Stroke

BackgroundThe sensitivity of emergency medical communication centers (EMCC) for stroke detection varies widely. However, few studies offer detailed insights into the entirety of prehospital pathways in patients with stroke. Therefore, this study aimed to lay the foundation for artificial intelligence (AI) decision support tools in EMCCs by exploring their ability to detect strokes in medical emergency calls, describe a novel method for stroke sensitivity calculation in the EMCC, and identify factors associated with stroke recognition during a call. MethodsIn total, 1,164 patients with stroke in the catchment area of Bergen EMCC in 2018 and 2019 were included, and a dataset from the EMCC was established manually and linked with data from the Norwegian Stroke Registry (NSR) for analysis. Descriptive statistics, Chi-square test for categorical variables, Mann-Whitney U test for continuous variables, and multivariate logistic regression (LR) were performed on data obtained from patients primarily assessed by EMCC (n=838). ResultsUsing a novel method, we found a stroke detection sensitivity of 76.8% in our study, compared to the 63.4% when using the traditional sensitivity detection method. LR analysis showed a positive association between stroke suspicion and ischemic strokes (odds ratio [OR]=0.317 [0.209-0.481]; p<0,001, with ischemic stroke as the reference) and wake-up strokes (OR=1.716 [1.110-2.653]; p=0.015). Among the NSR symptoms, only aphasia/dysarthria was positively associated with stroke suspicion (OR=1.600 [1.087-2.353]; p=0.017), while leg paresis (OR=0.609 [0.390-0.953]; p=0.009) and vertigo (OR=0.376 [0.204-0.694]; p=0.002) were negatively associated. ConclusionsThis study introduced a novel and more accurate method for calculating EMCC stroke sensitivity, which is relevant for developing decision support tools, such as AI. Moreover, we identified factors of particular interest for future EMCC research that are relevant to developing AI decision-support tools. Clinical trialshttps://clinicaltrials.gov/study/NCT04648449

BACKGROUND AND PURPOSEFocal cerebral arteriopathy-inflammatory type (FCA-i) is a leading cause of pediatric arterial ischemic stroke, but diagnostic challenges persist, particularly in East Asian populations where moyamoya disease (MMD) prevalence is high. The Focal Cerebral Arteriopathy Severity Score (FCASS) quantifies arteriopathy severity but has not been validated in East Asian cohorts. We aimed to validate FCASS in Korean pediatric patients with FCA-i and compare temporal progression patterns with unilateral moyamoya disease. METHODSWe conducted a retrospective cohort study of children with arterial ischemic stroke presenting to Seoul National University Hospital between January 2002 and December 2024. Patients were classified according to Childhood Arterial Ischemic Stroke Standardized Classification and Diagnostic Evaluation criteria. The FCASS was applied to serial magnetic resonance angiograms at baseline, peak severity, and final follow-up. Clinical outcomes were assessed using the Pediatric Stroke Outcome Measure at 12 months. RESULTSAmong 216 children with arterial ischemic stroke, 132 patients (61.1%) demonstrated arteriopathy, including 49 with FCA-i and 60 with MMD. In FCA-i patients, the severity score correlated significantly with baseline infarct burden ({rho}=0.42, P=0.0069) and exhibited characteristic monophasic evolution with early peak at 2 months followed by gradual recovery reaching lowest values at 11 months. Unilateral MMDpatients demonstrated consistently higher severity scores at all timepoints compared with FCA-i (baseline: 6.0 vs 2.0; final: 8.0 vs 3.0, P<0.001) without radiographic recovery. A baseline severity score [&ge;]8.0 predicted contralateral progression in unilateral MMD with area under the curve of 0.962 (sensitivity 0.83, specificity 0.91). CONCLUSIONSThe FCASS demonstrates validity as a dynamic biomarker for monitoring FCA-i in Korean pediatric patients, exhibiting characteristic monophasic recovery patterns that distinguish it from progressive unilateral MMD.

Background Adults aged 80 years and older are the fastest-growing segment of the stroke population. Whether contemporary advances in stroke care have produced sustained outcome gains in this group during the past decade, including the post-pandemic era, has not been examined in nationwide longitudinal data with concurrent age-specific comparison. Methods Using the Clinical Research Collaboration for Stroke in Korea-National Institutes of Health (CRCS-K-NIH) registry, we analyzed consecutive adults with acute ischemic stroke admitted within 7 days of symptom onset between 2011 and 2022. Patients aged 80 years and older formed the primary cohort; those aged 18-79 years served as comparators. Primary outcomes were 3-month utility-weighted modified Rankin Scale (UW-mRS) and 1-year all-cause mortality. Non-linear trends and age-group-by-year interaction were modeled using restricted cubic splines adjusted for sex, age, and baseline NIHSS. Results Of 83,953 patients, 18,514 (22.1%) were aged 80 years and older; their proportion rose from 17.4% to 27.3%. Despite treatment intensification (endovascular thrombectomy 4.2% to 10.6%; oral anticoagulation for atrial fibrillation 52.5% to 76.9%), 1-year mortality in this group fell from 27.5% in 2011 to 19.4% in 2019, then rose to 23.7% by 2022; 3-month UW-mRS improved from 0.47 to 0.51 over the same period, then stagnated at 0.48. Restricted cubic splines confirmed significant nonlinearity in both outcomes after adjustment for sex, age, and NIHSS (P < 0.01 for both). Younger patients showed no comparable functional deterioration. Age-group-by-year interaction was significant for 3-month UW-mRS (P < 0.001) but not for 1-year mortality (P = 0.058), which showed a similar direction in both age groups. Conclusion In this nationwide registry, patients aged 80 years and older experienced an age-specific inflection of functional recovery gains after 2019 despite continued intensification of acute stroke care. Sustaining outcome gains in this population may require attention to post-acute care infrastructure.

