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Stroke, Ahead of Print. Background:Early neurological status has been described as predictor of functional outcome in patients with anterior circulation stroke after mechanical thrombectomy. It remains unclear to what proportion the improvement of functional outcome at day 90 is already apparent at 24 hours and at hospital discharge and how later factors impact outcome.Methods:All patients enrolled in the German Stroke Registry (June 2015–December 2019) with anterior circulation stroke and availability of baseline data and neurological status were included. A mediation analysis was conducted to investigate the effect of successful recanalization (Thrombolysis in Cerebral Infarction scale score ≥2b) on good functional outcome (modified Rankin Scale score ≤2 at day 90) with mediation through neurological status (National Institutes of Health Stroke Scale [NIHSS] at 24 hours and at hospital discharge).Results:Three thousand fifty-seven patients fulfilled the inclusion criteria, thereof 2589 (85%) with successful recanalization and 1180 (39%) with good functional outcome. In a multivariate logistic regression analysis, probability of good outcome was significantly associated with age (odds ratio [95% CI], 0.95 [0.94–0.96]), prestroke modified Rankin Scale (0.48 [0.42–0.55]), admission-NIHSS (0.96 [0.94–0.98]), 24-hour NIHSS (0.83 [0.81–0.84]), diabetes (0.56 [0.43–0.72]), proximal middle cerebral artery occlusions (0.78 [0.62–0.97]), passes (0.88 [0.82–0.95]), Alberta Stroke Program Early CT Score (1.07 [1.00–1.14]), successful recanalization (2.39 [1.68–3.43]), intracerebral hemorrhage (0.51 [0.35–0.73]), and recurrent strokes (0.54 [0.32–0.92]). Mediation analysis showed a 20 percentage points (95% CI‚ 17–24 percentage points) increase of probability of good functional outcome after successful recanalization. Fifty-four percent (95% CI‚ 44%–66%) of the improvement in functional outcome was explained by 24-hour NIHSS and 75% (95% CI‚ 62%–90%) by NIHSS at hospital discharge.Conclusions:Fifty-four percent of the improvement in functional outcome after successful recanalization is apparent in NIHSS at 24 hours, 75% in NIHSS at hospital discharge. Other unknown factors not apparent in NIHSS at the 2 time points investigated account for the remaining effect on long term outcome, suggesting, among others, clinical relevance of delayed neurological improvement and deterioration.REGISTRATION:URL:https://www.clinicaltrials.gov; Unique identifier: NCT03356392.

Stroke, Ahead of Print. High blood pressure (BP) is common after ischemic stroke and associated with a poor functional outcome and increased mortality. The conundrum then arises on whether to lower BP to improve outcome or whether this will worsen cerebral perfusion due to aberrant cerebral autoregulation. A number of large trials of BP lowering have failed to change outcome whether treatment was started prehospital in the community or hospital. Hence, nuances on how to manage high BP are likely, including whether different interventions are needed for different causes, the type and timing of the drug, how quickly BP is lowered, and the collateral effects of the drug, including on cerebral perfusion and platelets. Specific scenarios are also important, including when to lower BP before, during, and after intravenous thrombolysis and endovascular therapy/thrombectomy, when it may be necessary to raise BP, and when antihypertensive drugs taken before stroke should be restarted. This narrative review addresses these and other questions. Although further large trials are ongoing, it is increasingly likely that there is no simple answer. Different subgroups of patients may need to have their BP lowered (eg, before or after thrombolysis), left alone, or elevated.

Stroke, Ahead of Print. Background:Cavernous cerebral malformations can arise because of mutations in theCCM1,CCM2, orCCM3genes, and lack ofCdc42has also been reported to induce these malformations in mice. However, the role of the CCM3 (cerebral cavernous malformation 3)-associated kinases in cavernoma development is not known, and we, therefore, have investigated their role in the process.Methods:We used a combination of an in vivo approach, using mice genetically modified to be deficient in the CCM3-associated kinases STK24 and STK25 (serine/threonine kinases 24 and 25), and the in vitro model of human endothelial cells in which expression ofSTK24andSTK25was inhibited by RNA interference.Results:Mice deficient for bothStk24andStk25, but not for either of them individually, developed aggressive vascular lesions with the characteristics of cavernomas at an early age.Stk25deficiency also gave rise to vascular anomalies in the context ofStk24heterozygosity. Human endothelial cells deficient for both kinases phenocopied several of the consequences ofCCM3loss, and singleSTK25deficiency also inducedKLF2expression, Golgi dispersion, altered distribution of β-catenin, and appearance of stress fibers.Conclusions:The CCM3-associated kinases STK24 and STK25 play a major role in the inhibition of cavernoma development.

