Miguel D'Haeseleer, Eva M M Strijbis, Gary Cutter, Laetitia Della Faille, Marie B D'hooghe, Daphne Kos, Anne-Lotte Lison, Jop Mostert, Guy Nagels, Pavle Repovic, Bernard M J Uitdehaag, Ann Van Remoortel, Jeroen Van Schependom, Marcus W Koch
Early RRMS shows spatially organised NAWM metabolic disruption. Regional NAA/Cr-cognition associations are detectable but weak and not independent of age or disability, and frontal NAWM integrity relates more to physical function than cognition, supporting a network-disconnection model with limited cognitive specificity. These findings are preliminary and need longitudinal confirmation.
BACKGROUND: Non-ambulatory patients are generally excluded from clinical trials in progressive multiple sclerosis (MS), even though they continue to experience disability worsening. Using hand function - assessed with the Nine Hole Peg Test (NHPT) - as a primary endpoint could enable their inclusion. We aimed to describe two-year NHPT trajectories and identify predictors of worsening in this population to inform the design of such trials.
METHODS: We included 131 patients from the Belgian National MS Center (Melsbroek) database with (1) progressive MS, (2) a baseline Expanded Disability Status Scale (EDSS) score of ≥ 7.0, and (3) available NHPT and EDSS scores at baseline, 12, and 24 months. We applied four definitions for NHPT worsening: classical (C), best hand (BH), worst hand (WH), and either hand (EH). We investigated associations between baseline characteristics and NHPT worsening with logistic regression.
RESULTS: Across all four definitions, NHPT performance consistently worsened over time. C, BH, and WH outcomes showed similar progression rates: approximately 25% at 12 months and 40% at 24 months. The EH-NHPT definition proved most sensitive (35.9% worsening at 12 months and 52.7% at 24 months), with paradoxical improvement observed in 15.3% and 9.2% of patients, respectively. Older age and poor hand function at baseline modestly decreased the likelihood of EH-NHPT worsening at 24 months; there were no significant predictors at 12 months.
CONCLUSION: Hand function deteriorates in non-ambulatory people with progressive MS. The EH-NHPT may represent a sensitive and feasible endpoint for future clinical trials in this often-neglected population.