Journal of Stroke and Cerebrovascular Diseases

BackgroundThe optimal noninvasive screening strategy for detecting patent foramen ovale (PFO) in patients with cryptogenic stroke (CS) remains uncertain. Although transthoracic echocardiography (TTE) and transcranial Doppler (TCD) are widely used, whether combining both modalities improves diagnostic performance has not been fully established. MethodsAmong 432 consecutive CS patients, 399 underwent collaborative screening with both TTE and TCD bubble tests performed by a multidisciplinary Heart-Brain Team, followed by transesophageal echocardiography (TEE) as the reference standard. Bubble tests were conducted at rest and during the Valsalva maneuver (VM). Diagnostic performance, concordance between modalities, and incremental value were evaluated using receiver operating characteristic analysis, Cohens kappa statistics, and sequential logistic regression models. ResultsTEE confirmed PFO in 156 patients (39.1%). Both TTE and TCD demonstrated significantly higher diagnostic accuracy during VM than at rest, with no significant difference in area under the curve between modalities under VM. Sequential logistic regression showed a significant incremental increase in predictive value when TCD during VM was added to TTE during VM ({chi}{superscript 2} increase from 271.4 to 297.2; p<0.0001). Although overall agreement between TTE and TCD during VM was substantial ({kappa}=0.63), 54 patients (14%) showed discordant results, among whom 15 (28%) had TEE-confirmed PFO. Applying an "OR" rule (positive if either test was positive) significantly improved sensitivity compared with either modality alone, at the expense of modestly reduced specificity. ConclusionsDual screening with TTE and TCD during VM within a Heart-Brain Team framework significantly enhances sensitivity for PFO detection and reduces missed diagnoses in patients with CS. An "OR" rule interpretation represents a practical and clinically effective screening strategy.

BackgroundStroke is a leading cause of public health burden in China, particularly among the elderly. This study aims to examine long-term trends in stroke incidence and the impact of population aging. MethodsUsing the Global Burden of Disease (GBD) Study 2021, we analyzed the incidence, mortality, and disability-adjusted life years (DALYs) for ischemic stroke (IS), cerebral hemorrhage (ICH), and subarachnoid hemorrhage (SAH) from 1990 to 2021. We applied the estimated annual percentage change (EAPC) and decomposition analysis to assess trends and the influence of population aging. FindingsFrom 1990 to 2021, the age-standardized incidence rate (ASIR) of IS rose from 110.05 to 135.79, with an EAPC of 0.94. The EAPCs for ICH and SAH were -2.24 and -3.70, respectively. Population aging significantly contributed to the stroke burden, with 800,000 IS-related deaths from 1980 to 2021. In 2021, the proportion of IS deaths due to aging was 279.4% for men and 204.8% for women. ConclusionsStroke incidence and mortality continue to rise, especially among the elderly. Aging exacerbates the stroke burden, highlighting the need for targeted policies to improve the quality of life for the aging population.

BackgroundMechanical thrombectomy has become standard-of-care in the treatment of emergent large vessel occlusion. However, it is not yet known if social factors impact post-thrombectomy recovery. We studied the association between clinical and sociodemographic factors with 3-month functional outcomes post thrombectomy. MethodsIn this prospective cohort study, 291 patients who underwent mechanical thrombectomy at Montefiore-Einstein Hospital in NYC between 1/1/2021 and 4/1/2024 were analyzed. The cohort spanned multiple census tracts across New York City and surrounding areas and included a diverse patient population. The primary outcome was change in modified Rankin Scale ({Delta}mRS) from pre-stroke baseline to 90-180 days post-stroke. Ordinal logistic regression was used to assess the relationship between {Delta}mRS and social vulnerability, adjusting for age, sex, stroke severity, and procedural success. ResultsWorse functional outcomes were associated with older age (OR 1.03; p = 0.004), male sex (OR 1.85; p = 0.006), higher stroke severity (OR 1.71; p < 0.001), and lower reperfusion success (OR 2.22; p = 0.011). Social vulnerability was not significantly associated with long-term outcomes (OR 0.88; p = 0.550). ConclusionIn this cohort, functional outcomes after mechanical thrombectomy were influenced by clinical and procedural factors rather than sociodemographic vulnerability. While equitable outcomes were observed in the acute setting, ongoing research is needed to explore potential disparities across the broader stroke care continuum, including post-acute recovery.

