Stroke

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.

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.

Background The optimal management of acute ischemic stroke caused by medium vessel occlusion (MeVO) remains uncertain. Recent randomized trials have failed to demonstrate a clear benefit of endovascular therapy in this population, whereas intra-arterial thrombolysis (IAT) has emerged as a biologically plausible alternative. However, prospective evidence supporting IAT in MeVO is lacking, and the optimal dosing strategy for stand-alone IAT remains undefined. Aim To preliminarily evaluate the efficacy and safety of intra-arterial tenecteplase (IA-TNK) plus standard medical therapy (SMT) compared with SMT alone in patients with acute MeVO stroke, and to explore a stepwise IA-TNK dosing strategy. Design The MeVO-TNK trial is a multicenter, prospective, randomized, open-label, blinded-endpoint (PROBE), exploratory phase II study. A total of 60 participants with imaging-confirmed MeVO will be randomized 1:1 to receive either IA-TNK plus SMT or SMT alone. Participants presenting beyond 6 hours from symptom onset must demonstrate salvageable penumbral tissue on advanced imaging. Those assigned to the intervention group will receive up to two intra-arterial boluses of tenecteplase (0.0625 mg/kg per bolus), with the second bolus administered based on angiographic assessment of reperfusion and safety. Outcomes The primary efficacy outcome is final infarct volume measured at 72{+/-}24 hours after randomization. Secondary efficacy outcomes include the proportions of patients achieving modified Rankin Scale (mRS) scores of 0-1, 0-2 and 0-3 at 90 days, a shift analysis of the mRS distribution at 90 days, early neurological deterioration, and National Institutes of Health Stroke Scale score at 7 days or discharge. The primary safety outcome is symptomatic intracranial hemorrhage within 24 hours. Conclusions This trial will provide preliminary evidence on the biological efficacy, reperfusion potential and safety of stand-alone IA-TNK for acute MeVO stroke, helping to address an important evidence gap and inform the design of future confirmatory studies.

Background: Integrating polygenic scores (PGS) into population-based stroke prevention strategies may help reduce the stroke burden at both individual and population levels. However, prospective evidence regarding the interaction between genetic and modifiable risk factors remains limited, particularly in East Asian populations. Methods: We evaluated the influence of modifiable risk factors across PGS levels in the prospective population-based Tohoku Medical Megabank Community-Based Cohort Study. Stroke PGS was calculated using a model developed by the GIGASTROKE project. Results: During a median follow-up of 4.84 years (121,843.2 person-years), 246 incident stroke events were identified. Compared with participants in the intermediate PGS group (third quintile), those in the highest PGS group (fifth quintile) had a 60% greater risk of incident stroke (hazard ratio [HR], 1.60; 95% confidence interval [CI], 1.10-2.34). When participants with intermediate genetic risk and no modifiable risk factors were used as the reference group, hypertension (HR, 2.17; 95% CI, 1.11-4.25) and diabetes (HR, 2.10; 95% CI, 1.04-4.27) were significantly associated with an increased stroke risk in the intermediate PGS group. In contrast, multiple modifiable risk factors were significantly associated with stroke risk in the highest PGS group, including hypertension (HR, 2.90; 95% CI, 1.53-5.48), diabetes (HR, 2.07; 95% CI, 1.02-4.20), dyslipidemia (HR, 2.20; 95% CI, 1.28-3.79), obesity (HR, 1.98; 95% CI, 1.19-3.30), and smoking (HR, 2.57; 95% CI, 1.34-4.89). Participants with both the highest PGS and [&ge;] 4 modifiable risk factors had a substantially elevated stroke risk (HR, 2.76; 95% CI, 1.28-5.92). The combination of genetic and modifiable risk factors significantly influenced the cumulative incidence of stroke (P<0.001). Conclusions: Modifiable risk factors substantially influenced stroke risk even among participants with high genetic susceptibility. The relative importance of modifiable risk factors for stroke prevention may differ according to an individual's genetic risk level.

