Endovascular therapy in patients with a large ischemic volume at presentation: An aggregate patient-level analysis.

INTRODUCTION Recently, four randomized controlled trials (RCTs) have demonstrated the benefits of mechanical thrombectomy (MT) in patients with acute ischemic stroke (AIS) caused by anterior large vessel occlusion (LVO) and a large ischemic core at baseline (LIC). The purpose of this study was to investigate the features influencing the clinical outcome and the benefits of mechanical thrombectomy in this subgroup. METHODS We conducted a multicenter retrospective aggregate cohort study of patients with AIS-LVO and a LIC, assessed with quantitative core volume measures, treated with MT between 2012 and 2019. The data were queried through four registries, including patients with core volumes ≥50cc. Multivariable logistic regression models were employed to determine factors independently associated with clinical outcomes in patients with successful recanalization (modified-Thrombolysis-in-Cerebral-Infarction-score, mTICI=2b-3) and unsuccessful recanalization group (mTICI=0-2a). The primary endpoint was a favorable functional outcome at day-90, defined as a modified Rankin scale (mRS) of 0-3, accounting for the inherent severity of AIS with baseline LIC. Secondary outcomes included functional independence (mRS 0-2) at day-90, mortality, and symptomatic Intracranial Hemorrhage (sICH). RESULTS A total of 460 patients were included (mean age 66±14.2 years; 39.6 % females). The mean baseline NIHSS was 20±5.2, and the core volume was 103.2±54.6 ml. Overall, 39.8 % (183/460) of patients achieved a favorable outcome at day-90 (mRS 0-3). Successful recanalization was significantly associated with a more frequent favorable outcome (aOR, 4.79; 95 %CI, 2.73-8.38; P<0.01) and functional independence (P<0.01). This benefit remained significant in older patients and in patients with cores above 100cc. At 90 days, 147/460 patients (32 %) were deceased, with successful recanalization significantly associated with less frequent mortality (OR, 0.34; 95 %CI, 0.22-0.53; P<0.01). The rate of sICH was 17.4 % and did not differ significantly between groups. CONCLUSIONS In this large, pooled-cohort study of AIS-LVO patients with infarct cores over 50cc at baseline, we demonstrated that successful recanalization was associated with a better functional outcome, lower mortality, and similar rates of symptomatic intracranial hemorrhage for a wide spectrum of patients

Interaction between intravenous thrombolysis and clinical outcome between slow and fast progressors undergoing mechanical thrombectomy: a post-hoc analysis of the SWIFT-DIRECT trial.

BACKGROUND In proximal occlusions, the effect of reperfusion therapies may differ between slow or fast progressors. We investigated the effect of intravenous thrombolysis (IVT) (with alteplase) plus mechanical thrombectomy (MT) versus thrombectomy alone among slow versus fast stroke progressors. METHODS The SWIFT-DIRECT trial data were analyzed: 408 patients randomized to IVT+MT or MT alone. Infarct growth speed was defined by the number of points of decay in the initial Alberta Stroke Program Early CT Score (ASPECTS) divided by the onset-to-imaging time. The primary endpoint was 3-month functional independence (modified Rankin scale 0-2). In the primary analysis, the study population was dichotomized into slow and fast progressors using median infarct growth velocity. Secondary analysis was also conducted using quartiles of ASPECTS decay. RESULTS We included 376 patients: 191 IVT+MT, 185 MT alone; median age 73 years (IQR 65-81); median initial National Institutes of Health Stroke Scale (NIHSS) 17 (IQR 13-20). The median infarct growth velocity was 1.2 points/hour. Overall, we did not observe a significant interaction between the infarct growth speed and the allocation to either randomization group on the odds of favourable outcome (P=0.68). In the IVT+MT group, odds of any intracranial hemorrhage (ICH) were significantly lower in slow progressors (22.8% vs 36.4%; OR 0.52, 95% CI 0.27 to 0.98) and higher among fast progressors (49.4% vs 26.8%; OR 2.62, 95% CI 1.42 to 4.82) (P value for interaction <0.001). Similar results were observed in secondary analyses. CONCLUSION In this SWIFT-DIRECT subanalysis, we did not find evidence for a significant interaction of the velocity of infarct growth on the odds of favourable outcome according to treatment by MT alone or combined IVT+MT. However, prior IVT was associated with significantly reduced occurrence of any ICH among slow progressors whereas this was increased in fast progressors

Interaction between intravenous thrombolysis and clinical outcome between slow and fast progressors undergoing mechanical thrombectomy: a post-hoc analysis of the SWIFT-DIRECT trial

