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Carotid Web (CaW) is a growingly recognized cause of ischemic stroke, associated with a high recurrence risk. Several therapeutic strategies have been proposed as a tertiary prevention including carotid stenting, endarterectomy and antithrombotic medications. Among these, carotid stenting with dual-layer stent may be promising to adequately cover the focal arterial dysplasia. Our aim was to investigate the safety and efficacy of the Casper stent in the treatment of symptomatic CaW.We conducted a retrospective analysis of consecutive patients presenting with a symptomatic CaW and included in the ongoing prospective observational multicenter CAROWEB registry. The study period was January 2015 to December 2021. Inclusion criteria were CaW treated with dual-layer Casper stent. Patients treated with other types of carotid stent, endarterectomy or antithrombotic medication were excluded. Clinical and radiological initial data and outcomes were recorded.twenty-seven patients (with 28 caw) were included. median age was 52 (iqr: 46-68). median delay between index cerebrovascular event and cervical stenting was 9 days (IQR: 6-101). In all cases, the cervical carotid stenting was successfully performed. No major perioperative complication was recorded. No recurrent stroke or transient ischemic attack was observed during a median follow-up time of 272 days (IQR: 114-635). Long-term imaging follow-up was available in 25/28 (89.3%) stented CaW with a median imaging follow-up of 183 days (IQR: 107-676; range: 90-1542). No in-stent occlusion or stenosis was detected.In this study, carotid stenting with dual-layer Casper stent in the treatment of symptomatic CaW was effective regarding stroke recurrence prevention and safe, without procedural nor delayed detected adverse event. However, the optimal therapeutic approach of symptomatic CaW still needs to be explored through randomized trials.

Patients with pre-stroke disability, defined as a modified Rankin Scale (mRS) ≥3, were excluded from most trials of endovascular thrombectomy (EVT) for acute stroke. We sought to evaluate the prognostic factors associated with favorable outcome in stroke patients with known disability undergoing EVT, and the impact of successful reperfusion.Consecutive acute stroke patients with pre-stroke disability, undergoing EVT, were retrospectively collected between 2016 to 2019 from a Canadian cohort and a multicenter French cohort (Endovascular Treatment in Ischemic Stroke registry-ETIS). Favorable outcome was defined as an mRS equal to pre-stroke mRS. Patients achieving successful reperfusion (defined as a modified Thrombolysis in Cerebral Infarction score of 2b/3) were compared with patients without successful reperfusion to determine if successful EVT was associated with better functional outcomes.Among 6220 patients treated with EVT, 280 (4.5%) patients with a pre-stroke mRS ≥3 were included. Sixty-one patients (21.8%) had a favorable outcome and 146 (52.1%) died at 3 months. Patients with successful reperfusion had a higher proportion of favorable 90-day mRS (27.6% versus 19.6%, p = 0.025) and a lower mortality (48.3% versus 69.6%, p = 0.008) than patients without successful reperfusion. After adjusting for baseline prognostic factors, successful reperfusion defined by TICI ≥2b was associated with favorable functional outcome (OR 3.16 CI95% [1.11-11.5]; p 0.048).In patients with pre-stroke disability, successful reperfusion is associated with a greater proportion of favorable outcome and lower mortality.

Despite continuous improvement and growing knowledge in the endovascular therapy of large vessel occlusion stroke (LVOS), mechanical thrombectomy (MT) still fails to obtain satisfying intracranial recanalization in 10% to 15% of cases. However, little is known regarding clinical and radiological outcomes among this singularly underexplored subpopulation undergoing failed MT. We aimed to investigate the outcome after failed MT and identify predictive factors of favorable outcome despite recanalization failure.We conducted a retrospective analysis of consecutive patients prospectively included in the ongoing observational multicenter Endovascular Treatment in Ischemic Stroke registry from January 2015 to September 2020. Patients presenting with anterior circulation LVOS treated with MT but experiencing failed intracranial recanalization defined as final modified Thrombolysis In Cerebral Infarction (mTICI) score of 0, 1 and 2a were included. Clinical and radiological outcomes were assessed along with the exploration of predictive factors of Day-90 favorable outcome.The study population comprised 533 patients. Mean age was 68.8 ± 16 years, and median admission National Institutes of Health Stroke Scale (NIHSS) and Alberta Stroke Program Early Computed Tomography Score (ASPECTS) were 17 (IQR 12-21) and 7 (IQR 5-8), respectively. Favorable outcomes were observed in 85 patients (18.2%) and 186 died (39.0%). The rate of symptomatic intracranial hemorrhage was 14.1%. In multivariable analysis, younger age (odds ratio [OR] 0.96, 95% CI 0.94-0.98, p lt; 0.001), a lower admission NIHSS (OR 0.87, 95% CI 0.83-0.91, p lt; 0.001), a lower number of MT passes (OR 0.77, 95% CI 0.77-0.87, p lt; 0.001), a lower delta ASPECTS between initial and Day-1 imaging (OR 0.83, 95% CI 0.71-0.98, p = 0.026) and stroke etiology [significant difference among etiological subtypes (p = 0.024) with a tendency toward more favorable outcomes for dissection (OR 2.01, 95% CI 0.71-5.67)] were significantly associated with a 90-day favorable outcome.In this large retrospective analysis of a multicenter registry, we quantified the poor outcome after MT failure. We also identified factors associated with favorable outcome despite recanalization failure that might influence therapeutic management.

Background: Behçet’s disease (BD) is a rare form of vasculitis involving both veins and arteries of all calibers. Psychological symptoms and cognitive impairment appear to be frequent, but few data are available. Methods: All consecutive patients in our center fulfilling the 2013 BD criteria underwent a psychometric evaluation with auto- (SCL-90-R and Modified Fatigue Index) and hetero-questionnaires (MINI). A standardized test battery assessed cognitive dysfunction. Data were correlated with BD activity as well as quality of life (SF-36). Results: We included 20 consecutive patients (16 men, four women) with a median [IQR] age of 38 (30.0–45.5) and a median disease duration of 7 years (1.8–11.0). Five patients had an abnormal brain MRI. The SCL-90-R questionnaire highlighted eight psychopathological profiles (42.1%) that correlated with altered quality of life and more severe fatigue. The most frequent symptoms were anxiety (9/19, 47.4%), somatization (8/19, 42.1%) and phobia (5/19, 26.3%). Psychopathological symptoms appeared to be more severe, but not more frequent, in neuro-Behçet’s patients. Based on standardized cognitive evaluation, nine patients had cognitive impairment defined by three or more altered tests. Notably, 6/9 patients did not have any complaint of memory loss and were thus considered ansognostic. Conclusion: Cognitive involvement was significantly associated with BD activity score (BSAS) but not with brain MRI abnormalities.

BackgroundThe number of mechanical thrombectomy (MT) passes is strongly associated with angiographic reperfusion as well as clinical outcomes in patients with anterior circulation ischemic stroke. However, these associations have not been analyzed in patients with basilar artery occlusion (BAO). We investigated the influence of the number of MT passes on the degree of reperfusion and clinical outcomes, and compared outcome after ≤3 passes versus >3 passes.MethodsWe used data from the prospective multicentric Endovascular Treatment in Ischemic Stroke (ETIS) Registry at 18 sites in France. Patients with BAO treated with MT were included. The primary outcome was a favorable outcome, defined as a modified Rankin Scale score of 0–3 at 90 days. We fit mixed multiple regression models, with center as a random effect.ResultsWe included 275 patients. Successful recanalization (modified Thrombolysis In Cerebral Infarction (mTICI) 2b-3) was achieved in 88.4%, and 41.8% had a favorable outcome. The odds ratio for favorable outcome with each pass above 1 was 0.41 (95% CI 0.23 to 0.73) and for recanalization (mTICI 2b-3) it was 0.70 (95% CI 0.57 to 0.87). In patients with ≤3 passes, the rate of favorable outcome in recanalized versus non-recanalized patients was 50.5% versus 10.0% (p=0.001), while in those with >3 passes it was 16.7% versus 15.2% (p=0.901).ConclusionsWe found that BAO patients had a significant relationship between the number of MT passes and both recanalization and favorable functional outcome. We further found that the benefit of recanalization in BAO patients was significant only when recanalization was achieved within three passes, encouraging at least three passes before stopping the procedure.