Stroke, Volume 53, Issue Suppl_1, Page AWMP86-AWMP86, February 1, 2022. Background:Previous studies have suggested that 24-hour NIHSS may serve as a surrogate marker for functional outcomes in acute ischemic stroke patients. Here, we examine if 24-hour NIHSS is a predictor of 90-day mRS in the prospective Systematic Evaluation of Patients Treated With Neurothrombectomy Devices for Acute Ischemic Stroke (STRATIS) Registry.Methods:Data from the STRATIS Registry, a multicenter, non-randomized, observational study of AIS LVO patients treated with the Solitaire stent-retriever as the first-choice therapy within 8 hours from symptoms onset, were analyzed. Patients with premorbid mRS >2, posterior circulation stroke, missing 24 NIHSS or 90-day mRS were excluded from the analysis. The ability of 24-hour NIHSS (continuous and thresholds ≤6 and ≤8) to predict 90-day mRS using logistic regression was examined. The models were adjusted for age, baseline NIHSS, hypertension, diabetes, atrial fibrillation, IV-tPA use, time to recanalization, and revascularization status.Results:Of the 938 STRATIS patients, 662 with 24-hour NIHSS and 90-day mRS were included. A model trained with the continuous 24-hours NIHSS had higher predictive power (sensitivity 0.89, specificity 0.76, AUC 0.89±0.013, P

Stroke, Volume 53, Issue Suppl_1, Page A24-A24, February 1, 2022. Introduction:Mobile Stroke Units (MSUs) improve clinical outcome in patients treated with tPA compared to standard management by Emergency Medical Services (EMS), but the impact of MSUs on outcomes in patients with large vessel occlusions (LVOs) having endovascular thrombectomy (EVT) has yet to be determined.Methods:A pre-specified substudy of tPA-eligible stroke patients with LVOs on CT and/or CTA who were enrolled in the Benefits of Stroke Treatment Using a Mobile Stroke Unit (BEST-MSU), a prospective multicenter controlled trial comparing MSU with standard EMS management, was conducted. The primary outcome was the score on the 90-day utility-weighted modified Rankin Scale (uw-mRS). Secondary outcomes were rate of early neurologic recovery (30% improvement in NIHSS score) at 24 hours and functional independence (mRS 0-1) at 90 days.Results:A total of 295 patients were included, 169 in the MSU group and 126 in the EMS group. Baseline characteristics were comparable between the groups, with the exception of baseline NIHSS (MSU median 19.0 [IQR 13.0, 23.0] vs EMS 16.0 [11.0, 20.0], p=0.003). 92% MSU vs 87% EMS LVO patients received tPA, and 78% vs 85% went on to have EVT. MSU LVO patients had faster tPA bolus from symptom onset (65.0 min [50.5, 92.0] vs 96.0 [79.3, 130.0], p

Stroke, Volume 53, Issue Suppl_1, Page A36-A36, February 1, 2022. Background:Limited data are available on endovascular thrombectomy (EVT) efficacy and safety in large vessel occlusion (LVO) patients presenting >24hr from last known well (LKW). We compared outcomes between patients receiving EVT and best medical management (MM) in a multicenter international cohort.Methods:Consecutive patients with anterior circulation LVO presenting >24h after LKW from 13 centers from 7/2012-4/2021 were analyzed. Multivariable models for 90d mRS distribution and symptomatic ICH were adjusted for age, NIHSS, glucose, IV tPA, transfer status, clot location, time from LKW, CT ASPECTS and ischemic core (rCBF6s volumes.Results:Of 240 patients with a median (IQR) LKW to presentation 28.3h (24.9-38.2), 153 (64%) received EVT. Baseline characteristics were similar except for NIHSS (EVT: 13 (8-20) vs MM: 17 (10-22), p=0.005), CT ASPECTS (EVT: 8(6-9) vs MM: 4(3-6), p

