Stroke

BackgroundSpontaneous, non-traumatic intracranial hemorrhage (ICH) is highly heritable disease. However, the identification of the genetic risk factors driving this high genetic predisposition has been limited by small sample sizes and underrepresentation of non-European populations. The ERICH-GENE study will gather and harmonize clinical, neuroimaging and genomic data on the largest and more diverse collection of ICH cases assembled to date. MethodsERICH-GENE is an NIH-funded, multi-center, international, genetic and neuroimaging study that aims to achieve the necessary sample size and diversity required to accurately describe the genetic architecture and trans-ethnic variation of ICH. ERICH-GENE will collect and harmonize clinical, neuroimaging and genomic data at least 10,000 multi-ethnic ICH cases. These data will be aggregated with 20,000 existing ICH cases and 600,000 ICH-free controls available through completed studies by the International Stroke Genetics Consortium. To ensure validity, data will undergo extensive harmonization, including expert review of neuroimages to ensure spontaneous etiology and hemorrhage location. We will conduct genome-wide association studies of risk, severity and outcome of ICH, testing for effect modification by race/ethnicity, sex and hemorrhage location. We will also conduct pathway, polygenic risk score and Mendelian randomization analyses. ResultsThis study will include whole genome sequencing data from 10,850 spontaneous ICH samples, including clinical and radiographic phenotypic data to ensure reliability of true non-traumatic, non-lesional ICH and lobar vs nonlobar location. Of these, 1,497 have already been genotyped using genome-wide arrays, 3,753 have undergone whole genome sequencing, and 5,600 will undergo genome-wide genotyping through ERICH-GENE. There are currently 42 contributing sites exceeding study milestone enrollments. 16,175 radiographic studies from 4,974 patients have been uploaded for harmonization to date, including 26% lobar and 64% nonlobar hemorrhages. Neuroimaging assessment will also include grading for white matter hyperintensities, cerebral atrophy, and presence and severity of IVH. Nearly 6,000 ICH cases will complete genotyping by August 2025. Data/material transfer agreements for summary statistics as well as additional samples are on target to meet the studys objectives. ConclusionERICH-GENE is the largest trans-ethnic genetic study of ICH conducted to date. Combining a diverse patient population with expert adjudication of neuroimaging data, ERICH-GENE will identify genetic risk loci that drive the high heritability observed for this disease and make a significant contribution to the understanding of the trans-ethnic variation of its genetic architecture.

BackgroundTimely intensive rehabilitation is crucial to contrast the negative escalation of events that follow a stroke injury, to promote tissue regeneration, and to restore the physiological function. This study aimed to identify measurable blood biomarkers that could be predictive of functional recovery in stroke survivors. Methods30 sub-acute stroke subjects were enrolled at Fondazione Don Carlo Gnocchi Onlus (Italy) during the observation prospective cohort study EXO4STROKE (NCT05370105). Among the clinical scales used for patient profiling, modified Barthel Index (MBI) was considered as primary outcome for the evaluation of rehabilitation recovery. Cytokines, Neurofilaments and circulating Extracellular Vesicles (EVs) were evaluated in the serum of patients at admission (T0) and at discharge (T1) in intensive rehabilitation unit. The Surface Plasmon Resonance imaging (SPRi) technique was exploited to obtain a multiplexed analysis of circulating EVs from brain (neurons, astrocytes, microglia) and non-brain (endothelium, skeletal muscle and platelets) cells, and for the relative quantification of markers of pathological or regenerative processes. Machine learning-based analysis complemented the study by integrating statistically significant features in a cross-validated prediction model targeting functional recovery at T1 from T0 data. ResultsHigh serum levels of IL-6 and Neurofilament Light Chain at T0 were associated with higher residual disability (lower outcome) at T1. In contrast, elevated circulating levels of EVs from neurons (CD171+) and microglia (CD11b+) were associated with better recovery after rehabilitaion. Moreover, the overexpression of the VEGF receptor on microglial EVs (IB4+ and CD11b+), was associated with higher functional improvement. Alternatively, the overexpression of TGF-{beta} receptor on IB4+ EVs during the subacute phase post-stroke was found associated with increased stroke severity. The MBI at T1 was predicted with a median [iqr] absolute error of 5.7[8.7] points. ConclusionThis study identifies a panel of few circulating biomarkers associated to Evs able to objectively assess post-stroke status and predict functional recovery after rehabilitation.