BackgroundEndovascular treatment (EVT) for basilar artery occlusions (BAO) is associated with a higher rate of futile recanalization compared with anterior circulation procedures. We aimed to identify the incidence and predictors of poor clinical outcome despite successful reperfusion in current clinical practice.MethodsWe used data from the ETIS (Endovascular Treatment in Ischemic Stroke) registry, a prospective multicenter observational registry of stroke treated with EVT in France. Patients undergoing EVT for acute BAO from January 2014 to May 2019 successfully treated within 8 hours from onset were included. Predictors of 90-day poor outcome (modified Rankin Scale (mRS) 4–6) were researched within patients with successful (modified Thrombolysis In Cerebral Infarction (mTICI 2b-3)) and excellent (mTICI 2c-3) reperfusion.ResultsAmong 242 patients treated within 8 hours, successful reperfusion was achieved in 195 (80.5%) and excellent reperfusion in 120 (49.5%). Poor outcome was observed in 107 (54.8%) and 60 (50%) patients, respectively. In patients with successful early reperfusion, age, higher initial National Institutes of Health Stroke Scale (NIHSS) score, lower posterior circulation Alberta Stroke Programme Early CT Score (pc-ASPECTS), and absence of prior intravenous thrombolysis were independent predictors of poor outcome. The only treatment factor with an independent predictive value was first-pass mTICI 2b-3 reperfusion (adjusted OR 0.13, 95% CI 0.05 to 0.37, pConclusionsEarly successful reperfusion with EVT occurred in 80.5% of patients, and the only treatment-related factor predictive of clinical outcome was first pass mTICI 2b-3 reperfusion. Further research is warranted to identify the optimal techniques and devices associated with first pass reperfusion in the posterior circulation.

Five trials published in 2015 showed the benefit of endovascular thrombectomy (ET) in patients with stroke and large vessel occlusion, extending the treatment window has become an obsession of all physicians. In 2018, the DAWN and DEFUSE-3 trials showed that, with careful selection of patients, the procedure could be carried out up to 24 hours after symptom onset with good outcomes. In addition, there have been cases where the DAWN criteria were met, and treatment occurred >24 hours after symptom onset. We present the case of a 68-year-old female whose groin puncture occurred 52 hours after the time last known well (TLKW), after neurological worsening of the initial situation, with a large mismatch ratio observed on magnetic resonance imaging, achieving TICI (the Thrombolysis in Cerebral Infarction scale) grade 3 recanalization. Five days after the procedure, the patient was discharged with NIHSS (National Institutes of Health Stroke Scale) score of 3. Some types of collateral circulation (slow progressors and “turtle” progressors, our term for very slow progressors) can extend the treatment window beyond 24 hours of the TLKW but can lead to a hyperperfusion-like syndrome immediately after the ET. Further studies are needed to evaluate the reproducibility of this hypothetical syndrome.

Background: Management of extracranial internal carotid artery steno-occlusive lesion during endovascular therapy remains debated. Stent occlusion within 24 hours of endovascular therapy is a frequent event after acute carotid artery stenting, and we currently lack large population results. We investigated the incidence, predictors, and clinical impact of stent occlusion after acute carotid artery stenting in current clinical practice. Methods: Patients treated by endovascular therapy with acute carotid artery stenting between 2015 and 2019 in 5 large-volume endovascular-capable centers were retrospectively analyzed. Patients were separated in 2 groups according to the stent patency at 24 hours after carotid artery stenting. We compared baseline characteristics, treatment modalities, and clinical outcome depending on 24-hour stent patency. Primary end point was favorable outcome, defined as a modified Rankin Scale score 0–2 at 3 months. Results: A stent occlusion was observed in 47/225 patients (20.9%). Patients with stent patency had a lower baseline National Institutes of Health Stroke Scale (median [interquartile range]: 13 [7–17] versus 18 [12–21]) and had more often stroke of atherothrombotic origin (77.0% versus 53.2%). A higher stent patency rate was found for patients treated with P2Y 12 antagonists at the acute phase (odds ratio [OR]‚ 2.95 [95% CI‚ 1.10–7.91]; P =0.026) and treated with angioplasty (OR‚ 2.42 [95% CI‚ 1.24–4.67]; P =0.008). A better intracranial angiographic reperfusion was observed in patients with 24-hour stent patency compared with patients without stent patency (OR‚ 8.38 [95% CI‚ 3.07–22.78]; P P P =0.009). Conclusions: One out of 5 patients treated with carotid artery stenting during endovascular therapy presented a stent occlusion within 24 hours. This event was associated with worse functional outcome. Stroke etiology, P2Y 12 antagonist administration, quality of intracranial reperfusion, and angioplasty were associated with 24-hour stent patency.

BackgroundIntravenous thrombolysis (IVT) for patients treated with mechanical thrombectomy (MT) for proximal occlusions has recently been questioned through randomized trials. However, few patients with M2 occlusions were included. We investigated the influence of prior IVT for patients presenting M2 occlusions treated with MT in comparison with MT alone.MethodsWe conducted a retrospective analysis of the Endovascular Treatment in Ischemic Stroke (ETIS) registry, a multicenter observational study. Data from consecutive patients treated with MT for M2 occlusions between January 2015 and January 2022 at 26 comprehensive stroke centers were analyzed. The primary endpoint was 90-day modified Rankin Scale score of 0–2. Outcomes were compared using propensity score approaches. We also performed sensitivity analysis in relevant subgroups of patients.ResultsAmong 1132 patients with M2 occlusions treated with MT, 570 received prior IVT. The two groups were comparable after propensity analysis. The rate of favorable functional outcome was significantly higher in the IVT+MT group compared with the MT alone group (59.8% vs 44.7%; adjusted OR 1.38, 95% CI 1.10 to 1.75, P=0.008). Hemorrhagic and procedural complications were similar in both groups. In sensitivity analysis excluding patients with anticoagulation treatment, favorable recanalization was more frequent in the IVT+MT group (OR 1.37, 95% CI 1.11 to 1.70, P=0.004).ConclusionsIn cases of M2 occlusions, prior IVT combined with MT resulted in better functional outcome than MT alone, without increasing the rate of hemorrhagic or procedural complications. These results suggest the benefit of IVT in patients undergoing MT for M2 occlusions.

ImportanceThere is to date limited evidence that revascularization strategies are associated with improved functional outcome in children with acute ischemic stroke (AIS).ObjectivesTo report clinical outcomes and provide estimates of revascularization strategy safety and efficacy profiles of intravenous thrombolysis (IVT) and/or endovascular treatment (EVT) in children with AIS.Design, Setting, and ParticipantsThe KidClot multicenter nationwide cohort study retrospectively collected data of children (neonates excluded) with AIS and recanalization treatment between January 1, 2015, and May 31, 2018. Data analysis was performed from January 1, 2015, to May 31, 2019.ExposureIVT and/or EVT.Main Outcomes and MeasuresPrimary outcome was day 90 favorable outcome (modified Rankin Scale [mRs] 0-2, with 0 indicating no symptoms and 6 indicating death). Secondary end points included 1-year favorable outcome (mRs, 0-2), mortality, and symptomatic intracerebral hemorrhage. Other measures included the Pediatric National Institutes of Health Stroke Scale (pedNIHSS), with pedNIHSS 0 indicating no symptoms, 1 to 4 corresponding to a minor stroke, 5 to 15 corresponding to a mild stroke, greater than 15 to 20: severe stroke, and the adult Alberta Stroke Program Early CT Score (ASPECTS), which provides segmental assessment of the vascular territory, with 1 point deducted from the initial score of 10 for every region involved (from 10 [no lesion] to 0 [maximum lesions]).ResultsOverall, 68 children were included in 30 centers (IVT [n = 44]; EVT [n = 40]; 44 boys [64.7%]; median [IQR] age, 11 [4-16] years; anterior circulation involvement, 57 [83.8%]). Median (IQR) pedNIHSS score at admission was 13 (7-19), higher in the EVT group at 16 (IQR, 10-20) vs 9 (6-17) in the IVT only group (P P = .04). Median admission ASPECTS score was 8 (IQR, 6-9). The main stroke etiologies were cardioembolic (21 [30.9%]) and focal cerebral arteriopathy (17 [25.0%]). Median (IQR) time from stroke onset to IVT was 3 hours and 30 minutes (IQR, 2 hours and 33 minutes to 4 hours and 28 minutes). In the EVT group, the rate of postprocedure successful reperfusion (≥modified Treatment in Cerebral Infarction 2b) was 80.0% (32 of 40). Persistent proximal arterial stenosis was more frequent in focal cerebral arteriopathy (P Conclusions and RelevanceThe findings of this cohort study suggest that use of EVT and/or IVT is safe in children with AIS.