Stroke, Volume 53, Issue Suppl_1, Page ATP149-ATP149, February 1, 2022. Introduction:Higher blood pressure (BP) most post mechanical thrombectomy (MT) can influence perfusion in the ischemic brain tissue depending on collateral status. We aim to determine the association of 24 hour post MT BP parameters with the functional outcome depending on the pre MT collateral status.Methods:We performed a retrospective chart review of patients who underwent MT at a comprehensive stroke center from 7/2014 to 12/2020. The patients were divided into two groups (good versus bad) depending on collateral status. A board certified neuroradiologist, who was blinded to the clinical outcomes, used collateral grading scales of Mass ≥3 and modified-Tan >50% to designate good collaterals on the pre MT CT Angiogram. A binary logistic regression analysis was performed, controlling for age, sex, NIHSS, ASPECTS≥6, TICI score≥2b, time to thrombectomy, LDL, Hemoglobin A1C, intravenous alteplase, with the 24 hour post MT BP parameters as the predictors. The outcomes were good functional outcome (90 day mRS≤2) and mortality.Results:220 patients met the inclusion criteria. Lower 24 hour BP parameters of standard deviation (SD) SBP (OR,1.16; 95% CI,1.01-1.33; P 0.047) and maximum DBP (OR,1.05; 95% CI,1.01-1.09; P 0.036) were associated with good functional outcome, while higher values of SD SBP (OR,1.15; 95% CI,1.01-1.31; P 0.045), coefficient variation (CV) SBP (OR,1.19; 95% CI,1.01-1.41; P 0.043), SBP range (OR,1.04; 95% CI,1.01-1.07; P 0.046), maximum DBP (OR,0.95; 95% CI,0.91-0.99; P 0.016), pulse pressure (OR,1.09; 95% CI,1.02-1.16; P 0.022) and SBP≥140 (OR,5.85; 95% CI,1.11-30.85; P 0.038) were associated with mortality in patients with good collaterals according to Mass grading. Higher values of BP parameters of SD SBP (OR,1.13; 95% CI,1.04-1.24; P 0.007), CV SBP (OR,1.18; 95% CI,1.05-1.32; P 0.006), SBP range (OR,1.04; 95% CI,1.01-1.06; P 0.008) and maximum DBP (OR,0.97; 95% CI,0.94-1; P 0.02) were associated with mortality in patients with good collaterals according to modified-Tan grading. There was no such association in patients with bad collaterals.Conclusion:Various higher 24 hour BP parameters post MT are associated with a bad functional outcome or mortality in patients with good collaterals, unlike in patients with bad collaterals.

Stroke, Ahead of Print. Background and Purpose:Collaterals govern the pace and severity of cerebral ischemia, distinguishing fast or slow progressors and corresponding therapeutic opportunities. The fate of sustained collateral perfusion or collateral failure is poorly characterized. We evaluated the nature and impact of collaterals on outcomes in the late time window DAWN trial (Diffusion-Weighted Imaging or Computed Tomography Perfusion Assessment With Clinical Mismatch in the Triage of Wake-Up and Late Presenting Strokes Undergoing Neurointervention With Trevo).Methods:The DAWN Imaging Core Lab prospectively scored collateral grade on baseline computed tomography angiography (CTA; endovascular and control arms) and digital subtraction angiography (DSA; endovascular arm only), blinded to all other data. CTA collaterals were graded with the Tan scale and DSA collaterals were scored by ASITN grade (American Society of Interventional and Therapeutic Neuroradiology collateral score). Descriptive statistics characterized CTA collateral grade in all DAWN subjects and DSA collaterals in the endovascular arm. The relationship between collateral grade and day 90 outcomes were separately analyzed for each treatment arm.Results:Collateral circulation to the ischemic territory was evaluated on CTA (n=144; median 2, 0–3) and DSA (n=57; median 2, 1–4) before thrombectomy in 161 DAWN subjects (mean age 69.8±13.6 years; 55.3% women; 91 endovascular therapy, 70 control). CTA revealed a broad range of collaterals (Tan grade 3, n=64 [44%]; 2, n=45 [31%]; 1, n=31 [22%]; 0, n=4 [3%]). DSA also showed a diverse range of collateral grades (ASITN grade 4, n=4; 3, n=22; 2, n=27; 1, n=4). Across treatment arms, baseline demographics, clinical variables except atrial fibrillation (41.6% endovascular versus 25.0% controls,P=0.04), and CTA collateral grades were balanced. Differences were seen across the 3 levels of collateral flow (good, fair, poor) for baseline National Institutes of Health Stroke Scale, blood glucose