Background: Remote ischemic perconditioning (RIperC) is a simple, noninvasive neuroprotective strategy based on brief cycles of limb ischemia-reperfusion during cerebral ischemia. REMOTE-CAT suggested a potential functional benefit of prehospital RIperC in acute ischemic stroke. However, its effect on poststroke cognitive outcomes, which may not be fully captured by global disability scales, remains uncertain. Methods: We performed an exploratory cognitive substudy of the multicenter, randomized, double-blind, sham-controlled REMOTE-CAT trial. Patients with suspected acute ischemic stroke within 8 hours, prestroke modified Rankin Scale score <3, and RACE motor score >0 were randomized prehospital to RIperC or sham. RIperC consisted of five 5-minute cuff inflation-deflation cycles during ambulance transfer. At 90 days, patients from one center underwent a standardized neuropsychological battery assessing five cognitive domains. Results: Among 122 patients in the primary analysis, 58 (47.5%) completed neuropsychological assessment: 26 allocated to RIperC and 32 to sham. No statistically significant between-group differences were observed in domain-specific Z scores. Cognitive impairment in at least one domain was numerically less frequent with RIperC than sham (26.9% versus 34.4%). Impairment in more than one domain was also less frequent with RIperC (7.7% versus 21.9%), although the overall distribution of impaired domains did not differ significantly between groups (P=0.244). The largest domain-specific difference was observed for visual memory impairment (3.8% versus 21.9%). Conclusions: In this exploratory substudy, prehospital RIperC did not significantly improve 90-day cognitive outcomes after acute ischemic stroke. Nevertheless, RIperC-treated patients showed numerically favorable trends, particularly in global cognitive burden and visual memory. These hypothesis-generating findings support incorporating standardized cognitive outcomes in future ischemic conditioning trials.

BackgroundAnimal studies suggest that high-density lipoprotein cholesterol (HDL-C) protects against reperfusion injury. We hypothesised that higher serum HDL-C levels would have a protective effect against cerebral reperfusion injury in human stroke survivors treated with thrombectomy. MethodsWe included consecutive patients from our prospective anterior circulation large-vessel occlusion (acLVO) registry who underwent thrombectomy between January 2017 and January 2023 at a tertiary stroke centre in Germany in a propensity score-matched analysis. We assessed the association between serum HDL-C levels and imaging indices of post-interventional reperfusion injury according to the Heidelberg Bleeding Classification as well as 90-day functional outcome quantified by the modified Rankin Scale (mRS). We performed sensitivity analyses using multivariable lasso logistic and linear regression adjusted for demographic, clinical and imaging characteristics. ResultsOut of 1702 patients assessed for eligibility, 807 acLVO patients treated with thrombectomy (420 females, median age 77 years [66-84, IQR]) were included. Reperfusion injury reduced the probability of a favourable functional outcome (90-day mRS 0-2) by 14.8% ({beta}=0.15; 95% CI [0.06;0.24]; p=0.001. A serum HDL-C level above the median (1.15 mmol/L) decreased the probability of reperfusion injury by 13.6% ({beta}=-0.14; 95CI% [-0.22; -0.05]; p=0.002) and increased the probability of favourable functional outcome by 13.2% ({beta}=-0.13; 95CI% [-0.22;-0.05]; p=0.003). In sensitivity analyses, higher HDL-C levels were associated with lower odds of reperfusion injury (adjusted OR 0.62; 95% CI [0.43;0.88]; p=0.008) and emerged as a predictor of a favourable functional outcome (adjusted OR 0.60; 95% CI [0.40; 0.90]; p=0.015). ConclusionsIn patients undergoing thrombectomy for acLVO, higher serum levels of HDL-C were associated with a reduced probability of reperfusion injury and favourable functional outcome at 90 days.