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.

AbstractO_ST_ABSObjectiveC_ST_ABSTo identify race/ethnic disparities in rehabilitation services after stroke and characterize the independent associations of each of race/ethnicity and rehabilitation to functional recovery post-stroke. MethodsThe Transitions of Care Stroke Disparities Study (TCSD-S) is a prospective cohort study designed to reduce disparities and to optimize the transitions of care for stroke survivors throughout the state of Florida. Participant characteristics were extracted from the American Heart Associations Get-With-The-Guidelines-Stroke dataset. Rehabilitation services, and modified Rankin Scale were recorded via follow up phone calls at 30- and 90-days after hospital discharge. Logistic regression models adjusted for potential confounders were used to determine: 1) race/ethnic differences in rehabilitation services received; 2) race/ethnic differences in functional change from discharge to 30- and 90-days, respectively; and 3) the influence of rehabilitation on functional change from discharge to 30- and 90-days. ResultsOf 1,083 individuals, 43% were female, 52% were Non-Hispanic White (NHW), 22% were Non-Hispanic Black (NHB), and were 22% Hispanic. Individuals who engaged in rehabilitation were more likely to show improvements [aOR=1.820, 95%CI (1.301,2.545)] at 90-days from hospital discharge. Irrespective of rehabilitation services, there were no differences in functional change between NHW and NHB individuals, yet Hispanic individuals were less likely to improve [aOR=0.647, 95%CI (0.425,0.983)] compared to NHW. Additionally, Hispanic individuals were significantly less likely to receive any rehabilitation services [aOR=0.626, 95%CI (0.442,0.886)] and were half as likely to receive outpatient services [aOR=0.543, 95%CI (0.368,0.800)] as compared to NHW. ConclusionsRehabilitation is key to functional improvement after stroke. We are making strides in health equity between NHW and NHB individuals, yet there remain disparities in functional outcomes and in rehabilitation services particularly for Hispanic individuals after stroke.

BackgroundStroke is a significant global health issue, serving as a leading cause of death and disability. The burden of this condition is especially severe in low- and middle-income countries, where the majority of stroke-related fatalities occur. Hyperglycemia, a common metabolic disturbance observed in acute stroke patients, is known to worsen clinical outcomes, contributing to higher rates of mortality and morbidity. This study aims to investigate the relationship between hyperglycemia, morbidity and mortality outcomes in patients with acute stroke, assessing how varying glycemic levels influence short-term (1 month), mid-term (3 months), and long-term (1 year) mortality rates. MethodsThe SHAPE study is a prospective cohort study conducted at the Emergency Department of Tribhuvan University Teaching Hospital (TUTH). The study will enroll adults aged over 40 who present with BEFAST-positive symptoms of acute stroke, confirmed through CT/MRI imaging. Participants will be classified into two groups: those exhibiting hyperglycemia (exposed group) and those with normal glycemic levels (unexposed group). Sixty participants will be recruited (30 hyperglycemic and 30 normoglycemic) and followed for one year to assess mortality and functional outcomes using the modified Rankin Scale (mRS). Data collection will involve regular follow-ups through phone calls, clinic visits, and home visits at 1, 3, and 12 months post-stroke. The analysis will include bivariate comparisons for categorical and continuous variables, logistic regression to identify independent predictors of mortality and functional outcomes, and Kaplan-Meier analysis for assessing survival rates. Ethical ConsiderationsThe SHAPE Study was approved by the Ethics Review Committee of the Institute of Medicine (Ref no.. 6-11E2), and written informed consent will be obtained from all participants. Results will be disseminated via a peer-reviewed journal. Trial registration numberClinicalTrials.gov ID NCT06560983