Background Whether thrombectomy alone is equally as effective as intravenous alteplase plus thrombectomy remains controversial. We aimed to determine whether thrombectomy alone would be non-inferior to intravenous alteplase plus thrombectomy in patients presenting with acute ischaemic stroke. Methods In this multicentre, randomised, open-label, blinded-outcome trial in Europe and Canada, we recruited patients with stroke due to large vessel occlusion confirmed with CT or magnetic resonance angiography admitted to endovascular centres. Patients were randomly assigned (1:1) via a centralised web server using a deterministic minimisation method to receive stent-retriever thrombectomy alone or intravenous alteplase plus stent-retriever thrombectomy. In both groups, thrombectomy was initiated as fast as possible with any commercially available Solitaire stent-retriever revascularisation device (Medtronic, Irvine, CA, USA). In the combined treatment group, intravenous alteplase (0.9 mg/kg bodyweight, maximum dose 90 mg per patient) was administered as early as possible after randomisation for 60 min with 10% of the calculated dose given as an initial bolus. Personnel assessing the primary outcome were masked to group allocation; patients and treating physicians were not. The primary binary outcome was a score of 2 or less on the modified Rankin scale at 90 days. We assessed the non-inferiority of thrombectomy alone versus intravenous alteplase plus thrombectomy in all randomly assigned and consenting patients using the one-sided lower 95% confidence limit of the Mantel-Haenszel risk difference, with a prespecified non-inferiority margin of 12%. The main safety endpoint was symptomatic intracranial haemorrhage assessed in all randomly assigned and consenting participants. This trial is registered with ClinicalTrials.gov, NCT03192332, and is closed to new participants. Findings Between Nov 29, 2017, and May 7, 2021, 5215 patients were screened and 423 were randomly assigned, of whom 408 (201 thrombectomy alone, 207 intravenous alteplase plus thrombectomy) were included in the primary efficacy analysis. A modified Rankin scale score of 0-2 at 90 days was reached by 114 (57%) of 201 patients assigned to thrombectomy alone and 135 (65%) of 207 patients assigned to intravenous alteplase plus thrombectomy (adjusted risk difference -7 .3%, 95% CI -16.6 to 2.1, lower limit of one-sided 95% CI -15.1%, crossing the non-inferiority margin of - 12%). Symptomatic intracranial haemorrhage occurred in five (2%) of 201 patients undergoing thrombectomy alone and seven (3%) of 202 patients receiving intravenous alteplase plus thrombectomy ( risk difference -1.0%, 95% CI -4.8 to 2 .7). Successful reperfusion was less common in patients assigned to thrombectomy alone (182 [ 91%] of 201 vs 199 [96%] of 207, risk difference -5.1%, 95% CI -10.2 to 0. 0, p=0.047). Interpretation Thrombectomy alone was not shown to be non-inferior to intravenous alteplase plus thrombectomy and resulted in decreased reperfusion rates. These results do not support omitting intravenous alteplase before thrombectomy in eligible patients. Copyright (C) 2022 Elsevier Ltd. All rights reserved.

BACKGROUND While randomized clinical trials have shown the benefit of thrombolysis and endovascular thrombectomy (EVT) in patients with acute ischemic stroke (AIS), we aimed to describe in a real-life study the differences between older (>80 years old) and younger patients treated for AIS. METHODS Thousand patients treated with thrombolysis and/or EVT were consecutively included in a prospective monocentric database (admitted from December 2015 to May 2019 in our comprehensive stroke center). Demographic data with detailed history, baseline physical examinations and treatments, laboratory and imaging data, prestroke functional status, and outcome 3 months after stroke were analyzed. RESULTS Older patients (n = 357) had more baseline comorbidities and lower levels of prestroke independence (modified Rankin scale ≤2; 67.2% vs. 96.1%) and more severe strokes (median National Institute of Health Stroke Score [NIHSS] 15 vs. 12; p

Background Atypical fibromuscular dysplasia (AFMD), also known as carotid web, is a rare underdiagnosed shelf-like fibrous tissue arising from the posterior carotid artery bulb that is a cause of cryptogenic stroke of the anterior cerebral vascularization. Despite the recurrence and severity of strokes caused by embolization associated with AFMD, there are no recommendations on the best strategy to manage single and bilateral lesions, which have unsatisfactory outcomes when treated with medical treatment exclusively. Methods From January 2016 to April 2019, 365 patients were operated on for a carotid stenosis in our institution. This cohort included 11 patients (3%), with a median age of 41 years (range, 39-51 years), referred by a stroke unit, treated for a symptomatic (10 strokes and 1 recurrent transient ischemic attack) AFMD lesion. Preoperative workup revealed a contralateral similar lesion in 45% of patients (5/11), which all also underwent surgery during a subsequent hospitalization. The diagnosis was confirmed by histologic examination when open surgery was performed. The 30-day and 1-year outcomes were retrospectively reviewed. Results Of the 16 AFMD lesions operated, 13 were treated by open surgery (2 by classic endarterectomy and 11 by internal carotid resection-anastomosis) and 3 by carotid artery stenting, respectively, with a mean delay of 85.5 days and 20.5 days after the latest stroke. There was one complication after stenting (external iliac rupture) that was treated by a covered stent, and no perioperative complications after open surgery. The follow-ups at 30 days and 1 year were uneventful for all patients, without any deaths or stroke recurrences. Conclusions Symptomatic AFMD is a rare cause of cryptogenic stroke. Bilateral lesions are frequent. Early intervention is associated with favorable perioperative and 1-year outcomes. Open surgery is the first-line therapeutic option in this young patient population.

Background: Behçet’s disease (BD) is a rare form of vasculitis involving both veins and arteries of all calibers. Psychological symptoms and cognitive impairment appear to be frequent, but few data are available. Methods: All consecutive patients in our center fulfilling the 2013 BD criteria underwent a psychometric evaluation with auto- (SCL-90-R and Modified Fatigue Index) and hetero-questionnaires (MINI). A standardized test battery assessed cognitive dysfunction. Data were correlated with BD activity as well as quality of life (SF-36). Results: We included 20 consecutive patients (16 men, four women) with a median [IQR] age of 38 (30.0–45.5) and a median disease duration of 7 years (1.8–11.0). Five patients had an abnormal brain MRI. The SCL-90-R questionnaire highlighted eight psychopathological profiles (42.1%) that correlated with altered quality of life and more severe fatigue. The most frequent symptoms were anxiety (9/19, 47.4%), somatization (8/19, 42.1%) and phobia (5/19, 26.3%). Psychopathological symptoms appeared to be more severe, but not more frequent, in neuro-Behçet’s patients. Based on standardized cognitive evaluation, nine patients had cognitive impairment defined by three or more altered tests. Notably, 6/9 patients did not have any complaint of memory loss and were thus considered ansognostic. Conclusion: Cognitive involvement was significantly associated with BD activity score (BSAS) but not with brain MRI abnormalities.

Symptomatic intracerebral hemorrhage (sICH) is a common complication of acute ischemic stroke (AIS) associated with limited treatments and poor outcomes. We aimed to identify predictive factors of sICH in patients with AIS following mechanical thrombectomy (MT) in a real-world setting. Patients with large vessel occlusion of the anterior circulation treated with MT were consecutively included in a prospective monocentric cohort. Clinical, biological, and radiological parameters were collected to identify pre-procedural predictors for sICH. 637 patients were included in our study. Magnetic resonance imaging was performed on most patients (86.7%). sICH occurred in 55 patients (8.6%). 428 patients (67.2%) were treated with intravenous thrombolysis. After multivariate analysis, prior use of antiplatelet therapies (odd ratio (OR) 1.84, 95% confidence interval (CI) 1.01–3.32), high C-reactive protein (OR per standard deviation (SD) increase 1.28, 95% 1.01–1.63), elevated mean arterial blood pressure (OR per 10 mmHg increase 1.22, 95% CI 1.03–1.44), hyperglycemia (OR per one SD-log increase 1.38, 95% CI 1.02–1.87), and low ASPECTS (OR per 1-point decrease 1.42, 95% CI 1.12–1.80) were found to be independent predictive factors of sICH. The pre-procedural predictors did not change when the absence of successful recanalization was considered as a covariate. Patients with strokes of unknown onset time were not especially vulnerable for sICH. sICH after MT was associated with several pre-procedural risk factors: prior use of antiplatelet therapies, high C-reactive protein and hyperglycemia at baseline, elevated mean arterial blood pressure, and low ASPECTS.

To determine whether reversal of DWI lesions (DWIr) on the DWI-ASPECTS (diffusion weighted imaging Alberta Stroke Program CT Score) template should serve as a predictor of 90-day clinical outcome in acute ischemic stroke (AIS) patients with pretreatment diffusion-weighted imaging (DWI)-ASPECTS 0-5 treated with thrombectomy, and to determine its predictors in current practice.We analyzed data of all consecutive patients included in the prospective multicenter national Endovascular Treatment in Ischemic Stroke Registry between 1 January 2015 and 31 December 2020 with a premorbid mRS ≤ 2, who presented with a pretreatment DWI-ASPECTS 0-5 score, underwent thrombectomy and had an available 24 h post-interventional MRI follow-up. Multivariable analyses were performed to evaluate the clinical impact of DWIr on early neurological improvement (ENI), 3‑month modified Rankin scale (mRS) score distribution (shift analysis) and to define independent predictors of DWIr.Early neurological improvement was detected in 82/211 (41.7%) of patients while 3‑month functional independence was achieved by 75 (35.5%) patients. The DWI reversal (39/211, 18.9%) resulted an independent predictor of both ENI (aOR 3.6, 95% CI 1.2-7.7; p 0.018) and 3‑month clinical outcome (aOR for mRS shift: 2.2, 95% CI 1-4.6; p 0.030). Only successful recanalization (mTICI 2c-3) independently predicted DWIr in the studied population (aOR 3.3, 95% CI 1.3-7.9; p 0.009).The DWI reversal occurs in a non-negligible proportion of DWI-ASPECTS 0-5 patients subjected to thrombectomy and significantly influences clinical outcome. The mTICI 2c-3 recanalization emerged as an independent DWIr predictor.