PurposeIntracranial atherosclerotic disease-related large vessel occlusion (ICAD-LVO) presents distinct challenges, particularly regarding the high risk of reocclusion and the need for specific management strategies. While several prediction scores exist to differentiate ICAD-LVO from embolic LVO (EMB-LVO), their external validity remains unproven. We aimed to externally validate six established prediction scores for differentiating the two. MethodsWe analyzed data from a prospectively maintained, two-center stroke registry (June 2021-March 2025). Consecutive patients who underwent mechanical thrombectomy and had complete clinical and imaging data necessary for calculating six scores (ISAT, REMIT, ABC2D, ATHE, ICAS-LVO, and Score-ICAD) were included. LVO etiology was defined based on angiographic findings during endovascular treatment. The discriminative performance of each score was assessed using the area under the receiver operating characteristic curve (AUC). ResultsOf 1,288 screened admissions, 91 patients met the inclusion criteria (ICAD-LVO, n = 18; embolic occlusion, n = 73). The AUCs (95% confidence interval) for differentiating etiology were: ISAT, 0.870 (0.664-1.000; P = 0.064); REMIT, 0.793 (0.676-0.911; P <0.001); Score-ICAD, 0.707 (0.582-0.833; P = 0.013); ABC2D, 0.627 (0.504-0.751; P = 0.095); ATHE, 0.600 (0.451-0.749; P = 0.230); and ICAS-LVO, 0.465 (0.301-0.630; P = 0.650). ConclusionIn this external validation, REMIT demonstrated the most robust and statistically significant discrimination between ICAD-LVO and EMB-LVO. Overall, scores incorporating imaging features outperformed those relying on clinical variables. These findings support the concept that ICAD-LVO represents a distinct pathophysiological entity from embolic occlusion and that accurate mechanism inference requires comprehensive imaging assessment of intracranial atherosclerotic disease beyond the occlusion site.

BackgroundTandem lesion strokes (TLS), defined by the coexistence of an intracranial large- or medium-vessel occlusion and a concomitant cervical internal carotid artery (ICA) stenosis or occlusion, represent a challenging subtype of acute ischemic stroke. Optimal endovascular management remains controversial, particularly regarding the role of emergent carotid artery stenting (eCAS) during mechanical thrombectomy. ObjectiveTo compare the safety and efficacy of emergent carotid artery stenting versus mechanical thrombectomy alone in patients with anterior circulation tandem lesion strokes treated at a comprehensive stroke center. MethodsWe conducted a retrospective observational cohort study of consecutive adults with anterior circulation TLS treated with endovascular therapy within 24 hours of symptom onset between January 2015 and July 2025. Patients were categorized into two groups according to treatment strategy: eCAS performed during thrombectomy or mechanical thrombectomy alone (MTa). Primary efficacy outcomes were ordinal shift in 90-day modified Rankin Scale (mRS), excellent outcome (mRS 0-1), and functional independence (mRS 0-2). Secondary efficacy outcome was successful recanalization (TICI [&ge;]2b). Primary safety outcomes included symptomatic intracranial hemorrhage (sICH), in-hospital mortality, and 90-day mortality. ResultsA total of 111 patients were included (mean age 71.2 {+/-} 12.6 years; 68.5% male), of whom 74 (67%) underwent eCAS and 37 (33%) received MTa. Patients treated with eCAS achieved higher rates of successful recanalization (97.3% vs 78.4%; OR 13.26, 95% CI 2.13-82.49; p = .006) and excellent functional outcomes at 90 days (41.9% vs 12.5%; OR 6.80, 95% CI 1.35-34.20; p = .020). There were no significant differences between groups in rates of sICH, early neurological deterioration, or mortality. Ordinal logistic regression showed a non-significant trend toward better functional outcomes with eCAS. ConclusionsIn this single-center experience, emergent eCAS during mechanical thrombectomy for TLS was associated with higher reperfusion rates and improved functional outcomes without increased hemorrhagic risk or mortality. These findings support eCAS as a feasible and safe strategy in selected patients and highlight the need for prospective randomized trials.

ObjectiveWe aimed to do an updated meta- analysis comparing outcomes of mechanical thrombectomy (MT) associated with standard medical treatment (SMT), compared to SMT alone, in adult patients with acute ischemic stroke (AIS) due to medium or distal vessel occlusion (MDVO). MethodologyWe systematically searched PubMed, LILACS, Scielo, Cochrane, and ClinicalTrials.gov databases. Randomized controlled trials (RCTs), retrospective cohort studies, and systematic reviews with meta-analysis comparing MT+SMT with SMT alone in adults with AIS due to MDVO, evaluating at least one of the outcomes of interest, were included. The evaluated outcomes were functional recovery (modified Rankin Scale [mRS] 0-1 and mRS 0-2) at 90 days, all-cause mortality at 90 days, and the occurrence of intracranial hemorrhage (ICH). Risk of bias was assessed using RoB 2, Newcastle-Ottawa, and AMSTAR 2 tools. Heterogeneity was assessed with Chi{superscript 2} and I{superscript 2}, and publication bias with funnel plots and Egger/Begg tests. ResultsTwelve studies (4 RCTs, 7 cohorts, 1 systematic review) were included. Meta-analyses showed no significant difference between MT+SMT and SMT alone for: mRS 0-1 (Excellent Recovery), mRS 0-2 (Good Recovery), mortality at 90 days, and Symptomatic Intracranial Hemorrhage. ConclusionCurrent evidence, combining RCTs and observational studies, does not support the routine use of MT over SMT alone for MDVO in terms of functional improvement at 90 days (mRS 0-1 or 0-2). Non-significant trends towards increased mortality and sICH risk with MT were observed, with considerable heterogeneity for sICH. KEY MESSAGESeveral randomized controlled trials (RCTs) have demonstrated the benefit of mechanical thrombectomy associated with standard medical treatment (SMT), in patients with IS caused by large vessel occlusion (LVO). There for the boundaries of MT began to be questioned, raising the possibility of performing it for medium and distal vessel occlusions (MDVO). As a result of this study, there was no evidence to support the use of MT over SMT alone for MDVO, therefore the therapeutic decisions should remain individualized and further research is crucial to define the exact role of the MT.

BackgroundStenosis and dolichoectasia of cranial arteries likely reflect distinct mechanisms. Their contributions to lacunar stroke and cerebral small vessel disease (cSVD) remain contentious. We investigated associations of large artery stenosis (LAS) and arterial widening with stroke subtype, cSVD markers, incident infarcts, and clinical outcomes. MethodsWe prospectively recruited patients with lacunar or mild non-lacunar stroke, with demographic, stroke-related, cognitive, functional, and MRI (index and incident infarcts, cSVD markers) assessments at baseline and one year. LAS was defined as [&ge;]50% intracranial or cervical artery stenosis; basilar artery dolichoectasia (BADE) by basilar artery diameter, bifurcation height, and lateral displacement; and intracranial carotid and middle cerebral artery diameters were also measured. Associations were estimated using multivariable regression adjusted for age, sex, and vascular risk factors. We further conducted a systematic literature review to synthesize evidence on relationships between large artery pathology and cSVD. ResultsAmong 229 patients (mean age 65.9{+/-}11.1 years; 131 [57.2%] lacunar stroke), LAS and BADE were present in 20.5% and 15.7%, respectively. After adjustment, LAS (odds ratio [OR], 0.49; 95%CI, 0.23-0.99) and the presence of any embolic source were associated with lower odds of lacunar versus non-lacunar stroke, and not with cSVD markers or incident infarcts. In contrast, BADE was strongly associated with lacunar stroke (OR, 4.67; 95%CI, 1.87-13.14), higher cSVD scores (ordinal analysis; OR, 2.57; 95%CI, 1.28-5.25), incident infarcts (75% subcortical; OR, 2.29; 95%CI, 1.01-5.14), and greater progression of white matter hyperintensities over one year ({beta}, 0.15; 95%CI, 0.01-0.29; per log10-transformed volume). Similar associations were observed for wider intracranial arteries. The systematic review supported these findings. ConclusionscSVD, including lacunar stroke, was unrelated to LAS, but strongly associated with dolichoectasia and wider arteries. These findings support a non-atheromatous, intrinsic microvascular pathology, particularly segmental arteriolar disorganization, as the principal mechanism of lacunar stroke and cSVD. Mechanism-specific diagnostic and therapeutic strategies are warranted. Clinical PerspectiveO_ST_ABSWhat Is New?C_ST_ABS[bullet] Large artery stenosis was unlikely to represent a causal mechanism for lacunar stroke and showed no association with cerebral small vessel disease (cSVD) imaging markers. [bullet]Dolichoectasia and intracranial arterial widening emerged as vascular phenotypes strongly associated with cSVD, including its progression and lacunar stroke subtype. What Are the Clinical Implications?[bullet] Distinct large artery phenotypes have divergent etiopathological implications for cSVD. Our findings support a non-atheromatous, intrinsic microvascular pathology as the principal mechanism of lacunar stroke and cSVD. [bullet]Mechanism-based therapeutic strategies for lacunar stroke and cSVD, moving beyond conventional approaches focused on atherosclerosis or cardioembolism, are warranted.

BackgroundStroke is a leading cause of mortality and disability globally. However, information about stroke burden in the Philippines is limited. We sought to analyze stroke burden in the Philippines from 1990 to 2023. MethodsIncidence, prevalence, mortality, and disability-adjusted life-years (DALYs) estimates from the Global Burden of Disease Study 2023 data were used as indicators to analyze the burden of stroke by sex and age. Temporal trends in both crude and age-standardized rates were analyzed using joinpoint regression analysis. ResultsIn 2023, stroke incidence was estimated at 156.2 (95% uncertainty interval [UI]: 140.8-175.4) thousand, prevalence at 1.2 (95% UI: 1.2-1.4) million, mortality at 72.2 (95% UI: 63.2-83.0) thousand, and DALYs at 2.1 (95% UI: 1.8-2.3) million. High systolic blood pressure was the leading contributor to risk-attributable stroke mortality and DALYs. Since 1990, age-standardized rates declined significantly, whereas crude rates increased markedly. Compared with women, men had a higher fatal burden and consistently exhibited a higher age-standardized burden. Although older adults ([&ge;] 55 years) had the highest stroke burden and achieved reductions in stroke incidence and fatal outcomes, both fatal and non-fatal burdens consistently increased among young adults (35-54 years). ConclusionWhile age-standardized rates have improved, the rising crude burden and shift towards younger adults present significant public health challenges. These trends highlight the pressing need for aggressive and targeted risk factor control, sustained risk monitoring, and strengthened acute and post-stroke care to mitigate the growing health burden of stroke in the Philippines.

BackgroundCerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a monogenic hereditary cerebral small vessel disease (CSVD). Existing studies have confirmed that it is caused by mutations in the NOTCH3 gene, but the specific mechanisms underlying its pathogenesis and progression remain elusive. Existing research indicates that inflammation plays a critical role in the development and progression of CSVD. The Systemic Immune-Inflammation Index (SII) has revealed to be a reliable new marker to assess immune status and inflammatory response intensity. This study reveals the relationship of SII with cognitive impairment and magnetic resonance imaging (MRI) markers of CSVD in patients with CADASIL. MethodsThis cross-sectional investigate included patients diagnosed with CADASIL who had confirmed NOTCH3 gene mutations and complete clinical data. Cognitive function in patients with CADASIL was appraised by the Mini-Mental State Examination (MMSE). SII is obtained by calculating the number of platelets, neutrophils and lymphocytes in blood routine examination. Summary SVD score and imaging markers of CSVD, including cerebral microbleeds, lacunae, white enlarged perivascular space and matter hyperintensity were evaluated based on magnetic resonance imaging. The association between cognitive impairment and SII and MRI markers in CADASIL were evaluated using logistic regression models and Spearman correlation. ResultsAt baseline, A total of 96 Patients with CADASIL were enrolled in this cross-sectional study. the median age of patients with CADASIL was 59.00 (interquartile range 52.25-66.75) years, and 58.3% of patients were male. The correlation analysis results indicate that the SII level was negatively correlated with MMSE scores in patients with CADASIL (rs=-0.336, P <0.001). An elevated SII was statistically significantly linked with the risk of cognitive impairment (Q4 vs. Q1: OR 5.230, 95% CI 1.040-26.297; P=0.045) after adjusting for age, sex and education. In contrast, there was no considerable difference between SII and summary SVD score or MRI imaging markers. ConclusionsElevated SII was linked with cognitive impairment in CADASIL patients. Nevertheless, there were no significant differences between SII and summary SVD score or MRI imaging markers.

BackgroundRecurrent ischemic stroke remains a major concern in patients with nonvalvular atrial fibrillation (NVAF) despite anticoagulation. However, not all NVAF-related strokes are purely cardioembolic--concomitant large artery steno-occlusion (cLASO) is frequently observed and may represent an independent contributor to stroke recurrence. Current guidelines address these cases but focusing almost exclusively on the cardioembolic source. This approach contrasts sharply with the management of acute coronary syndrome in patients with NVAF, where identifying and targeting the culprit lesion is standard practice. We evaluated whether the presence and clinical relevance of cLASO predict stroke recurrence in NVAF-related acute ischemic stroke (AIS). MethodsThis prospective multicenter cohort study enrolled 2,035 patients with NVAF-related AIS at 14 stroke centers in South Korea between October 2017 and April 2020. Patients underwent brain magnetic resonance imaging and angiography. cLASO, defined as any degree of stenosis or occlusion in major cerebral arteries, was categorized by anatomical severity (mild, moderate-to-severe, or occlusion) and clinical relevance. Clinically relevant cLASO was defined as a steno-occlusive lesion topographically concordant with the infarction, thereby sufficiently explaining the index stroke regardless of concurrent cardioembolic source; otherwise, lesions were classified as bystander. The primary outcome was recurrent ischemic stroke within 3 years, analyzed using competing risk analysis. ResultsAmong 2,035 patients (mean age, 74.9 years; 54.8% male), 1,308 (64.3%) had cLASO, and 583 (28.6%) had clinically relevant cLASO. The 3-year cumulative incidence of recurrent ischemic stroke was 7.0%, with over 40% of recurrences occurring within the first month. Recurrence risk increased significantly with cLASO presence (4.5% vs. 8.1%), severity (mild, 5.7%; moderate-to-severe, 9.7%; occlusion, 9.1%) and clinical relevance (bystander, 3.8%; relevant, 13.9%) (all Ps < 0.05). In multivariable analysis, clinical relevance--rather than severity--was independently associated with recurrence (aHR, 4.10; 95% CI, 2.57-6.54). ConclusionsClinically relevant cLASO identifies a mechanistically distinct, high-risk phenotype that warrants a paradigm shift from a uniform cardioembolic model toward a lesion-specific approach. The early clustering of recurrence suggests an urgent window for intervention. This well-characterized phenotype may represent a potential target population for future trials evaluating intensified antithrombotic strategies that address both cardioembolic and atherothrombotic pathways. Clinical PerspectiveO_ST_ABSWhat is New?C_ST_ABSO_LITwo-thirds of patients with AF-related stroke harbor concomitant large artery steno-occlusion (cLASO), yet current guidelines provide no recommendations for this common dual-mechanism scenario C_LIO_LIThis prospective multicenter study introduces a novel classification distinguishing clinically relevant cLASO from bystander atherosclerosis; only clinical relevance--not anatomic severity--independently predicted stroke recurrence, conferring a fourfold increased risk. C_LIO_LIOver 40% of recurrences occurred within the first month, with relevant cLASO conferring a 6.0% early recurrence risk--substantially exceeding reported annual major hemorrhage risks in landmark anticoagulant trials. C_LI What Are the Clinical Implications?O_LIAF-related stroke is mechanistically heterogeneous; assuming all cases are cardioembolic may lead to suboptimal risk stratification and missed opportunities for targeted prevention. C_LIO_LIRoutine vascular imaging should assess not merely stenosis severity, but topographic concordance with the infarct pattern--a straightforward approach using standard DWI and MRA that can be applied in diverse healthcare settings. C_LIO_LIThe early clustering of recurrence in patients with relevant cLASO highlights a critical unmet need and identifies a well-characterized target population for future trials evaluating intensified antithrombotic strategies. C_LI