BACKGROUNDThis study aimed to determine the association of brain frailty with acute complications and prognosis in patients with acute ischemic stroke (AIS) due to occlusion of large vessels in the anterior circulation, and to further assess its predictive value. METHODS AND RESULTSThis multicenter, retrospective study included patients with AIS due to large vessel occlusion in the anterior circulation. All patients underwent MRI within seven days of stroke onset, measuring subcortical and cortical atrophy and leukoaraiosis as indicators of brain frailty.The study included 1,090 patients with a median age of 64 (interquartile range, 55-73) years and a median National Institutes of Health Stroke Scale (NIHSS) score of 9 (interquartile range, 4.5-15). Multivariable logistic regression analysis showed that independent risk factors for the unfavorable clinical outcome included: NIHSS score (OR, 1.17; 95% CI, 1.13-1.22), blood glucose (OR, 1.15; 95% CI, 1.04-1.26), infarct volume (OR, 1.32; 95% CI, 1.15-1.52), subcortical atrophy (OR, 1.27; 95% CI, 1.18-1.37), severe cortical atrophy (OR, 5.46; 95% CI, 1.71-17.45), and severe leukoaraiosis (OR, 4.68; 95% CI, 1.93-11.31). However, brain frailty was not significantly associated with AIS complications (malignant cerebral edema, parenchymal hemorrhage). Including brain atrophy indicators in the model significantly improved its unfavorable clinical outcome predictive power (AUC increased from 0.762 to 0.822; p < 0.001). The results remained stable in subgroup analyses across treatment modalities. CONCLUSIONSBrain frailty was significantly associated with the unfavorable clinical outcome but not with acute complications. Brain frailty indicators contributed to the predictive efficacy, regardless of treatment modality.

BackgroundEndovascular thrombectomy (EVT) revolutionized large vessel occlusion (LVO) stroke. However, treatment decisions and prognostication are challenging without advanced imaging. We sought to determine the relationship of simple CTA collateral patterns and outcomes after EVT. MethodsWe identified patients with anterior LVO who underwent guideline based EVT from a single center from 2019-2020. Inclusion criteria were available CTA and 90-day modified Rankin Scale (mRS). Arterial-phase CTA collaterals were categorized as malignant, other, or symmetric. ResultsAmong 74 patients, the median age was 75 and 49% were female. Collaterals were symmetric (36%), malignant (24%), or other (39%). Comparing collateral patterns there were no differences in demographics, presentations, time from last well, good reperfusion, or intracerebral hemorrhage. Median NIHSS was 18 for malignant, 19 for other, and 11 for symmetric (p=0.02). Intracranial ICA occlusions were present in 28% of malignant, 3% of other, and 11% of symmetric (p=0.04). Ninety-day mRS [&le;]2 was achieved in 17% of malignant, 38% of other, and 67% of symmetric. Collateral pattern was a significant determinant of 90-day mRS [&le;]2 (aOR=6.62, 95%CI=2.24,19.53; p=0.001) in a multivariable model including age, NIHSS, baseline mRS, thrombolysis, LVO location, and good reperfusion. ConclusionsSimple CTA collateral pattern is a robust determinant of 90-day outcomes after EVT. Further prospective studies are needed to understand how collateral pattern can guide EVT treatment decisions and long-term prognosis.

IntroductionThis study aimed to correlate cerebral collateral status and MRI-derived oxygen metabolism at admission in acute ischemic stroke (AIS) patients treated with mechanical thrombectomy. MethodsThe HIBISCUS-STROKE cohort (CoHort of Patients to Identify Biological an Imaging markerS of CardiovascUlar Outcomes in Stroke; NCT: 03149705), a single-center observational study, enrolled AIS patients for thrombectomy following MRI triage due to anterior circulation large vessel occlusion treated with mechanical thrombectomy. Dynamic-Susceptibility Contrast perfusion (DSC perfusion), Diffusion-Weighted Imaging (DWI) and penumbral volume (Tmax [&ge;] 6 secs) were post-processed to generate oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen (CMRO2) maps within DWI and penumbral anomalies, compared to contralateral areas. Collateral status, assessed via pretreatment digital subtraction angiography, was categorized as poor (0-2) or good (3-4) based on ASITN/SIR collateral grading system score from Higashida. ResultsBetween October 2016 and October 2022, 321 participants were enrolled in the cohort. Of these, 184 (57.3%) were excluded due to missing admission DSC perfusion MRI in 61 patients and artifacts precluding collateral status evaluation on DSA. A total of 137 patients were included (mean age 71 years; 56.2% male). The median National Institutes of Health Stroke Scale (NIHSS) score was 15 (interquartile range [IQR]: 8.0-18.0), and the median time from symptom onset to admission was 96.0 minutes ([IQR]: 78.0-137.0). Patients with good collaterals (78) exhibited a smaller baseline infarct core (median 9.83 mL; (P<0.0001) less impairment cerebral blood flow (CBF) within the DWI lesion (median -65.89%; (P<0.0001), and less severe decrease CMRO2 within the ischemic penumbra (median -17.29%; (P=0.03). Good collaterals were independently associated with a smaller baseline infarct core volume and less decrease in CMRO2 within the ischemic penumbra (respectively OR = 0.94; 95% CI: [0.92; 0.96]; (P<0.0001), and (OR = 1.30; 95% CI: [1.06; 1.82]; P=0.001). ConclusionGood collaterals are associated with a smaller infarct core and better CMRO2 within the ischemic penumbra.