Background: We recently reported a worrying 30% rate of early neurological deterioration (END) occurring within 24 hours following intravenous thrombolysis (IVT) in minor stroke with isolated internal carotid artery occlusion (ie, without additional intracranial occlusion), mainly due to artery-to-artery embolism. Here, we hypothesize that in this setting IVT—as compared to no-IVT—may foster END, in particular by favoring artery-to-artery embolism from thrombus fragmentation. Methods: From a large multicenter retrospective database, we compared minor stroke (National Institutes of Health Stroke Scale score 7d ) and 3-month modified Rankin Scale score 0 to 1. Results: Overall, 189 patients were included (IVT=95; antithrombotics=94 [antiplatelets, n=58, anticoagulants, n=36]) from 34 centers. END within 24 hours and END 7d occurred in 46 (24%) and 60 (32%) patients, respectively. Baseline clinical and radiological variables were similar between the 2 groups, except significantly higher National Institutes of Health Stroke Scale (median 3 versus 2) and shorter onset-to-imaging (124 versus 149min) in the IVT group. END within 24 hours was more frequent following IVT (33% versus 16%, adjusted hazard ratio, 2.01 [95% CI, 1.07–3.92]; P =0.03), driven by higher odds of artery-to-artery embolism (20% versus 9%, P =0.09). However, END 7d and 3-month modified Rankin Scale score of 0 to 1 did not significantly differ between the 2 groups (END 7d : adjusted hazard ratio, 1.29 [95% CI, 0.75–2.23]; P =0.37; modified Rankin Scale score of 0–1: adjusted odds ratio, 1.1 [95% CI, 0.6–2.2]; P =0.71). END 7d occurred earlier in the IVT group: median imaging-to-END 2.6 hours (interquartile range, 1.9–10.1) versus 20.4 hours (interquartile range, 7.8–34.4), respectively, P Conclusions: In our population of minor strokes with iICAO, although END rate at 7 days and 3-month outcome were similar between the 2 groups, END—particularly END due to artery-to-artery embolism—occurred earlier following IVT. Prospective studies are warranted to further clarify the benefit/risk profile of IVT in this population.

ObjectiveAdolescence represents a transition period between childhood and adulthood, and only limited information exists about stroke characteristics in this population. Our aim was to describe the clinical and neuroradiologic features, etiologies, initial management, and outcome of ischemic stroke in adolescents.MethodsThis retrospective cohort study evaluated all consecutive patients 10 to 18 years with a first-ever ischemic stroke hospitalized between 2007 and 2017 in 10 French academic centers representing a population of ≈10 million. Extracted data from the national database served as validation.ResultsA total of 60 patients were included (53% male, median age 15.2 years). Diagnosis at first medical contact was misevaluated in 36%, more frequently in posterior than anterior circulation strokes (55% vs 20% respectively, odds ratio 4.8, 95% confidence interval 1.41–16.40, p = 0.01). Recanalization treatment rate was high (n = 19, 32%): IV thrombolysis (17%), endovascular therapy (11.7%), or both IV and intra-arterial thrombolysis (3.3%); safety was good (only 1 asymptomatic hemorrhagic transformation). Despite thorough etiologic workup, 50% of strokes remained cryptogenic. The most common determined etiologies were cardioembolism (15%), vasculitis and autoimmune disorders (12%, occurring exclusively in female patients), and arterial dissections (10%, exclusively in male patients). Recurrent ischemic cerebrovascular events occurred in 12% (median follow-up 19 months). Recurrence rate was 50% in patients with identified vasculopathy but 0% after cryptogenic stroke. Functional outcome was favorable (Rankin Scale score 0–2 at day 90) in 80% of cases.ConclusionsIschemic strokes in adolescents harbor both pediatric and adult features, emphasizing the need for multidisciplinary collaboration in their management. Recanalization treatments appear feasible and safe.

The best treatment for acute ischemic stroke (AIS) due to isolated cervical internal carotid artery occlusion (CICAO) (i.e., without associated occlusion of the circle of Willis) is still unknown. In this study, we aimed to describe EVT safety and clinical outcome in patients with CICAO.We analyzed data of all consecutive patients, included in the Endovascular Treatment in Ischemic Stroke (ETIS) Registry between 2013 and 2020, who presented AIS and proven CICAO on angiogram and underwent EVT. We assessed carotid recanalization, procedural complications, National Institutes of Health Stroke Scale (NIHSS) at 24 h post-EVT, and 3-month favorable outcome (modified Rankin Scale, mRS ≤ 2 or equal to the pre-stroke value).Forty-five patients were included (median age: 70 years; range: 62-82 years). The median NIHSS before EVT was 14 (9-21). Carotid stenting was performed in 23 (51%) patients. Carotid recanalization at procedure end and on control imaging was observed in 37 (82%) and 29 (70%) patients, respectively. At day 1 post-EVT, the NIHSS remained stable or decreased in 25 (60%) patients; 12 (29%) patients had early neurologic deterioration (NIHSS ≥ 4 points). The rate of procedural complications was 36%, including stent thrombosis (n = 7), intracranial embolism (n = 7), and symptomatic intracranial hemorrhage (n = 1). At 3 months, 18 (40%) patients had a favorable outcome, and 10 (22%) were dead.Our study suggests that EVT in AIS patients with moderate/severe initial deficit due to CICAO led to high rate of recanalization at day 1, and a 40% rate of favorable outcome at 3 months. There was a high rate of procedural complication which is of concern. Randomized controlled trials assessing the superiority of EVT in patients with CICAO and severe deficits are needed.

Importance The best reperfusion strategy in patients with acute minor stroke and large vessel occlusion (LVO) is unknown. Accurately predicting early neurological deterioration of presumed ischemic origin (ENDi) following intravenous thrombolysis (IVT) in this population may help to select candidates for immediate transfer for additional thrombectomy. Objective To develop and validate an easily applicable predictive score of ENDi following IVT in patients with minor stroke and LVO. Design, Setting, and Participants This multicentric retrospective cohort included 729 consecutive patients with minor stroke (National Institutes of Health Stroke Scale [NIHSS] score of 5 or less) and LVO (basilar artery, internal carotid artery, first [M1] or second [M2] segment of middle cerebral artery) intended for IVT alone in 45 French stroke centers, ie, including those who eventually received rescue thrombectomy because of ENDi. For external validation, another cohort of 347 patients with similar inclusion criteria was collected from 9 additional centers. Data were collected from January 2018 to September 2019. Main Outcomes and Measures ENDi, defined as 4 or more points' deterioration on NIHSS score within the first 24 hours without parenchymal hemorrhage on follow-up imaging or another identified cause. Results Of the 729 patients in the derivation cohort, 335 (46.0%) were male, and the mean (SD) age was 70 (15) years; of the 347 patients in the validation cohort, 190 (54.8%) were male, and the mean (SD) age was 69 (15) years. In the derivation cohort, the median (interquartile range) NIHSS score was 3 (1-4), and the occlusion site was the internal carotid artery in 97 patients (13.3%), M1 in 207 (28.4%), M2 in 395 (54.2%), and basilar artery in 30 (4.1%). ENDi occurred in 88 patients (12.1%; 95% CI, 9.7-14.4) and was strongly associated with poorer 3-month outcomes, even in patients who underwent rescue thrombectomy. In multivariable analysis, a more proximal occlusion site and a longer thrombus were independently associated with ENDi. A 4-point score derived from these variables-1 point for thrombus length and 3 points for occlusion site-showed good discriminative power for ENDi (C statistic = 0.76; 95% CI, 0.70-0.82) and was successfully validated in the validation cohort (ENDi rate, 11.0% [38 of 347]; C statistic = 0.78; 95% CI, 0.70-0.86). In both cohorts, ENDi probability was approximately 3%, 7%, 20%, and 35% for scores of 0, 1, 2 and 3 to 4, respectively. Conclusions and Relevance The substantial ENDi rates observed in these cohorts highlights the current debate regarding whether to directly transfer patients with IVT-treated minor stroke and LVO for additional thrombectomy. Based on the strong associations observed, an easily applicable score for ENDi risk prediction that may assist decision-making was derived and externally validated.