ObjectiveA comparative analysis was conducted on the rehabilitation effects of limb functions in patients with post-stroke yawning-induced parakinesia brachialis oscitansysis (PBO), patients without PBO, and patients whose PBO naturally disappeared after the onset of the disease. MethodsThe study included ischemic stroke patients diagnosed and treated in our hospital from March 2024 to June 2024. Patients were divided into two groups: the PBO group and the non-PBO group, based on whether PBO was administered. Propensity score matching was employed to account for all covariates and perform a 1:2 matching to balance the baseline characteristics of the two groups. The matched data were used for subsequent analysis to observe the Lovett scores and FMA scores of the two groups 3 months after the onset. For 33 patients with PBO, they were divided into two groups: the persistent group and the disappearing group, based on whether the PBO lasted for more than 1 month. The Lovett scores and FMA scores of the two groups were observed 3 months after the onset. ResultsAfter propensity score matching, there were 26 patients in the PBO group and 52 patients in the non-PBO group. The baseline characteristics of the two groups were basically balanced, and the difference was not statistically significant (P>0.05). Compared with the non-PBO group, the Lovett scores and FMA scores of the PBO group 3 months after the onset were higher, and the difference was statistically significant (P < 0.05). Compared with the PBO persistent group, the FMA score of the PBO disappearing group 3 months after the onset was higher than that of the persistent group, and the difference was statistically significant (P < 0.05). There was no statistically significant difference in Lovett muscle strength between the two groups (P > 0.05). ConclusionThe functional recovery of patients with PBO was better than that of patients without PBO manifestation 3 months after the initial diagnosis. Moreover, patients whose PBO appeared first and then disappeared had better functional recovery than those whose PBO persisted.

BackgroundSuccessful recanalisation without functional independence is a frequent phenomenon following endovascular thrombectomy for large vessel occlusion stroke. AimTo demonstrate safety and efficacy of adjunct tirofiban therapy after endovascular thrombectomy in patients with anterior circulation large vessel occlusion stroke achieving successful recanalization defined as modified Thrombolysis In Cerebral Infarction (mTICI) 2b-3. DesignThe study of adjunct tirofiban treatment after successful endovascular thrombectomy recanalisation (ATTRACTION) is a multicenter, prospective, double-blind, randomized trial enrolling 1360 patients in China. Eligible patients will be randomised 1:1 to either the tirofiban or placebo group. OutcomeThe primary efficacy outcomes is assessed as the proportion of participants with a modified Rankin Scale (mRS) score of 0-2 at 90 days, and the primary safety outcome is symptomatic intracranial haemorrhage within 48 hours from randomisation. ConclusionThis study will provide evidence on the efficacy and safety of sequential tirofiban therapy after successful recanalisation in patients with anterior circulation large vessel occlusion stroke. Trial registration numberNCT06265051 WHAT IS ALREADY KNOWN ON THIS TOPICSuccessful recanalization without functional independence is a frequent phenomenon following endovascular thrombectomy and previous small-sample, retrospective studies supported the administration of adjunct tirofiban therapy in patients after endovascular thrombectomy achieving successful recanalization. WHAT THIS STUDY ADDSThe ATTRACTION trial aims to access the efficacy and safety of adjunct tirofiban therapy and the protocol describes the rationale and design of the trial. HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICYATTRACTION trial will inform whether tirofiban therapy after successful recanalisation by endovascular thrombectomy can improve patient outcomes.

BackgroundAmong patients with acute ischemic stroke (AIS) secondary to large vessel occlusion (LVO) who undergo successful reperfusion following endovascular thrombectomy (EVT), only one-third are disability-free at 90 days, which may be related to persistent microvascular hypoperfusion after thrombectomy known as the "no-reflow phenomenon". Adenosine is administered to prevent percutaneous coronary intervention (PCI)-related no-reflow through microvasculature dilation and neutrophil-mediated inflammation modulation. However, its role in in the setting of AIS has not been clearly elucidated. ObjectiveTo evaluate the safety and efficacy of adjunctive intra-arterial adenosine following successful EVT in LVO patients. Methods and designIn this multicenter, open-label, randomized, phase 2 trial, we evaluated the safety and efficacy of adjunctive intra-arterial adenosine following successful EVT in AIS patients. Up to 160 eligible stroke patients with anterior intracranial large vessel occlusion presenting within 24 hours from symptom onset (time last known well) are planned to be consecutively randomized. The primary outcome was the shift in the distribution of mRS scores at 90 days. Safety outcomes included symptomatic intracranial hemorrhage (sICH) within 48 hours and mortality at 90 days. DiscussionsThis pivotal trial will provide first-hand data on the efficacy and safety of adjunctive intra-arterial adenosine following successful EVT in patients with acute ischemic stroke due to LVO. Trial registry numberChiCTR2400092051 (www.chictr.org.cn).

