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IntroductionCerebral small vessel disease (cSVD) is one of the most prevalent neurological disorders. The progressive remodeling of brain microvessels due to arterial hypertension or other vascular risk factors causes subtle, but constant cognitive decline through to manifest dementia and substantially increases the risk for stroke. Preliminary evidence suggests the contribution of the immune system to disease initiation and progression, but a more detailed understanding is impaired by the unavailability of appropriate animal models. Here, we introduce the spontaneously hypertensive rat (SHR) as a model for early onset cSVD and unveiled substantial immune changes in conjunction with brain abnormalities that resemble clinical findings.ResultsIn contrast to age-matched normotensive Wistar Kyoto (WKY) rats, male SHR exhibited non-spatial memory deficits. Magnetic resonance imaging showed brain atrophy and a reduction of white matter volumes in SHR. Histological analyses confirmed white matter demyelination and unveiled a circumscribed blood brain barrier dysfunction in conjunction with micro- and macrogliosis in deep cortical regions. Flow cytometry and histological analyses further revealed substantial disparities in cerebral CD45high leukocyte counts and distribution patterns between SHR and WKY. SHR showed lower counts of T cells in the choroid plexus and meningeal spaces as well as decreased interleukin-10 levels in the cerebrospinal fluid. On the other hand, both T and NK cells were significantly augmented in the SHR brain microvasculature.ConclusionsOur results indicate that SHR share behavioral and neuropathological characteristics with human cSVD patients and further undergird the relevance of immune responses for the initiation and progression of cSVD.Electronic supplementary materialThe online version of this article (doi:10.1186/s40478-014-0169-8) contains supplementary material, which is available to authorized users.

IMPORTANCE Randomized clinical trials have shown the efficacy of thrombectomy of large intracranial vessel occlusions in adults; however, any association of therapy with clinical outcomes in children is unknown. OBJECTIVE To evaluate the use of endovascular recanalization in pediatric patients with arterial ischemic stroke. DESIGN, SETTING, AND PARTICIPANTS This retrospective, multicenter cohort study, conducted from January 1, 2000, to December 31, 2018, analyzed the databases from 27 stroke centers in Europe and the United States. Included were all pediatric patients (<18 years) with ischemic stroke who underwent endovascular recanalization. Median follow-up time was 16 months. EXPOSURES Endovascular recanalization. MAIN OUTCOMES AND MEASURES The decrease of the Pediatric National Institutes of Health Stroke Scale (PedNIHSS) score from admission to day 7 was the primary outcome (score range: 0 [no deficit] to 34 [maximum deficit]). Secondary clinical outcomes included the modified Rankin scale (mRS) (score range: 0 [no deficit] to 6 [death]) at 6 and 24 months and rate of complications. RESULTS Seventy-three children from 27 participating stroke centers were included. Median age was 11.3 years (interquartile range [IQR], 7.0-15.0); 37 patients (51%) were boys, and 36 patients (49%) were girls. Sixty-three children (86%) received treatment for anterior circulation occlusion and 10 patients (14%) received treatment for posterior circulation occlusion; 16 patients (22%) received concomitant intravenous thrombolysis. Neurologic outcome improved from a median PedNIHSS score of 14.0 (IQR, 9.2-20.0) at admission to 4.0 (IQR, 2.0-7.3) at day 7. Median mRS score was 1.0 (IQR, 0-1.6) at 6 months and 1.0 (IQR, 0-1.0) at 24 months. One patient (1%) developed a postinterventional bleeding complication and 4 patients (5%) developed transient peri-interventional vasospasm. The proportion of symptomatic intracerebral hemorrhage events in the HERMES meta-analysis of trials with adults was 2.79 (95% CI, 0.42-6.66) and in Save ChildS was 1.37 (95% CI, 0.03-7.40). CONCLUSIONS AND RELEVANCE The results of this study suggest that the safety profile of thrombectomy in childhood stroke does not differ from the safety profile in randomized clinical trials for adults; most of the treated children had favorable neurologic outcomes. This study may support clinicians' practice of off-label thrombectomy in childhood stroke in the absence of high-level evidence.

Introduction: Endovascular therapy (EVT) is established as first-line treatment for acute ischemic stroke (AIS) due to large vessel occlusion (LVO) in the anterior circulation. For basilar artery occlusion, recent randomized clinical trials demonstrated not only equipoise but also advantages for EVT under particular circumstances. It remains unclear whether EVT offers an advantage over best medical management (BMM) including thrombolysis (IVT) in isolated occlusion of the proximal posterior cerebral artery (PCAO).Methods: Patients with AIS due to PCAO proven by CT or MR angiography were retrospectively identified from local databases at four comprehensive stroke centers in Germany, USA, and Taiwan between 2012 and 2020. Demographic and clinical data were collected, and imaging characteristics including pretherapeutic, interventional, and follow-up imaging were reviewed locally at each center. Patients were grouped according to therapy, i.e., BMM including IVT alone vs. BMM and EVT. Efficacy endpoints were early neurological improvement (ENI) after 24 h or at discharge, good outcome (modified Rankin scale 0–2) after 3 months, as well as hemorrhagic complications and in-house deaths as safety endpoints.Results: We included 130 patients of whom 23 (17.7%) received EVT. EVT patients had more proximal occlusions (69.9 vs. 43%, p = 0.023) and had a better premorbid function [premorbid mRS, 0 (0–4) vs. 1 (0–3), p &lt; 0.01] when compared to BMM patients. IVT showed a trend toward being less performed in the EVT group (21.7 vs. 41.1%, p = 0.1), while other baseline parameters were balanced. Successful reperfusion was achieved in 52% of EVT patients. ENI was more frequent in the EVT group (61 vs. 35.5%, p = 0.034). Good outcome at 90 days and safety endpoints did not differ. In a bivariate analysis, ENI was independently predicted by the use of EVT (OR, 2.76; CI, 1.055–7.04) and the baseline National Institutes of Health Stroke Scale (NIHSS) (OR, 1.082; CI, 1.027–1.141 per point increase).Discussion: EVT in isolated PCAO appears safe and feasible. Positive effects on clinical outcome are primarily on ENI but also depend on the initial stroke severity. Further prospective or randomized studies are needed to better describe the potential long-term clinical benefits of EVT for PCAO as compared with best medical management.

Background and Purpose— The benefit of endovascular therapy in extended time windows has been demonstrated in patients with anterior circulation large vessel occlusion ischemic stroke and favorable imaging profile. We evaluated whether collaterals and thrombus burden influence the associations between revascularization, time-to-treatment, and outcome in endovascular therapy-treated patients with basilar artery occlusion. Methods— We retrospectively analyzed clinical and imaging data of consecutive endovascular therapy-treated patients with basilar artery occlusion included in the multicenter Basilar Artery Treatment and Management Collaboration. The BATMAN (Basilar Artery on Computed Tomography Angiography score, which evaluates thrombus burden and collaterals) and the PC-CS (Posterior Circulation Collateral score, which evaluates collaterals) were assessed on computed tomography angiography, blinded to clinical outcome. Good outcome was defined as modified Rankin Scale score of ≤3 within 3 months; revascularization (successful reperfusion) as modified Thrombolysis in Cerebral Infarction 2b–3 (or TIMI [Thrombolysis in Myocardial Infarction] 2–3 in the BASICS [Basilar Artery International Cooperation Study] registry). Results— We included 172 patients with basilar artery occlusion treated with endovascular therapy (124 with mechanical thrombectomy): mean (SD) age 65 (13) years, median National Institutes of Health Stroke Scale 22 (interquartile range 12–30), 64 (37%) treated >6 hours. Revascularization (achieved in 79% of patients) was associated with good outcome ( P =0.003). The use of new generation thrombectomy devices was associated with good outcome ( P =0.03). In patients who achieved revascularization, 29/46 (63%) of patients with a favorable BATMAN score and 26/51 (51%) with favorable PC-CS had good outcomes. In logistic regression analysis (adjusted for age, National Institutes of Health Stroke Scale, and time-to-treatment ≤6/>6 hours), revascularization was associated with good outcome in patients with favorable BATMAN score (odds ratio, 15.8; 95% CI, 1.4–175; P =0.02) or PC-CS (odds ratio, 9.4; 95% CI, 1.4–64; P =0.02). In patients who achieved revascularization, early (time-to-treatment ≤6 hours) but not late treatment was associated with improved outcome in patients with unfavorable BATMAN score (18/52 [35%]; odds ratio, 15; 95% CI, 1.9–124; P =0.01) or PC-CS (16/44 [36%]; odds ratio, 5.5; 95% CI, 1.4–21; P =0.01). Conclusions— Revascularization is associated with good outcome in patients with basilar artery occlusion with good collaterals and less extensive occlusion, even >6 hours after onset.

