all-cause hospital readmissions among hospitalizations with primary diagnosis of SCI, utilizing the Nationwide Readmissions Database (NRD). Methods: NRD data were abstracted from 2016 to 2022 including all hospitalizations of adult patients (≥18 years) with a primary diagnosis of SCI. Multiple-predictor logistic regression models were estimated to assess the association of demographic and clinical variables with all-cause 90-day readmissions. We included specific comorbidities often used in comorbidity scoring systems and added conditions or complications that are known to be associated with SCI. Statistically significant covariates from the unadjusted model were retained in the multiple-predictor model. Odds ratios (OR) with associated 95% Confidence intervals (CI) and p-values were reported. Results: From 2016 to 2022, there were an estimated 3321 hospitalizations with a primary diagnosis of SCI, out of which 27% (95% CI: 24-30%) were readmitted within 90 days. Demographic factors that were associated with lower odds of readmission included private insurance (vs. Medicare) and high-income quartile (Fig. 1). [AH1] [AAs2] Clinical factors that were associated with increased odds of readmission included autonomic dysfunction (OR = 5.44, 95% CI: 1.86 to 15.94), renal disease (OR = 3.57, 95% CI: 1.83 to 6.96), liver disease (OR = 2.40, 95% CI: 1.34 to 4.32), full clinical associations shown in Figure 2. Conclusion: We identified several clinical and demographic factors that were significantly associated with increased all-cause readmissions after SCI hospitalizations. Autonomic dysfunction and renal disease were among the top predictors of readmissions. We uncovered socioeconomic disparities in readmissions rates following SCI. This data may assist vascular neurologists, physicians and healthcare administrators in reducing readmissions after SCI and addressing these disparities. Additionally, our results can guide future studies focusing on the management of this rare entity.

Background: Stroke is a frequent manifestation of non-bacterial thrombotic endocarditis (NBTE), yet current knowledge largely stems from case reports and small series. This systematic review aimed to comprehensively describe stroke presentation, imaging features, management, and outcomes in NBTE patients. Methods: A comprehensive search of EMBASE, PubMed, MEDLINE, Web of Science and PsycINFO databases was conducted through September 2023. Studies reporting individual cases or case series of NBTE-related stroke were included. Extracted data included demographics, vascular risk factors, stroke presentation, imaging features, NBTE etiology, treatment modalities (unfractionated heparin/low molecular weight heparin (UFH/LMWH), warfarin, direct oral anticoagulants (DOACs), and valvular intervention), stroke recurrence, and mortality. Multivariate regression was performed to identify predictors of recurrent stroke and mortality. Results: A total of 129 patients from 118 studies were included (median age 56 [IQR:44-64], 62% females). Right (28%) and left (26%) hemispheric stroke syndromes accounted for the majority of clinical presentation, and multivessel ischemic infarcts (>2 territories) were observed in 66%. Conventional vascular risk factors were infrequent (1%-21%), while deep vein thrombosis and systemic embolism occurred in 59% and 38% of patients, respectively, either preceding or coinciding with stroke onset. Malignancy and autoimmune diseases were identified in 72% and 22%, respectively. Anticoagulation was initiated in 66% and 21% underwent valvular treatment. Over a median follow-up of 1.3 months, stroke recurrence and death occurred in 48% and 50%, respectively. Malignancy significantly increased mortality risk (OR 16.8, P<0.001), while autoimmune-related NBTE (OR 0.2, P=0.029), and anticoagulation with UFH/LMWH (OR 0.3, P=0.011) and VKA (OR 0.09, P=0.002) reduced mortality. Recurrent stroke was more likely in patients with malignancy (OR 16.8, P=0.001) and those receiving DOACs (OR 6.2, P=0.057) Conclusion: NBTE should be considered in stroke patients lacking conventional risk factors, particularly with underlying malignancy or autoimmune disease. Malignancy and DOAC use may increase the risk of recurrent strokes in this patient population.