ObjectiveTo compare early cerebrospinal fluid (CSF) cytokine profiles in intracerebral hemorrhage (ICH) versus subarachnoid hemorrhage (SAH), with a focus on angiography-negative SAH (anSAH). MethodsWe conducted a retrospective observational cohort study of adults with spontaneous hemorrhagic stroke (ICH or SAH). For cytokine analyses, we included patients with external ventricular drains (EVDs) and analyzed the first CSF sample obtained within 72 hours of symptom onset. Cytokines were measured using a multiplex bead-based assay and included interleukin-6 (IL-6), interleukin-8 (IL-8), vascular endothelial growth factor A (VEGF-A), C-C motif chemokine ligand-2 (CCL2), and granulocyte colony-stimulating factor (G-CSF). Cytokine concentrations were log-transformed due to non-normal distribution. Functional outcomes were assessed using the modified Rankin Scale (mRS) at discharge and 3 months. ResultsCSF cytokine analyses included 120 patients with available CSF samples (43 ICH and 77 SAH), while functional outcome analyses included a broader cohort of 490 patients with ICH or SAH to characterize discharge and 3-month outcomes across hemorrhage subtypes. Compared with SAH, ICH demonstrated higher early CSF log[IL-8] and log[VEGF-A] and had worse functional outcomes at discharge and 3 months. Within SAH, anSAH had higher log[IL-8] and log[VEGF-A] than aSAH, and its cytokine profile more closely aligned with that of primary ICH in hemorrhages without vascular malformations. DiscussionEarly CSF cytokine patterns suggest anSAH shares a more ICH-like inflammatory signature than aneurysmal SAH, supporting anSAH as a potentially biologically distinct SAH phenotype.

BackgroundMiddle meningeal artery embolization (MMAE) has emerged as an adjunct or alternative strategy for the management of chronic subdural hematoma (cSDH). Although accumulating studies suggest potential benefit, uncertainty remains regarding its safety profile, recurrence-prevention effect, and the reliability of adverse event reporting. This systematic review and meta-analysis re-evaluate contemporary evidence, incorporating new randomized trials and large observational cohorts. MethodsThis systematic review was conducted in accordance with PRISMA 2020 guidelines and prospectively registered in PROSPERO. PubMed, Scopus, Web of Science Core Collection, Embase, and CENTRAL were searched from inception to 12 September 2025 without language restrictions. Randomized controlled trials, prospective or retrospective cohort studies, and non-randomized clinical studies evaluating middle meningeal artery embolization (MMAE) for chronic subdural hematoma were eligible. Data extraction and risk-of-bias assessment were performed independently using Joanna Briggs Institute appraisal tools. Where outcomes were sufficiently comparable, quantitative synthesis was undertaken using random-effects single-arm proportion meta-analysis with logit transformation. Recurrence after MMAE was pooled across observational studies and MMAE arms of randomized trials with available event-level data, with prespecified subgroup analyses by study design. Mortality was synthesized from randomized trials reporting event-level data within a [&le;]90-day follow-up window. Complication rates and technical success were analyzed descriptively due to heterogeneity in definitions and follow-up durations. ResultsNineteen studies met eligibility criteria, including seven randomized controlled trials, sixteen retrospective cohorts, and one prospective cohort, comprising an elderly and medically complex population (mean ages 61-89 years). Common comorbidities included hypertension, diabetes, cardiovascular and cerebrovascular disease, renal dysfunction, and antithrombotic use. Technical success of middle meningeal artery embolization (MMAE) was consistently high, with a pooled success rate of 100% (95% CI 0.99-1.00; I2 = 0%). Recurrence after MMAE was consistently low across randomized and observational studies, including high-risk populations, and was uniformly lower than in comparator groups. Radiographic outcomes showed substantial hematoma volume reduction and high rates of complete or near-complete resolution, with favorable functional recovery. Complications were uncommon but heterogeneous; the pooled overall complication rate was 14% (95% CI 0.08-0.21). Pooled 90-day all-cause mortality from randomized trials was 8% (95% CI 0.07-0.10; I2 = 0%). ConclusionMMAE is a safe and effective adjunctive or alternative treatment for chronic subdural hematoma, demonstrating a reproducible and clinically meaningful reduction in recurrence across randomized and observational datasets with homogeneous outcome definitions. However, variability in adverse event reporting, insufficient documentation of rare complications, and inconsistent definitions of radiographic versus clinical recurrence highlight the need for standardized outcome frameworks and harmonized follow-up protocols. Future well-designed trials with robust adverse event adjudication are essential to define the long-term safety profile of MMAE and to guide its optimal integration into cSDH management pathways.