Background: Mobility recovery after stroke is highly variable, yet is typically described using average patterns that obscure meaningful differences between individuals. Identifying distinct recovery trajectories may improve prognostication and guide rehabilitation strategies. Methods: We conducted a retrospective cohort study of adults admitted for stroke to a large health system between 2016 and 2024. Mobility was assessed using Activity Measure for Post-Acute Care (AM-PAC) Basic Mobility, which was collected during routine clinical care. Growth mixture modeling was used to identify subgroups with distinct mobility recovery trajectories during the first 180 days after stroke. Subgroups were then characterized with baseline personal and clinical characteristics. Results: Seven hundred and fifty individuals contributed 3,389 mobility observations (median 4 per person). A five-class solution was selected based on model fit and classification quality. Distinct trajectories were identified: low stable (n=127), low rapidly improving (n=29), mid declining (n=169), mid improving (n=365), and high stable (n=60). Subgroups differed in both baseline mobility and patterns of change over time, with some demonstrating improvement, others remaining stable, and one declining. Individuals in improving subgroups were generally younger, more likely to be independent before stroke, received physical therapy on a greater proportion of hospital days, and were more frequently discharged to inpatient rehabilitation. In contrast, those in low or declining trajectories had lower baseline function, longer hospital stays, and were more likely to be discharged to skilled nursing facilities. Conclusions: The distinct mobility recovery trajectories identified in this work reflect the heterogeneity present in routine clinical practice. Subgroups differed in both recovery patterns and characteristics. Early identification of trajectory membership may improve prognostication and inform more targeted rehabilitation strategies.

Background and Purpose- Prehospital large-vessel occlusion (LVO) scales identify severe stroke syndromes but may not distinguish LVO from intracerebral hemorrhage (ICH). We aimed to prospectively validate the PreICH scale, with the primary diagnostic objective of differentiating ICH from confirmed LVO, and to explore whether additional hemorrhage-oriented variables could refine its performance. Methods- We conducted a prospective observational study of consecutive stroke-code activations evaluated before neuroimaging by a vascular neurologist. PreICH was calculated prospectively. Patients with calculable PreICH and valid final diagnosis were included. The primary diagnostic cohort comprised confirmed LVO and ICH. Secondary cohorts included ischemic stroke versus ICH and the overall stroke-code cohort, including stroke mimics. Multivariable NIHSS-adjusted models identified variables associated with ICH. A modified PreICH score (mPreICH) was derived post hoc and evaluated as exploratory apparent performance. Results- Among 1012 screened activations, 982 patients were analyzed: 597 ischemic strokes, 91 ICH, and 294 stroke mimics. The LVO-versus-ICH cohort included 144 LVO and 91 ICH. NIHSS and RACE were higher in ICH than in ischemic stroke, but did not differ between LVO and ICH (NIHSS, 13 [IQR, 7-20] versus 15 [5-23], P=0.300; RACE, 5 [2-8] versus 6 [2-8], P=0.435). In the LVO-versus-ICH cohort, PreICH showed an AUC of 0.758 (95% CI, 0.696-0.820), whereas RACE did not discriminate LVO from ICH (AUC, 0.530 [95% CI, 0.453-0.607]). The exploratory mPreICH showed apparent AUCs of 0.835 (95% CI, 0.785-0.884) for ischemic stroke versus ICH and 0.798 (95% CI, 0.740-0.856) for LVO versus ICH. Conclusions- In this prospective stroke-code cohort, severity-based scales distinguished ICH from the overall ischemic stroke population but showed limited ability to differentiate LVO from ICH. An exploratory modified PreICH scale incorporating additional hemorrhage-oriented variables improved apparent discriminative performance, including in the LVO-versus-ICH setting. External validation is required before potential implementation in prehospital decision-making.