Background: Embolic stroke of undetermined source (ESUS) comprises infarct mechanisms presumed to be embolic and non-lacunar. One explanation for the lack of superiority of anticoagulation over aspirin is the inclusion of subcortical infarcts with white matter disease (WMD), reflecting small vessel pathology. We hypothesized that WMD is associated with recurrent ischemic stroke (RIS) in ESUS and this risk is not lessened by anticoagulation. Methods: We conducted a secondary analysis of the multicenter Cardiac Abnormalities in Stroke Prevention and Recurrence (CASPR) registry, including ESUS patients from 27 U.S. centers (2015–2024). WMD severity was graded using the Fazekas scale from MRI and dichotomized as mild (0–1) vs. moderate-to-severe (2–3). The primary outcome was RIS. Secondary outcomes were major bleeding and all-cause mortality. Inverse probability of treatment weighting (IPTW) adjusted for baseline differences. Cox proportional hazards models assessed associations between WMD and outcomes. Subgroup analyses explored effect modification by age, risk factors, and treatment type. Results: Among 1,890 ESUS patients with MRI data, 684 (36.2%) had Fazekas 2–3. These patients were older with more vascular risk factors, but IPTW achieved covariate balance. In the weighted cohort, RIS occurred more frequently in Fazekas 2–3 vs. 0–1 (7.1% vs. 4.6%/year; HR 1.56, 95% CI 1.10–2.22, p = 0.01). Major bleeding and mortality were similar (bleeding: 1.7% vs. 1.8%/yr, HR 0.96, p = 0.92; death: 7.0% vs. 6.7%/yr, HR 1.04, p = 0.81). Subgroup analyses showed no interaction between WMD and age, vascular risk factors, or treatment type (antiplatelet vs. anticoagulation), suggesting consistent RIS risk in those with higher WMD. Discussion: Moderate-to-severe WMD identifies ESUS patients at higher risk of ischemic stroke recurrence, with no mitigation by anticoagulation. These findings suggest that WMD may indicate non-embolic mechanisms and support the use of imaging-based risk stratification in ESUS.

Background and Objectives: Pregnancy and the postpartum period increase the risk of cervical artery dissection (CEAD), a notable cause of stroke in young women. We aimed to describe the clinical presentation, imaging findings, and outcomes of CEAD occurring during pregnancy or shortly after delivery. Methods: We analyzed data from the STOP-CAD registry, a large international multicenter study of patients treated with antithrombotic therapy for non-traumatic CEAD between 2015 and 2021. This sub-study focused on women who were pregnant or within 12 weeks postpartum at the time of symptom onset. We assessed baseline clinical features, imaging results, acute stroke treatments, and functional outcomes. Results: Among 1,783 women in the registry, 62 (3.5%) had pregnancy-associated CEAD, with a median age of 34 years (IQR, 30-38). One-third had a history of migraine (33.9%), one-fifth had hypertension (21.0%), while other vascular risk factors were rare. Recent minor neck trauma was reported in 17.7%. Ischemic stroke symptoms occurred in 25 (40.3%) patients, and 23 (37.1%) had acute infarcts on imaging. However, most (59.7%) presented with non-ischemic symptoms. Vertebral artery dissections were more common than carotid dissections (62.9% vs. 48.4%), and 33.9% had multivessel involvement. Among patients presenting with ischemic stroke symptoms, 4 received thrombolysis and 7 underwent thrombectomy. Remarkably, 92% had excellent functional recovery (modified Rankin Score 0–1) at 90 days, and there were no stroke recurrences at 180 days. Conclusion: Pregnancy- and postpartum-associated CEAD is uncommon and associated with ischemic stroke in nearly half of patients. A history of migraine and hypertension may be potential risk factors. Despite the severity of presentation, most patients had favorable outcomes with timely treatment.

Background: High-grade intracranial atherosclerosis (ICAS) is associated with an elevated risk of recurrent ischemic stroke, particularly in patients with severe stenosis (70–99%). Identifying predictors of early recurrence can inform risk stratification and guide treatment strategies. Methods: The Biomarkers and Recurrence Risk in Symptomatic Intracranial Arterial Stenosis (BIORISK-ICAS) study is a multicenter, international, retrospective cohort analysis pooling data from 35 comprehensive stroke centers. We included hospitalized adult patients with symptomatic ICAS, defined as 50–99% stenosis of an intracranial artery (intracranial vertebral, basilar, distal ICA, or M1 MCA), confirmed by vascular imaging and associated with a qualifying ischemic event. Patients with only high-grade stenosis (70-99%) were included in this analysis. The primary outcome was to determine predictors of recurrent ischemic stroke in the territory of the symptomatic artery within 90 days of the index event. Baseline demographic, clinical, and imaging characteristics were recorded. Multivariable Cox proportional hazards regression with stepwise selection (p < 0.1) was used to identify independent predictors of recurrence; model discrimination was assessed using Harrell’s C-statistics. Results: Among 2,050 patients, 1,476 had high-grade (70-99%) symptomatic ICAS. The mean age was 67 ± 12.5 years, and 767 (55%) were male. Most patients were non-Hispanic (90.1%), taking dual antiplatelet therapy (77.8%), and statins (94.5%). Recurrent stroke occurred in 160 patients (10.8%) within 90 days. In multivariable Cox model, independent predictors of recurrence included atrial fibrillation (HR 2.05; 95% CI, 1.26–3.33; p = 0.004), hyperlipidemia (HR 1.57; 95% CI, 1.10–2.24; p = 0.014), diabetes mellitus (HR 1.36; 95% CI, 0.98–1.88; p = 0.064), and home use of dual antiplatelet therapy (HR 1.60; 95% CI, 1.01–2.54; p = 0.043)(Harrell’s C-statistic=0.62). In patients who underwent perfusion(n=402), mistmatch >10seconds were associated with increased recurrence (HR 1.80; 95% CI 0.95-3.38, p=0.07) and atrial fibrillation (HR 2.06: 95% CI 0.03-4.60, p=0.78) though did not reach statistical significance. Conclusion: In this population, diabetes, hyperlipidemia, atrial fibrillation, and prior use of dual antiplatelet therapy were associated with increased risk of 90-day recurrent ischemic stroke. Perfusion imaging may help identify high-risk patients who could benefit from intensified secondary prevention.

Introduction: Cerebral amyloid angiopathy (CAA) is a progressive cerebrovascular disease caused by amyloid-beta (Aβ) deposition in cerebral vasculature. While CAA is a recognized cause of intracerebral hemorrhage (ICH) and cognitive decline, emerging evidence suggests that seizures are among a broader array of CAA clinical manifestations. However, the risk of seizures and status epilepticus in CAA remains poorly characterized. This study aimed to estimate incidence of seizures and status epilepticus in CAA using real-world data. Methods: A retrospective, longitudinal study was conducted using a nationally representative sample of administrative claims from US Medicare and commercial insurance beneficiaries (2017–2024). Patients with CAA (aged > 50 years with > 1 physician encounter with a validated ICD-10 code (I68.0)) were matched 1:4 to age- and sex-matched controls. The primary outcome was occurrence of seizure, ascertained using validated ICD-10 codes during acute care; the secondary outcome was hospitalization for status epilepticus. Follow-up continued until the end of enrollment or death. Descriptive statistics summarized patient characteristics and Poisson regression estimated incidence rates with 95% CIs. Cox proportional hazards regression assessed associations between CAA and outcomes of interest vs controls, adjusted for chronic kidney disease, liver disease, prior ICH, and seizure history. Results: We included 7294 patients with CAA and 29176 controls (median age: 77 years; 53.7% women; median follow-up: 29.4 months). Patients with CAA had higher rates of prior ICH (32.4% vs 0.5%) and prior seizure (18.7% vs 1.8%) than controls. The incidence rate of seizures was higher in patients with CAA than controls: 8.1 per 100 person-years (PY; 95% CI: 7.6–8.6) vs 0.4 per 100 PY (95% CI: 0.4–0.5). In the CAA cohort, seizure incidence rate was higher for those with prior ICH than those with no ICH history: 13.6 per 100 PY (95% CI: 12.5–14.8) vs 5.7 per 100 PY (95% CI: 5.2–6.3). Status epilepticus rates were higher in patients with CAA than controls: 0.7 per 100 PY (95% CI: 0.6–0.9) vs 0.03 per 100 PY (95% CI: 0.02–0.04). Adjusted models showed that CAA was associated with higher risk of seizures (HR: 6.7, 95% CI: 5.8–7.7) and status epilepticus (HR: 8.1, 95% CI: 4.8–13.7) than controls (Table 1). Conclusions: Patients with CAA have an increased risk of seizures and status epilepticus. These findings broaden the possible clinical spectrum of CAA.