ImportancePrognosticating functional independence after an acute stroke is critical for anticipatory guidance and rehabilitation planning. Here we demonstrate that poor brain health at the time of incident stroke is linked to worse functional outcomes for women compared to men. ObjectiveTo determine if brain health at time of stroke presentation has a differential effect on functional outcomes between men and women. DesignRetrospective cross-sectional study. SettingAnalysis conducted in 2025 with multi-center patient data that included participants from two large acute ischemic stroke cohorts; local (GASROS) and multinational (MRI-GENIE) between the years 2003 and 2011. ParticipantsClinical data collected for enrolled study participants included demographic data, medical history of hypertension, diabetes mellitus, hyperlipidemia, smoking status, acute stroke severity as measured by National Institutes of Health Stroke Scale (NIHSS), stroke etiology, and modified Rankin Scale (mRS) score at 90 days post-stroke. Brain health was quantified as effective reserve derived from acute neuroimaging data. Exposure(s)designated sex, retrieved from registration records. Main OutcomeFunctional outcome was measured by mRS scores at 90 days post-stroke, in men and women with poor, moderate, or good brain health at time of stroke injury. ResultsA total of 1039 patients were included in the analysis, 37.8 % women, median age 67 [interquartile range 56-77]. Women with poor brain health (i.e. lowest quartile of effective reserve) had worse functional outcomes at 90 days (55.6% with mRS>2) compared to men with poor brain health (31.2% with mRS>2: p < 0.001). This difference between men and women was not observed in categories of moderate or good brain health. There was no observed significant difference in stroke severity, volume of acute lesion, burden of white matter hyperintensities, or stroke etiology between men and women with poor brain health. Conclusions and RelevanceBrain health at the time of incident stroke has a differential effect on functional outcomes at 90 days between men and women. Women with poor brain health endure disproportionately worse outcomes compared to men. This highlights an important step in understanding sex-specific vulnerability in early recovery post-stroke, and can inform disposition, rehabilitation services, and resource allocation planning.

BACKGROUNDSteno-occlusive diseases of the internal carotid artery (ICA) or middle cerebral artery (MCA) can lead to hemodynamic impairment, yet conventional imaging often fails to reflect metabolic dysfunction. Integrated positron emission tomography and magnetic resonance imaging (PET/MRI) allows simultaneous assessment of cerebral blood flow (CBF) and glucose metabolism. This study compared baseline perfusion and metabolic characteristics between patients receiving medical therapy or extracranial-intracranial (EC-IC) bypass surgery. METHODSThis retrospective study enrolled 34 patients with unilateral ICA/MCA stenosis or occlusion confirmed by digital subtraction angiography. All patients underwent 18F-FDG PET/MRI before treatment. Glucose metabolism was quantified using the cerebral metabolic rate of glucose (CMRGlu) from dynamic PET and the standard uptake value ratio (SUVR) from static PET. CBF was measured using three-dimensional arterial spin labeling with post-labeling delays of 2.0 and 2.5 seconds. Perfusion and metabolic parameters were compared across vascular territories. RESULTSBaseline clinical characteristics and long-term outcomes did not differ between groups (all P>0.05). Cerebral blood flow was similar across all arterial territories and post-labeling delays, with no hemispheric asymmetry detected (all P>0.05). In contrast, glucose metabolism was significantly lower in the surgical group, with reduced CMRGlu in the ischemic middle cerebral artery (23.58{+/-}7.46 vs 18.82{+/-}5.04mol/100g-1/min-1, P=0.037) and anterior cerebral artery territories (26.37{+/-}8.76 vs 20.71{+/-}5.78mol/100g-1/min-1, P=0.034). No differences were observed in the posterior cerebral artery or in SUVR across all regions (all P>0.05). CONCLUSIONSDespite similar perfusion profiles, the surgical group demonstrated lower glucose metabolism, suggesting that metabolic imaging may aid in identifying patients who could benefit from revascularization.

