DMTs and Covid-19 severity in MS: a pooled analysis from Italy and France

We evaluated the effect of DMTs on Covid-19 severity in patients with MS, with a pooled-analysis of two large cohorts from Italy and France. The association of baseline characteristics and DMTs with Covid-19 severity was assessed by multivariate ordinal-logistic models and pooled by a fixed-effect meta-analysis. 1066 patients with MS from Italy and 721 from France were included. In the multivariate model, anti-CD20 therapies were significantly associated (OR = 2.05, 95%CI = 1.39–3.02, p < 0.001) with Covid-19 severity, whereas interferon indicated a decreased risk (OR = 0.42, 95%CI = 0.18–0.99, p = 0.047). This pooled-analysis confirms an increased risk of severe Covid-19 in patients on anti-CD20 therapies and supports the protective role of interferon

Quantitative neuroimaging biomarkers in a series of 20 adult patients with POLG mutations

International audienceMutations in the gene encoding polymerase gamma (POLG) are a common cause of mitochondrial diseases in adults. We retrospectively analyzed volumetric and diffusion tensor imaging data from 20 adult POLG-mutated patients compared to healthy controls. We used an original clinical binary load score and electroneuromyography to evaluate disease severity. Patients showed atrophy in the basal ganglia, amygdala, and brainstem (p < 0.05) compared to controls, as well as decreased fractional anisotropy (FA) in the cingulate gyrus, the internal capsule and the corona radiata (p < 0.05). Clinical scores correlated with decreased FA and increased radial diffusivity in several brain regions (p < 0.05)

Dynamic imaging of individual remyelination profiles in multiple sclerosis

International audienceBackground: Quantitative in vivo imaging of myelin loss and repair in patients with multiple sclerosis (MS) is essential to understand the pathogenesis of the disease and to evaluate promyelinating therapies. Selectively binding myelin in the central nervous system white matter, [11C]PIB can be used as a positron emission tomography (PET) tracer to explore myelin dynamics in MS.Methods: Patients with active relapsing-remitting MS (n=20) and healthy controls (n=8) were included in a longitudinal trial combining PET with [11C]PIB and magnetic resonance imaging. Voxel-wise maps of [11C]PIB distribution volume ratio, reflecting myelin content, were derived. Three dynamic indices were calculated for each patient: the global index of myelin content change; the index of demyelination; and the index of remyelination.Results: At baseline, there was a progressive reduction in [11C]PIB binding from the normal-appearing white matter to MS lesions, reflecting a decline in myelin content. White matter lesions were characterized by a centripetal decrease in the tracer binding at the voxel level. During follow-up, high between-patient variability was found for all indices of myelin content change. Dynamic remyelination was inversely correlated with clinical disability (p=0.006 and beta-coefficient=-0.67 with the Expanded Disability Status Scale; p=0.003 and beta-coefficient=-0.68 with the MS Severity Scale), whereas no significant clinical correlation was found for the demyelination index.Conclusions: [11C]PIB PET allows quantification of myelin dynamics in MS and enables stratification of patients depending on their individual remyelination potential, which significantly correlates with clinical disability. This technique should be considered to assess novel promyelinating drugs. This article is protected by copyright. All rights reserved

Contact Aspiration Versus Stent Retriever in Patients With Acute Ischemic Stroke With M2 Occlusion in the ASTER Randomized Trial (Contact Aspiration Versus Stent Retriever for Successful Revascularization)

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Post-Thrombolysis Recanalization in Stroke Referrals for Thrombectomy