Background and ObjectivesWe aimed to analyze the epidemiologic, clinical, and paraclinical features of adolescents with cerebral venous thrombosis (CVT) and its therapeutic management and outcome.MethodsThis multicenter retrospective cohort included patients 10 to 18 years of age hospitalized for a first episode of CVT in 2 French regions between 1999 and 2019. The number of cases was compared to the number recorded by the French health insurance system. The CVT registry of the Lariboisière hospital allowed comparisons with adults.ResultsOne hundred two patients were included (52.9% female; median age 15.1 years). Estimated incidence was 0.37 to 0.38 per 100,000 adolescents per year; 45.5% of patients presented with focal deficits or seizures or in a coma. Male patients were younger than female patients (14.2 vs 15.6 years; p < 0.01) and more often admitted to intensive care (52.1% vs 24.1%; p = 0.0,035). The lateral sinus was the most common CVT location (72.3%), and 29.4% of adolescents had associated venous infarction or hematoma. Most patients (94.1%) received anticoagulation. Treatment also included an endovascular procedure (2.9%), decompressive craniectomy (4.9%), and CSF shunt (6.9%). The most frequently identified CVT-associated condition was local infection in male (18.6%) and systemic disease in female (14.8%; p < 0.001) patients. The proportion of CVTs in adolescents without an identified associated condition or risk factor was low (1.9% vs 11.4% in adults; p < 0.002). Adverse outcome at 1 year was more frequent than in adults (33.3% vs 11.8%; p = 0.0,001).DiscussionCVT in adolescents is rare and complex with specific epidemiology, including differences in clinical presentation and associated conditions between sexes, and more severe outcomes than in adults. Careful specialized management and follow-up are therefore recommended.

Background and Purpose: Ischemic stroke has been reported in various conditions associated with eosinophilia. FIP1L1-PDGFRA fusion ([Fip1-like 1-platelet-derived growth factor receptor alpha]; F/P ) leads to the proliferation of the eosinophilic lineage and thus to a clonal hypereosinophilic syndrome that is highly responsive to imatinib. Methods: We previously reported on a nationwide retrospective study of 151 patients with F/P -associated clonal hypereosinophilic syndrome. Patients from this cohort with a clinical history of ischemic stroke (as well as 2 additional cases) were further analyzed to better define their clinical picture and outcomes. Results: Sixteen male patients (median age, 51 [43–59] years) with low-to-intermediate cardiovascular risk were included. Median National Institutes of Health Stroke Scale was 4 (range, 1–6). Most cerebral imaging disclosed multiple bilateral infarctions of watershed distribution (69%). Despite frequent cardiac involvement (50%), cardiac thrombus was evidenced in a single patient and, according to the TOAST classification (Trial of ORG 10172 in Acute Stroke Treatment), 62.5% of strokes were presumably of undetermined etiology. Among the 15 patients treated with imatinib, and after a median follow-up of 4.5 years, stroke recurred in only 3 patients (consisting of either cardio embolic or hemorrhagic events, unrelated to the first episode). Conclusions: F/P + clonal hypereosinophilic syndrome is a diagnosis to consider in patients with unexplained ischemic stroke and hypereosinophilia (especially in the setting of multiple cortical borderzone distribution) and warrants prompt initiation of imatinib.

Background and ObjectivesTo investigate in routine care the efficacy and safety of IV thrombolysis (IVT) with tenecteplase prior to mechanical thrombectomy (MT) in patients with large vessel occlusion acute ischemic strokes (LVO-AIS), either secondarily transferred after IVT or directly admitted to a comprehensive stroke center (CSC).MethodsWe retrospectively analyzed clinical and procedural data of patients treated with 0.25 mg/kg tenecteplase within 270 minutes of LVO-AIS who underwent brain angiography. The main outcome was 3-month functional independence (modified Rankin Scale score ≤2). Recanalization (revised Treatment in Cerebral Ischemia score 2b–3) was evaluated before (pre-MT) and after MT (final).ResultsWe included 588 patients (median age 75 years [interquartile range (IQR) 61–84]; 315 women [54%]; median NIH Stroke Scale score 16 [IQR 10–20]), of whom 520 (88%) were secondarily transferred after IVT. Functional independence occurred in 47% (n = 269/570; 95% confidence interval [CI] 43.0–51.4) of patients. Pre-MT recanalization occurred in 120 patients (20.4%; 95% CI 17.2–23.9), at a similar rate across treatment paradigms (direct admission, n = 14/68 [20.6%]; secondary transfer, n = 106/520 [20.4%]; p > 0.99) despite a shorter median IVT to puncture time in directly admitted patients (38 [IQR 23–55] vs 86 [IQR 70–110] minutes; p < 0.001). Final recanalization was achieved in 492 patients (83.7%; 95%CI 80.4–86.6). Symptomatic intracerebral hemorrhage occurred in 2.5% of patients (n = 14/567; 95% CI 1.4–4.1).DiscussionsTenecteplase before MT is safe, effective, and achieves a fast recanalization in everyday practice in patients secondarily transferred or directly admitted to a CSC, in line with published results. These findings should encourage its wider use in bridging therapy.Classification of EvidenceThis study provides Class IV evidence that tenecteplase within 270 minutes of LVO-AIS increases the probability of functional independence.

Background and Purpose: The influence of prior antiplatelet therapy (APT) uses on the outcomes of patients with acute ischemic stroke treated with endovascular therapy is unclear. We compared procedural and clinical outcomes of endovascular therapy in patients on APT or not before stroke onset. Methods: We analyzed 2 groups from the ongoing prospective multicenter Endovascular Treatment in Ischemic Stroke registry in France: patients on prior APT (APT+) and patients without prior APT (APT−) treated by endovascular therapy, with and without intravenous thrombolysis. Multilevel mixed-effects logistic models including center as random effect were used to compare angiographic (rates of reperfusion at the end of procedure, procedural complications) and clinical (favorable and excellent outcome, 90-day all-cause mortality, and hemorrhagic complications) outcomes according to APT subgroups. Comparisons were adjusted for prespecified confounders (age, admission National Institutes of Health Stroke Scale score, Alberta Stroke Program Early CT Score, intravenous thrombolysis, and time from onset to puncture), as well as for meaningful baseline between-group differences. Results: A total of 2939 patients were analyzed, of whom 877 (29.8%) were on prior APT. Patients with prior APT were older, had more frequent vascular risk factors, cardioembolic stroke mechanism, and prestroke disability. Rates of complete reperfusion (37.9% in the APT− group versus 42.7 % in the APT+ group; aOR, 1.09 [95% CI, 0.88–1.34]; P =0.41) and periprocedural complication (16.9% versus 13.3%; aOR, 0.90 [95% CI, 0.7–1.2]; P =0.66) did not differ between the two groups. Symptomatic intracerebral hemorrhage (aOR, 0.93 [95% CI, 0.63–1.37]; P =0.73), 3 months favorable clinical outcome (modified Rankin Scale score of 0–2; aOR, 0.98 [95% CI, 0.77–1.25]; P =0.89), and mortality (aOR, 0.95 [95% CI, 0.72–1.26]; P =0.76) at 90 days did not differ between the groups. Conclusions: Prior APT does not influence angiographic and functional outcomes following endovascular therapy and should not be taken into account for acute revascularization strategies.

BackgroundIt is unknown whether collateral status modifies the effect of pretreatment intravenous thrombolysis (IVT) on the outcomes of patients with large vessel occlusions treated with endovascular therapy (EVT). We aimed to assess whether collateral status modifies the effect of IVT on the outcomes of EVT in clinical practice.MethodsWe used data from the ongoing prospective multicentric Endovascular Treatment in Ischemic Stroke (ETIS) Registry in France. Patients with anterior circulation proximal large vessel occlusions treated with EVT within 6 hours of symptom onset were enrolled. Patients were divided into two groups based on pretreatment with IVT. The two groups were matched based on baseline characteristics. We tested the interaction between collateral status and IVT in unadjusted and adjusted models.ResultsA total of 1589 patients were enrolled in the study, of whom 55% received IVT. Using a propensity score matching method, 724 no IVT patients were matched to 549 IVT patients. In propensity score weighted analysis, IVT was associated with higher odds of early neurological improvement (OR 1.74; 95% CI 1.33 to 2.26), favorable functional outcome (OR 1.66; 95% CI 1.23 to 2.24), excellent functional outcome (OR 2.04; 95% CI 1.47 to 2.83), and successful reperfusion (OR 2.18; 95% CI 1.51 to 3.16). IVT was not associated with mortality or hemorrhagic complications. There was no interaction between collateral status and IVT association with any of the outcomes.ConclusionsCollateral status does not modify the effect of pretreatment IVT on the efficacy and safety outcomes of EVT.