Acute lower-limb arterial thrombosis is a vascular emergency that often reaches internists and emergency physicians before a vascular specialist, and data from Central Asia are scarce. We asked which patient-level factors mark limb-threatening severity at first presentation, and whether routine admission laboratory tests add to that judgement. We studied a registry of 288 consecutive patients hospitalised with acute lower-limb arterial thrombosis between 2017 and 2022 at a tertiary centre in Karaganda, Kazakhstan. Severity was graded with the Savelyev classification, with grades IIB-IIIA defined as limb-threatening. Associations were tested by logistic regression with Firth-penalised and bootstrap sensitivity analyses, and predictors of tissue loss were modelled separately. Patients were mostly elderly men (median age 67 years, 72.2% male) with a heavy atherosclerotic burden (hypertension 74.0%, coronary disease 54.9%, diabetes 19.1%, prior revascularisation 35.8%). At presentation 142 (49.3%) had limb-threatening ischaemia and 31 (10.8%) tissue loss. Independent markers of limb-threatening severity were diabetes (adjusted odds ratio 2.15, 95% CI 1.02-4.55), hypertension (2.14, 1.05-4.37), tissue loss (2.55, 1.01-6.45) and lower body-mass index (0.71 per 5 kg/m2, 0.52-0.97). Admission haematology, coagulation and metabolic values did not differ between severity groups (all p>0.10), and the chronic-disease model discriminated modestly (area under the curve 0.68). Low body-mass index (0.49 per 5 kg/m2, p=0.005) and prior amputation (7.08, p=0.04) independently predicted tissue loss. Limb-threatening severity tracked the chronic vascular-metabolic phenotype rather than the admission laboratory profile, which did not discriminate. Low body weight was a consistent danger signal. Bedside assessment, not routine bloods, should anchor early triage.

Objective: Outcome after surgical hematoma evacuation for intracerebral hemorrhage (ICH) depends on hematoma location. As corticospinal tract (CST) integrity affects motor recovery after stroke, we hypothesized that CST integrity drives heterogeneity in surgical outcomes and investigated this in a secondary analysis of MISTIE-III participants. Methods: Risk of CST injury was categorized into four levels, based on the interaction between the CST, the hematoma, and perihematomal edema (PHE) on automatically segmented stability CT: no risk, PHE infiltration, hematoma infiltration, and complete interruption of the CST. Associations with outcome were tested using multivariable linear regression for motor National Institutes of Health Stroke Scale (NIHSS) at day 180 and ordinal regression for modified Rankin Scale (mRS) at day 365, introducing an interaction term between CST risk and treatment group. Results: Day 180 motor NIHSS was significantly lower for 'no risk' ({beta}:-3.77, [95% confidence interval [CI]: -5.8 to -1.70], p=0.0003) and 'PHE infiltration' ({beta}:-2.3, [95%CI: -3.5 to -1.1]; p=0.0002) vs. 'complete interruption'. Surgery was associated with lower Day 180 motor NIHSS in participants with hematoma infiltration ({beta}:-2.07, [95%CI: -3.8 to -0.4], p=0.016). Compared to complete interruption, 'no risk' (adjusted odds ratio [aOR]:0.27, [95%CI: 0.10 to 0.74], p=0.01) and 'PHE infiltration' (aOR:0.41, [95%CI: 0.23 to 0.74]; p=0.003) were associated with lower odds of unfavorable day 365 mRS. Surgery was associated with lower mRS in participants with no risk (aOR:0.23, [95%CI: 0.05 to 0.97, p=0.045). Interpretation: Increasing CST risk is associated with worse motor recovery (day 180) and disability (day 365). CST risk modifies the effect of the MISTIE-III procedure on motor recovery and disability.

Optimal blood pressure management after thrombectomy remains uncertain, and individualized autoregulation-based targets typically require continuous neuromonitoring. We developed an angiography-derived autoregulatory metric using intraprocedural data and applied it retrospectively to a single-center cohort of patients who underwent thrombectomy for acute stroke. From 62 patients with 3-month functional outcomes, greater time within the predicted autoregulatory range during the first 24 hours after thrombectomy was independently associated with improved outcome after adjustment for covariates (odds ratio per 10% increase, 1.86; 95% CI, 1.31-2.66; P = .0006). These findings support routine angiography as a potential source of early, patient-specific hemodynamic targets after thrombectomy.