Introduction: Functional outcome scales are commonly used in neurological clinical trials. Prior studies suggested that these scales may reflect symptomatic hemorrhage (SH), but their performance in detecting treatment effects has not been assessed in clinical trials of cerebral cavernous malformations (CCM). And they have not been correlated with CCM bleeding as reflected by lesional iron content assessed by quantitative susceptibility mapping (QSM) MRI. Hypothesis: We hypothesized that functional outcome measures would detect differences between treatment arms in a randomized clinical trial of hemorrhagic CCM, and reflect new SH or a ≥6% increase in mean lesional QSM reflective of CCM bleeding. Methods: Eighty adults with CCM-related SH in the prior 12 months of enrollment were randomized 1:1 to atorvastatin 80 mg/day or placebo for 2 years. Functional outcomes, including mRS, EQ-5D index, EQ-VAS, and PROMIS-29 domains, were collected at baseline, Year 1, and Year 2. Analyses were conducted in 63 participants (32 atorvastatin, 31 placebo) in the modified intention-to-treat trial cohort who had contributed at least one paired annual clinical and imaging assessment. Results: No significant differences were found between atorvastatin and placebo groups in any functional outcome measure across timepoints. Rates of functional decline and improvement were comparable, except for PROMIS Fatigue which improved more in the atorvastatin than placebo patients from baseline to Year 1 (p=0.019). Pooled analyses showed that several functional domains had strong specificity for identifying SH. PROMIS Sleep Disturbance decline from baseline to Year 2 was associated with SH (p=0.0045; specificity 92.3%, sensitivity 57.1%). A ≥10-point drop in EQ-VAS from baseline to Year 1 identified all SH cases during that interval (p=0.007; sensitivity 100%, specificity 83.6%). Functional decline had low sensitivity in detecting CCM bleeding on QSM, though specificity was high (>75%) across domains. Conclusions: Atorvastatin did not influence functional change over 2 years by any measure. PROMIS Sleep Disturbance and EQ-VAS demonstrated high specificity, and in the case of EQ-VAS also a high sensitivity for identifying SH. Functional outcomes across domains also had high specificity for occult bleeding in CCMs as measured by QSM. Poor sensitivity and consistent improvements over time demonstrate the limitations of functional outcome measures as endpoints of drug effects on CCM bleeding.

Background: It is not clear if changes in lesion volume might represent a clinically relevant and statistically advantageous outcome parameter in early phase trials of novel drugs aimed at preventing bleeding in cerebral cavernous malformations (CCM). Methods: We analyzed the modified intention to treat cohort (33 patients receiving atorvastatin and 31 placebo) who contributed at least one paired imaging biomarker in the recently completed double-blinded randomized controlled AT CASH EPOC trial (clinicaltrials.gov NCT02603328). We examined prospective changes in CCM lesion volume and correlated these with symptomatic hemorrhage (SH) events. We contemporaneously assessed changes in lesional iron content by quantitative susceptibility mapping (QSM) on MRI, and objective (mRS) and subjective (EQ-VAS) functional status. We also simulated sample sizes needed to detect potential effects of a drug on lesion volume. Results: There was excellent correlation between independently assessed maximum lesion diameter and CCM lesion volume (R 2 = 0.68, P<0.0001). The mean (SD) percentage change in lesion volume per year was +6 (65) and +18 (94) in atorvastatin and placebo patients, respectively (P= 0.43). All cases with SH had increases in lesion volume as well as increases in mean lesional iron content by QSM, and most had declines in functional status on mRS and EQ-VAS. But there were many cases with increases in lesion volume with improved functional status or decreased mean lesional QSM, and other cases with worsening in function or increased lesional QSM and decreased lesion volume. There were no significant correlations of changes in lesion volume with concomitant changes in mean lesional QSM, mRS or EQ-VAS (all R/R 2 <0.5 and Bonferroni corrected P>0.05), including in brainstem lesions analyzed separately. Sample size simulations indicate larger numbers of cases needed to demonstrate a drug effect on changes in lesion volume than those needed to detect an effect on QSM change with a=0.05 and b=0.8, and even larger samples to detect effects on the proportion of cases with increased or decreased lesion volume. Conclusion: Changes in lesion volume occur frequently in CCM lesions after recent SH, but do not correlate with measures of bleeding in the lesions, nor appear to reflect functional changes. And they are not statistically advantageous in comparison to QSM measures for detecting potential drug effects.