BackgroundPrevious genome-wide association studies (GWAS) have identified several risk genes for stroke; however, it remains unclear how they confer risk for the disease. We conducted an integrative analysis to identify candidate genes for stroke and stroke subtypes by integrating blood-derived multi-omics data with genetic data. MethodWe systematically integrated the latest stroke GWAS database (73,652 patients and 1,234,808 controls) with human plasma proteomes (N=7,213) and performed proteome-wide association studies (PWAS), Mendelian randomization (MR), Bayesian colocalization analysis, and transcriptome-wide association study (TWAS) to prioritize genes that associate the risk of stroke and its subtypes with their expression and protein abundance in plasma. Cell-type specificity and functional enrichment analysis using single-cell RNA sequencing (scRNA-seq) and Gene Ontology (GO) databases were then performed to select target genes. A two-step MR analysis was followed to explore the potential mechanisms. ResultsWe found that the protein abundance of seven genes (MMP12, F11, SH3BGRL3, ENGASE, SCARA5, SWAP70, and SPATA20) in the plasma was associated with stroke and its subtypes, with six genes (MMP12, F11, SH3BGRL3, SCARA5, SWAP70, and SPATA20) causally related with stroke and its subtypes (P < 0.05/proteins identified for PWAS; P < 0.05/8 for MR; posterior probability of hypothesis 4 [&ge;] 75 % for Bayesian colocalization). The effect of F11, SH3BGRL, SPATA20, and SWAP70 on each subtype was mediated by Factor XI inhibitors (FXI), atrial fibrillation, T2D, and SBP respectively (p<0.05). We also found that SCARA5 and SWAP70 were related to stroke and ischemic stroke at the transcriptome level. ConclusionsOur present proteomic findings have identified new causal genes in the pathogenesis of stroke, which may offer potential future therapeutic targets for stroke prevention.

Background and PurposeEndovascular thrombectomy (EVT) is a time-critical treatment for acute ischemic stroke; however, timely access to comprehensive stroke centers (CSCs) is often limited by distance. Regional variations in prehospital transport strategies, particularly Helicopter Emergency Medical Services (HEMS) use, exist in Sweden, which may contribute to inequities in care. This study analyzed how transport modality affected the time to EVT for rural patients across two large Swedish regions with differing transport strategies. MethodsA retrospective registry-based study was performed, using comprehensive stroke registries and ambulance records from 2018 to 2022. All patients who underwent EVT in two healthcare regions (Vastra Gotaland and Southeastern healthcare regions) were included. The primary analysis focused on those located [&ge;]50 km from the CSC. The main outcome was the time from emergency medical service (EMS) dispatching to EVT start. Logistic regression was used to assess the odds of receiving EVT within 180 minutes. ResultsAmong the 1,222 patients, 623 (51%) were [&ge;]50 km from a CSC. Direct CSC transfer and HEMS use were more frequent in Vastra Gotaland compared to the Southeastern region (52.0% vs. 28.4% and 8.9% vs. 0.9%, respectively; P<0.001 and P=0.003, respectively). For patients [&ge;]50 km away, HEMS transport yielded a shorter median dispatch-to-EVT time than ground transport (224.2 vs 287.5 min; P<0.001). After adjusting for distance, HEMS was associated with a 3.6-fold higher likelihood of EVT within 180 min (OR 3.6 [95% CI 1.6-7.8], P=0.001). ConclusionsGeographical distance significantly delays time to EVT. Use of HEMS markedly shortens transport time leading to timelier EVT for patients with long distances to CSC and has the potential to mitigate regional disparities. Integrating HEMS into stroke transport protocols is essential to ensure timely and equitable EVT access for rural patients.

Background and ObjectivesTo explore whether the presence, burden or distribution of cerebral microbleeds (CMBs) modifies the effect of early versus delayed antihypertensive treatment on clinical outcomes in acute ischemic stroke (AIS) patients. MethodsA secondary analysis of the China Antihypertensive Trial in Acute Ischemic Stroke II (CATIS-2) trial was performed. Participants with baseline cerebral magnetic resonance imaging (MRI) data for CMB evaluation were included. The primary outcome was functional dependency or death at 90 days, defined as a modified Rankin Scale (mRS) score [&ge;]3. ResultsAmong 815 eligible participants (mean age 62.4 years; 34.5% female), 396 (48.6%) had at least one CMB. The presence of strictly deep CMBs was associated with an increased risk of functional dependency or death at 90 days compared to the absence of CMBs (15.3% vs 7.9%; adjusted odds ratio [aOR] 1.92, 95% CI 1.08-3.40, P=0.03). Early versus delayed antihypertensive treatment significantly increased the risk of functional dependency or death in patients with CMBs (17.1% vs 8.7%; aOR 2.17, 95% CI 1.16-4.07; P=0.02). This effect was particularly pronounced among patients with moderate-to-severe CMBs (17.5% vs 6.6%; aOR, 2.85; 95% CI, 1.06-7.67; P=0.04) and strictly deep CMBs (20.8% vs 9.0%; aOR, 2.76; 95% CI, 1.15-6.64; P=0.02). However, no statistically significant interaction was observed between CMBs and treatment assignment for the primary outcome (pinteraction>0.05). ConclusionsThis secondary analysis of CATIS-2 indicates that the presence of CMBs, particularly those predominantly located in deep regions or with a greater burden, may increase the risk of adverse clinical outcomes following early antihypertensive treatment in AIS patients. These findings highlight the imperative for further research on individualized blood pressure (BP) management strategies in AIS patients with CMBs. RegistrationURL: https://www.clinicaltrials.gov; Unique identifier: NCT03479554.