Background Patients with acute ischemic stroke (AIS) attributable to symptomatic intracranial atherosclerotic disease (sICAD) remain at substantial risk of early neurological deterioration (END) despite standard medical treatment. Aim To determine whether early addition of a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor to statin therapy reduces END in patients with AIS attributable to sICAD within 48 hours of symptom onset. Design The study of Combined Therapy with PCSK9 Inhibitor and Statin in Acute Ischemic Stroke (CAPTAIN) is a multicenter, prospective, randomized, open-label, blinded-endpoint trial conducted in China, with a planned sample size of 416 patients. Eligible patients will be randomized in a 1:1 ratio to receive either early evolocumab plus standard-dose statin or standard-dose statin therapy. Outcomes The primary efficacy outcome is the occurrence of END within 3 days after randomization, defined as an increase in the National Institutes of Health Stroke Scale score of at least 2 points from baseline. Secondary efficacy outcomes include neurological improvement, changes in National Institutes of Health Stroke Scale (NIHSS) score, shift in the 90-day modified Rankin Scale score distribution, recurrent stroke, and changes in lipid parameters. The primary safety outcome is the incidence of moderate-to-severe systemic bleeding within 3 days after randomization, as defined by the GUSTO criteria. Conclusions This study is expected to provide evidence on the efficacy and safety of the early addition of a PCSK9 inhibitor to statin therapy in patients with AIS attributable to sICAD. Trial registration number NCT06696820

Stroke is a leading cause of disability and mortality worldwide, with ischaemic stroke the most prevalent type. Statins, used for cholesterol management, have demonstrated benefits in reducing stroke risk and improving outcomes in preclinical studies. However, the impact of pre-stroke statin use on stroke outcomes remain inconsistent. In this study, we aim to evaluate whether pre-stroke statin use is associated with greater volume of salvaged tissue and improved cerebral collateral perfusion. A retrospective analysis was conducted using data from 281 patients presenting with acute ischemic stroke to the John Hunter Hospital between May 2015 and May 2020. Patients were grouped based on pre-stroke statin use, and clinical variables, including infarct volume and collateral perfusion, were assessed. The primary outcome was salvage volume derived from baseline perfusion lesion volume minus infarct volume at follow-up. Collateral perfusion was measured by the hypoperfusion volume defined by delay time (DT)>6 seconds divided by the hypoperfusion volume defined by DT >2 seconds. Patients on statins at admission were significantly older and had more comorbidities. No significant association was found between pre-stroke statin use and salvage volume or collateral perfusion after adjusting for covariates. Larger initial infarct core was a significant predictor of salvage volume due to larger salvageable tissue volume at baseline. These findings indicate that pre-morbid statin use is not associated with larger salvage volume or improved cerebral collateral perfusion.

Background: Stroke remains a leading cause of death and long-term disability worldwide, and a substantial proportion of patients experience incomplete recovery despite modern reperfusion strategies. Minocycline is an inexpensive, widely available agent with anti-inflammatory, anti-apoptotic and matrix metalloproteinase-modulating properties that make it an attractive neuroprotective adjunct in acute ischemic stroke or intracerebral hemorrhage. Despite new evidence for minocycline use, its needed an updated quantitative synthesis focused on clinically meaningful outcomes. Methods: This systematic review and meta-analysis was conducted to evaluate the efficacy and safety of minocycline in adults with AIS and ICH. A total of 1,633 records were screened. A total of 11 studies comprising 2428 patients were included in the review dataset. Outcomes were analyzed including 90-day disability, neurological recovery, recurrent stroke, and composite vascular events (cardiovascular event, non-fatal stroke, and non-fatal MI). Results: Minocycline was associated with better 90-day neurological recovery, with a greater reduction in NIHSS score at 90 days (mean difference [MD] -2.17, 95% CI -2.68 to -1.65, moderate certainty) and lower functional disability at 90 days measured by mean modified Rankin Scale (mRS) score (MD -0.25, 95% CI -0.38 to -0.13, moderate certainty). Categoric functional outcomes also favored minocycline, including mRS 0-1 at 90 days (odds ratio [OR] 1.21, 95% CI 1.02 to 1.45, high certainty), while the effect for mRS 0-2 at 90 days was borderline (OR 1.21, 95% CI 1.00 to 1.47, moderate certainty). No significant difference was observed for stroke recurrence at 90 days (OR 1.13, 95% CI 0.78 to 1.64). Composite vascular events at 90 days also favored minocycline (OR 1.21, 95% CI 1.02 to 1.45). Conclusions: Minocycline appears to be a promising, low-cost adjunctive therapy for acute ischemic stroke and intracerebral hemorrhage with evidence of improved 90-day functional and neurological outcomes. These findings support prioritization of minocycline for confirmatory trials and highlight its relevance in stroke care and clinical practice.