Background: In proximal occlusions, the effect of reperfusion therapies may differ between slow or fast progressors. We investigated the effect of intravenous thrombolysis (IVT) (with alteplase) plus mechanical thrombectomy (MT) versus thrombectomy alone among slow versus fast stroke progressors. Methods: The SWIFT-DIRECT trial data were analyzed: 408 patients randomized to IVT+MT or MT alone. Infarct growth speed was defined by the number of points of decay in the initial Alberta Stroke Program Early CT Score (ASPECTS) divided by the onset-to-imaging time. The primary endpoint was 3-month functional independence (modified Rankin scale 0–2). In the primary analysis, the study population was dichotomized into slow and fast progressors using median infarct growth velocity. Secondary analysis was also conducted using quartiles of ASPECTS decay.ResultsWe included 376 patients: 191 IVT+MT, 185 MT alone; median age 73 years (IQR 65–81); median initial National Institutes of Health Stroke Scale (NIHSS) 17 (IQR 13–20). The median infarct growth velocity was 1.2 points/hour. Overall, we did not observe a significant interaction between the infarct growth speed and the allocation to either randomization group on the odds of favourable outcome (P=0.68). In the IVT+MT group, odds of any intracranial hemorrhage (ICH) were significantly lower in slow progressors (22.8% vs 36.4%; OR 0.52, 95% CI 0.27 to 0.98) and higher among fast progressors (49.4% vs 26.8%; OR 2.62, 95% CI 1.42 to 4.82) (P value for interaction <0.001). Similar results were observed in secondary analyses. Conclusion: In this SWIFT-DIRECT subanalysis, we did not find evidence for a significant interaction of the velocity of infarct growth on the odds of favourable outcome according to treatment by MT alone or combined IVT+MT. However, prior IVT was associated with significantly reduced occurrence of any ICH among slow progressors whereas this was increased in fast progressors

Recanalization Therapies for Large Vessel Occlusion Due to Cervical Artery Dissection: A Cohort Study of the EVA-TRISP Collaboration

Background and Purpose: This study aimed to investigate the effect of endovascular treatment (EVT, with or without intravenous thrombolysis [IVT]) versus IVT alone on outcomes in patients with acute ischemic stroke (AIS) and intracranial large vessel occlusion (LVO) attributable to cervical artery dissection (CeAD). Methods: This multinational cohort study was conducted based on prospectively collected data from the EVA-TRISP (EndoVAscular treatment and ThRombolysis for Ischemic Stroke Patients) collaboration. Consecutive patients (2015–2019) with AIS-LVO attributable to CeAD treated with EVT and/or IVT were included. Primary outcome measures were (1) favorable 3-month outcome (modified Rankin Scale score 0–2) and (2) complete recanalization (thrombolysis in cerebral infarction scale 2b/3). Odds ratios with 95% confidence intervals (OR [95% CI]) from logistic regression models were calculated (unadjusted, adjusted). Secondary analyses were performed in the patients with LVO in the anterior circulation (LVOant) including propensity score matching. Results: Among 290 patients, 222 (76.6%) had EVT and 68 (23.4%) IVT alone. EVT-treated patients had more severe strokes (National Institutes of Health Stroke Scale score, median [interquartile range]: 14 [10–19] vs. 4 [2–7], Padjusted 0.56 [0.24–1.32]). EVT was associated with higher rates of recanalization (80.5% vs. 40.7%; ORadjusted 8.85 [4.28–18.29]) compared to IVT. All secondary analyses showed higher recanalization rates in the EVT-group, which however never translated into better functional outcome rates compared to the IVT-group. Conclusion: We observed no signal of superiority of EVT over IVT regarding functional outcome in CeAD-patients with AIS and LVO despite higher rates of complete recanalization with EVT. Whether pathophysiological CeAD-characteristics or their younger age might explain this observation deserves further research

Safety and efficacy of ApTOLL in patients with ischemic stroke undergoing endovascular treatment: a phase 1/2 randomized clinical trial