To compare outcomes of minor stroke patients with intracranial vessel occlusions (IVO) underwent mechanical thrombectomy (MT) versus those treated with intravenous thrombolysis alone (IVT).We retrospectively reviewed two large prospective stroke databases from two European centers searching for patients admitted with minor stroke (i.e. NIHSS Score░≤░5), baseline mRS░=░0 and occlusion of the M1-M2 segment of the middle cerebral artery (MCA). Groups receiving (A) IVT alone and (B) MT+/-IVT were compared. Primary outcome measures were MT safety, successful recanalization rate (mTICI 2b-3) and NIHSS shift (discharge NIHSS minus admission NIHSS); secondary outcomes included discharge rates and excellent outcome (mRS 0-1) at 3 months. Univariate and multivariate analyses were performed.Thirty-two patients were enrolled in Group B (19░MT alone; 13 MT░+░IVT) and 24 in Group A. Successful recanalization (mTICI 2b-3) was obtained in 100% of cases in Group B vs 38% in Group A. Symptomatic hemorrhagic transformation rate did not differ between the two groups. Multivariate analysis reported MT as the only predictor of early (░12░h) favorable NIHSS shift and lower NIHSS at discharge. Moreover, discharge at home and excellent outcome at 3-month follow-up were statistically associated with MT.MT in patients with minor strokes and intracranial vessel occlusion (IVO) is safe and can determine a rapid improvement of NIHSS Score. MT seems also associated with a higher rate of patients discharged at home after hospitalization and better clinical outcome at 3-month follow-up. Larger randomized trials are warranted to confirm these results.

Neurological immune-related adverse events are complications of programmed-cell death 1 or programmed-cell death 1 ligand immunotherapies that can be life threatening and often lead to anticancer immunotherapy withdrawal. Scant clinical data are available that integrate the clinical presentation, therapeutic management and long-term outcome. All consecutive adult patients treated by programmed-cell death 1 or programmed-cell death 1 ligand immunotherapies, given alone or in combination with other treatment, who experienced a neurological immune-related adverse event with a severity grade ≥2 in Paris Saclay-University hospitals were investigated from June 2014 to February 2019. The frequency of neurological immune-related adverse events was calculated from the prospective Registre des Effets Indésirables Sévères des Anticorps Monoclonaux Immunomodulateurs en Cancérologie cohort. Forty patients presenting with 51 distinct neurological immune-related adverse events were included. The prevalence of grade ≥2 neurological immune-related adverse events was estimated to be 1.22% in the Registre des Effets Indésirables Sévères des Anticorps Monoclonaux Immunomodulateurs en Cancérologie cohort. Among 40 patients with neurological immune-related adverse events, 65% received programmed-cell death 1 or programmed-cell death 1 ligand monotherapy and 35% received a combination of programmed-cell death 1 plus anti-CTLA4 (Common Terminology Criteria for Adverse Events). Clinical neurological presentations were peripheral (48%), central (35%), or mixed (18%). The severity of neurological immune-related adverse events was grade 2 for 14 (35%) and ≥grade 3 for 26 patients (65%). The mortality rate related to neurological immune-related adverse events was 8%. Corticosteroid treatment led to neurological recovery in 74%. Long-term follow-up highlighted that 53% of patients experienced long-term neurological sequelae. Five patients were rechallenged by programmed-cell death 1 monotherapy without recurrence of their neurological immune-related adverse event(s). Neurological immune-related adverse events induced by programmed-cell death 1 or programmed-cell death 1 ligand are rare but are severe with a mortality rate of 8% and long-term sequelae for 53% of patients. Corticosteroids should be started when neurological immunological complications are identified to avoid long-term sequelae., Plaçais et al. report a large case-series of 40 patients presenting with 51 neurological adverse events of immune checkpoint inhibitors, wherein corticosteroid therapy was associated with a 74% rate of neurological recovery. Neurological adverse events were severe, as 7.5% of the included patients died and 53% kept long-term neurological sequelae., Graphical Abstract Graphical Abstract

BackgroundThe predictors of successful reperfusion and the effect of reperfusion after endovascular treatment (EVT) for M2 occlusions have not been well studied. We aimed to identify predictors of successful reperfusion and the effect of reperfusion on outcomes of EVT for M2 occlusions in current practice.MethodsPatients with acute ischemic stroke due to isolated M2 occlusions who were enrolled in the prospective multicenter Endovascular Treatment in Ischemic Stroke (ETIS) Registry in France between January 2015 and March 2020 were included. The primary outcome was a favorable outcome, defined as modified Rankin Scale (mRS) score of 0–2 at 90 days. Successful reperfusion was defined as an improvement of ≥1 points in the modified Thrombolysis In Cerebral Infarction score between the first and the last intracranial angiogram.ResultsA total of 458 patients were included (median National Institutes of Health Stroke Scale (NIHSS) score 14; 61.4% received prior intravenous thrombolysis). Compared with the non-reperfused patients, reperfused patients had an increased rate of excellent outcome (OR 2.3, 95% CI 0.98 to 5.36; p=0.053), favorable outcome (OR 2.79, 95% CI 1.31 to 5.93; p=0.007), and reduced 90-day mortality (OR 0.39, 95% CI 0.19 to 0.79; pConclusionsSuccessful reperfusion of M2 occlusions reduced disability and mortality. However, safety is a concern, especially if the procedure failed.

Background and Purpose: Although the efficacy of endovascular treatment (EVT) in patients with anterior circulation ischemic stroke (AIS) is well documented, early neurological deterioration after EVT remains a serious issue associated with poor outcome. Besides obvious causes, such as lack of reperfusion, procedural complications, or parenchymal hemorrhage, early neurological deterioration may remain unexplained (UnEND). Our aim was to investigate predictors of UnEND after EVT in patients with AIS. Methods: Patients who underwent EVT for AIS, with an initial National Institutes of Health Stroke Scale score >5, Alberta Stroke Program Early CT Score ≥6, and included in a multicenter prospective observational registry were analyzed. Predictors of UnEND, defined as ≥4-point increase in the National Institutes of Health Stroke Scale score between baseline and day 1 after EVT, were determined via center-adjusted analyses. Results: Among the 1925 included in the analysis, 128 UnEND (6.6%) were recorded. In multivariate analysis, predictors of UnEND were diabetes mellitus (odds ratio [OR], 2.17 [95% CI, 1.32–3.56]), prestroke modified Rankin Scale score ≥2 (OR, 2.22 [95% CI, 1.09–4.55]), general anesthesia (OR, 2.55 [95% CI, 1.51–4.30]), admission systolic blood pressure (OR, 1.10 [95% CI, 1.01–1.20]), age (OR, 1.38 [95% CI, 1.14–1.67]), number of passes (OR, 1.16 [95% CI, 1.04–1.28]), direct admission or not to a comprehensive stroke center (OR, 0.49 [95% CI, 0.30–0.81]), and initial National Institutes of Health Stroke Scale score (OR, 0.65 [95% CI, 0.52–0.81]). Conclusions: Severely impaired AIS patients with nonmodifiable factors are more likely to develop UnEND. Some modifiable predictors of UnEND such as the number of EVT passes could be the object of improvement in AIS management.

BACKGROUND AND PURPOSE: Ischaemic stroke has been described in association with COVID-19. Several pathophysiological mechanisms have been suggested, i.e. prothrombotic state, cardiac injury etc. It was sought to assess the potential association between ischaemic stroke associated with SARS-CoV-2 infection and underlying atherosclerotic lesions. METHODS: A retrospective analysis of stroke related to large vessel occlusion was conducted amongst patients with SARS-CoV-2 infection and underlying mild atherosclerotic disease, between 19 March and 19 April 2020 in six different stroke centers in the Ile-de France area, France. RESULTS: The median age was 52 years, median body mass index was 29.5 kg/m2 . All patients displayed previous vascular risk factors such as high blood pressure, diabetes, dyslipidemia or body mass index > 25. The delay between the first respiratory symptoms of COVID-19 and stroke was 11.5 days. At baseline, all had tandem occlusions, i.e. intracerebral and extracerebral thrombus assessed with computed tomography or magnetic resonance imaging. Cases displayed a large thrombus in the cervical carotid artery with underlying mild non-stenosing atheroma, after an etiological workup based on angio-computed tomography or magnetic resonance imaging and/or cervical echography. CONCLUSION: Our study should alert clinicians to scrutinize any new onset of ischaemic stroke during COVID-19 infection, mainly in patients with vascular risk factors or underlying atherosclerotic lesions.

