Cervical spinal cord gray matter damage predicts disability worsening in multiple sclerosis: a longitudinal study

Objective: Cervical spinal cord (cSC) gray matter (GM) damage is associated with current disability in multiple sclerosis (MS), but its prognostic value remains unexplored. We aimed to investigate whether cSC GM damage may predict disability worsening in MS. Materials and methods: Seventy-nine MS patients and 49 healthy controls (HC) underwent 3 T brain and cSC MRI at baseline and two neurological evaluations after median follow-up of 1.3 years. Total and GM cSC lesions were identified on axial T2-weighted sequences, whereas global and GM cSC cross-sectional areas (CSAs) at C3–C4 level were quantified on phase-sensitive inversion recovery sequences. Brain lesional and volumetric measures were also assessed. At follow-up, disability worsening was defined as deterioration on ≥ 1/3 components of the Expanded Disability Status Scale (EDSS)-plus score (EDSS worsening or ≥ 20% change in timed 25-foot walk [T25FWT] or 9-hole peg test [9-HPT]). Results: At follow-up, 40/79 (50.6%) patients showed EDSS-plus worsening, with 13/79 (16.4%) worsening at EDSS score, 13/79 (16.4%) at 9-HPT, and 29/79 (36.7%) at T25FWT. Progressive phenotype (odds ratio [OR] = 8.65) predicted EDSS worsening (p = 0.001, C-index = 0.79). Progressive phenotype (OR = 5.56), lower cortical volume (OR = 0.41), and higher cSC GM T2-hyperintense lesion volume (OR = 2.28) (p ≤ 0.035, C-index = 0.88) predicted 9-HPT worsening. Longer disease duration (OR = 1.64), progressive phenotype (OR = 4.74), and lower cSC GM CSA (OR = 0.51) predicted T25FWT worsening (p ≤ 0.050, C-index = 0.77). Male sex (OR = 6.12), older age (OR = 1.71), progressive phenotype (OR = 7.40), and lower cSC GM CSA (OR = 0.47) predicted EDSS-plus worsening (p ≤ 0.055, C-index = 0.83). Conclusions: cSC GM damage emerged as a relevant MRI predictor of disability worsening in MS, highlighting its prognostic relevance.