Clinical trial[Abstract] Importance: ApTOLL is a TLR4 antagonist with proven preclinical neuroprotective effect and a safe profile in healthy volunteers. Objective: To assess the safety and efficacy of ApTOLL in combination with endovascular treatment (EVT) for patients with ischemic stroke. Design, setting, and participants: This phase 1b/2a, double-blind, randomized, placebo-controlled study was conducted at 15 sites in Spain and France from 2020 to 2022. Participants included patients aged 18 to 90 years who had ischemic stroke due to large vessel occlusion and were seen within 6 hours after stroke onset; other criteria were an Alberta Stroke Program Early CT Score of 6 to 10, estimated infarct core volume on baseline computed tomography perfusion of 5 to 70 mL, and the intention to undergo EVT. During the study period, 4174 patients underwent EVT. Interventions: In phase 1b, 0.025, 0.05, 0.1, or 0.2 mg/kg of ApTOLL or placebo; in phase 2a, 0.05 or 0.2 mg/kg of ApTOLL or placebo; and in both phases, treatment with EVT and intravenous thrombolysis if indicated. Main outcomes and measures: The primary end point was the safety of ApTOLL based on death, symptomatic intracranial hemorrhage (sICH), malignant stroke, and recurrent stroke. Secondary efficacy end points included final infarct volume (via MRI at 72 hours), NIHSS score at 72 hours, and disability at 90 days (modified Rankin Scale [mRS] score). Results: In phase Ib, 32 patients were allocated evenly to the 4 dose groups. After phase 1b was completed with no safety concerns, 2 doses were selected for phase 2a; these 119 patients were randomized to receive ApTOLL, 0.05 mg/kg (n = 36); ApTOLL, 0.2 mg/kg (n = 36), or placebo (n = 47) in a 1:1:√2 ratio. The pooled population of 139 patients had a mean (SD) age of 70 (12) years, 81 patients (58%) were male, and 58 (42%) were female. The primary end point occurred in 16 of 55 patients (29%) receiving placebo (10 deaths [18.2%], 4 sICH [7.3%], 4 malignant strokes [7.3%], and 2 recurrent strokes [3.6%]); in 15 of 42 patients (36%) receiving ApTOLL, 0.05 mg/kg (11 deaths [26.2%], 3 sICH [7.2%], 2 malignant strokes [4.8%], and 2 recurrent strokes [4.8%]); and in 6 of 42 patients (14%) receiving ApTOLL, 0.2 mg/kg (2 deaths [4.8%], 2 sICH [4.8%], and 3 recurrent strokes [7.1%]). ApTOLL, 0.2 mg/kg, was associated with lower NIHSS score at 72 hours (mean difference log-transformed vs placebo, -45%; 95% CI, -67% to -10%), smaller final infarct volume (mean difference log-transformed vs placebo, -42%; 95% CI, -66% to 1%), and lower degrees of disability at 90 days (common odds ratio for a better outcome vs placebo, 2.44; 95% CI, 1.76 to 5.00). Conclusions and relevance: In acute ischemic stroke, 0.2 mg/kg of ApTOLL administered within 6 hours of onset in combination with EVT was safe and associated with a potential meaningful clinical effect, reducing mortality and disability at 90 days compared with placebo. These preliminary findings await confirmation from larger pivotal trials.This study was sponsored by aptaTargets, Madrid, Spain, and cofunded by grants from the Spanish Ministry of Science, Innovation and Universities (RTC-2017-6651-1 and RTC-2019-006795-1).España. Ministerio de Ciencia, Innovación e Universidades; RTC-2017-6651-1España. Ministeriod e Ciencia, Innovación e Universidades; RTC-2019-006795-

Profile of and risk factors for poststroke cognitive impairment in diverse ethno-regional groups

OBJECTIVE: To address the variability in prevalence estimates and inconsistencies in potential risk factors for poststroke cognitive impairment (PSCI) using a standardized approach and individual participant data (IPD) from international cohorts in the Stroke and Cognition Consortium (STROKOG) consortium. METHODS: We harmonized data from 13 studies based in 8 countries. Neuropsychological test scores 2 to 6 months after stroke or TIA and appropriate normative data were used to calculate standardized cognitive domain scores. Domain-specific impairment was based on percentile cutoffs from normative groups, and associations between domain scores and risk factors were examined with 1-stage IPD meta-analysis. RESULTS: In a combined sample of 3,146 participants admitted to hospital for stroke (97%) or TIA (3%), 44% were impaired in global cognition and 30% to 35% were impaired in individual domains 2 to 6 months after the index event. Diabetes mellitus and a history of stroke were strongly associated with poorer cognitive function after covariate adjustments; hypertension, smoking, and atrial fibrillation had weaker domain-specific associations. While there were no significant differences in domain impairment among ethno-racial groups, some interethnic differences were found in the effects of risk factors on cognition. CONCLUSIONS: This study confirms the high prevalence of PSCI in diverse populations, highlights common risk factors, in particular diabetes mellitus, and points to ethno-racial differences that warrant attention in the development of prevention strategies.OBJECTIVE: To address the variability in prevalence estimates and inconsistencies in potential risk factors for poststroke cognitive impairment (PSCI) using a standardized approach and individual participant data (IPD) from international cohorts in the Stroke and Cognition Consortium (STROKOG) consortium. METHODS: We harmonized data from 13 studies based in 8 countries. Neuropsychological test scores 2 to 6 months after stroke or TIA and appropriate normative data were used to calculate standardized cognitive domain scores. Domain-specific impairment was based on percentile cutoffs from normative groups, and associations between domain scores and risk factors were examined with 1-stage IPD meta-analysis. RESULTS: In a combined sample of 3,146 participants admitted to hospital for stroke (97%) or TIA (3%), 44% were impaired in global cognition and 30% to 35% were impaired in individual domains 2 to 6 months after the index event. Diabetes mellitus and a history of stroke were strongly associated with poorer cognitive function after covariate adjustments; hypertension, smoking, and atrial fibrillation had weaker domain-specific associations. While there were no significant differences in domain impairment among ethnoracial groups, some interethnic differences were found in the effects of risk factors on cognition. CONCLUSIONS: This study confirms the high prevalence of PSCI in diverse populations, highlights common risk factors, in particular diabetes mellitus, and points to ethnoracial differences that warrant attention in the development of prevention strategies.Peer reviewe