BackgroundCerebral cavernous malformations (CCMs) are vascular malformations mostly located within the central nervous system. Most deleterious variants are loss of function mutations in one of the three CCM genes. These genes code for proteins that form a ternary cytosolic complex with CCM2 as a hub. Very few CCM2 missense variants have been shown to be deleterious by modifying the ternary CCM complex stability.ObjectivesTo investigate the causality of novel missense CCM2 variants detected in patients with CCM.MethodsThe three CCM genes were screened in 984 patients referred for CCM molecular screening. Interaction between CCM1 and CCM2 proteins was tested using co-immunoprecipitation experiments for the CCM2 missense variants located in the phosphotyrosine binding (PTB) domain.Results11 distinct CCM2 rare missense variants were found. Six variants predicted to be damaging were located in the PTB domain, four of them were novel. When co-transfected with CCM1 in HEK293T cells, a loss of interaction between CCM1 and CCM2 was observed for all six variants.ConclusionWe showed, using co-immunoprecipitation experiments, that CCM2 missense variants located in the PTB domain were actually damaging by preventing the normal interaction between CCM1 and CCM2. These data are important for diagnosis and genetic counselling, which are challenging in patients harbouring such variants.

Background and Purpose: The efficiency of prehospital care chain response and the adequacy of hospital resources are challenged amid the coronavirus disease 2019 (COVID-19) outbreak, with suspected consequences for patients with ischemic stroke eligible for mechanical thrombectomy (MT). Methods: We conducted a prospective national-level data collection of patients treated with MT, ranging 45 days across epidemic containment measures instatement, and of patients treated during the same calendar period in 2019. The primary end point was the variation of patients receiving MT during the epidemic period. Secondary end points included care delays between onset, imaging, and groin puncture. To analyze the primary end point, we used a Poisson regression model. We then analyzed the correlation between the number of MTs and the number of COVID-19 cases hospitalizations, using the Pearson correlation coefficient (compared with the null value). Results: A total of 1513 patients were included at 32 centers, in all French administrative regions. There was a 21% significant decrease (0.79; [95%CI, 0.76–0.82]; P P P R 2 −0.51; P =0.04). Patients treated during the COVID outbreak were less likely to receive intravenous thrombolysis and to have unwitnessed strokes (both P Conclusions: Our study showed a significant decrease in patients treated with MTs during the first stages of the COVID epidemic in France and alarming indicators of lengthened care delays. These findings prompt immediate consideration of local and regional stroke networks preparedness in the varying contexts of COVID-19 pandemic evolution.

Summary Background S44819, a selective GABAA α5 receptor antagonist, reduces tonic post-ischaemic inhibition of the peri-infarct cortex. S44819 improved stroke recovery in rodents and increased cortical excitability in a transcranial magnetic stimulation study in healthy volunteers. The Randomized Efficacy and Safety Trial of Oral GABAA α5 antagonist S44819 after Recent ischemic Event (RESTORE BRAIN) aimed to evaluate the safety and efficacy of S44819 for enhancing clinical recovery of patients with ischaemic stroke. Methods RESTORE BRAIN was an international, randomised, double-blind, parallel-group, placebo-controlled, multicentre phase 2 trial that evaluated the safety and efficacy of oral S44189 in patients with recent ischaemic stroke. The study was done in specialised stroke units in 92 actively recruiting centres in 14 countries: ten were European countries (Belgium, Czech Republic, France, Germany, Hungary, Italy, Netherlands, Poland, Spain, and the UK) and four were non-European countries (Australia, Brazil, Canada, and South Korea). Patients aged 18–85 years with acute ischaemic stroke involving cerebral cortex (National Institute of Health Stroke Scale [NIHSS] score 7–20) without previous disability were eligible for inclusion. Participants were randomly assigned to receive 150 mg S44819 twice a day, 300 mg S44819 twice a day, or placebo twice a day by a balanced, non-adaptive randomisation method with a 1:1:1 ratio. Treatment randomisation and allocation were centralised via the interactive web response system using computer-generated random sequences with a block size of 3. Blinding of treatment was achieved by identical appearance and taste of all sachets. Patients, investigators and individuals involved in the analysis of the trial were masked to group assignment. The primary endpoint was the modified Rankin Scale (mRS) score 90 days from onset of treatment, evaluated by shift analysis (predefined main analysis) or by dichotomised analyses using 0–1 versus 2–6 and 0–2 versus 3–6 cutoffs (predefined secondary analysis). Secondary endpoints were the effects of S44819 on the NIHSS and Montreal Cognitive Assessment (MoCA) scores, time needed to complete parts A and B of the Trail Making Test, and the Barthel index. Efficacy analyses were done on all patients who received at least one dose of treatment and had at least one mRS score taken after day 5 (specifically, on or after day 30). Safety was compared across treatment groups for all patients who received at least one dose of treatment. The study was registered at ClinicalTrials.gov , NCT02877615 . Findings Between Dec 19, 2016, and Nov 16, 2018, 585 patients were enrolled in the study. Of these, 197 (34%) were randomly assigned to receive 150 mg S44819 twice a day, 195 (33%) to receive 300 mg S44819 twice a day, and 193 (33%) to receive placebo twice a day. 189 (96%) of 197 patients in the 150 mg S44819 group, 188 (96%) of 195 patients in the 300 mg S44819 group, and 191 (99%) patients in the placebo group received at least one dose of treatment and had at least one mRS score taken after day 5, and were included in efficacy analyses. 195 (99%) of 197 patients in the 150 mg S44819 group, 194 (99%) of 195 patients in the 300 mg S44819 group, and 193 (100%) patients in the placebo group received at least one dose of treatment, and were included in safety analyses. The primary endpoint of mRS at day 90 did not differ between each of the two S44819 groups and the placebo group (OR 0·91 [95% CI 0·64–1·31]; p=0·80 for 150 mg S44819 compared with placebo and OR 1·17 [95% CI 0·81–1·67]; p=0·80 for 300 mg S44819 compared with placebo). Likewise, dichotomised mRS scores at day 90 (mRS 0–2 vs 3–6 or mRS 0–1 vs 2–6) did not differ between groups. Secondary endpoints did not reveal any significant group differences. The median NIHSS score at day 90 did not differ between groups (4 [IQR 2–8] in 150 mg S44819 group, 4 [2–7] in 300 mg S44819 group, and 4 [2–6] in placebo group), nor did the number of patients at day 90 with an NIHSS score of up to 5 (95 [61%] of 156 in 150 mg S44819 group, 106 [66%] of 161 in 300 mg S44819 group, and 104 [66%] of 157 in placebo group) versus more than 5 (61 [39%] in 150 mg S44819 group, 55 [34%] in 300 mg S44819 group, and 53 [34%] in placebo group). Likewise, the median MoCA score (22·0 [IQR 17·0–26·0] in 150 mg S44819 group, 23·0 [19·0–26·5] in 300 mg S44819 group, and 22·0 [17·0–26·0] in placebo group), time needed to complete parts A (50 s [IQR 42–68] in 150 mg S44819 group, 49 s [36–63] in 300 mg S44819 group, and 50 s [38–68] in placebo group) and B (107 s [81–144] in 150 mg S44819 group, 121 s [76–159] in 300 mg S44819 group, and 130 s [86–175] in placebo group) of the Trail Making Test, and the Barthel index (90 [IQR 60–100] in 150 mg S44819 group, 90 [70–100] in 300 mg S44819 group, and 90 [70–100] in placebo group) were similar in all groups. Number and type of adverse events were similar between the three groups. There were no drug-related adverse events and no drug-related deaths. Interpretation There was no evidence that S44819 improved clinical outcome in patients after ischaemic stroke, and thus S44819 cannot be recommended for stroke therapy. The concept of tonic inhibition after stroke should be re-evaluated in humans. Funding Servier.

French national guidelines recommend searching for anti-SS-A antibodies during the second-line assessment of stroke in adults55 years of age in the absence of an identified etiology. We aimed to assess the impact of finding anti-SS-A antibodies during the etiological investigations of stroke in young adults.Medical files from all patients ≤ 55 years of age admitted to a single stroke unit during a five-year period and for whom anti-SS-A antibodies were positive were retrospectively analyzed.Twelve patients were included (9 women; median age 48.5 years), with a rate of anti-SS-A antibody positivity of 1.6% (95% confidence interval [0.71-2.55] %; 12/735 admissions). The etiologies of the 12 ischemic events based on the TOAST classification were large-artery atherosclerosis (n = 1), cardioembolism (n = 1), small-vessel disease (n = 1), other determined etiology (n = 3), multiple etiology (n = 1), and no determined etiology (n = 5). A connective tissue disease (CTD) was discovered in 8/12 patients (1 primary Sjögren's Syndrome, 1 mixed CTD, 1 systemic sclerosis, 2 antiphospholipid syndromes, 1 undetermined CTD, 2 lupus). Anti-SSA antibodies were not directly responsible for the stroke in any of the 12 cases. A link between the autoimmune disease and the neurological vascular episode could be hypothesized for four patients, but it never influenced the therapeutic decision.Finding anti-SS-A antibodies during the etiological assessment of a stroke of young adults is rare. However, it may be worthwhile to refer the patient to a rheumatologist/an internist because CTD may be discovered and may require specific follow-up.