Background: Frailty is common in acute ischemic stroke (AIS) and predicts poor outcomes, but is not routinely captured in acute stroke care. Manual frailty tools are difficult to apply consistently in busy inpatient settings, while existing electronic frailty indices (eFIs) often rely on limited data modalities. We developed a scalable pre-stroke electronic frailty index (eFI) using multisource electronic medical record (EMR) data and evaluated its clinical utility. Methods: We conducted a retrospective cohort study of AIS admissions to Singapore General Hospital from July 1, 2024, to January 31, 2025. A fully automated pipeline derived an eFI from EMR data over a 3-year lookback period, incorporating ICD-10 codes, vital signs, anthropometry, laboratory results, medications, and free-text documentation processed using artificial intelligence?augmented extraction of predefined, clinically interpretable deficits. Candidate variables were screened using a validated 10-step frailty index framework and refined by multidisciplinary expert consensus. Results: Among 501 AIS cases, the pipeline generated 75 candidate variables and a final 33-variable eFI, with scores derived for 492 cases (98.2%). Frail patients had greater premorbid disability, higher stroke severity, longer hospitalization, greater rehabilitation use, worse discharge disability, higher 30-day readmission, and higher cumulative post-discharge mortality. In multivariable analyses adjusted for age, sex, NIHSS, premorbid mRS, and reperfusion therapy, each 0.1-unit increase in eFI was associated with mortality beyond 90 days after discharge (adjusted HR, 1.47; 95% CI, 1.19?1.81), 30-day readmission (adjusted OR, 1.91; 95% CI, 1.43?2.59), longer hospital stay (?, 2.8 days; 95% CI, 1.4?4.2), and discharge to inpatient rehabilitation rather than home (adjusted RRR, 1.66; 95% CI, 1.27?2.16). Conclusions: In a well-documented acute stroke service supported by comprehensive longitudinal EMR data, automated multisource eFI derivation was feasible and clinically informative in AIS, capturing baseline vulnerability beyond conventional stroke measures and supporting frailty-informed risk stratification and discharge planning.

BackgroundIntracranial atherosclerotic stenosis (ICAS) is a major cause of ischemic stroke with high recurrence rates despite intensive therapy. The efficacy of proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) as adjunctive treatment in ICAS remains unclear. MethodsWe conducted a prospective, randomized, open-label, blinded-endpoint trial involving 62 patients with symptomatic ICAS. Participants were randomized 1:2 to receive either a PCSK9i (alirocumab 75 mg every two weeks) plus high-intensity statin or high-intensity statin alone for six months. The primary outcome was the change in intracranial artery stenosis measured by high-resolution vessel-wall magnetic resonance imaging. Secondary outcomes included plaque enhancement volume, low-density lipoprotein cholesterol (LDL-C) target achievement (<55 mg/dL), recurrent stroke events, modified Rankin Scale, and safety assessments. ResultsAmong 62 participants (median age, 66 years; 68% men), 60 completed the study per protocol. At 6 months, median stenosis reduction was greater in the PCSK9i group (7.1%; 95% CI, 3.6-12.8%) than in controls (- 1.2%; 95% CI, -4.9-4.5%) (p < 0.01). Both groups showed significant reduction in plaque enhancement volume, but between-group difference was not significant (4.3 vs 4.0 mm3; p = 0.28). LDL-C <55 mg/dL was achieved in 85% of the PCSK9i group vs 13% of controls (p < 0.01). Recurrent stroke occurred in 5% vs 13% of patients (p = 0.39). No serious adverse events were reported in either group. ConclusionIn patients with symptomatic ICAS, adjunctive PCSK9i therapy significantly reduced intracranial stenosis and improved LDL-C control over 6 months. While both treatment strategies reduced plaque enhancement, PCSK9i provided additional benefit in stenosis regression. Larger and longer-term studies are warranted to confirm these findings and clarify optimal LDL-C targets for ICAS management. Trial RegistrationClinicalTrials.gov Identifier: NCT05001984

