Cerebellar pathology and disability worsening in relapsing‐remitting multiple sclerosis: A retrospective analysis from the CombiRx trial

Abstract

Background and purpose Cerebellar damage is a valuable predictor of disability, particularly in progressive multiple sclerosis. It is not clear if it could be an equally useful predictor of motor disability worsening in the relapsing‐remitting phenotype. Aim We aimed to determine whether cerebellar damage is an equally useful predictor of motor disability worsening in the relapsing‐remitting phenotype. Methods Cerebellar lesion loads and volumes were estimated using baseline magnetic resonance imaging from the CombiRx trial (n = 838). The relationship between cerebellar damage and time to disability worsening (confirmed disability progression [CDP], timed 25‐foot walk test [T25FWT] score worsening, nine‐hole peg test [9HPT] score worsening) was tested in stagewise and stepwise Cox proportional hazards models, accounting for demographics and supratentorial damage. Results Shorter time to 9HPT score worsening was associated with higher baseline Expanded Disability Status Scale (EDSS) score (hazard ratio [HR] 1.408, p = 0.0042) and higher volume of supratentorial and cerebellar T2 lesions (HR 1.005 p = 0.0196 and HR 2.211, p = 0.0002, respectively). Shorter time to T25FWT score worsening was associated with higher baseline EDSS (HR 1.232, p = 0.0006). Shorter time to CDP was associated with older age (HR 1.026, p = 0.0010), lower baseline EDSS score (HR 0.428, p < 0.0001) and higher volume of supratentorial T2 lesions (HR 1.024, p < 0.0001). Conclusion Among the explored outcomes, single time‐point evaluation of cerebellar damage only allows the prediction of manual dexterity worsening. In clinical studies the selection of imaging biomarkers should be informed by the outcome of interest.

Predictors of multiple sclerosis progression: A systematic review of conventional magnetic resonance imaging studies

“…In white matter (WM), EDSS score was significantly correlated with WM lesion volume, central atrophy, lesion probability in the periventricular WM at the left frontal horn and around the posterior horns and with whole-brain volume particularly with widths of third and lateral ventricle [ 32 , 37 , 43 – 45 ]. The presence of confluent lesions (in RRMS), higher number of T2 lesions, lower baseline T2-lesion volume (T2LV), lower normalized brain volume (NBV), higher percentage brain volume change (PBVC) between year 2 and baseline and presence of ≥ 4 slowly expanding lesions (SELs) were defined as prognostic factors for EDSS worsening and disability progression [ 46 – 48 , 83 ].…”

A prospective study to validate the expanded timed get-up-and-go in a population with multiple sclerosis

“…Given that the cerebellum is recently linked as a driver of disability in early and progressive MS, an easy walking test sensitive to cerebellar pathology could be of significant predictive benefit. 20,21 Indicators of gait coordination in PwMS have been previously associated only with cerebellar volume and no correlations with other brain structures were found. 22 Moreover, a recent study showed that physical disability can be explained by gray matter atrophy of the cerebellum lobules I-IV and the vermis.…”