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.

BackgroundMechanical thrombectomy (MT) has revolutionized the management of acute ischemic stroke (AIS) due to large vessel occlusion (LVO), particularly when performed within the first 6 hours after symptom onset. The development of perfusion imaging software has enabled patient selection to thrombectomy for up to 24 hours in selected cases with salvageable brain tissue, following the criteria of trials such as DEFUSE 3. However, the real-world application of these criteria, remains understudied. ObjectiveTo determine the clinical outcomes of patients with AIS treated with MT in an extended window (>6 hours), comparing patients who met DEFUSE 3 perfusion criteria versus those who did not. MethodsA retrospective analysis was conducted on patients undergoing MT between 6 and 24 hours after symptom onset. Clinical outcomes were assessed at hospital discharge and 90 days using the modified Rankin Scale (mRS). Patients were divided into two groups based on whether they met DEFUSE 3 perfusion criteria. ResultsA total of 80 patients were treated. Median age was 76 years (IQR 62,5-83). Wake-up strokes accounted for 45. Median ASPECTS score was 7 (SD 2.25) and median ischemic core volume was 18.9 ml (IQR 8,2 - 44,7). Of 76 patients analyzed, 37 (48.7%) met DEFUSE 3 criteria and 39 (51.3%) did not. Although patients meeting the criteria showed a trend toward better functional outcomes (mRS 0-3 at discharge: 66.6% vs 33.3%; p = 0.14), similar outcomes were observed at 90 days (63.6% vs 36.3% p = 0.34). Additionally, the group that did not meet DEFUSE 3 criteria had a higher proportion of wake-up strokes (p = 0.02), a relevant factor in extended-window decision-making. No statistically significant differences were found in mortality or severe disability between groups. ConclusionIn our study a good functional outcomes was more frequent in patients selected by DEFUSE 3 perfusion criteria, but a notable number of patients outside these criteria also achieved functional recovery. These findings support a more flexible and context-aware approach to patient selection in extended windows. Future prospective studies should aim to refine patient selection protocols that balance safety, efficacy, and accessibility.

BackgroundMechanical thrombectomy (MT) has significantly improved outcomes in acute ischemic stroke (AIS) due to large vessel occlusions (LVOs) up to 24 hours post-onset. The effectiveness of MT for medium vessel occlusions (MeVOs) in the M2 or M3 segments of the middle cerebral artery beyond 6 hours is less investigated. MethodsThis retrospective study analyzed 80 patients who underwent MT for primary, isolated M2 or M3 segment occlusions between January 2020 and August 2023. Patients were categorized by time from stroke onset to groin puncture into two groups: [&le;]6 hours (n=61) and >6 hours (n=19). Outcomes assessed included clinical severity (NIH Stroke Scale [NIHSS]), functional outcomes (modified Rankin Scale [mRS]), symptomatic intracranial hemorrhages (sICH), and reperfusion success (modified Thrombolysis in Cerebral Infarction [mTICI] scale). ResultsMean onset-to-puncture time was 192{+/-}57 minutes for the [&le;]6 hours group and 611{+/-}327 minutes for the >6 hours group. Baseline NIHSS scores were 9.5 (IQR 9) and 7 (IQR 8), respectively (p=0.418). While the NIHSS improvement was greater in the [&le;]6 hours group (median: -5 vs. -2; p=0.028), both groups showed significant improvement from baseline NIHSS scores (p<0.001 and p=0.014). Rates of sICH were low in both groups (1.5% vs. 0.5%; p=0.421). Recanalization rates were lower in the >6 hours group (84.2% vs. 96.7%; p=0.084), with more attempts (2.37 vs. 1.66; p=0.024). ConclusionMT for M2 and M3 segment occlusions in the MCA shows benefits beyond 6 hours from stroke onset, with earlier treatment yielding greater improvement. Extending MTs treatment window could be valuable for MeVOs in the MCA.

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.