BackgroundIntravenous thrombolysis (IVT) failure in acute ischemic stroke (AIS) due to large vessel occlusion (LVO) is frequent but its causes remain elusive. Several non-exclusive mechanisms have been proposed to explain IVT failure, including failed delivery of tPA and inhibition of its activity. We investigated whether biologically relevant intrathrombus concentrations of t-PA were achieved in failed IVT in patients with LVO AIS, and whether neutrophil extracellular traps (NETs) contributed to IVT failure. MethodsIn this cohort study, a total of 205 thrombi from AIS patients with LVO were analyzed. 83 of these thrombi were compared for tPA content and 53 for their susceptibility to ex vivo thrombolysis according to IVT status. An additional subset of 69 AIS thrombi was used to decipher if and how NETs interfere with intrathrombus fibrinolysis. ResultsAIS thrombi from IVT patients contained more tPA than those from no-IVT patients (0.209 vs 0.093 {micro}g/mg of thrombus, p<0.0001). Plasminogen and tPA in AIS thrombi were found in association with fibrin and NETs. The ability of NETs to bind tPA and plasminogen, titrating them away from fibrin, was confirmed in a microfluidic model of thrombosis. While ex vivo addition of plasminogen did not cause lysis of either no-IVT or IVT thrombi, combining plasminogen with DNase 1 helped translate the increased tPA content of IVT thrombi into increased thrombolysis. We further show that DNase 1 enables tPA- and plasmin-mediated thrombolysis by eliminating fibrinolysis inhibitors from AIS thrombi. ConclusionsThese results indicate that intrathrombus tPA concentrations reached in failed IVT bear a therapeutic potential that is however impaired by NETs, which favor intrathrombus retention of fibrinolysis inhibitors and compete with fibrin for tPA and plasminogen binding. Our results stress the interest of DNase 1 to enhance the efficacy of current IVT tPA regimens. Clinical PerspectiveO_ST_ABSWhat is new?C_ST_ABSO_LIIntravenous thrombolysis increases thrombus tPA content even when it fails to cause arterial recanalization in acute ischemic stroke C_LIO_LIThe fibrinolytic activity of intravenously-administered tPA is blocked by neutrophil extracellular traps in acute ischemic stroke thrombi C_LIO_LINeutrophil extracellular traps participate in thrombolysis resistance by retaining fibrinolysis inhibitors and titrating tPA and plasminogen away from fibrin in acute ischemic stroke thrombi C_LIO_LIDNase 1 can convert increased tPA content into increased fibrinolysis by eliminating NETs-associated fibrinolysis inhibitors in acute ischemic stroke thrombi C_LI 2) What are the clinical implications?O_LIDespite therapeutic failure, biologically significant intrathrombus tPA concentrations are achieved following intravenous thrombolysis at current tPA regimens C_LIO_LISequential administration of DNase 1 prior to intravenous thrombolysis could clear the way for tPA and potentiate its fibrinolytic activity for improved arterial recanalization efficacy C_LI

BackgroundRadiomic and transcriptomic analyses have independently identified features linked to mechanical thrombectomy (MT) outcomes in acute ischemic stroke (AIS). In this study, we integrate paired radiomic and transcriptomic profiling of AIS clots to identify Neutrophil Extracellular Trap (NET) enrichment as a predictor of first-pass MT success. We further assess the potential to non-invasively detect NET enrichment using pre-thrombectomy CT imaging. MethodsWe performed radiomic and transcriptomic analysis of 32 stroke clots retrieved by MT (n=16 each of modified first pass [mFP] success and failure). Clots were segmented from pre-MT CTA and nCCT scans and radiomic features (RFs) were extracted using pyRadiomics. Normality, equal variance, and two-sample testing were completed to identify which RFs were significantly different between mFP outcomes. Differentially expressed genes (DEGs) were identified between transcriptomes of mFP success and failure using the criteria of logFC[&ge;]1.5 and q<0.05. A NET enrichment score was computed from expression data and correlated with RFs to identify a RF signature predictive of NET enrichment. Immunofluorescence (IF) staining was completed on retrieved clot tissue to provide ground truth labeling of NETs. Results44 DEGs were identified between mFP outcomes. From ontology analysis, NET Formation, Neutrophil Degranulation, and the NET Signaling Pathway were among the most enriched terms in the mFP failure group, with related genes downregulated in the mFP success group. 40 RFs were significantly different between mFP outcomes. Of these, 6 were found to be correlated with and predictive of clot NET enrichment. IF quantification validated that transcriptomic NET signatures accurately reflected NET presence within clot tissues. ConclusionOur findings indicate that NET enrichment within thrombi is associated with reduced mFP success, and that radiomic features extracted from pre-thrombectomy CT imaging can serve as non-invasive biomarkers of clot NET content. This radiomic signature may aid in pre-procedural decision-making, including thrombolytic therapy planning and thrombectomy device selection.

