Centre Hospitalier General de St. Denis

In patients with acute ischemic stroke due to large vessel occlusion (AIS-LVO), the benefit of intravenous thrombolysis (IVT) administered beyond 4.5 hours from the last time known well before endovascular therapy (EVT) is uncertain. Recently, the TIMELESS trial failed to demonstrate a benefit of IVT in this setting, but this trial focused on patients directly admitted to comprehensive stroke centers (CSCs) with fast access to EVT.

To assess the efficacy and safety of IVT initiated beyond 4.5 hours in patients with AIS-LVO initially admitted to primary stroke centers (PSCs) and subsequently transferred to a CSC for EVT, allowing substantial time for the IVT to take effect.

This multicenter retrospective cohort study was conducted between January 2020 and December 2024, with 3-month follow-up, at 20 French PSCs. All consecutive patients with AIS-LVO admitted beyond 4.5 hours from the last time they were known well in the PSC and subsequently transferred to a CSC for EVT, with or without IVT administered prior to transfer, were eligible for inclusion. Data analysis was performed between May 2025 and July 2025.

The primary outcome was the 3-month modified Rankin Scale score, analyzed in the ordinal approach. Propensity score with overlap weighting (PSOW) balanced covariates between patients treated with IVT vs those without.

A total of 584 patients were included, among whom 309 patients (52.9%) were female. Median (IQR) age was 71 (61-81) years, median (IQR) baseline National Institutes of Health Stroke scale score was 15 (10-19), median (IQR) time from last known well to PSC imaging was 10.5 (6.9-14.0) hours, and 232 patients (39.7%) received IVT before transfer. Advanced brain imaging (magnetic resonance imaging or computed tomography [CT] with CT-perfusion) was performed at the PSC in 544 patients (93.2%). IVT use before transfer was independently associated with a shift toward better 3-month outcomes (PSOW–common odds ratio [OR], 1.97; 95% CI, 1.33-2.92; P  = .001) and higher odds of recanalization during transfer (PSOW-OR, 8.69; 95% CI, 3.16-23.87; P  < .001) compared with those without. The rate of any intracerebral hemorrhage and symptomatic intracerebral hemorrhage were similar between groups.

In this multicenter cohort study, IVT initiated beyond 4.5 hours prior to interhospital transfer for EVT was associated with higher rates of recanalization during transfer and improved 3-month functional outcomes, without safety concerns. These findings offer encouraging support for clinical trials evaluating IVT in the late time window before interhospital transfer.

In women with multiple sclerosis (MS), disease-modifying therapy (DMT) management during pregnancy might impact relapse risk.

To estimate the effect of DMT management during pregnancy on MS relapse rate and compare different therapeutic strategies.

This was a multicenter retrospective cohort study using data from January 1990 to December 2023. Data were extracted in December 2023 from the French MS registry. Among 52 955 women in the registry, we included pregnancies identified through childbirths in patients with relapsing-onset MS who were monitored for at least 18 months before delivery and 9 months after. Pregnancies occurring less than 18 months apart or with missing month of birth were excluded.

Mediation analysis was used to estimate the total, direct, and indirect (mediated by DMT management) effects of pregnancy. Different therapeutic strategies were compared: DMT interruption, switching to or maintaining interferon β or glatiramer acetate, switching to or maintaining natalizumab until the third trimester, and switching to or maintaining intravenous anti-CD20 and interrupting it 3 months before conception.

The primary outcome was the annualized relapse rate (ARR) during the preconception, gestation, and postpartum periods. Within a causal inference framework, counterfactual ARRs were estimated using longitudinal g-computation, combining a random forest algorithm for predicting DMTs, and a mixed-effects Poisson model for relapses.

We included 6341 pregnancies occurring in 4998 women (mean [SD] age at conception, 31.5 [4.5] years). DMT management during pregnancy significantly increased ARR during gestation (causal rate ratio [cRR], 1.13; 95% CI, 1.06-1.22) and postpartum (cRR, 1.08; 95% CI, 1.01-1.16) periods. This led to a deleterious total effect of pregnancy on ARR, particularly in women receiving natalizumab before pregnancy with prolonged interruption (ie, interruption before the second trimester or resumption more than 3 months after delivery; cRR, 2.18; 95% CI, 1.76-2.69), and in women receiving fingolimod (cRR, 2.15; 95% CI, 1.60-2.93). Compared to DMT interruption, anti-CD20 strategy was the most effective (cRR, 0.38; 95% CI, 0.25-0.52), followed by the natalizumab strategy with short interruption (cRR, 0.80; 95% CI, 0.71-0.90), whereas interferon β (cRR, 0.93; 95% CI, 0.86-0.99) and glatiramer acetate strategies (cRR, 0.91; 95% CI, 0.84-0.99) were less effective.

In this study, DMT management during pregnancy significantly increased relapse risk, particularly in patients receiving natalizumab with prolonged interruption or fingolimod. The strategy based on the use of anti-CD20 before pregnancy was the most effective to mitigate this risk.