Neurology

Noninvasive neuromodulation trials for migraine and cluster headache are heterogeneous and often not IHS-aligned.

Seventy trials (1990–2024) of modalities including nVNS, e-TNS, sTMS, rTMS, and REN were reviewed for IHS guideline adherence. Acute migraine trials were more often randomized and sham-controlled, while preventive trials showed substantial heterogeneity in design and endpoints. For cluster headache, only nVNS has trial evidence in the reviewed literature. Authors conclude promising signals exist but additional robust, sham-controlled studies are required to validate efficacy. 1

Futility (Simon two-stage) designs using CDR-SB appear feasible for AD-associated dementia but need careful thresholds.

Analysis of 2,665 ADNI participants (424 with AD dementia) found the CDR-SB showed the largest proportion worsening at 12 months. Using thresholds (e.g., ≥1.0 point CDR-SB at 12 months), short 6–12 month phase 2 futility trials may be feasible in AD-associated dementia with small samples. MCI cohorts required longer follow-up and selective entry criteria including age, APOE ε4, and baseline CDR-SB. Authors recommend validating thresholds and sample-size assumptions before adopting futility designs prospectively. 2

NPSLE research is shifting toward precision diagnostics and therapies but lacks standardized diagnostic thresholds.

Bibliometric analysis of 1,569 publications (2006–2025) shows increasing research volume and emphasis on neuroimaging and cognitive assessment. Major barriers identified include clinical heterogeneity, lack of standardized diagnostic thresholds, and exclusion of active NPSLE from many trials. The field is moving toward precision approaches but needs NPSLE-specific trials and CNS-penetrant therapies to change outcomes. Authors call for standardized diagnostic frameworks and inclusion of active NPSLE cases in future trials. 3