Background: Telestroke evaluation and treatment programs are a promising option for geographically underserved populations. Adherence to guideline-based secondary prevention measures among telestroke programs remains understudied, particularly for patients with symptomatic intracranial atherosclerosis. The primary objective of this study was to evaluate whether routine telestroke consultation provides guideline-concordant management comparable to on-site vascular neurology consultation. Methods: This retrospective cohort review identified patients with stroke due to intracranial atherosclerosis within a single healthcare system comprising nine hospitals, including two comprehensive stroke centers with on-site stroke coverage and seven sites with remote telestroke coverage. Data was collected from January 2019 to December 2023. Adherence to guideline-based quality indicators was determined using four primary outcome measures including rates of permissive hypertension, high-intensity statin prescription at discharge, time to initiation of first antiplatelet medications, and appropriate antithrombotic therapy at discharge. Results: A total of 132 patients were included in the final analysis (median age, 69 years; 65 female [49.2], 67 male [50.8%]), with 87 patients evaluated and managed on-site and 45 via telestroke. Guideline adherence was similar between groups for permissive hypertension and discharge antithrombotic therapy. Patients managed via telestroke were more likely to receive high-intensity statins at discharge (absolute difference 27.1% (95% CI 11.4, 42.8)) and received antiplatelet therapy earlier than patients managed on-site. Conclusion: In this multisite, single-system cohort, routine telestroke consultation was associated with similar or greater adherence to selected guideline-based management measures compared with on-site vascular neurology consultation.

Background Spontaneous intracerebral hemorrhage (ICH) is the most devastating type of stroke but lacks the established time-critical treatment guidelines available for acute ischemic stroke. This study investigated the impact of Code Stroke activation and warfarin use on anticoagulation reversal times to identify opportunities for quality improvement. Methods We retrospectively assessed patients with anticoagulation-associated ICH admitted to our medical center between January 1, 2020, and December 31, 2025. Patients with warfarin- or direct oral anticoagulant (DOAC)-associated ICH were identified from our ICH clinical trial screening log, Vizient, and AHA's Get With The Guidelines-Stroke registry. Code Stroke activation, warfarin or DOAC use, anticoagulation reversal times, causes of delay, and clinical outcomes at hospital discharge were analyzed. Results Of 892 ICH admissions, 50 patients had confirmed anticoagulation-associated ICH. Among those who underwent reversed at our center (n=34), Code Stroke activation (n=24) significantly reduced door-to-CT time (16.5 [12.8-22.0] vs 172.5 [49.0-261.5] minutes, p <0.001), reversal agent order-to-needle time (37.5 [24.7-56.9] vs 57.0 [39.0-85.0] minutes, p <0.001), and door-to-treatment (DTT) time (64 [48-98] vs 277 [159-305] minutes, p <0.001) compared to non-activation (n=10). Conversely, warfarin use was associated with higher international normalized ratios (INR) (2.7 [2.2-3.6] vs 1.3 [1.2-1.9], p =0.003) and significantly longer DTT time (95 [51-108] vs 64 [48-77] minutes, p =0.007). Primary DTT delays stemmed from the absence of a time-critical treatment protocol, weight-based dosing for 4F-PCC, waiting for INR results, and a lack of Code Stroke activation for patients with mild symptoms, trauma or unexplained unresponsiveness. Conclusions Our findings suggest that Code Stroke activation for all suspected cases of ICH, a time-critical emergency department algorithm targeting a DTT time of less than 60 minutes, and immediate anticoagulation reversal with fixed-dose 4F-PCC without waiting for INR results may optimize the acute management of anticoagulation-associated ICH.

