Neurology, distilled.

To evaluate the efficacy and safety of subcutaneous ofatumumab in adults with relapsing multiple sclerosis who switched from oral fingolimod or fumarates because of breakthrough disease activity.

Adjusted annualized relapse rate was 0.06 (95% CI 0.05-0.08; p<0.0001) over 96 weeks, meeting the primary endpoint

Describe baseline decision-making, cohort selection, and reasons for declining randomization in a pragmatic RCT plus parallel observational study of early highly-effective (EHT) vs escalation (ESC) DMT approaches in treatment-naive relapsing-remitting multiple sclerosis (RRMS).

Of 816 enrolled (mITT 767: 393 RCT, 374 OBS), participants declined randomization mainly for preference for a specific DMT (317/371 = 85%), efficacy concerns (74/371 = 20%), and safety concerns (32/371 = 8.6%); insurance denial only 3/371 (0.8%).

In adults with migraine (≥4 migraine days/month), compare tolerability, safety, and efficacy of oral atogepant 60 mg once daily versus highest tolerated dose of topiramate (50, 75, or 100 mg/day) over 24 weeks.

Primary — treatment discontinuation due to TEAEs across 24 weeks: 12% (33/273) atogepant vs 30% (79/267) topiramate; RR 0·4 (95% CI 0·3–0·6), p<0·0001.

To test whether a multidomain lifestyle intervention is related to brain biomarker changes, whether brain changes correlate with intervention-specific cognition changes, and whether brain imaging biomarkers identify who is likely to benefit from a lifestyle intervention.

No intervention group differences in longitudinal cognitive or imaging outcomes (global Aβ, ERC tau, HC volume, WMH volume)

In adults with anterior-circulation large vessel occlusion stroke and successful thrombectomy (expanded TICI 2b50-3), does adjunctive intra-arterial alteplase (0.225 mg/kg, max 20 mg over 15 min) improve 90-day functional outcome and cerebral reperfusion vs thrombectomy alone.

Primary: mRS 0-1 at 90 days in 57.5% (123/214) with adjunctive IA alteplase vs 42.5% (93/219) with thrombectomy alone — adjusted risk difference 15.0% (95% CI, 5.7-24.3); P=.002.

To determine whether standard-dose tenecteplase (0.25 mg/kg) achieves higher early substantial reperfusion than low-dose alteplase (0.6 mg/kg) prior to mechanical thrombectomy in acute ischemic stroke from large-vessel occlusion

Tenecteplase (0.25 mg/kg) achieved a 2.9-fold higher rate of substantial reperfusion on initial angiogram vs low-dose alteplase (10.3% vs 3.6%; absolute difference 6.5 pp, 90% CI 0.89–12.1), meeting the prespecified success criterion

In patients with large-core anterior circulation ischemic stroke selected by noncontrast CT (ASPECTS 2-5), does intra-arterial thrombectomy plus medical management improve 1-year functional outcomes vs medical management alone?

Primary 1-year endpoint: mean utility-weighted mRS was higher (better) with IAT vs MM (3.65 [SD 0.22] vs 2.78 [SD 0.17]; bayesian adjusted mean difference 1.18, 95% CrI 0.42-1.93; posterior probability of superiority 0.999).

To assess the safety and pharmacodynamic effects of VERVE-102, an in vivo base-editing therapy designed to durably inactivate PCSK9 in the liver, in adults with heterozygous familial hypercholesterolemia or premature coronary artery disease.

No dose-limiting toxic effects; mild-to-moderate infusion-related reactions and transient ALT elevations observed