International audienceBackground and Purpose—Whether all acute stroke patients with large vessel occlusion need to undergo intravenous thrombolysis before mechanical thrombectomy (MT) is debated as (1) the incidence of post-thrombolysis early recanalization (ER) is still unclear; (2) thrombolysis may be harmful in patients unlikely to recanalize; and, conversely, (3) transfer for MT may be unnecessary in patients highly likely to recanalize. Here, we determined the incidence and predictors of post-thrombolysis ER in patients referred for MT and derive ER prediction scores for trial design. Methods—Registries from 4 MT-capable centers gathering patients referred for MT and thrombolyzed either on site (mothership) or in a non MT-capable center (drip-and-ship) after magnetic resonance– or computed tomography–based imaging between 2015 and 2017. ER was identified on either first angiographic run or noninvasive imaging. In the magnetic resonance imaging subsample, thrombus length was determined on T2*-based susceptibility vessel sign. Independent predictors of no- ER were identified using multivariable logistic regression models, and scores were developed according to the magnitude of regression coefficients. Similar registries from 4 additional MT-capable centers were used as validation cohort. Results—In the derivation cohort (N=633), ER incidence was ≈20%. In patients with susceptibility vessel sign (n=498), no-ER was independently predicted by long thrombus, proximal occlusion, and mothership paradigm. A 6-point score derived from these variables showed strong discriminative power for no-ER (C statistic, 0.854) and was replicated in the validation cohort (n=353; C statistic, 0.888). A second score derived from the whole sample (including negative T2* or computed tomography–based imaging) also showed good discriminative power and was similarly validated. Highest grades on both scores predicted no-ER with >90% specificity, whereas low grades did not reliably predict ER. Conclusions—The substantial ER rate underlines the benefits derived from thrombolysis in bridging populations. Both prediction scores afforded high specificity for no-ER, but not for ER, which has implications for trial design

Endovascular therapy with or without intravenous thrombolysis in acute stroke with tandem occlusion

International audienceBackground Endovascular therapy (EVT) is effective and safe in patients with tandem occlusion. The benefit of intravenous thrombolysis (IVT) prior to EVT in acute tandem occlusion is debatable. Objective To compare EVT alone with EVT plus IVT in patients with acute ischemic stroke due to anterior circulation tandem occlusions. Methods This is an individual patient pooled analysis of the Thrombectomy In TANdem lesions (TITAN) and Endovascular Treatment in Ischemic Stroke (ETIS) Registries. Patients were divided into two groups based on prior IVT treatment: (1) IVT+ group, which included patients who received IVT prior to EVT, (2) IVT− group, which included patients who did not receive IVT prior to EVT. Propensity score (inverse probability of treatment weighting (IPTW)) was used to reduce baseline between-group differences. The primary outcome was favorable outcome—that is, modified Rankin Scale (mRS) score 0 to 2 at 90 days. Results Overall, 602 consecutive patients with an acute stroke with tandem occlusion were included (380 and 222 in the bridging therapy and EVT alone groups, respectively). Onset to imaging time was shorter in the IVT+ group (median 103 vs 140 min). In contrast, imaging to puncture time was longer in the IVT+ group (median 107 vs 91 min). In IPTW analysis, the IVT+ group had higher odds of favorable outcome, excellent outcome (90-day mRS score 0–1), and successful reperfusion (modified Thrombolysis in Cerebral Infarction score 2b/3 at the end of EVT). There was no difference in the risk of significant hemorrhagic complications between groups. In secondary analysis of patients treated with acute cervical internal carotid artery stenting, bridging therapy was associated with higher odds of favorable outcome and lower odds of mortality at 90 days. Conclusions Our results suggest that bridging therapy in patients with acute ischemic stroke due to anterior tandem occlusion is safe and may improve functional outcome, even in the setting of acute cervical internal carotid artery stenting during EVT

Safety and Outcome of Carotid Dissection Stenting During the Treatment of Tandem Occlusions: A Pooled Analysis of TITAN and ETIS