BackgroundStroke mimics pose diagnostic challenges in the emergency department, particularly in patients presenting within the 4.5-24 hour thrombectomy window. Misdiagnosis may result in unnecessary interventions or delayed stroke treatment. This study aimed to determine the prevalence, clinical characteristics, and predictors of stroke mimics among suspected stroke patients in this timeframe. MethodsWe conducted a cross-sectional study at Peoples Hospital 115, Vietnam (February-June 2024). Patients presenting with acute neurological deficits underwent standardized magnetic resonance imaging. Logistic regression identified independent predictors of stroke mimics. ResultsAmong 1,180 patients (mean age 62.6 years; 58.6% male), 346 (29.3%) were diagnosed with SMs. Compared to stroke patients, stroke mimics were more likely to be male (77.2% vs. 50.8%, P < 0.001), had lower NIHSS scores (median 8 vs. 12.5, P = 0.013), and shorter hospital stays (median 2 vs. 4 days, P < 0.001). Independent predictors included bilateral leg weakness (OR 23.9; 95% CI, 6.9-33.8), quadriparesis (OR 25.4; 95% CI, 7.8-35.1), dizziness (OR 14.6; 95% CI, 7.1-32.7), headache (OR 13.2; 95% CI, 6.5-26.8), seizures (OR 13.9; 95% CI, 6.7-28.5), altered consciousness (OR 4.9; 95% CI, 2.4-9.8), numbness (OR 6.4; 95% CI, 2.1-12.5), and male sex (OR 3.3; 95% CI, 2.5-4.4). Atrial fibrillation was a negative predictor (OR 0.33). ConclusionsStroke mimics account for nearly one-third of suspected strokes within the extended thrombectomy window. Recognizing specific clinical predictors can improve diagnostic accuracy, reduce unnecessary interventions, and optimize ED resource allocation. Integration of these predictors into triage protocols could support faster, safer decision-making in clinical practice. Key PointsO_ST_ABSWhat is already known on this topicC_ST_ABSStroke mimics are common and complicate triage in the era of thrombectomy; prevalence varies widely but data from Southeast Asia are scarce. What this study addsIn this large Vietnamese cohort, nearly one-third were stroke mimics; distinct clinical predictors were identified. How this study might affect research, practice or policyIncorporating these predictors into triage could reduce unnecessary interventions and optimize ED resources.

Introduction: High-intensity locomotor training (HIT) is recommended for improving walking capacity, but treatment responses are variable. Understanding the brain changes underlying responsiveness to training could provide insight into this variability. Emerging evidence suggests upregulation of the contralesional cortico-reticulospinal tract (CRST) may contribute to walking function after stroke. However, it is unclear whether CRST upregulation is supportive or maladaptive, and no studies have examined CRST changes after HIT. This study investigated how CRST and corticospinal tract (CST) strength and laterality reorganize, and their relationship with walking capacity after locomotor HIT. Methods: Ten participants with chronic stroke completed a 4-week no-intervention control phase then 4-weeks of HIT. Diffusion MRI and 6-minute walk distance were obtained at weeks 0, 4, and 8. Analysis tested changes in ipsilesional and contralesional CRST and CST strength and laterality. Associations between changes in tract laterality and walking capacity were examined. Results: During the treatment phase (vs. the control phase), there were significantly greater increases in contralesional CRST strength (1.02 SD [95% CI: 0.25, 1.79]), contralesional CRST laterality (4.44 [2.15, 6.72]), and 6-minute walk distance (33 meters [17, 50]). Walking capacity improvements were associated with changes in CRST laterality (r = 0.77, p = 0.01), but not CST laterality (r = -0.01, p = 0.98). Discussion: Following HIT, increases in contralesional CRST strength and laterality were observed. CRST laterality changes were strongly associated with walking improvements, suggesting a possible supportive role of contralesional CRST in mediating training-related improvements in walking function after stroke.

Recent studies have identified > 40 genetic variants robustly associated with ischemic stroke, most identified through genome wide association studies and primarily marking common variants in non-coding regions presumed to have regulatory roles on gene and protein expression. To evaluate the contribution of coding variants, which are mostly rare, to the etiology of ischemic stroke, we performed an exome array analysis of 9,721 ischemic stroke cases with mean age of onset at 67.1 years from the SiGN Consortium, and 12,345 subjects with no history of stroke (mean age 67.0 years) from the Health Retirement Study and SiGN consortium. Both cohorts included people with diverse ancestries. Genotyping for both SiGN and HRS was performed using similar array content at the Center for Inherited Disease Research (CIDR), albeit as two separate studies. Following extensive SNP- and sample-level quality control, a total of 106,101 SNPs from the exome content was used for exome association analysis. We identified 15 coding variants significantly associated with all ischemic stroke at array-wide threshold for statistical significance (i.e., p < 3.6 x 10-7) that also showed good genotyping quality, including two common SNPs in ABO that have previously been associated with stroke. Twelve of the remaining 13 variants were extremely rare in European Caucasians (MAF<0.1%) and the associations were driven by substantially higher allele frequencies in African American cases than in African American controls. A variant in PRIM2, rs199585353, was present exclusively in the stroke cases of European Caucasians while absent in all other samples from our data. There was no evidence for replication of these associations in either TOPMed Stroke samples (n = 5613 cases) or UK Biobank (n = 5,874 stroke cases), although power to replicate was very low given the low allele frequencies of the associated variants. In conclusion our analyses revealed 13 novel associations, but the low allele counts of associated variants and difficulty in acquiring large, well-powered replication highlight the challenges of rare variant association analysis, especially using array-based genotyping technologies.