BACKGROUNDA strokes functional outcome presents vast variability among patients, which is influenced by age, sex, characteristics of the lesion, and genetic factors. However, there is very little knowledge about stroke recovery genetics. Recently, some GWAS (Genome-Wide Association Studies) have highlighted the involvement of common or low-frequency variants near or within PATJ, PPP1R21, PTCH1, NTN4 and TEK genes, whereas the role of rare variants is still unclear. This study aims to identify the genetic contributions to differences in stroke outcome analyzing the effect of rare variants. METHODSWe performed a pilot study analyzing 90 exomes of extreme good or bad recovery (modified Rankin Scale (mRS) at 3 months 0-1 vs 4-5) to select target genes involved in stroke recovery. To expand this study, 702 additional samples were sequenced by Targeted Next-Generation Sequencing capturing loci selected from the pilot study, GWAS studies and literature input. Here, we performed continuous (mRS 0-6) and dichotomous (mRS 0-1 vs 3-6) analyses, yielding one candidate gene. Protein structure and stability analysis were performed on selected variants. RESULTSOur work identified rare coding variants in VNN2 associated with patients with a better stroke recovery ({Delta}DIC > 10, equivalent to p-value < 0.001). Six rare variants were predicted to significantly affect protein stability ({Delta}{Delta}G > 1.6 kcal/mol), meanwhile, another variant, located in the active site, could affect the electrostatic surface. CONCLUSIONSVNN2 could play a role in post-stroke inflammation altering the cell adhesion and migration of neutrophils during recovery.

BackgroundWhile endovascular thrombectomy (EVT) is considered as the most effective treatment for a select group of patients with acute ischemic stroke and large vessel occlusion, its safety and efficacy in older patients are still debated especially in "read-world" settings. This study reports outcomes of EVT in acute ischemic stroke patients aged 90 and older in our community hospital setting. MethodsData between January 2018 and December 2022 were aggregated for all acute ischemic stroke patients with aged 90 and older at the time of EVT. Thirty-one patients met the criteria and were included in this report. The data valuables included, but are not limited to, demographics, stroke risk factors, thrombolysis in cerebral infarction (TICI), modified Rankin Scale (mRS), and NIH Stroke Scale (NIHSS). ResultsAll 31 patients had improvement in TICI scale. One had symptomatic intracranial hemorrhage after EVT not related to the procedure, but likely on the basis of reperfusion breakthrough. Three patients expired prior to their discharge from non-stroke related causes. Of remaining 28, four expired, six went into hospice care, and four lost to follow-up by 30-days post DC. Of six hospice cases, one expired by 90-day post DC, and additional three were lost to follow-up. Given this data, 20/27 (74%) survived to 30 days and 16/24 (67%) to 90 days. For their NIHSS symptomatic categories, 15/28 (54%) patients improved, 10/28 (36%) remained the same, and 3/28 (11%) declined. For mRS, at 30-days post DC, 7/24 (30%) patients showed improvement, 7/24 (30%) remained the same, and 10/24 (40%) declined. At 90-days post DC, 7/21 (33%) showed improvement from DC, 4/21 (19%) remained the same, and 10/21 (48%) declined. ConclusionsWhile a larger cohort study is necessary, our report supports the safety and efficacy of EVT in this patient aged 90 and older in a real-world setting.

BackgroundEndovascular stroke treatment (EST) has become the treatment of choice for middle cerebral artery (MCA) M1-segment occlusions. Little is known about the implications for revascularization success of occlusions with persisting antegrade perfusion before initiation of treatment (modified Treatment In Cerebral Ischemia (mTICI 1)) compared to a complete occlusion (mTICI 0). Here, we compared the impact of these two states of target vessel occlusion on recanalization success and clinical outcome. MethodsRetrospective, single-center analysis of patients treated for M1-segment MCA occlusion with EST from 01/2015 until 05/2020 in a tertiary stroke center. Primary study endpoint was successful recanalization (mTICI 2c-3) after one thrombectomy attempt (first pass effect). Secondary endpoints were the clinical outcome (as modified Rankin Scale 90 days after stroke onset) and the complication rate. The two study groups were compared in univariate analysis including patient characteristics and procedural details. ResultsIn this study, 422/581 patients (72.6 %) presented with complete M1-occlusion compared to 159/581 (27.4 %) with incomplete M1-occlusion. Neither did the rate of FPE differ between the study groups nor the rate of procedural complications (mTICI 0: 10 (2.4%), mTICI 1: 1 (0.6%), p = 0.304). Patients with incomplete initial occlusion showed a lower mRS at discharge (median (IQR) mTICI0: 4 (3-5) vs. mTICI1: 3 (2 - 6), p = 0.014), but a comparable mRS 90 days after stroke onset (mTICI0: 3 (2-6) vs. mTICI:1 4 (2-6), p = 0.479). ConclusionComplete M1-occlusions (mTICI 0) and incomplete occlusions (mTICI 1) show the same recanalization success and complication rate as well as a comparable clinical outcome. Thus, incomplete M1-occlusions should be treated with the same urgency as initial complete occlusions.