Background: Clinical outcomes of switching versus continuing direct oral anticoagulant (DOAC) among atrial fibrillation (AF) patients who experienced an ischemic stroke despite receiving DOAC therapy are uncertain. Methods: We included patients with AF who were hospitalized for ischemic stroke (index stroke) between January 1, 2016, and June 30, 2022, while receiving DOAC therapy and who resumed DOAC within 90 days after discharge in the Merative MarketScan Commercial and Medicare databases. Patients were classified as DOAC-switched or DOAC-continued according to whether the DOAC agent changed or remained the same after the index stroke; secondary analyses considered individual DOACs. The primary outcome was recurrent ischemic stroke; secondary outcomes included major bleeding and a composite outcome (bleeding or ischemic stroke). Propensity score-based overlap weighting and weighted Cox models were used to estimate adjusted hazard ratios (aHRs). Results: A total of 1175 patients were eligible for the study, of whom 970 (82.6%) continued and 205 (17.4%) switched DOAC therapy. Comparing DOAC-switched to DOAC-continued was not significantly associated with recurrent ischemic stroke (aHR, 1.20; 95% CI, 0.63-2.30), major bleeding (aHR, 0.60; 95% CI, 0.21-1.72), or the composite outcome (aHR, 0.98; 95% CI, 0.56-1.70). However, among patients who received apixaban before stroke, switching to rivaroxaban was associated with a higher risk of recurrent ischemic stroke (aHR, 2.70; 95% CI, 1.05-6.95). Conclusions: Overall, switching DOAC therapy after ischemic stroke was not associated with improved clinical outcomes. Switching from apixaban to rivaroxaban, however, could increase risk of recurrent ischemic stroke.

Endovascular thrombectomy (EVT) improves outcomes in acute ischemic stroke caused by large vessel occlusion. Despite successful recanalization, early neurological deterioration (END) remains frequent and predicts poor outcomes. Disturbances in cerebral autoregulation may contribute to END, yet reliable bedside predictors are limited. Transcranial Doppler (TCD) provides noninvasive bedside assessment of cerebral blood flow velocities and may identify hemodynamic patterns associated with post-EVT deterioration. PRECISE-TCD is a prospective, single-center observational study enrolling 180-300 patients undergoing EVT for anterior circulation large vessel occlusion at a tertiary academic medical center. TCD examinations will be performed as soon as feasible after EVT, daily through 72 hours, and near END events. Hemodynamic parameters including peak systolic velocity (PSV), end-diastolic velocity (EDV), mean flow velocity (MFV), and pulsatility index (PI) will be measured in bilateral MCA, ACA, PCA, carotid siphon, vertebrobasilar, and ophthalmic artery territories. The primary outcome is the association between TCD-derived parameters and END within 72 hours, defined as an increase of [&ge;]4 points in total NIHSS score, an increase of [&ge;]1 point in NIHSS subcategory 1a, radiologic evidence of intracranial hemorrhage within 72 hours, or any neurological change prompting emergent head CT at clinician discretion. Secondary outcomes include NIHSS at 24 hours and discharge, discharge disposition, and modified Rankin Scale (mRS) at 90 {+/-} 10 days after hospital discharge. Joint models for longitudinal and time-to-event data will determine the association between TCD parameter trajectories and time to END. Unsupervised clustering will identify TCD-based hemodynamic phenotypes using vessel velocities, pulsatility indices, hemispheric asymmetry measures, collateral flow, and temporal trajectory patterns. We hypothesize that abnormal post-EVT hemodynamic phenotypes will correlate with END and hemorrhagic transformation. Identifying such signatures may support development of TCD-guided, individualized blood pressure strategies to reduce secondary injury after reperfusion and inform future interventional trials. The study is registered at ClinicalTrials.gov (NCT07013396).

Background: Recent AHA guidelines recommend the use of IV Tenecteplase (TNK) in adult stroke patients, but there is minimal safety and dosing data on TNK in pediatric patients. We performed a safety surveillance study aiming to evaluate risk of symptomatic intracranial hemorrhage (ICH) in children who received TNK for suspected acute ischemic stroke (AIS). Methods: This was a prospective observational cohort surveillance study analyzing responses from a monthly email survey sent to members of two large international pediatric stroke and neurocritical care research consortia querying recent use of TNK in children. Limited demographic, clinical, and outcome data were collected. A Bayesian beta-binomial model for risk of symptomatic ICH with IV TNK was fit using a prior distribution based on the risk level in adults. Results: Between February 2023-June 2026, 44 children received TNK for suspected AIS. Most patients (n=37, 84.1%) were adolescents; no children under 5 received TNK. Twelve patients (27.3%) were ultimately diagnosed with a stroke mimic. Symptomatic ICH was not reported in any children who received IV TNK; 3 had asymptomatic ICH on follow-up imaging. One patient received intra-arterial TNK and experienced symptomatic ICH. No other major bleeding events were reported. Conclusions: IV TNK is being administered to pediatric patients with suspected stroke in clinical practice, and may be safe in older children with AIS. Rigorous prospective studies are needed to better assess risk and outcomes in this unique population.