Objective:To investigate the efficacy of tenecteplase (TNK), a genetically modified variant of alteplase with greater fibrin specificity and longer half-life than alteplase, prior to endovascular thrombectomy (EVT) in patients with basilar artery occlusion (BAO).Methods:To determine whether tenecteplase is associated with better reperfusion rates than alteplase prior to EVT in BAO, clinical and procedural data of consecutive BAO patients from the Basilar Artery Treatment and MANagement (BATMAN) registry and the Tenecteplase versus Alteplase before Endovascular Therapy for Ischemic Stroke (EXTEND-IA TNK) trial were retrospectively analyzed. Reperfusion >50% or absence of retrievable thrombus at the time of the initial angiogram was evaluated.Results:We included 110 BAO patients treated with intravenous thrombolysis prior to EVT [mean age 69(SD 14); median NIHSS 16(IQR 7-32)]. Nineteen patients were thrombolysed with TNK (0.25mg/kg or 0.40mg/kg) and 91 with alteplase (0.9mg/kg). Reperfusion>50% occurred in 26% (n=5/19) of patients thrombolysed with TNK vs 7% (n=6/91) thrombolysed with alteplase (RR 4.0 95%CI 1.3-12; p=0.02), despite shorter thrombolysis-to-arterial-puncture time in the TNK-treated patients (48[IQR 40-71]mins) vs alteplase-treated patients (110[IQR 51-185]mins, p=0.004). No difference in symptomatic intracranial hemorrhage was observed (0/19(0%) TNK, 1/91(1%) alteplase, p=0.9).Conclusions:Tenecteplase may be associated with an increased rate of reperfusion in comparison with alteplase before EVT in BAO. Randomized controlled trials to compare tenecteplase with alteplase in BAO patients are warranted.Classification of evidence:This study provides Class III evidence that tenecteplase leads to higher reperfusion rates in comparison with alteplase prior to EVT in BAO patients.

In primarily embolic BAO, aspiration thrombectomy was faster, effective and not detrimental to outcome as compared to stentriever thrombectomy. Thus, it may be justified to use aspiration thrombectomy as first-line treatment in these patients.

Background and purpose Endovascular therapy (EVT) is increasingly reported for treatment of isolated posterior cerebral artery (PCA) occlusions although its clinical benefit remains uncertain. This study‐level meta‐analysis investigated the functional outcomes and safety of EVT and best medical management (BMM) compared to BMM alone for treatment of PCA occlusion stroke. Methods We conducted a literature search in PubMed, Web of Science and Embase for studies in patients with isolated PCA occlusion stroke treated with EVT + BMM or BMM including intravenous thrombolysis. There were no randomized trials and all studies were retrospective. The primary outcome was modified Rankin Scale score of 0–2 at 3 months, while safety outcomes included mortality rate and incidence of symptomatic intracranial hemorrhage (sICH). Results Twelve studies with a total of 679 patients were included in the meta‐analysis: 338 patients with EVT + BMM and 341 patients receiving BMM alone. Good functional outcome at 3 months was achieved in 58.0% (95% confidence interval [CI] 43.83–70.95) of patients receiving EVT + BMM and 48.1% (95% CI 40.35–55.92) of patients who received BMM alone, with respective mortality rates of 12.6% (95% CI 7.30–20.93) and 12.3% (95% CI 8.64–17.33). sICH occurred in 4.2% (95% CI 2.47–7.03) of patients treated with EVT + BMM and 3.2% (95% CI 1.75–5.92) of patients treated with BMM alone. Comparative analyses were performed on studies that included both treatments and these demonstrated no significant differences. Conclusions Our results demonstrate that EVT represents a safe treatment for patients with isolated PCA occlusion stroke. There were no differences in clinical or safety outcomes between treatments, supporting randomization of future patients into distal vessel occlusion trials.