BackgroundPandemics may promote hospital avoidance among patients with emergencies, and added precautions may exacerbate treatment delays. There is a paucity of population-based data on these phenomena for stroke. We examined the effect of the COVID-19 pandemic on the presentation and treatment of ischemic stroke in an entire population. MethodsWe used linked provincial administrative data and data from the Quality Improvement and Clinical Research Alberta Stroke Program - a registry capturing stroke-related data on the entire population of Alberta(4.3 million)- to identify all patients presenting with stroke in the pre-pandemic(1-January-2016 to 27-February-2020, n=19,531) and pandemic(28-February-2020 to 30-August-2020, n=2,255) periods. We examined changes in thrombolysis and endovascular therapy(EVT) rates, workflow, and in-hospital outcomes. ResultsHospitalizations/presentations for ischemic stroke dropped (weekly adjusted-incidence-rate-ratio[aIRR]:0.48, 95%CI:0.46-0.50, adjusted for age, sex, comorbidities, pre-admission care needs), as did population-level incidence of thrombolysis(aIRR:0.49,0.44-0.56) or EVT(aIRR:0.59,0.49-0.69). However, the proportions of presenting patients receiving acute therapies did not decline (e.g. thrombolysis:11.7% pre-pandemic vs 13.1% during-pandemic, aOR:1.02,0.75-1.38). Onset-to-door times were prolonged; EVT recipients experienced longer door-to-reperfusion times (median door-to-reperfusion:110-minutes, IQR:77-156 pre-pandemic vs 132.5-minutes, 99-179 during-pandemic; adjusted-coefficient:18.7-minutes, 95%CI:1.45-36.0). Hospitalizations were shorter but stroke severity and in-hospital mortality did not differ. InterpretationThe first COVID-19 wave was associated with a halving of presentations and acute therapy utilization for ischemic stroke at a population level, and greater pre-hospital and in-hospital treatment delays. Our data can inform public health messaging and stroke care in current and future waves. Messaging should encourage attendance for emergencies and stroke systems should re-examine "code stroke" protocols to mitigate inefficiencies.

BackgroundThe safety and efficacy of anticoagulation in the presence of hemorrhagic transformation (HT) in cardioembolic acute ischemic stroke (AIS) remain uncertain. MethodsThis retrospective study enrolled patients presenting with cardioembolic AIS within 48 hours at a tertiary stroke center between January 2011 and August 2023. Patients who developed HT during hospitalization and underwent follow-up imaging were included, focusing on those with hemorrhagic infarction or parenchymal hematoma type 1. Primary outcomes were HT exacerbation on follow-up imaging and 3-month modified Rankin Scale (mRS) distribution shift, comparing anticoagulation therapy (AC), antiplatelet therapy (APT), and drug discontinuation (NM). The safety outcome was symptomatic intracerebral hemorrhage (sICH) occurrence. ResultsAmong 763 patients with HT (mean age 74.6{+/-}8.9 years, 48.1% male), AC was associated with a higher incidence of HT exacerbation compared to APT (adjusted OR 0.48, 95% CI 0.29-0.80, p-value =0.005). However, AC demonstrated improved 3-month mRS outcomes versus APT (adjusted OR 0.63, 95% CI 0.43-0.92, p-value =0.017) and NM (adjusted OR 0.38, 95% CI 0.26-0.55, p-value <0.001). sICH occurred in 5% of cases overall, with rates of 1.5%, 2.1%, and 11.7% in the AC, APT, and NM groups, respectively (adjusted OR for NM vs. AC: 3.93, 95% CI 1.18-13.16, p-value =0.026). ConclusionIn cardioembolic AIS patients with HT, excluding those with PH-2, anticoagulation may lead to radiological exacerbation without increasing sICH risk, while potentially improving functional outcomes. These findings suggest that the presence of HT should not necessarily preclude the use of anticoagulation therapy in this patient population.