ObjectivesTo validate whether cerebrospinal fluid oxyhaemoglobin (CSF-Hb), measured from external ventricular or lumbar drains, is associated with secondary brain injury (SAH-SBI) after aneurysmal subarachnoid haemorrhage (aSAH), and to assess its value as a real-time monitoring biomarker. DesignPreregistered multicentre prospective observational cohort study. SettingEight neurosurgical tertiary centres in Switzerland, Germany, and Austria, between August 2021 and June 2024. Participants366 patients with aSAH (mean age 58 years; 65% women). Of these, 260 provided cerebrospinal fluid (CSF) samples via external ventricular drain (EVD; 2,467 samples, median 10 days per patient) and 66 via lumbar drain (LD; 379 samples, median 6 days). InterventionsDaily CSF samples were collected via EVD or LD from day 1 to day 14 after haemorrhage; no therapeutic interventions were tested. Main outcome measuresCSF-Hb and its metabolites were analysed post hoc in a blinded manner. The primary outcome was SAH-SBI, defined as a composite of angiographic vasospasm (aVSP), delayed cerebral ischaemia (DCI), and delayed ischaemic neurological deficits (DIND), assessed daily over 14 days. Secondary outcomes included temporal CSF-Hb profiles and associations with aneurysm location, haematoma volume, intraventricular haemorrhage, chronic hydrocephalus, and 3-month functional outcome. ResultsCSF-Hb showed a delayed peak pattern: concentrations were low after aSAH, rose to a maximum on day 10 (EVD-derived CSF-Hb median 11.3 {micro}M, IQR 2.64 to 25.90), and then declined. Larger haematoma volume (p<0.001) and intraventricular haemorrhage (p<0.001) were associated with higher EVD-derived CSF-Hb. SAH-SBI occurred in 209/366 patients (57%). Daily EVD-derived CSF-Hb showed no association with SAH-SBI (p=0.25) and only poor prognostic potential of same-day SAH-SBI (area under the curve 0.59, 95% confidence interval 0.56-0.63), with substantial between-centre heterogeneity. The oxidised haemoglobin metabolite methaemoglobin was positively associated with SAH-SBI (p=0.023; odds ratio 1.18 per log[{micro}M], 95% confidence interval 1.02-1.36). Acute-phase EVD-derived CSF-Hb correlated with chronic hydrocephalus (p=0.012) and poor 3-month functional outcome (p=0.008). Catheter-related infection rates were low (2.2%). ConclusionsIn this preregistered multicentre validation study, EVD-derived CSF-Hb did not perform as a robust real-time monitoring biomarker for SAH-SBI, showing limited same-day discrimination and substantial between-centre heterogeneity. These findings argue against clinical implementation of CSF-Hb point-measurement as a single-parameter biomarker. In contrast, CSF methaemoglobin remained consistently associated with SAH-SBI, supporting the mechanistic relevance of haemolysis-related pathways. Future work using the HeMoVal biobank will apply multi-marker, pathway-level analyses to define haemolysis-related biomarker signatures and provide a platform for robust external validation of future candidates. Study registrationClinicalTrials.gov NCT04998370; date of registration 10 August 2021. Summary BoxesO_ST_ABSWhat is already known on this topicC_ST_ABSO_LIPreclinical animal models link cell-free haemoglobin in cerebrospinal fluid (CSF-Hb) to secondary brain injury after aneurysmal subarachnoid haemorrhage (SAH-SBI). C_LIO_LIA single-centre study reported strong associations between daily external ventricular drain (EVD) derived CSF-Hb levels and SAH-SBI, and suggested a strong predictive potential(area under the curve 0.89). C_LIO_LICSF-Hb monitoring has therefore been proposed as a bedside biomarker, but it has not undergone multicentre validation. C_LI What this study addsO_LIIn a preregistered multicentre cohort of 366 patients from eight neurosurgical centres, once-daily EVD-derived CSF-Hb measurements showed poor same-day discrimination for SAH-SBI (area under the curve 0.59) and substantial between-centre heterogeneity. C_LIO_LIIn contrast, CSF methaemoglobin was consistently associated with SAH-SBI, and higher acute-phase CSF-Hb was related to chronic hydrocephalus and worse 3-month functional outcome. C_LIO_LIThese findings argue against routine adoption of CSF-Hb point-measurements as bedside single-analyte, while supporting haemolysis-related pathways as mechanistic targets. C_LI

BackgroundSarcopenia is associated with mortality and morbidity following acute ischemic stroke (AIS), but the diagnosis requires specialized equipment or time-consuming assessments. Computed tomography (CT) measures of temporal muscle volume (TMV) and density (TMD) can be opportunistically measured from existing scans and automated using deep learning (DL). This study sought to demonstrate the incremental prognostic value of DL-derived TMV and TMD from CT scans on mortality and length of stay (LOS) in AIS. MethodsIn this retrospective, single-centre cohort study, consecutive AIS patients admitted from 2014 to 2023 were included. Admission CT scans were retrieved alongside clinical data from electronic health records. TMV and TMD were quantified by a novel DL model and represented as continuous or trichotomous categorical variables. TMV and TMD thresholds were derived in a cohort of 50 healthy adults and used to classify AIS patients as non-sarcopenic, pre-sarcopenic, or sarcopenic. The primary outcome was 30-day all-cause mortality. Secondary outcomes were 365-day all-cause mortality and LOS. Multivariable logistic and linear regression were used. ResultsThe cohort consisted of 2285 patients with 1151 (50%) females, and a mean (SD) age of 74.7 (13.7) years. Based on TMV and TMD, 877 patients (38%) were non-sarcopenic, 838 (37%) pre-sarcopenic, and 570 (25%) sarcopenic. Adjusted ORs for 30-day mortality were 2.70 (1.64 to 4.46) and 2.91 (1.72 to 4.91) for pre-sarcopenia and sarcopenia. Adjusted ORs for 365-day mortality were 2.42 (95% CI 1.74 to 3.36) and 2.96 (95% CI 2.09 to 4.17) and the additional days in hospital were 2.79 (1.69 to 3.98) and 3.26 (2.00 to 4.64) for pre-sarcopenia and sarcopenia. The association between CT-derived sarcopenia and mortality was preserved after adding HFRS to the models. ConclusionsTMV and TMD extracted using a novel DL model were incrementally predictive of AIS mortality. These metrics may be used to refine risk estimates, inform shared decision-making, and individualize treatment plans.

Optimal blood pressure (BP) management following endovascular treatment (EVT) for acute ischemic stroke (AIS) secondary to intracranial large vessel occlusion remains unestablished. The randomized HOPE trial (Hemodynamic Optimization of Cerebral Perfusion after Successful Endovascular Therapy in Patients with Acute Ischemic Stroke) (NCT04892511) seeks to determine if a strategy of hemodynamic optimization using different systolic BP targets, tailored to the degree of final recanalization, is superior to standard BP management in improving functional outcomes for these patients. This document outlines the final Statistical Analysis Plan (SAP) for the trial. This plan will be executed after the last follow-up is complete and the dataset has been locked.