Endovascular Therapy in the Extended Time Window for Large Vessel Occlusion in Patients With Pre-Stroke Disability.

BACKGROUND AND PURPOSE We compared the outcomes of endovascular therapy (EVT) in an extended time window in patients with large-vessel occlusion (LVO) between patients with and without pre-stroke disability. METHODS In this prespecified analysis of the multinational CT for Late Endovascular Reperfusion study (66 participating sites, 10 countries between 2014 and 2022), we analyzed data from patients with acute ischemic stroke with a pre-stroke modified Rankin Scale (mRS) score of 0-4 and LVO who underwent EVT 6-24 hours from the time last seen well. The primary outcome was the composite of functional independence (FI; mRS score 0-2) or return to the pre-stroke mRS score (return of Rankin, RoR) at 90 days. Outcomes were compared between patients with pre-stroke disability (pre-stroke mRS score 2-4) and those without (mRS score 0-1). RESULTS A total of 2,231 patients (median age, 72 years; median National Institutes of Health Stroke Scale score, 16) were included in the present analysis. Of these, 564 (25%) had pre-stroke disability. The primary outcome (FI or RoR) was observed in 30.7% of patients with pre-stroke disability (FI, 16.5%; RoR, 30.7%) compared to 44.1% of patients without (FI, 44.1%; RoR, 13.0%) (P<0.001). In multivariable logistic regression analysis with inverse probability of treatment weighting, pre-stroke disability was not associated with significantly lower odds of achieving FI or RoR (adjusted odds ratio 0.73, 95% confidence interval 0.43-1.25). Symptomatic intracranial hemorrhage occurred in 6.3% of both groups (P=0.995). CONCLUSION A considerable proportion of patients with late-presenting LVO and pre-stroke disability regained pre-stroke mRS scores after EVT. EVT may be appropriate for patients with pre-stroke disability presenting in the extended time window

Research Progresses in Understanding the Pathophysiology of Moyamoya Disease

Background: The pathogenesis of moyamoya disease (MMD) is still unknown. The detection of inflammatory molecules such as cytokines, chemokines and growth factors in MMD patients' biological fluids supports the hypothesis that an abnormal angiogenesis is implicated in MMD pathogenesis. However, it is unclear whether these anomalies are the consequences of the disease or rather causal factors as well as these mechanisms remain insufficient to explain the pathophysiology of MMD. The presence of a family history in about 9-15% of Asian patients, the highly variable incidence rate between different ethnic and sex groups and the age of onset support the role of genetic factors in MMD pathogenesis. However, although some genetic loci have been associated with MMD, few of them have been replicated in independent series. Recently, RNF213 gene was shown to be strongly associated with MMD occurrence with a founder effect in East Asian patients. However, the mechanisms leading from RNF213 mutations to MMD clinical features are still unknown. Summary: The research on pathogenic mechanism of MMD is in its infancy. MMD is probably a complex and heterogeneous disorder, including different phenotypes and genotypes, in which more than a single factor is implicated. Key Message: Since the diagnosis of MMD is rapidly increasing worldwide, the development of more efficient stratifying risk systems, including both clinical but also biological drivers became imperative to improve our ability of predict prognosis and to develop mechanism-tailored interventions. (C) 2016 S. Karger AG, BaselPeer reviewe

INFLUENCE DES TROUBLES COGNITIFS SUR LE LIEU DE VIE A COURT ET A LONG TERME DES PATIENTS AYANT PRESENTE UN ACCIDENT VASCULAIRE CEREBRAL

LILLE2-BU Santé-Recherche (593502101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF