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Data from 46 schools in western Kenya were used to investigate the performance of school-based questionnaires, on reported blood in stool and water-contact patterns, as indicators of the prevalence of human infection with Schistosoma mansoni. Prevalence of infection was associated with the prevalence of self-reported blood in stool, recent history of swimming and recent history of fishing. It was shown that use of a threshold of 30% of subjects reporting blood in stool would identify 42.9% of the 'high-prevalence' schools (i.e. prevalence ≥ 50%) and 87.5% of the 'low-prevalence' schools (i.e. prevalence < 50%). A threshold of 25% reporting swimming would identify 57.1% and 93.7% of the high- and low-prevalence schools, respectively. Blood in stool appears to be too coarse an indicator to identify schools for mass treatment correctly. Although the use of multiple questions improved the diagnostic performance of the questionnaire in identifying the high-prevalence schools, it was unclear how questions can best be combined in other settings. However, there is a direct relationship between prevalence of S. mansoni infection and distance of the school from the lakeshore; analysis indicated that use of a threshold of 5 km from the lakeshore would correctly identify most (90%) of both the low- and high-prevalence schools. Distance to the lakeshore may therefore be used to screen schools in much of East Africa (i.e. those areas close to the Great Lakes where the infection is known to be prevalent and where much of the region's population is concentrated). In other areas of transmission, such as irrigation areas, further studies are still required. [ABSTRACT FROM AUTHOR]

Background: We evaluated the clinical and safety outcomes of emergent carotid artery stenting (eCAS) plus endovascular thrombectomy (EVT) among patients with anterior tandem lesion (TL) and large ischemic core (LIC)., Methods: This retrospective study included consecutive stroke patients enrolled in the Endovascular Treatment in Ischemic Stroke Registry in France between January 2015 and June 2023. We compared the outcomes of carotid stenting vs no stenting in tandem lesion with pre-treatment LIC (Alberta Stroke Program Early CT Score (ASPECTS) 3-5) and stenting in tandem lesion vs thrombectomy alone for isolated intracranial occlusions with pre-treatment LIC. Primary outcome was a score of 0 to 3 on the modified Rankin scale (mRS) at 90 days. Multivariable mixed-effects logistic regression was performed., Results: Among 218 tandem patients with LIC, 55 were treated with eCAS plus EVT. The eCAS group had higher odds of 90-day mRS 0-3 (adjusted Odds Ratio (aOR) 2.40, 95% confidence interval (CI) 1.10 to 5.21; p=0.027). There were no differences in the risk of any intracerebral hemorrhage (OR 1.41, 95% CI 0.69 to 2.86; p=0.346), parenchymal hematoma (aOR 1.216, 95% CI 0.49 to 3.02; p=0.675), symptomatic intracerebral hemorrhage (aOR 1.45, 95% CI 0.60 to 3.48; p=0.409), or 90-day mortality (aOR 0.74, 95% CI 0.33 to 1.68; p=0.472). eCAS was associated with a higher rate of carotid patency at day 1 (aOR 3.54, 95% CI 1.14 to 11.01; p=0.028). Safety outcomes were similar between EVT+eCAS group in TL-LIC and EVT alone group in isolated intracranial occlusions with LIC., Conclusion: eCAS appears to be a safe and effective strategy in patients with TL and LIC volume., Competing Interests: Competing interests: Dr. Marnat reports consulting fees from Microvention and Stryker outside the submitted work. Dr. Soize reports personal fees from Balt and Microvention outside the submitted work. Dr. Richard reports consulting fees from Stryker and Microvention outside the submitted work. Dr. Bourcier reports consulting fees from ACTICOR and payments for lectures from ACTICOR, BMS, Pfizer, and Bayer outside the submitted work. Dr. Casolla reports consulting fees from ACTICOR and payments for lectures from ACTICOR, BMS, Pfizer, and Bayer outside the submitted work. The other authors report no conflicts., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Aims: The clinical evolution of acute ischemic stroke patients with isolated proximal posterior cerebral artery (PCA) occlusion treated with medical management alone has been poorly described. We aimed to determine the clinical and radiological factors associated with poor functional outcome in this population., Methods: We conducted a multicenter international retrospective study of consecutive stroke patients with isolated occlusion of the first (P1) or second (P2) segment of PCA admitted within 6 h from symptoms onset in 26 stroke centers in France, Switzerland, and the United States, treated with the best medical management alone. Poor functional outcome was defined as a modified Rankin scale (mRS) ⩾2 at 3 months or no return to pre-stroke mRS. The associations between pretreatment variables and poor outcome were studied in univariable and then multivariable analyses, as well as the association between poor outcome and key follow-up radiological variables., Results: Overall, 585 patients were included. The median age was 74 years (interquartile range (IQR) = 63-83), median National Institutes of Health Stroke Scale (NIHSS) was 6 (3-10), 80% received intravenous thrombolysis (IVT), and 22% and 78% had P1 and P2 occlusions, respectively. Poor outcome occurred in 56% of patients. In multivariable analysis focusing on pretreatment variables, age (adjusted odds ratio (OR) = 1.12 per 5-year increase [95% confidence interval (CI) = 1.05-1.20]; p  = 0.001), NIHSS score (aOR = 1.12 per each point increase [1.08-1.18]; p  < 0.001), infarct volume (aOR = 1.16 per 5 mL increase [1.07-1.25]; p  < 0.001), and the lack of IVT use (aOR = 1.79 [1.10-2.94], p  = 0.020) were independently associated with poor outcome. Regarding 24-h follow-up radiological variables, complete recanalization (defined as no clot in the vascular tree at or beyond the primary occlusive lesion, aOR = 0.37 [95% CI = 0.21-0.65], p  < 0.001) and parenchymal hematoma occurrence (aOR = 2.37 [95% CI = 1.01-5.56], p  = 0.048) were independently associated with poor 3-month outcome., Conclusions: Poor outcome occurred in more than half of medically treated PCA-related acute stroke patients. Facilitating IVT use may improve functional outcome. Therapeutic approaches aimed at enhancing recanalization and reducing hemorrhagic transformation need to be studied in clinical trials., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Dr M.R.H. reports grants from Swiss National Science Foundation, SITEM Research Support Funds, and Swiss Heart Foundation, not directly related to this manuscript. Professor C.R. receives fees from OTR3 for her participation in a DSMB. Y.B. reports personal fees from BMS, Pfizer, Medtronic, Amgen, Servier, NovoNordisk, Novartis, and Laboratoire XO, outside the submitted work. Dr G.W.A. reports stock holdings in iSchemaView; compensation from Biogen, iSchemaView, and Genentech for consultant services. Dr G.T. reports lecture fees from Guerbert France and consultant services for AI-Stroke. Professor M.M. reports consulting fees from Acticor Biotech, and Boerhinger. Dr P.S. receives speaker fees from Acticor Biotech. Other authors have nothing to disclose.

Background and Purpose: Vasospasm is a common iatrogenic event during mechanical thrombectomy (MT). In such circumstances, intra-arterial nimodipine administration is occasionally considered. However, its use in the treatment of iatrogenic vasospasm during MT has been poorly studied. We investigated the impact of iatrogenic vasospasm treated with intra-arterial nimodipine on outcomes after MT for large vessel occlusion stroke., Methods: We conducted a retrospective analysis of the multicenter observational registry Endovascular Treatment in Ischemic Stroke (ETIS). Consecutive patients treated with MT between January 2015 and December 2022 were included. Patients treated with medical treatment alone, without MT, were excluded. We also excluded patients who received another in situ vasodilator molecule during the procedure. Outcomes were compared according to the occurrence of cervical and/or intracranial arterial vasospasm requiring intraoperative use of in situ nimodipine based on operator's decision, using a propensity score approach. The primary outcome was a modified Rankin Scale (mRS) score of 0-2 at 90 days. Secondary outcomes included excellent outcome (mRS score 0-1), final recanalization, mortality, intracranial hemorrhage and procedural complications. Secondary analyses were performed according to the vasospasm location (intracranial or cervical)., Results: Among 13,678 patients in the registry during the study period, 434 received intra-arterial nimodipine for the treatment of MT-related vasospasm. In the main analysis, comparable odds of favorable outcome were observed, whereas excellent outcome was significantly less frequent in the group with vasospasm requiring nimodipine (adjusted odds ratio [aOR] 0.78, 95% confidence interval [CI] 0.63-0.97). Perfect recanalization, defined as a final modified Thrombolysis In Cerebral Infarction score of 3 (aOR 0.63, 95% CI 0.42-0.93), was also rarer in the vasospasm group. Intracranial vasospasm treated with nimodipine was significantly associated with worse clinical outcome (aOR 0.64, 95% CI 0.45-0.92), in contrast to the cervical location (aOR 1.37, 95% CI 0.54-3.08)., Conclusion: Arterial vasospasm occurring during the MT procedure and requiring intra-arterial nimodipine administration was associated with worse outcomes, especially in case of intracranial vasospasm. Although this study cannot formally differentiate whether the negative consequences were due to the vasospasm itself, or nimodipine administration or both, there might be an important signal toward a substantial clinical impact of iatrogenic vasospasm during MT., (© 2024 The Author(s). European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Background and Objectives: Although rituximab failed to demonstrate a significant effect on disability progression in primary progressive multiple sclerosis (PPMS), ocrelizumab succeeded. Our main objective was to analyze confirmed disability progression (CDP) in a cohort of patients with PPMS treated with anti-CD20 therapies compared with a weighted untreated control cohort., Methods: This was a retrospective study using data from the French MS registry (Observatoire Français de la Sclérose En Plaques). We included patients with PPMS treated or never treated with anti-CD20 therapies from 2016 to 2021, with an Expanded Disability Status Scale score of ≤6.5 at baseline. The primary outcome was time to first CDP. The secondary outcomes were time to first relapse, MRI activity at 2 years, identification of risk factors associated with CDP, and serious infection incidence rates (IIRs). Each outcome was studied using an inverse probability of treatment weighting method. The outcomes were modeled using a weighted proportional Cox model for the time-to-event outcomes and by a logistic regression regarding the MRI activity., Results: A total of 1,184 patients (426 treated and 758 untreated) fulfilled the inclusion criteria. Median age (Q1-Q3) was 56 years (49.3-63.8), and 52.7% were female. Among treated patients, 295 received rituximab, whereas 131 received ocrelizumab. At baseline, anti-CD20-treated patients were younger (median 51.9 vs 58.6 years, Cohen d = 0.683) and had more active disease (54.5 vs 27.8%, Cohen d = 0.562). 91.6% were drug-naive at inclusion. In time to first CDP analysis, no statistical significance was observed (hazard ratio [HR], 1.13; 95% CI 0.93-1.36, p = 0.2113). In time to first relapse analysis, a nonsignificant trend toward fewer patients relapsing in the treated group was observed (HR 0.83; 95% CI 0.48-1.28, p = 0.0809). For MRI activity, no significant difference was found between the 2 groups. Risk factors associated with CDP in the treated group were male sex and MS duration. IIR was 6.67 (95% CI 3.12-14.25) per 100 person-years in the treated group vs 2.67 (95% CI 0.80-8.86) in the untreated group., Discussion: Time to first CDP was not different between anti-CD20 treated and untreated patients with PPMS. Although our study is retrospective and mainly included patients treated by rituximab, our results indicate that there should be a constant evaluation of all available data to ascertain the best risk/benefit ratio for patients with PPMS., Classification of Evidence: This study provides Class III evidence that anti-CD20 therapy of previously untreated patients with PPMS was not superior to no therapy in delaying time to first CDP.

Introduction: Depressive symptoms are commonly reported after spontaneous intracerebral haemorrhage (ICH) and frequently associated with cognitive decline. Using hierarchical clustering analysis (HCA), we aimed to identify different post-ICH depressive symptoms profiles and to evaluate their association with dementia risk., Methods: We included consecutive patients from the prospective Prognosis of Intracerebral Haemorrhage (PITCH) study who survived 6 months after the ICH. We performed HCA using depressive symptoms severity (assessed using the Montgomery-Åsberg Depression Rating Scale (MADRS)), along with the presence of apathy and anxiety (screened using Neuropsychiatric Inventory questionnaire). Baseline clinical/neuroimaging characteristics and risk of incident dementia were compared between different profiles using univariate and multivariable models., Results: Of 265 six-month ICH survivors, 221 (83%) underwent neuropsychiatric screening (mean age 65.5 years; 57% male). Using HCA, 3 profiles were identified: (1) without significant depressive symptoms ( n  = 152; median MADRS score = 2 [IQR 0-4]); (2) depressive symptoms with predominant apathy ( n  = 41; median MADRS score = 15 [IQR 5-20], 68% with apathy); (3) depressive symptoms profile with predominant anxiety ( n  = 28; median MADRS score = 17 [IQR 9-25]; 100% with anxiety). Compared to patients without depressive symptoms, patients with depressive symptoms and predominant apathy (but not those with predominant anxiety) were more likely to have cerebral atrophy (OR = 2.4, 95% CI = 1.4-4.2) and had significantly higher long-term new-onset dementia risk (adjusted hazard ratio = 2.2, 95% CI = 1.3-3.8)., Conclusion: Screening for apathy and anxiety on top of depressive symptoms might help identifying patients at risk for dementia. Future studies on treatment should account for different post-ICH depressive symptoms profiles that may impact on cognitive function., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Importance: Understanding the association between clinically defined relapses and radiological activity in multiple sclerosis (MS) is essential for patient treatment and therapeutic development., Objective: To investigate clinical events identified as relapses but not associated with new T2 lesions or gadolinium-enhanced T1 lesions on brain and spinal cord magnetic resonance imaging (MRI)., Design, Setting, and Participants: This multicenter observational cohort study was conducted between January 2015 and June 2023. Data were extracted on June 8, 2023, from the French MS registry. All clinical events reported as relapses in patients with relapsing-remitting MS were included if brain and spinal cord MRI was performed within 12 and 24 months before the event, respectively, and 50 days thereafter with gadolinium injection., Exposures: Events were classified as relapses with active MRI (RAM) if a new T2 lesion or gadolinium-enhanced T1 lesion appeared on brain or spinal cord MRI or as acute clinical events with stable MRI (ACES) otherwise., Main Outcomes and Measures: Factors associated with ACES were investigated; patients with ACES and RAM were compared regarding Expanded Disability Status Scale (EDSS) course, relapse rate, confirmed disability accrual (CDA), relapse-associated worsening (RAW), progression independent of relapse activity (PIRA), and transition to secondary progressive (SP) MS, and ACES and RAM rates under each disease-modifying therapy (DMT) were estimated., Results: Among 31 885 clinical events, 637 in 608 patients (493 [77.4%] female; mean [SD] age, 35.8 [10.7] years) were included. ACES accounted for 166 (26.1%) events and were more likely in patients receiving highly effective DMTs, those with longer disease duration (odds ratio [OR], 1.04; 95% CI, 1.01-1.07), or those presenting with fatigue (OR, 2.14; 95% CI, 1.15-3.96). ACES were associated with significant EDSS score increases, lower than those found for RAM. Before the index event, patients with ACES experienced significantly higher rates of relapse (relative rate [RR], 1.21; 95% CI, 1.01-1.46), CDA (hazard ratio [HR], 1.54; 95% CI, 1.13-2.11), and RAW (HR, 1.72; 95% CI, 1.20-2.45). Patients with ACES were at significantly greater risk of SP transition (HR, 2.58; 95% CI, 1.02-6.51). Although RAM rate decreased with DMTs according to their expected efficacy, ACES rate was stable across DMTs., Conclusions and Relevance: The findings in this study introduce the concept of ACES in MS, which accounted for one-fourth of clinical events identified as relapses.

Background: The Brush Sign (BrS) is a radiological biomarker (MRI) showing signal decrease of subependymal and deep medullary veins on paramagnetic-sensitive magnetic resonance sequences. Previous studies have shown controversial results regarding the prognostic value of BrS. We aimed to assess whether BrS on T2*-weighted sequences could predict functional prognosis in patients treated with mechanical thrombectomy (MT)., Methods: We included all consecutive patients with large artery occlusion related stroke in anterior circulation treated with MT between February 2020 and August 2022 at Reims University Hospital. Multivariable logistic regression models were used to investigate factors associated with BrS and its impact on outcomes., Results: Of the 327 included patients, 124 (37,9%) had a BrS on baseline MRI. Mean age was 72 ± 16 years and 184 (56,2 %) were female. In univariate analysis, BrS was associated with a younger age (67 vs 74; p<0.001), a higher NIHSS score (16(10-20) vs 13(8-19); p = 0.047) history of diabetes (15.3% vs 26.1 %; p = 0.022) and a shorter onset to MRI time (145.5 (111.3-188.5) vs 162 (126-220) p = 0.008). In multivariate analyses, patients with a BrS were younger (OR:0.970 (0.951 - 0.989)), tend to have a higher NIHSS score at baseline (OR:1.046 (1.000 - 1.094) and were less likely to have diabetes (OR: 0.433; 0.214-0.879). The presence of BrS was independently associated with functional independence (OR: 2.234(1.158-4,505) at 3 months but not with mortality nor with symptomatic intracerebral hemorrhage., Conclusion: BrS on pre-treatment imaging could be considered as a biomarker of physiological adaptation to cerebral ischemia, allowing prolonged viability of brain tissue and might participate in the therapeutic decision., Competing Interests: Declaration of competing interest The authors report no disclosures relevant to this work., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Background: Fatigue is a major complaint in stroke survivors, but data focusing on intracerebral haemorrhage (ICH) survivors are scarce. In a cohort of spontaneous ICH survivors, we assessed the long-term prevalence of fatigue and its associated factors., Methods: We included consecutive 1-year ICH survivors from the prospective, observational, single-centre Prognosis of Intracerebral Haemorrhage (PITCH) study. We evaluated fatigue (defined as a score ≥ 4 in Chalder Fatigue Scale); the severity of neurological, depressive, and anxiety symptoms; and functional disability 1, 3, and 6 years after ICH. We performed univariable and multivariable models to evaluate clinical factors and brain magnetic resonance imaging (MRI) small vessel disease (SVD) markers associated with fatigue., Results: Of 255 1-year ICH survivors, 153 (60%) underwent fatigue screening and were included in this study. Seventy-eight patients (51%) reported fatigue at 1-year, 56/110 (51%) at 3-year, and 27/67 (40%) at 6-year follow-up. Patients with fatigue exhibited more severe concomitant depressive/anxiety symptoms, but the severity of depressive symptoms was the only clinical factor significantly associated with 1-year fatigue in multivariable analysis (adjusted odds ratio 1.4 for one-point increase; 95% confidence interval 1.2-1.6). Patients with severe cortical atrophy at baseline had increased risk of fatigue at 1-year follow-up compared to patients with mild/no cortical atrophy (adjusted odds ratio 2.5; 95% confidence interval 1.1-5.8)., Conclusions: Fatigue after ICH is frequent and long-lasting, and it is associated with cortical atrophy (but not with other MRI markers of cerebral SVD). The link between fatigue and depressive symptoms may represent a potential therapeutic target., (© 2023. Fondazione Società Italiana di Neurologia.)

Importance: A recent randomized clinical trial concluded that discontinuing medium-efficacy therapy might be a reasonable option for older patients with nonactive multiple sclerosis (MS), but there is a lack of data on discontinuing high-efficacy therapy (HET). In younger patients, the discontinuation of natalizumab and fingolimod is associated with a risk of rebound of disease activity., Objective: To determine whether discontinuing HET in patients 50 years and older with nonactive MS is associated with an increased risk of relapse compared with continuing HET., Design, Setting, and Participants: This observational cohort study used data from 38 referral centers from the French MS registry (Observatoire Français de la Sclérose en Plaques [OFSEP] database). Among 84704 patients in the database, data were extracted for 1857 patients 50 years and older with relapsing-remitting MS treated by HET and with no relapse or magnetic resonance imaging activity for at least 2 years. After verification of the medical records, 1620 patients were classified as having discontinued HET or having remained taking treatment and were matched 1:1 using a dynamic propensity score (including age, sex, disease phenotype, disability, treatment of interest, and time since last inflammatory activity). Patients were included from February 2008 to November 2021, with a mean (SD) follow-up of 5.1 (2.9) years. Data were extracted in June 2022., Exposures: Natalizumab, fingolimod, rituximab, and ocrelizumab., Main Outcomes and Measures: Time to first relapse., Results: Of 1620 included patients, 1175 (72.5%) were female, and the mean (SD) age was 54.7 (4.8) years. Among the 1452 in the HET continuation group and 168 in the HET discontinuation group, 154 patients in each group were matched using propensity scores (mean [SD] age, 57.7 [5.5] years; mean [SD] delay since the last inflammatory activity, 5.6 [3.8] years; mean [SD] follow-up duration after propensity score matching, 2.5 [2.1] years). Time to first relapse was significantly reduced in the HET discontinuation group compared with the HET continuation group (hazard ratio, 4.1; 95% CI, 2.0-8.5; P < .001) but differed between HETs, with a hazard ratio of 7.2 (95% CI, 2.1-24.5; P = .001) for natalizumab, 4.5 (95% CI, 1.3-15.5; P = .02) for fingolimod, and 1.1 (95% CI, 0.3-4.8; P = .85) for anti-CD20 therapy., Conclusion and Relevance: As in younger patients, in patients 50 years and older with nonactive MS, the risk of relapse increased significantly after stopping HETs that impact immune cell trafficking (natalizumab and fingolimod). There was no significant increase in risk after stopping HETs that deplete B-cells (anti-CD20 therapy). This result may inform decisions about stopping HETs in clinical practice.

Background: The clinical benefit of mechanical thrombectomy(MT) for stroke patients with tandem occlusion is similar to that of isolated intracranial occlusions. However, the management of cervical internal carotid artery(ICA) occlusion during the MT, particularly in the setting of carotid dissection, remains controversial. We aimed to investigate the clinical impact of cervical ICA patency at day 1 on 3-month functional outcome., Methods: We collected data from the Endovascular Treatment in Ischemic Stroke, a prospective national registry in 30 French centers performing MT between January 2015 and January 2022. Inclusion criteria were consecutive tandem occlusions related to cervical ICA dissection treated with MT. Tandem occlusions of other etiology, isolated cervical ICA occlusions without intracranial thrombus and patients without day-1 ICA imaging were excluded. Primary endpoint was the 3-month functional outcome. Secondary endpoints included intracranial hemorrhage(ICH), excellent outcome, mortality and early neurological improvement. A sensitivity analysis was performed in patients with intracranial favorable recanalization after MT., Results: During the study period, 137 patients were included of which 89(65%) presented ICA patency at day 1. The odds of favorable outcome did not significantly differ between patients with patent and occluded ICA at day 1(68.7 vs 59.1%;aOR=1.30;95%CI 0.56-3.00,p=0.54). Excellent outcome, early neurological improvement, mortality and ICH were also comparable between groups. Sensitivity analysis showed similar results., Conclusion: ICA patency at day 1 in patients with tandem occlusions related to dissection did not seem to influence functional outcome. Endovascular recanalization of the cervical ICA including stenting might not be systematically required in this setting., Competing Interests: Declaration of competing interest The authors have no disclosure related to the present publication., (Copyright © 2024 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)

Rationale: Mechanical thrombectomy (MT) associated with the best medical treatment (BMT) has recently shown efficacy for the management of acute ischemic stroke (AIS) secondary to a large vessel occlusion. However, evidence is lacking regarding the benefit of MT for more distal occlusions., Aim: To evaluate the efficacy in terms of good clinical outcome at 3 months of MT associated with the BMT over the BMT alone in AIS related to a distal occlusion., Methods: The DISCOUNT trial is a multicenter open-label randomized controlled trial involving French University hospitals. Adult patients (⩾18 years) with an AIS involving the anterior or posterior circulation secondary to a distal vessel occlusion within 6 h of symptom onset or within 24 h if no hyperintense signal on fluid attenuation inversion recovery acquisition will be randomized 1:1 to receive either MT associated with the BMT (experimental group) or BMT alone (control group). The number of patients to be included is 488., Study Outcomes: The primary outcome is the rate of good clinical outcome at 3 months defined as a modified Rankin scale (mRS) ⩽2 and evaluated by an independent assessor blinded to the intervention arm. Secondary outcomes include recanalization of the occluded vessel within 48 h, angiographic reperfusion in the experimental group, 3-month excellent clinical outcome (mRS ⩽ 1), all adverse events, and death. A cost utility analysis will estimate the incremental cost per quality-adjusted life year (QALY) gained., Discussion: If positive, this study will open new insights in the management of AISs., Trial Registration: ClinicalTrials.gov: NCT05030142 registered on 1 September 2021., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: B.G. has received grants from the French Ministry of Health and is the primary investigator of the TITAN, DIRECT ANGIO, and IA-RESCUE trial, and consulting fees from Boerhinger Ingelheim, Air Liquide, MIVI, Medtronic, Microvention, and Penumbra. A.S. reports conflicts of interest with Medtronic, Balt Extrusion, and Microvention (consultant). F.C. reports conflicts of interest with Medtronic, Balt Extrusion (consultant), ClinSearch (core lab), Penumbra, Stryker (payment for reading), and Artedrone (Board). J.-C.G. reports conflicts of interest with Stryker (consultant), Medtronic (consultant), Microvention (consultant), Balt, and Intradys (consultant). I.D.-Z. reports a conflict of interest with Medtronic (honoraria for research, lecturing and acting as an advisor). G.T. reports a conflict of interest with Guerbet France (Lecturing fees). N.B. reports a conflict of interest with Stryker and QApel (consultant). I.S. reports a conflict of interest with Sanofi Synthé-Labo, Servier, Boheringer Ingelheim, Astra-Zeneca, Novonordisk, Medtronic (consultant), and BMS-Pfizer (Lecturing fees). Prof. Cognard reports a conflict of interest with Medtronic, Stryker, Microvention, Cerenovus, and MIVI (consultant). S.A. reports a conflict of interest with Boehringer Ingelheim, Astra-Zeneca, Pfizer, and Amgen (participation in advisory meetings and satellite symposia). S.A. is also the principal investigator of the Tenecteplase treatment in Ischemic Stroke (TETRIS) registry (financial support from Boehringer Ingelheim) and of the ToGiac trial (supported by a research grant from Roche-Shugai). S.R. reports conflict of interest with Boheringer Ingelheim, Bristol-Myers Squibb (scientific expertise), and Acticor (study coordination).

Background: Tandem occlusions are a singular large vessel occlusion entity involving specific endovascular and perioperative antithrombotic management. In this context, data on safety and efficacy of prior intravenous thrombolysis (IVT) with tenecteplase is scarce. We aimed to compare IVT with tenecteplase or alteplase in patients with acute tandem occlusions intended for endovascular treatment., Patients and Methods: A retrospective pooled analysis of two large observational registries (ETIS (Endovascular Treatment of Ischemic Stroke) and TETRIS (Tenecteplase Treatment in Ischemic Stroke)) was performed on consecutive patients presenting with anterior circulation tandem occlusion treated with IVT using either alteplase (ETIS) or tenecteplase (TETRIS) followed by endovascular treatment between January 2015 and June 2022. Sensitivity analyses on atherosclerosis related tandem occlusions and on patient treated with emergent carotid stenting were conducted. Propensity score overlap weighting analyses were performed., Results: We analyzed 753 patients: 124 in the tenecteplase and 629 in the alteplase group. The overall odds of favorable outcome (3-month modified Rankin score 0-2) were comparable between both groups (49.4% vs 47.1%; OR = 1.10, 95%CI 0.85-1.41). Early recanalization, final successful recanalization and mortality favored the use of tenecteplase. The occurrence of any intracranial hemorrhage (ICH) was more frequent after tenecteplase use (OR = 2.24; 95%CI 1.75-2.86). However, risks of symptomatic ICH and parenchymal hematoma remained similar. In atherosclerotic tandems, favorable outcome, mortality, parenchymal hematoma, early recanalization, and final successful recanalization favored the tenecteplase group. In the carotid stenting subgroup, PH were less frequent in the tenecteplase group (OR = 0.18; 95%CI 0.05-0.69)., Conclusion: In patients with tandem occlusions, IVT with tenecteplase seemed reasonably safe in particular with increased early recanalization rates. These findings remain preliminary and should be further confirmed in randomized trials., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Patients treated with acute carotid stenting (CAS) may have higher odds of a favorable outcome than those treated without CAS during thrombectomy in tandem occlusions. Antiplatelet therapy is associated with CAS to avoid stent thrombosis, which occurs in around 20% of patients and negatively impacts outcomes. In this study we compared two antiplatelet strategies in tandem occlusion strokes treated with CAS and intracranial thrombectomy in clinical practice., Methods: The Endovascular Treatment in Ischemic Stroke Registry is an ongoing prospective observational study involving 21 comprehensive stroke centers performing thrombectomy in France. We analyzed patients with atherosclerotic tandem occlusions treated with acute CAS and intracranial thrombectomy who received at least one antiplatelet agent. Aggressive antiplatelet therapy included oral or intravenous glycoprotein (GP) IIb/IIIa or P2Y12 inhibitors. The primary outcome was cervical carotid artery patency at day 1 imaging follow-up., Results: Among the 187 included patients, 124 (66.3%) received aspirin alone and 63 (33.7%) received aggressive antiplatelet therapy. There was no significant difference regarding safety outcomes, especially in symptomatic intracerebral hemorrhage, parenchymal hematoma, and procedural complications. There was a significantly higher rate of carotid stent patency at day 1 in the aggressive antiplatelet therapy group (81.7% vs 97.1%, aOR 17.49, 95% CI 1.10 to 277.2, p=0.042). Odds of favorable functional outcome (90-day modified Rankin Scale score 0-2) were similar between the groups (OR 3.04, 95% CI 0.64 to 14.25, p=0.158)., Conclusions: In tandem occlusions treated with CAS plus thrombectomy, an aggressive antiplatelet regimen was associated with an increased rate of carotid stent patency at day 1 without safety concerns. Randomized trials are warranted to confirm these findings., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Intravenous 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., Methods: We 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., Results: Among 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)., Conclusions: In 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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Obstructive sleep apnea syndrome (OSAS) is associated with chronic intermittent hypoxia (cIH) that causes disturbances in glucose and lipid metabolism. Animals exposed to cIH show lower body weight and food intake, but the protein-energy metabolism has never been investigated. Here, to address the gap, we studied the impact of cIH on nutritional status in rats. A total of 24 male Wistar rats were randomized into 3 groups ( n = 8): a control group (Ctrl), a cIH group (cIH) exposed to cIH (30 s 21-30 s 5% fraction of inspired oxygen, 8 h per day, for 14 days), and a pair-fed group (PF) exposed to normoxia with food intake adjusted to the intake of the cIH group rats with anorexia. Body weight and food intake were measured throughout the study. After 14 days, the rats were euthanized, the organs were collected, weighed, and the liver, intestine mucosa, and muscles were snap-frozen to measure total protein content. Food intake was decreased in the cIH group. Body weight was significantly lower in the cIH group only (-11%, p < 0.05). Thymus and liver weight as well as EDL protein content tended to be lower in the cIH group than in the Ctrl and PF groups. Jejunum and ileum mucosa protein contents were lower in the cIH group compared to the PF group. cIH causes a slight impairment of nutritional status and immunity. This pre-clinical work argues for greater consideration of malnutrition in care for OSAS patients. Further studies are warranted to devise an adequate nutritional strategy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Breuillard, Moulin, Bouyon, Couchet, Moinard and Belaidi.)

Background Whether intravenous thrombolysis (IVT) prior to endovascular thrombectomy (EVT) provides additional benefits in patients with acute ischemic stroke (AIS) and a large infarct core (LIC) remains unclear. Purpose To examine whether treatment with IVT before EVT is beneficial in patients with LIC identified with CT or MRI (Alberta Stroke Program Early CT score 0-5). Materials and Methods This retrospective study included consecutive adult patients diagnosed with AIS due to large vessel occlusion (LVO) and LIC treated with EVT who were enrolled in the ETIS (Endovascular Treatment in Ischemic Stroke) Registry in France between January 2015 and January 2022. The primary outcome measure was a favorable outcome (modified Rankin Scale [mRS] score 0-3) at 90 days. Secondary outcomes included functional independence (mRS score 0-2) at 90 days, improvement in degree of disability (ordinal shift in mRS score toward a better outcome) at 90 days, early neurologic improvement at 24 hours, and successful reperfusion (modified Thrombolysis in Cerebral Infarction score of 2b or higher). Safety outcomes included symptomatic intracerebral hemorrhage within 24 hours and mortality at 90 days. Inverse probability of treatment weighting (IPTW)-adjusted analysis was used to assess the treatment effect of IVT adjusted for baseline variables. Results Of 1408 patients (mean age, 68.3 years ± 15.4 [SD]; 789 men), 654 (46.4%) were treated with IVT prior to EVT. In the IPTW-adjusted data set, IVT plus EVT was associated with a higher rate of favorable outcome at 90 days (odds ratio [OR], 1.24 [95% CI: 1.05, 1.46]; P = .01), functional independence at 90 days (OR, 1.47 [95% CI: 1.22, 1.77]; P < .001), improvement in degree of disability at 90 days (common OR, 1.30 [95% CI: 1.13, 1.49]; P < .001), early neurologic improvement (OR, 1.26 [95% CI: 1.07, 1.49]; P = .005), and successful reperfusion (OR, 1.43 [95% CI: 1.14, 1.79]; P = .002) than EVT alone. Rates of brain hemorrhage within 24 hours and mortality at 90 days were similar between groups. Conclusion In patients with AIS due to LVO with LIC identified with CT or MRI, treatment with IVT before EVT appeared to provide a clinical benefit over EVT alone. Clinical trial registration no. NCT03776877 © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Kallmes and Rabinstein in this issue.

Background: Emergent stenting in tandem occlusions and mechanical thrombectomy (MT) of acute ischemic stroke related to large vessel occlusion (LVO-AIS) with a large core are tested independently. We aim to assess the impact of reperfusion with MT in patients with LVO-AIS with a large core and a tandem occlusion and to compare the safety of reperfusion between large core with tandem and nontandem occlusions in current practice., Methods: We analyzed data of all consecutive patients included in the prospective Endovascular Treatment in Ischemic Stroke Registry in France between January 2015 and March 2023 who presented with a pretreatment ASPECTS (Alberta Stroke Program Early CT Score) of 0-5 and angiographically proven tandem occlusion. The primary end point was a favorable outcome defined by a modified Rankin Scale (mRS) score of 0-3 at 90 days., Results: Among 262 included patients with a tandem occlusion and ASPECTS 0-5, 203 patients (77.5%) had a successful reperfusion (modified Thrombolysis in Cerebral Infarction grade 2b-3). Reperfused patients had a favorable shift in the overall mRS score distribution (adjusted odds ratio [aOR], 1.57 [1.22-2.03]; P < 0.001), higher rates of mRS score 0-3 (aOR, 7.03 [2.60-19.01]; P < 0.001) and mRS score 0-2 at 90 days (aOR, 3.85 [1.39-10.68]; P = 0.009) compared with nonreperfused. There was a trend between the occurrence of successful reperfusion and a decreased rate of symptomatic intracranial hemorrhage (aOR, 0.5 [0.22-1.13]; P = 0.096). Similar safety outcomes were observed after large core reperfusion in tandem and nontandem occlusions., Conclusions: Successful reperfusion was associated with a higher rate of favorable outcome in large core LVO-AIS with a tandem occlusion, with a safety profile similar to nontandem occlusion., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: We hypothesized that treatment delays might be an effect modifier regarding risks and benefits of intravenous thrombolysis (IVT) before mechanical thrombectomy (MT)., Methods: We used the dataset of the SWIFT-DIRECT trial, which randomized 408 patients to IVT+MT or MT alone. Potential interactions between assignment to IVT+MT and expected time from onset-to-needle (OTN) as well as expected time from door-to-needle (DTN) were included in regression models. The primary outcome was functional independence (modified Rankin Scale (mRS) 0-2) at 3 months. Secondary outcomes included mRS shift, mortality, recanalization rates, and (symptomatic) intracranial hemorrhage at 24 hours., Results: We included 408 patients (IVT+MT 207, MT 201, median age 72 years (IQR 64-81), 209 (51.2%) female). The expected median OTN and DTN were 142 min and 54 min in the IVT+MT group and 129 min and 51 min in the MT alone group. Overall, there was no significant interaction between OTN and bridging IVT assignment regarding either the functional (adjusted OR (aOR) 0.76, 95% CI 0.45 to 1.30) and safety outcomes or the recanalization rates. Analysis of in-hospital delays showed no significant interaction between DTN and bridging IVT assignment regarding the dichotomized functional outcome (aOR 0.48, 95% CI 0.14 to 1.62), but the shift and mortality analyses suggested a greater benefit of IVT when in-hospital delays were short., Conclusions: We found no evidence that the effect of bridging IVT on functional independence is modified by overall or in-hospital treatment delays. Considering its low power, this subgroup analysis could have missed a clinically important effect, and exploratory analysis of secondary clinical outcomes indicated a potentially favorable effect of IVT with shorter in-hospital delays. Heterogeneity of the IVT effect size before MT should be further analyzed in individual patient meta-analysis of comparable trials., Trial Registration Number: URL: https://www., Clinicaltrials: gov ; Unique identifier: NCT03192332., Competing Interests: Competing interests: MA reports honoraria for lectures from AstraZeneca, Bayer, Covidien, Medtronic and Sanofi; Participation on Scientific Advisory Boards of Amgen, Bayer, BMS, Daiichi Sankyo, Medtronic, and Pfizer. CC reports consulting fees from Medtronic (payment made to CC). EC reports grants from the Swiss Heart Foundation and Swiss National Science Foundation, not related to present study. HCD reports that in the last 3 years, he received honoraria for participation in clinical trials, contribution to advisory boards or oral presentations from: Abbott, BMS, Boehringer Ingelheim, Daiichi Sankyo, Novo-Nordisk, Pfizer, Portola and WebMD Global. Boehringer Ingelheim provided financial support for research projects. HCD also received research grants from the German Research Council (DFG) and German Ministry of Education and Research (BMBF). HCD serves as editor of Neurologie up2date, Info Neurologie & Psychiatrie, Arzneimitteltherapie, as co-editor of Cephalalgia and on the editorial board of Lancet Neurology and Drugs. MTF reports research grants from Medtronic, Siemens, Genentech, Idorsia, and Vesalio; consulting fees from Genentech, Balt USA, Cerenovus, and Oculus Imaging; participation on a Data Safety Monitoring Board or Advisory Board for Balt USA, Jacobs Institute, and Imperative Care. UF reports financial support for the present study from Medtronic. SWIFT DIRECT is an investigator-initiated trial. The sponsor was not involved in the final study design, protocol, conduct, evaluation of results or preparation of the manuscript. UF also reports research grants from Medtronic BEYOND SWIFT registry, Swiss National Science Foundation, Swiss Heart Foundation; consulting fees from Medtronic, Stryker and CSL Behring (fees paid to institution); membership of a Data Safety Monitoring Board for the IN EXTREMIS trial and TITAN trial and Portola (Alexion) Advisory board (fees paid to institution); and Vice Presidency of the Swiss Neurological Society. UF is a member of the editorial board of JNIS. JG reports a Swiss National Funds (SNF) grant for MRI in stroke. JK reports financial support of Medtronic for the BEYOND SWIFT Registry (fees paid to institution); research grant from the Swiss National Science Foundation supporting the TECNO trial (fees paid to institution); Swiss Academy of Medical Sciences research grant supporting MRI research (fees paid to institution); Swiss Heart Foundation research grant supporting cardiac MRI in the etiological workup of stroke patients (fees paid to institution). AL reports grants from the University of Zurich, the LOOP Zurich, and P&K Pühringer Foundation; consulting fees from Bayer AG; and a lecture honorarium from Moleac Pte, Singapore. DSL reports consulting fees from Cerenovus, Genentech, Medtronic, Stryker, Rapid Medical as imaging core lab. GM reports consulting fees from Stryker Neurovascular; paid lectures for Medtronic and Microvention Europe. PM reports research funding (fees paid to institution) from the Swiss National Science Foundation, Swiss Heart Foundation and Medtronic Research Grant. PM reports grants from the Swiss National Science Foundation; Consulting fees Medtronic, Stryker; payment or honoraria from Medtronic, Stryker; participation on a Data Safety Monitoring Board or Advisory Board of MicroVention. ON reports funding from a Stryker Research grant; payment or honoraria for Phenox lecture and Stryker lecture. WP reports grants from the German Research Foundation, LOEWE (research funding of the federal state of Hesse); royalties or licenses STROKE TEAM-Training (LAERDAL medical); payment or honoraria from LAERDAL medical, Alexion, Pfizer-BMS, Stryker Neurovascular; support for attending meetings and/or travel from LAERDAL medical, Alexion, Pfizer-BMS and Stryker Neurovascular. MR reports consulting fees from Medtronic, Stryker, Cerenovus, Philips and Apta Targets; payment or honoraria from Ischemia View; participation on a Data Safety Monitoring Board or Advisory Board of Sensome; stock or stock options in Anaconda Biomed, CVAid and Methinks. AHS reports being a co-investigator for NIH - 1R01EB030092-01, Project Title: High Speed Angiography at 1000 frames per second; Mentor for Brain Aneurysm Foundation Carol W. Harvey Chair of Research, Sharon Epperson Chair of Research, Project Title: A Whole Blood RNA Diagnostic for Unruptured Brain Aneurysm: Risk Assessment Prototype Development and Testing; receipt of consulting fees from Amnis Therapeutics, Apellis Pharmaceuticals, Inc, Boston Scientific, Canon Medical Systems USA, Inc, Cardinal Health 200, LLC, Cerebrotech Medical Systems, Inc, Cerenovus, Cerevatech Medical, Inc, Cordis, Corindus, Inc, Endostream Medical, Ltd, Imperative Care, InspireMD, Ltd, Integra, IRRAS AB, Medtronic, MicroVention, Minnetronix Neuro, Inc, Peijia Medical, Penumbra, Q’Apel Medical, Inc, Rapid Medical, Serenity Medical, Inc, Silk Road Medical, StimMed, LLC, Stryker Neurovascular, Three Rivers Medical, Inc, VasSol, Viz.ai, Inc (payments made to AHS); Secretary – Board of the Society of NeuroInterventional Surgery 2020-2021 (unpaid) Chair – Cerebrovascular Section of the AANS/CNS 2020-2021 (unpaid); stock or stock options Adona Medical, Inc, Amnis Therapeutics, Bend IT Technologies, Ltd, BlinkTBI, Inc, Cerebrotech Medical Systems, Inc, Cerevatech Medical, Inc, Cognition Medical, CVAID Ltd, E8, Inc, Endostream Medical, Ltd, Galaxy Therapeutics, Inc, Imperative Care, Inc, InspireMD, Ltd, Instylla, Inc, International Medical Distribution Partners, Launch NY, Inc, NeuroRadial Technologies, Inc, NeuroTechnology Investors, Neurovascular Diagnostics, Inc, Peijia Medical, PerFlow Medical, Ltd, Q’Apel Medical, Inc, QAS.ai, Inc, Radical Catheter Technologies, Inc, Rebound Therapeutics Corp (purchased 2019 by Integra Lifesciences, Corp), Rist Neurovascular, Inc (Purchased 2020 by Medtronic), Sense Diagnostics, Inc, Serenity Medical, Inc, Silk Road Medical, Sim & Cure, SongBird Therapy, Spinnaker Medical, Inc, StimMed, LLC, Synchron, Inc, Three Rivers Medical, Inc, Truvic Medical, Inc, Tulavi Therapeutics, Inc, Vastrax, LLC, VICIS, Inc, Viseon, Inc (payments made to AHS); Other financial or non-financial interests: National PI/Steering Committees: Cerenovus EXCELLENT and ARISE II Trial; Medtronic SWIFT PRIME, VANTAGE, EMBOLISE and SWIFT DIRECT Trials; MicroVention FRED Trial & CONFIDENCE Study; MUSC POSITIVE Trial; Penumbra 3D Separator Trial, COMPASS Trial, INVEST Trial, MIVI neuroscience EVAQ Trial; Rapid Medical SUCCESS Trial; InspireMD C-GUARDIANS IDE Pivotal Trial (payments made to AHS). IS reports consulting fees (paid to IS) from Sanofi Synthé-Labo, Servier, Boheringer Ingelheim, AstraZeneca, Novonordisk and Medtronic; payment or honoraria (paid to IS) from Sanofi Synthé-Labo, Medtronic, Boheringer Ingelheim, AstraZeneca and BMS-Pfizer. JS reports funding for the present manuscript from Medtronic (paid to JS); consulting fees from Cerenovus (paid to JS); participation on a Data Safety Monitoring Board or Advisory Board – MIVI (paid to JS), Phillips (paid to JS); stock or stock options in Rapid Medical (paid to JS). MW reports a grant from Stryker Neurovascular; consulting fees from Stryker Neurovascular (payments to MW); payment or honoraria from Stryker Neurovascular, Bracco Imaging (payments to MW); German Society of Neuroradiology (DGNR) Board member (no payments); receipt of equipment, materials, drugs, medical writing, gifts or other services from ab medica, Acandis, Bracco Imaging, Cerenovus, Kaneka Pharmaceuticals, Medtronic, Mentice AB, Phenox, Stryker Neurovascular (support to institution). All other authors report no competing interests., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

Background and Objectives: The question of the long-term safety of pregnancy is a major concern in patients with multiple sclerosis (MS), but its study is biased by reverse causation (women with higher disability are less likely to experience pregnancy). Using a causal inference approach, we aimed to estimate the unbiased long-term effects of pregnancy on disability and relapse risk in patients with MS and secondarily the short-term effects (during the perpartum and postpartum years) and delayed effects (occurring beyond 1 year after delivery)., Methods: We conducted an observational cohort study with data from patients with MS followed in the Observatoire Français de la Sclérose en Plaques registry between 1990 and 2020. We included female patients with MS aged 18-45 years at MS onset, clinically followed up for more than 2 years, and with ≥3 Expanded Disease Status Scale (EDSS) measurements. Outcomes were the mean EDSS score at the end of follow-up and the annual probability of relapse during follow-up. Counterfactual outcomes were predicted using the longitudinal targeted maximum likelihood estimator in the entire study population. The patients exposed to at least 1 pregnancy during their follow-up were compared with the counterfactual situation in which, contrary to what was observed, they would not have been exposed to any pregnancy. Short-term and delayed effects were analyzed from the first pregnancy of early-exposed patients (who experienced it during their first 3 years of follow-up)., Results: We included 9,100 patients, with a median follow-up duration of 7.8 years, of whom 2,125 (23.4%) patients were exposed to at least 1 pregnancy. Pregnancy had no significant long-term causal effect on the mean EDSS score at 9 years (causal mean difference [95% CI] = 0.00 [-0.16 to 0.15]) or on the annual probability of relapse (causal risk ratio [95% CI] = 0.95 [0.93-1.38]). For the 1,253 early-exposed patients, pregnancy significantly decreased the probability of relapse during the perpartum year and significantly increased it during the postpartum year, but no significant delayed effect was found on the EDSS and relapse rate., Discussion: Using a causal inference approach, we found no evidence of significantly deleterious or beneficial long-term effects of pregnancy on disability. The beneficial effects found in other studies were probably related to a reverse causation bias., (© 2022 American Academy of Neurology.)

This article innovatively combines the analysis of both cultural and outdoor activities in Canada, activities that have been mostly studied separately until now. This study thus feeds into the debate between the distinction framework (focusing on the highbrow/lowbrow opposition) and the omnivorism thesis (distinguishing between omnivorous and univorous groups) in cultural sociology. From Latent Class Analysis (LCA), this study identifies five clusters, which differentiate people practicing either or both cultural and outdoor activities. The clusters are labelled as follow: "tele-univore," "digital indoor," "conventional indoor," "outdoor univore," and "omnivore." Binary logistic regressions reveal that education, age and rural/urban identity are the key factors in identifying who practices which activities. The findings are threefold. First, while confirming the omnivore theory, our results show that cultural capital matters more than economic capital in explaining who participates in which activities. Second, rural people tend to be slightly more engaged than urban people in consumptive and motorized outdoor activities and less in all cultural activities. Third, the shift to digitization and the increase in outdoor activities appears to have exacerbated the divide between older and younger generations., (© 2023 Canadian Sociological Association/La Société canadienne de sociologie.)

Background: Although anxiety is common in several neurological conditions, it has been poorly investigated after spontaneous intracerebral hemorrhage (ICH)., Aims: In consecutive ICH survivors, we assessed the long-term prevalence of anxiety and its clinical and radiological determinants., Methods: Using the Hospital Anxiety and Depression Scale (HADS), we evaluated ICH survivors enrolled in the prospective, single-center Prognosis of Intracerebral Hemorrhage (PITCH) study. The prevalence of anxiety (defined as a HADS-anxiety subscale score >7) was evaluated at three time points (1-2, 3-5, and 6-8 years after ICH), along with neurological symptoms severity, functional disability, and cognitive impairment scores. Clinical and radiological characteristics associated with anxiety were evaluated in univariate and multivariable models., Results: Of 560 patients with spontaneous ICH, 255 were alive 1 year later, 179 of whom completed the HADS questionnaire and were included in the study. Thirty-one patients (17%; 95% confidence interval (CI) = 12-23) had anxiety 1-2 years, 38 (27%; 95% CI = 19-34) 3-5 years, and 18 (21%; 95% CI = 12-30) 6-8 years after ICH. In patients with anxiety, the prevalence of associated depressive symptoms was 48% 1-2 years, 61% 3-5 years, and 56% 6-8 years after ICH. Among clinical and radiological baseline characteristics, only lobar ICH location was significantly associated with anxiety 1-2 years after ICH (odds ratio = 2.8; 95% CI = 1.2-6.5). Anxiety was not associated with concomitant neurological symptoms severity, functional disability, or cognitive impairment., Conclusion: Anxiety is frequent in ICH survivors, often in association with depressive symptoms, even many years after the index event.

Objective: This study aimed at identifying the incidence, predictors, and impact on long-term mortality and dementia of early-onset delirium in a cohort of patients with spontaneous intracerebral hemorrhage., Methods: We prospectively recruited consecutive patients in the Prognosis of InTra-Cerebral Hemorrhage (PITCH) cohort and analyzed incidence rate of early-onset delirium (i.e. during the first seven days after intracerebral hemorrhage onset) with a competing risk model. We used a multivariable Fine-Gray model to identify baseline predictors, a Cox regression model to study its impact on the long-term mortality risk, and a Fine-Gray model adjusted for pre-specified confounders to analyze its impact on new-onset dementia., Results: The study population consisted of 248 patients (mean age 70 years, 54% males). Early-onset delirium incidence rate was 29.8% (95% confidence interval (CI) 24.3-35.6). Multivariate analysis showed that pre-existing dementia (subhazard ratio (SHR) 2.08, 95%CI 1.32-3.32, p = 0.002), heavy alcohol intake (SHR 1.79, 95%CI 1.13-2.82, p = 0.013), and intracerebral hemorrhage lobar location (SHR 1.56, 95%CI 1.01-2.42, p = 0.049) independently predicted early-onset delirium. Median follow-up was 9.5 years. Early-onset delirium was associated with higher mortality rates during the first five years of follow-up (HR 1.52, 95%CI 1.00-2.31, p = 0.049), but did not predict new-onset dementia (SHR 1.31, 95%CI 0.60-2.87)., Conclusion: Early-onset delirium is a frequent complication after intracerebral hemorrhage; it is associated with markers of pre-existing brain vulnerability and with higher mortality risk, but not with higher dementia rates during long-term follow-up.

Document fraud is a transnational form of crime, and its serial character has already been highlighted. To combat this phenomenon, the Interstate Database of Fraudulent Identity Documents (BIDIF) has been created and implemented in Switzerland. It supports the comparison of documents and the detection of series, i.e., documents that share a common source. To efficiently use such a system, forensic document examiners would benefit from a harmonised and proven profiling method. Thus, the aim of this study is to develop a method for comparing documents and establishing series. The method is meant to improve the detection capabilities of forensic document examiners operating BIDIF or engaged in the profiling of fraudulent documents. First, a method based on the visual characteristics of digitised images of fraudulent identity documents has been developed. Subsequently, the method was qualitatively and quantitatively evaluated using four tests. The first test verified the ability of the method to detect pre-existing series. The second test checked the capability of the method to detect links amongst isolated documents. Finally, two further tests were carried out to compare the method impact on the successful detection of series. These tests were carried out by professional forensic document examiners and Master students in forensic science, respectively. This allowed a comparison of the method influence on series detection. The method allowed a significant increase in the number of series and links detected, while also decreasing the occurrence of false negatives and false positives. Furthermore, links were more rapidly detected., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Rationale: Intermittent hypoxia (IH) is one of the main features of sleep-disordered breathing (SDB). Recent findings indicate that hypoxia inducible factor-1 (HIF-1) promotes cardiomyocytes apoptosis during chronic IH, but the mechanisms involved remain to be elucidated. Here, we hypothesize that IH-induced ER stress is associated with mitochondria-associated ER membrane (MAM) alteration and mitochondrial dysfunction, through HIF-1 activation., Methods: Right atrial appendage biopsies from patients with and without SDB were used to determine HIF-1α, Grp78 and CHOP expressions. Wild-type and HIF-1α +/- mice were exposed to normoxia (N) or IH (21-5% O 2 , 60 cycles/h, 8 h/day) for 21 days. Expressions of HIF-1α, Grp78 and CHOP, and apoptosis, were measured by Western blot and immunochemistry. In isolated cardiomyocytes, we examined structural integrity of MAM by proximity ligation assay and their function by measuring ER-to-mitochondria Ca 2+ transfer by confocal microscopy. Finally, we measured mitochondrial respiration using oxygraphy and calcium retention capacity (CRC) by spectrofluorometry. MAM structure was also investigated in H9C2 cells incubated with 1 mM CoCl 2 , a potent HIF-1α inducer., Results: In human atrial biopsies and mice, IH induced HIF-1 activation, ER stress and apoptosis. IH disrupted MAM, altered Ca 2+ homeostasis, mitochondrial respiration and CRC. Importantly, IH had no effect in HIF-1α +/- mice. Similar to what observed under IH, HIF-1α overexpression was associated with MAM alteration in H9C2., Conclusion: IH-induced ER stress, MAM alterations and mitochondrial dysfunction were mediated by HIF-1; all these intermediate mechanisms ultimately inducing cardiomyocyte apoptosis. This suggests that HIF-1 modulation might limit the deleterious cardiac effects of SDB.

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., Funding: Medtronic and University Hospital Bern., Competing Interests: Declaration of interests UF reports financial support for the present study from Medtronic; research grants from Medtronic BEYOND SWIFT registry, the Swiss National Science Foundation, and the Swiss Heart Foundation; consulting fees from Medtronic, Stryker, and CSL Behring (fees paid to institution); has membership of a data safety monitoring board for the IN EXTREMIS trial and the TITAN trial; was on the advisory board for Portola (Alexion; fees paid to institution); and is Vice President of the Swiss Neurological Society. JK reports financial support from Medtronic for the BEYOND SWIFT registry (fees paid to institution); and research grants from the Swiss National Science Foundation supporting the TECNO trial (fees paid to institution), Swiss Academy of Medical Sciences supporting MRI research (fees paid to institution), and Swiss Heart Foundation supporting cardiac MRI in the aetiological work-up of stroke patients (fees paid to institution). CC reports consulting fees from Medtronic. PMo reports research funding (fees paid to institution) from the Swiss National Science Foundation, the Swiss Heart Foundation, and Medtronic. GM reports consulting fees from Stryker Neurovascular; and was paid for lectures for Medtronic and Microvention Europe. IS reports consulting fees from Sanofi Synthé-Labo, Servier, Boheringer Ingelheim, AstraZeneca, Novonordisk, and Medtronic; and payment or honoraria from Sanofi Synthé-Labo, Medtronic, Boheringer Ingelheim, AstraZeneca, and BMS—Pfizer. ON reports funding from a Stryker Research grant; and payment or honoraria for lectures for Phenox and Stryker. MR reports consulting fees from Medtronic, Stryker, Cerenovus, Philips, and Apta Targets; payment or honoraria from Ischemia View; participates on a data safety monitoring board or advisory board of Sensome; and has stock or stock options in Anaconda Biomed, CVAid, and Methinks. EC reports grants from the Swiss Heart Foundation and Swiss National Science Foundation, not related to the present study. ARL reports grants from the University of Zurich, the LOOP Zurich, and P&K Pühringer Foundation; consulting fees from Bayer; and a lecture honorarium from Moleac Pte, Singapore. WP reports grants from the German Research Foundation, LOEWE (research funding of the federal state of Hesse); royalties or licenses from the Stroke Team Training (Laerdal Medical); payment or honoraria from Laerdal Medical, Alexion, Pfizer—BMS, and Stryker Neurovascular; and support for attending meetings or travel from Laerdal Medical, Alexion, Pfizer—BMS, and Stryker Neurovascular. MA reports honoraria for lectures from AstraZeneca, Bayer, Covidien, Medtronic, and Sanofi; and participates on scientific advisory boards of Amgen, Bayer, BMS, Daiichi Sankyo, Medtronic, and Pfizer. AHS reports being a coinvestigator for the US National Institutes of Health (1R01EB030092-01); is mentor for the Carol W Harvey Chair of Research and Sharon Epperson Chair of Research at the Brain Aneurysm Foundation; receipt of consulting fees from Amnis Therapeutics, Apellis Pharmaceuticals, Boston Scientific, Canon Medical Systems USA, Cardinal Health 200, Cerebrotech Medical Systems, Cerenovus, Cerevatech Medical, Cordis, Corindus, Endostream Medical, Imperative Care, InspireMD, Integra, IRRAS AB, Medtronic, MicroVention, Minnetronix Neuro, Peijia Medical, Penumbra, Q’Apel Medical, Rapid Medical, Serenity Medical, Silk Road Medical, StimMed, Stryker Neurovascular, Three Rivers Medical, VasSol, and Viz.ai; is Secretary of the Board of the Society of NeuroInterventional Surgery 2020–2021 (unpaid); is Chair of the Cerebrovascular Section of the AANS/CNS 2020–2021 (unpaid); has stock or stock options in Adona Medical, Amnis Therapeutics, Bend IT Technologies, BlinkTBI, Cerebrotech Medical Systems, Cerevatech Medical, Cognition Medical, CVAID, E8, Endostream Medical, Galaxy Therapeutics, Imperative Care, InspireMD, Instylla, International Medical Distribution Partners, Launch NY, NeuroRadial Technologies, NeuroTechnology Investors, Neurovascular Diagnostics, Peijia Medical, PerFlow Medical, Q’Apel Medical, QAS.ai, Radical Catheter Technologies, Rebound Therapeutics (purchased 2019 by Integra Lifesciences), Rist Neurovascular, (purchased 2020 by Medtronic), Sense Diagnostics, Serenity Medical, Silk Road Medical, Sim & Cure, SongBird Therapy, Spinnaker Medical, StimMed, Synchron, Three Rivers Medical, Truvic Medical, Tulavi Therapeutics, Vastrax, VICIS, and Viseon; and other financial or non-financial interests: national principal investigator or steering committees for Cerenovus EXCELLENT and ARISE II Trial; Medtronic SWIFT PRIME, VANTAGE, EMBOLISE and SWIFT DIRECT Trials; MicroVention FRED Trial and CONFIDENCE Study; MUSC POSITIVE Trial; Penumbra 3D Separator Trial, COMPASS Trial, INVEST Trial, MIVI neuroscience EVAQ Trial; Rapid Medical SUCCESS Trial; and InspireMD C-GUARDIANS IDE Pivotal Trial. MTF reports research grants from Medtronic, Siemens, Genentech, Idorsia, and Vesalio; consulting fees from Genentech, Balt USA, CereNovus, and Oculus Imaging; and participates on a data safety monitoring board or advisory board for Balt USA, Jacobs Institute, and Imperative Care. MW reports a grant from Stryker Neurovascular; consulting fees from Stryker Neurovascular; payment or honoraria from Stryker Neurovascular and Bracco Imaging; is board member for the German Society of Neuroradiology (no payments); and receipt of equipment, materials, drugs, medical writing, gifts, or other services from Ab medica, Acandis, Bracco Imaging, Cerenovus, Kaneka Pharmaceuticals, Medtronic, Mentice, Phenox, and Stryker Neurovascular (support to institution). PMa reports grants from the Swiss National Science Foundation; consulting fees from Medtronic and Stryker; payment or honoraria from Medtronic and Stryker; and participated on a data safety monitoring board or advisory board of MicroVention. H-CD reports honoraria for participation in clinical trials, contribution to advisory boards, or oral presentations from Abbott, BMS, Boehringer Ingelheim, Daiichi-Sankyo, Novo-Nordisk, Pfizer, Portola, and WebMD Global; financial support for research projects from Boehringer Ingelheim; received research grants from the German Research Council and German Ministry of Education and Research; serves as Editor of Neurologie up2date, InFo Neurologie & Psychiatrie, Arzneimitteltherapie, and coeditor of Cephalalgia; and is on the editorial board of The Lancet Neurology and Drugs. MM reports payment or honoraria from Boehringer Ingelheim. DSL reports consulting fees from Cerenovus, Genentech, Medtronic, Stryker, and Rapid Medical as imaging core laboratory. JLS reports funding for the present study from Medtronic; consulting fees from Cerenovus; participates on a data safety monitoring board or advisory board for MIVI and Phillips; and has stock or stock options in Rapid Medical. JG reports a Swiss National Funds grant for MRI in stroke. All other authors declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Competing Interests: Conflict of interest None disclosed.