BackgroundStroke-associated respiratory dysfunction has been increasingly recognized, yet whether diaphragmatic impairment after stroke involves lateralized neuromuscular imbalance remains unclear. MethodsIn this controlled experimental study, transient left middle cerebral artery occlusion and reperfusion (tMCAO) was performed in mice, followed by multimodal assessment of treadmill-based peak oxygen uptake testing, diaphragm ultrasonography, bilateral diaphragmatic electromyography (dEMG) with simultaneous respiratory flow monitoring, behavioral assessment, and whole-mount immunofluorescence imaging of the diaphragm. ResultsIschemic stroke reduced exercise capacity and diaphragmatic excursion without detectable diaphragm thinning, indicating functional impairment rather than overt atrophy. Bilateral dEMG revealed a subacute left-right asymmetry in inspiratory activation, with the ipsilesional hemidiaphragm exhibiting reduced amplitude, decreased area under the curve, and altered burst duration, consistent with a relative contralateral-dominant pattern rather than frank hyperactivation. Whole-mount imaging demonstrated asymmetric nerve remodeling, characterized by a nadir in ipsilesional nerve fiber density at 1 week and partial recovery by 2 weeks after stroke. These structural changes closely paralleled the dEMG alterations, suggesting a neural substrate for lateralized dysfunction. Exploratory analyses further linked dEMG parameters with motor recovery. ConclusionsThese findings provide novel evidence that ischemic stroke induces a left-right diaphragmatic neuromuscular imbalance, with structural and functional correlates in diaphragmatic innervation. The study further supports the utility of bilateral dEMG as a functional marker for assessing diaphragmatic dysfunction and monitoring recovery after stroke. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=190 SRC="FIGDIR/small/737872v1_ufig1.gif" ALT="Figure 1"> View larger version (41K): org.highwire.dtl.DTLVardef@10001a4org.highwire.dtl.DTLVardef@16bc3d5org.highwire.dtl.DTLVardef@5e40aorg.highwire.dtl.DTLVardef@be53b7_HPS_FORMAT_FIGEXP M_FIG C_FIG

Background: Stroke remains a leading cause of mortality and long-term disability worldwide, with high residual vascular risk among survivors despite optimal secondary prevention. The contribution of inherited polygenic risk to this residual vulnerability remains unclear. Methods: We analyzed 2,701 stroke survivors (mean age 59.8{+/-}7.1 years, 61.7% male) from the UK Biobank. Stroke- and coronary artery disease (CAD)-polygenic risk scores (metaGRS), comprising approximately 3.2 million and 1.7 million genetic variants, respectively, were derived from large-scale genome-wide association studies using penalized regression. The primary outcome was major adverse cardiovascular events (MACE), while secondary outcomes included recurrent stroke and vascular risk factor control. metaGRS associations with incident MACE and recurrent stroke were tested using Cox models, whereas associations with baseline risk-factor control were assessed using logistic regression. Mediation analyses quantified indirect effects of metaGRS to MACE via HbA1c, LDL cholesterol, and blood pressure. Results: Over 12 years, 731 MACE events (27.1%) and 351 recurrent stroke events (13.0%) occurred. CAD-metaGRS was independently associated with future MACE (age- and sex-adjusted HR per SD increment 1.15, 95%CI 1.07-1.24; p<0.001), whereas higher stroke- and CAD metaGRS were both associated with poorer glycemic control. A higher CAD-metaGRS was also associated with poorer lipid control. Mediation analyses identified glycemic regulation as a significant pathway linking polygenic risk to recurrent vascular events. Conclusions: Polygenic risk scores for cardiovascular disease are associated with recurrent vascular events and vascular risk factor control among stroke survivors, pointing to potentially actionable insights in secondary prevention that merit further investigation.