International audienceBackground and Purpose: The efficacy of endovascular therapy in patients with acute ischemic stroke due to tandem occlusion is comparable to that for isolated intracranial occlusion in the anterior circulation. However, the optimal management of acute cervical internal carotid artery lesions is unknown, especially in the setting of carotid dissection, but emergency carotid artery stenting (CAS) is frequently considered. We investigated the safety and efficacy of emergency CAS for carotid dissection in patients with acute stroke with tandem occlusion in current clinical practice. Methods: We retrospectively analyzed a prospectively maintained database composed of 2 merged multicenter international observational real-world registries (Endovascular Treatment in Ischemic Stroke and Thrombectomy in Tandem Lesion). Data from endovascular therapy performed in the treatment of tandem occlusions related to acute cervical carotid dissection between January 2012 and January 2019 at 24 comprehensive stroke centers were analyzed. Results: The study assessed 136 patients with tandem occlusion due to dissection, including 65 (47.8%) treated with emergency CAS and 71 (52.2%) without. The overall rates of favorable outcome (90-day modified Rankin Scale score, 0–2) and successful reperfusion (modified Thrombolysis in Cerebral Infarction, 2b–3) were 58.0% (n=76 [95% CI, 49.6%–66.5%]) and 77.9% (n=106 [95% CI, 71.0%–85.0%]), respectively. In subgroup analyses, the rate of successful reperfusion (89.2% versus 67.6%; adjusted odds ratio, 2.24 [95% CI, 1.33–3.77]) was higher after CAS, whereas the 90-day favorable outcome (54.3% versus 61.4%; adjusted odds ratio, 0.84 [95% CI, 0.58–1.22]), symptomatic intracerebral hemorrhage (sICH; 10.8% versus 5.6%; adjusted odds ratio, 1.59 [95% CI, 0.79–3.17]), and 90-day mortality (8.0% versus 5.8%; adjusted odds ratio, 1.00 [95% CI, 0.48–2.09]) did not differ. In sensitivity analyses of patients with successful intracranial reperfusion, CAS was not associated with an improved clinical outcome. Conclusions: Emergency stenting of the dissected cervical carotid artery during endovascular therapy for tandem occlusions seems safe, whatever the quality of the intracranial reperfusion

Prognosis and risk factors associated with asymptomatic intracranial hemorrhage after endovascular treatment of large vessel occlusion stroke: a prospective multicenter cohort study

International audienceBackground and purpose: Asymptomatic intracranial hemorrhage (aICH) is a common occurrence after endovascular treatment (EVT) for acute ischemic stroke (AIS). The aims of this study were to address its impact on 3-month functional outcome and to identify risk factors for aICH after EVT. Methods: Patients with AIS attributable to anterior circulation large vessel occlusion who underwent EVT were enrolled in a multicenter prospective registry. Based on imaging performed 22–36 h post-EVT, we included patients with no intracranial hemorrhage (ICH) or aICH. Poor outcome defined as a 3-month modified Rankin Scale (mRS) score 4–6 and overall 3-month mRS score distribution were compared according to presence/absence of aICH, and aICH subtype using logistic regression. We assessed the risk factors of aICH using a multivariate logistic regression model. Results: Of the 1526 patients included in the study, 653 (42.7%) had aICH. Patients with aICH had a higher rate of poor outcome: odds ratio (OR) 1.88 (95% confidence interval [CI] 1.44–2.44). Shift analysis of mRS score found a fully adjusted OR of 1.79 (95% CI 1.47–2.18). Hemorrhagic infarction (OR 1.63 [95% CI 1.22–2.18]) and parenchymal hematoma (OR 2.99 [95% CI 1.77–5.02]) were associated with higher risk of poor outcome. Male sex, diabetes, coronary artery disease, baseline National Institutes of Health Stroke Scale score and Alberta Stroke Program Early Computed Tomography Score, number of passes and onset to groin puncture time were independently associated with aICH. Conclusions: Patients with aICH, irrespective of the radiological pattern, have a worse functional outcome at 3 months compared with those without ICH after EVT for AIS. The number of EVT passes and the time from onset to groin puncture are factors that could be modified to reduce deleterious ICH