Background and PurposeAs populations age, there is an increasing need to optimize endovascular treatment (EVT) for acute ischemic stroke. We harmonized prospective stroke registries from Korea and Taiwan to enable direct comparisons of patient characteristics and clinical outcomes, with a particular focus on the impact of advanced age. MethodsProspective stroke registries in South Korea (CRCS-K) and Taiwan (TREAT-AIS) were harmonized to form a unified dataset of patients treated with EVT. EVT outcomes included 3-month modified Rankin Scale (mRS), symptomatic intracranial hemorrhage (SICH), and successful recanalization. We assessed the association between age and outcomes in the overall population and in those aged [&ge;]80 years, adjusting for relevant covariates. ResultsA total of 9941 EVT cases (7835 from Korea and 2106 from Taiwan) were included. Patients had a mean age of 70.1 {+/-} 12.9 years (57.6% male, median NIHSS: 14 [IQR: 9-19]). Compared to Korean patients, Taiwanese patients had a higher prevalence of vascular risk factors and more severe strokes, contributing to lower rates of favorable 3-month outcomes. Increasing age was associated with poorer EVT results; among patients [&ge;]80 years, only 18% achieved mRS 0-2, compared to 47% of younger patients. However, the risk of SICH did not significantly increase with age (adjusted OR per year: 1.00 [0.99-1.01]; adjusted OR [&ge;]80 years: 1.05 [0.85-1.29]). Pre-stroke functional independence and bridging thrombolysis were identified as key modifiers of better outcomes even in the oldest patients. ConclusionTaiwanese EVT patients had more risk factors and worse outcomes than Korean patients. Advanced age is associated with poorer functional recovery, yet selected older patients--particularly those who were functionally independent before the stroke or received bridging thrombolysis--demonstrated meaningful benefit. These results underscore the importance of individualized treatment strategies and careful patient selection, especially as populations continue to age.

BackgroundPrevious research demonstrated that the numerical Cincinnati Prehospital Stroke Scale (CPSS) identifies large vessel occlusion (LVO) at similar rates compared to a limited number of stroke severity screening tools. We aimed to compare numerical CPSS to additional stroke scales using a national EMS database. MethodsUsing the ESO Data Collaborative, the largest EMS database with hospital linked data, we retrospectively analyzed prehospital patient records for the year 2022. Stroke and LVO diagnoses were determined by ICD-10 codes from linked hospital discharge and emergency department records. Prehospital CPSS was compared to the Cincinnati Stroke Triage Assessment Tool (C-STAT), the Field Assessment Stroke Triage for Emergency Destination (FAST-ED), and the Balance Eyes Face Arm Speech Time (BE-FAST). The optimal prediction cut-points for LVO screening were determined by intersecting the sensitivity and specificity curves for each scale. To compare the discriminative abilities of each scale among those diagnosed with LVO, we used the area under the receiver operating curve (AUROC). ResultsWe identified 17,442 prehospital records from 754 EMS agencies with [&ge;] 1 documented stroke scale of interest: 30.3% (n=5,278) had a hospital diagnosis of stroke, of which 71.6% (n=3,781) were ischemic; of those, 21.6% (n=817) were diagnosed with LVO. CPSS score [&ge;] 2 was found to be predictive of LVO with 76.9% sensitivity, 68.0% specificity, and AUROC 0.787 (95% CI 0.722-0.801). All other tools had similar predictive abilities, with sensitivity / specificity / AUROC of: C-STAT 62.5% / 76.5% / 0.727 (0.555-0.899); FAST-ED 61.4% / 76.1%/ 0.780 (0.725-0.836); BE-FAST 70.4% / 67.1% / 0.739 (0.697-0.788). ConclusionThe less complex CPSS exhibited comparable performance to three frequently employed LVO detection tools. EMS agency leadership, medical directors, stroke system directors, and other stroke leaders may consider the complexity of stroke severity instruments and challenges with ensuring accurate recall and consistent application when selecting which instrument to implement. Use of the simpler CPSS may enhance compliance with the utilization of LVO screening instruments while maintaining the accuracy of prehospital LVO determination.

BackgroundFalls are a frequent and serious complication after stroke, affecting more than 30% of survivors within the first year. While age and comorbidities are established risk factors for falls, stroke-specific contributors--particularly lesion-related impairments in mobility and gait--are less well understood and may inform targeted secondary prevention. MethodsWe analyzed data from 94 patients with disabling subacute ischemic stroke enrolled in the prospective BAPTISe cohort, a predefined imaging and biomarker sub-cohort of the multicenter PHYS-STROKE trial. Detailed gait and mobility assessments were performed at baseline. Principal component (PC) analysis reduced seven mobility-related and four gait-related variables into two composite scores: PC1-Mobility and PC1-Gait, explaining 56% and 82% of variance, respectively. PC1-Mobility reflected global disability and functional mobility in daily life, whereas PC1-Gait captured spatiotemporal walking capacity and efficiency. Lesion network mapping (LNM) using a normative connectome identified functional networks associated with each domain. Patient-reported falls up to six months post-enrollment were the primary endpoint. ResultsLNM of PC1-Mobility revealed a predominantly cortical network involving pre- and postcentral gyri, superior and middle frontal gyri, and sensorimotor integration areas. In contrast, PC1-Gait was associated with subcortical and infratentorial connectivity, including bilateral thalamus, brainstem, and cerebellum. In multivariable regression, network similarity scores were not independently associated with falls; only older age was significant (adjusted OR1.08, 95%CI1.02-1.15,p=0.013). LNM of fall occurrence showed a cortical network with significant spatial overlap with the PC1-Mobility network(p<0.001). ConclusionThis exploratory, hypothesis-generating study identified distinct lesion-derived functional networks associated with post-stroke mobility and gait impairment. Our findings suggest that falls may be more closely linked to disruptions in cortical networks involved in voluntary motor control and whole-body coordination, rather than subcortical structures primarily modulating gait. These results provide a foundation for future research aimed at improving fall risk stratification and targeted prevention strategies in stroke survivors.

ObjectiveTo establish a time-to-surgery threshold for elderly aneurysmal subarachnoid hemorrhage patients before the risk of mortality increases. MethodsA cohort study using data with consecutive patients 70 years and older(N=743). Risk-adjusted restricted cubic splines modeled the mortality according to wait-time. The inflection point (in hours) when mortality began to increase was used to define early-time, middle-time and late-time surgery. To evaluate the robustness of this definition, outcomes among propensity-score matched non-middle surgical and middle-time surgical patients were compared using percent absolute risk differences. ResultsThere were a total of 535 patients who met inclusion. Their mean age was 74.3 (4.38) years. Cox models with restricted cubic spline showed a statistically significant U shaped association for onset-to-surgery time with two year all cause mortality. 66 patients (12.3%) received middle-time surgery and 469 patients (87.7%) received early-time or late-time surgery. There were 60 (91%) patients in the middle-time surgery group matched to those in the non-middle-time group. Of the 60 matched patients who received surgery after less than 49 hours or more than 68 hours, 23 patients (38.3%) died within 24 months vs 14 patients (23.3%) of 60 who received surgery within 49 to 68 hours, for an absolute risk difference of 15% (95% CI, -2.68% to 31.50%). ConclusionsIn this study, onset-to-treatment time showed a U shaped association with 24 months all cause mortality. Early surgery was superior to delayed surgery in reducing death rate. Elderly patients with poor tolerance to ultra-early surgery in whom operation was probably postponed.

IntroductionPathophysiological distinctions among stroke subtypes--acute ischemic stroke (AIS), subarachnoid hemorrhage (SAH), intracerebral hemorrhage (ICH), and other nontraumatic intracranial hemorrhage (ONIH)--are well described, but their associations with long-term mortality, cognitive outcomes, and dementia risk remain incompletely characterized. We examined whether stroke subtypes differ in post-stroke survival, cognitive performance, dementia risk, and neuroimaging phenotypes. MethodsUsing data from the UK Biobank, we evaluated subtype-specific associations with all-cause mortality, incident all-cause dementia, post-stroke cognitive performance, and white matter hyperintensity (WMH) burden. We assessed time to mortality and all-cause dementia using multivariable Cox proportional hazards models. Cognitive outcomes were compared cross-sectionally between stroke subtypes and stroke-free participants using covariate-adjusted linear models with ANOVA and Tukey post hoc tests. Neuroimaging analyses assessed associations between stroke subtype and WMH volume. ResultsMortality risk varied substantially by stroke subtype. Of UKB participants who had a stroke during surveillance (n=14,806), we found that 69.24% of strokes were ischemic, 9.51% subarachnoid, 9.78% ONIH, and 11.78% ICH. Compared with stroke-free person-time, intracerebral hemorrhage was associated with the highest post-stroke hazard of death (HR 7.62, 95% CI 7.10-8.18), followed by other nontraumatic intracranial hemorrhage (HR 5.41, 95% CI 4.89-5.98), subarachnoid hemorrhage (HR 3.89, 95% CI 3.52-4.31), and ischemic stroke (HR 3.99, 95% CI 3.82-4.16). At 1 year after stroke, absolute mortality risk was highest following ICH (36.4%), followed by ONIH (31.9%) and SAH (26.0%), while ischemic stroke was associated with substantially lower risk (11.7%); by 5 years, corresponding risks increased to 43.5%, 39.8%, 30.0%, and 20.0%, respectively. Dementia risk also differed by subtype, with the highest risk observed following ICH. Post-stroke cognitive performance varied across domains, with slower reaction times observed across multiple stroke subtypes and lower fluid intelligence scores among AIS and ICH patients. Reaction time and fluid intelligence assessments were completed a median of approximately 6-9 years after stroke. WMH burden was higher in ICH and AIS compared with stroke-free participants. ConclusionsStroke subtype is associated with distinct patterns of mortality, dementia risk, cognitive performance, and brain imaging phenotypes. These findings highlight the heterogeneity of long-term outcomes following stroke and support the importance of subtype-aware post-stroke monitoring and prognostication.