BackgroundStudies have suggested that collateral status modifies the effect of successful reperfusion on functional outcome after endovascular therapy (EVT). We aimed to assess the association between collateral status and EVT outcomes and to investigate whether collateral status modified the effect of successful reperfusion on EVT outcomes.MethodsWe used data from the ongoing, prospective, multicenter Endovascular Treatment in Ischemic Stroke (ETIS) Registry. Collaterals were graded according to the American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology (ASITN/SIR) guidelines. Patients were divided into two groups based on angiographic collateral status: poor (grade 0–2) versus good (grade 3–4) collaterals.ResultsAmong 2020 patients included in the study, 959 (47%) had good collaterals. Good collaterals were associated with favorable outcome (90-day modified Rankin Scale (mRS) 0–2) (OR 1.5, 95% CI 1.19 to 1.88). Probability of good outcome decreased with increased time from onset to reperfusion in both good and poor collateral groups. Successful reperfusion was associated with higher odds of favorable outcome in good collaterals (OR 6.01, 95% CI 3.27 to 11.04) and poor collaterals (OR 5.65, 95% CI 3.32 to 9.63) with no significant interaction. Similarly, successful reperfusion was associated with higher odds of excellent outcome (90-day mRS 0–1) and lower odds of mortality in both groups with no significant interaction. The benefit of successful reperfusion decreased with time from onset in both groups, but the curve was steeper in the poor collateral group.ConclusionsCollateral status predicted functional outcome after EVT. However, collateral status on the pretreatment angiogram did not decrease the clinical benefit of successful reperfusion.

Treatment with progesterone protects the male and female brain against damage after middle cerebral artery occlusion (MCAO). However, in both sexes, the brain contains significant amounts of endogenous progesterone. It is not known whether endogenously produced progesterone enhances the resistance of the brain to ischemic insult. Here, we used steroid profiling by gas chromatography-tandem mass spectrometry (GC-MS/MS) for exploring adaptive and sex-specific changes in brain levels of progesterone and its metabolites after MCAO. We show that, in the male mouse brain, progesterone is mainly metabolized via 5α-reduction leading to 5α-dihydroprogesterone (5α-DHP), also a progesterone receptor (PR) agonist ligand in neural cells, then to 3α,5α-tetrahydroprogesterone (3α,5α-THP). In the female mouse brain, levels of 5α-DHP and 3α,5α-THP are lower and levels of 20α-DHP are higher than in males. After MCAO, levels of progesterone and 5α-DHP are upregulated rapidly to pregnancy-like levels in the male but not in the female brain. To assess whether endogenous progesterone and 5α-DHP contribute to the resistance of neural cells to ischemic damage, we inactivated PR selectively in the CNS. Deletion of PR in the brain reduced its resistance to MCAO, resulting in increased infarct volumes and neurological deficits in both sexes. Importantly, endogenous PR ligands continue to protect the brain of aging mice. These results uncover the unexpected importance of endogenous progesterone and its metabolites in cerebroprotection. They also reveal that the female reproductive hormone progesterone is an endogenous cerebroprotective neurosteroid in both sexes.SIGNIFICANCE STATEMENTThe brain responds to injury with protective signaling and has a remarkable capacity to protect itself. We show here that, in response to ischemic stroke, levels of progesterone and its neuroactive metabolite 5α-dihydroprogesterone are upregulated rapidly in the male mouse brain but not in the female brain. An important role of endogenous progesterone in cerebroprotection was demonstrated by the conditional inactivation of its receptor in neural cells. These results show the importance of endogenous progesterone, its metabolites, and neural progesterone receptors in acute cerebroprotection after stroke. This new concept could be exploited therapeutically by taking into account the progesterone status of patients and by supplementing and reinforcing endogenous progesterone signaling for attaining its full cerebroprotective potential.

Background and Purpose— To evaluate hyperacute management of pediatric arterial ischemic stroke, setting up dedicated management pathways is the first recommended step to prove the feasibility and safety of such treatments. A regional pediatric stroke alert protocol including 2 centers in the Paris-Ile-de-France area, France, was established. Methods— Consecutive pediatric patients (28 days–18 years) with confirmed arterial ischemic stroke who had acute recanalization treatment (intravenous r-tPA [recombinant tissue-type plasminogen activator], endovascular procedure, or both) according to the regional pediatric stroke alert were retrospectively reviewed during a 40-month period. Results— Thirteen children, aged 3.7 to 16.6 years, had recanalization treatment. Median time from onset to magnetic resonance imaging was 165 minutes (150–300); 9 out of 13 had large-vessel occlusion. Intravenous r-tPA was used in 11 out of 13 patients, with median time from onset to treatment of 240 minutes (178–270). Endovascular procedure was performed in patients time-out for intravenous r-tPA (n=2) or after intravenous r-tPA inefficiency (n=2). No intracranial or peripheral bleeding was reported. One patient died of malignant stroke; outcome was favorable in 11 out of 12 survivors (modified Rankin Scale score 0–2). Conclusions— Hyperacute recanalization treatment in pediatric stroke, relying on common protocols and adult/pediatric ward collaboration, is feasible. Larger systematic case collection is encouraged.

Introduction Leukoencephalopathy with calcifications and cysts (LCC) is a rare autosomal recessive cerebral angiomatous-like microangiopathy characterized by diffuse and asymmetric white-matter lesions associated with multiple calcifications and cysts. The disease is caused by SNORD118 mutations. The entire clinical spectrum of LCC is not yet fully determined. Material and methods To define the clinical spectrum of LCC, we analyzed data from recently diagnosed cases and from the litterature. Both clinical and imaging features from our five LCC cases harboring compound heterozygous SNORD118 mutations were presented and all cases reported in the litterature reviewed. Results Ninety-two LCC cases including our five patients were identified. Consanguinity was rare (4%), and 97% of cases were symptomatic. Mean age of first clinical manifestations was 16.1 ± 16.1 years (range 1 month–71 years) and was earlier in men (10.3 ± 14.3 years) than in women (20.2 ± 22.8 years) (P = 0.02). The main inaugural symptoms were seizures (36%; mean age at onset: 5.2 ± 9.5 years) and progressive neurological symptoms including ataxia, dystonia and spasticity (26%; 27.8 ± 23.6 years). Intracranial hypertension was less frequently observed (14%), mostly in adults (mean age 31.5 ± 13.2 years). Ischemic or hemorrhagic strokes were inaugural symptoms in two adults (2%). During follow-up, most patients developed progressive extrapyramidal, cerebellar and pyramidal signs (83%), cognitive decline (56%), seizures (37%), intracranial hypertension (30%) or stroke (2%). Conclusion In LCC, the clinical spectrum is largely heterogeneous and the course of the disease appears highly variable in contrast to other hereditary cerebral small vessel diseases.

Background: Randomized controlled trials for calcium antagonists therapy in patients with acute ischemic stroke have failed to show a benefit as a stand-alone therapy, due largely to the reduction of blood pressure, especially in the absence of early recanalization. Since mechanical thrombectomy (MT) has led to high successful recanalization rates, the effect of nimodipin as an adjuvant therapy during MT has not been evaluated. Materials and Methods: We retrospectively reviewed all consecutive cases of MT for which Nimodipin was used as an adjuvant therapy after at least one pass of any device. Clinical and angiographic characteristics, as well as immediate vessel caliber modifications, reperfusion status and early neurological improvement were collected between January 2016 and December 2017. Results: Procedural intra-arterial nimodipin infusion was administered in 10.3 % (58/559; 95%CI 7.8-12.8 %) of patients, after at least one pass of MT device. In 52/58 patients, < 3 manoeuvers of MT were performed. Angiographic vasospasm was identified on the carotid artery in 17/58 (29.3%) cases, on the middle cerebral artery in 35/58 (60.4%) cases and in vertebro-basilar artery in 6/58 (10.3%) cases. The vasospasm was responsible for an immediate reocclusion in 12% of the patients. Angiographic effect of nimodipin with the restauration of a normal vessel caliber and the improvement of the reperfusion without supplementary maneuver was observed in 77.5% % of the cases. Successful recanalization TICI 2b/3 was reached in 81% patients. Significant drop of blood pressure (BP) with need for additional vasopressive drugs was observed in 6 cases. Symptomatic hemorrhage occurred in 3 patients (5%). Concomitant fibrinolytic therapy did not influence the rate of intracranial hemorrhage rate after procedural nimodipin infusion (p=0.912). Early neurological improvement was reached in 46% and was not associated with a high initial systolic and diastolic BP at the admission (p=0.89) or with the modality of anesthesia (p =0.76). Conclusion: Nimodipin can be an efficient and safe adjuvant therapy in the setting of vasospasm due to MT, by normalizing the caliber of the recanalized artery and then, improving the reperfusion status without supplementary maneuver of MT.