BackgroundIn patients with acute ischemic stroke secondary to large vessel occlusion (AIS-LVO), improved functional outcomes have been reported in patients who achieve Modified Thrombolysis In Cerebral Infarction (mTICI) 2c/3 (excellent recanalization) over mTICI 2b. We aimed to determine pretreatment and interventional variables that could predict achieving mTICI 2c/3 over 2b reperfusion in patients who underwent technically successful mechanical thrombectomy (MT). MethodsIn this retrospective study, consecutive AIS patients with anterior circulation LVO who underwent MT and achieved recanalization with mTICI 2b/2c/3 were included. We evaluated the association between pretreatment clinical and imaging variables and interventional parameters in patients who achieved mTICI 2c/3 vs. 2b using logistic regression and ROC analyses. ResultsFrom 5/11/2019 to 10/09/2022, 149 consecutive patients met our inclusion criteria (median 70 years old [IQR 65 - 78.5], 57.7% female). Adjusted multivariate regression analyses showed that patients with excellent recanalization had lower admission NIHSS (aOR 0.93, p = 0.036), were less likely to have a history of diabetes mellitus (DM) (aOR 0.42, p = 0.050) and prior stroke (aOR 0.27, p = 0.007), had a cerebral blood volume (CBV) index >= 0.7 (aOR 3.75, p = 0.007), and were more likely to achieve excellent recanalization with aspiration alone (aOR 2.89, p = 0.012). A multivariate logistic regression model comprising these independent factors predicted mTICI 2c/3 with an AUC 0.79 (95% CI: 0.68-0.86; p < 0.001), sensitivity of 94%; specificity of 41%. ConclusionRobust collateral status (CS) defined by CBV index >= 0.7, absence of DM and prior stroke, lower initial stroke severity, and direct aspiration are all predictive of excellent recanalization in successfully recanalized AIS-LVO patients. Our findings highlight the prognostic implications of robust CS, DM and stroke prevention, as well as use of aspiration alone in maximizing the likelihood of excellent recanalization.

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.

IntroductionSeveral trials have demonstrated the benefits of endovascular thrombectomy (EVT) for large-core strokes (ASPECTS < 6). However, its effectiveness in lower-middle-income countries with resource-limited settings remains uncertain. This study evaluated the feasibility of EVT for large-core strokes using a simplified imaging protocol with non-contrast CT (NCCT) and CT angiography (CTA) in a resource-constrained environment. MethodsWe conducted a prospective, single-center, observational study from May 2023 to May 2024 at Da Nang Hospital, Vietnam. Patients with anterior circulation large-vessel occlusion strokes, ASPECTS < 6 on NCCT, admission NIHSS [&ge;] 6, and EVT within 24 hours were included. The primary outcome was the modified Rankin Scale (mRS) score at 90 days. Functional independence was defined as mRS 0-2 and ambulatory independence as mRS 0-3. Safety outcomes included symptomatic intracranial hemorrhage (sICH). Outcomes were compared based on reperfusion success (mTICI [&ge;]2b vs. 0-2a), ASPECTS (0-2 vs. 3-5), and time window ([&le;]6 vs. >6 hours). ResultsAmong 157 EVT-treated patients, 52 (33.1%) had ASPECTS < 6. The median age was 62.5 years, and 57.7% were male. Median onset-to-hospital time was 4.1 hours (IQR 1.8-7.9), admission NIHSS 15 (IQR 13-19.5), and initial ASPECTS 4 (IQR 3-4). Successful reperfusion (mTICI [&ge;]2b) was achieved in 78.9%. At 90 days, the median mRS was 3.5 (IQR 3-5.5). Functional independence was observed in 23.1% and ambulatory independence in 50%. sICH occurred in 9.6%, and mortality was 25%. Successful reperfusion was the only independent predictor of ambulatory independence (OR 14.7, 95% CI 1.6-134). Patients with ASPECTS 3-5 had significantly higher ambulatory independence than those with ASPECTS 0-2 (58.5% vs. 18.2%, p=0.017). No significant differences were found between early and late-window groups. ConclusionEVT is feasible for large-core stroke patients in lower-income countries using a simplified NCCT-CTA protocol. Successful reperfusion is a key determinant of improved outcomes.