Abstract
Cerebellar symptoms in multiple sclerosis (MS) are well described; however, the exact contribution of cerebellar damage to MS disability has not been fully explored. Longer-term observational periods are necessary to better understand the dynamics of pathological changes within the cerebellum and their clinical consequences. Cerebellar lobe and single lobule volumes were automatically segmented on 664 3D-T1-weighted MPRAGE scans (acquired at a single 1.5 T scanner) of 163 MS patients (111 women; mean age: 47.1 years; 125 relapsing–remitting (RR) and 38 secondary progressive (SP) MS, median EDSS: 3.0) imaged annually over 4 years. Clinical scores (EDSS, 9HPT, 25FWT, PASAT, SDMT) were determined per patient per year with a maximum clinical follow-up of 11 years. Linear mixed-effect models were applied to assess the association between cerebellar volumes and clinical scores and whether cerebellar atrophy measures may predict future disability progression. SPMS patients exhibited faster posterior superior lobe volume loss over time compared to RRMS, which was related to increase of EDSS over time. In RRMS, cerebellar volumes were significant predictors of motor scores (e.g. average EDSS, T25FWT and 9HPT) and SDMT. Atrophy of motor-associated lobules (IV-VI + VIII) was a significant predictor of future deterioration of the 9HPT of the non-dominant hand. In SPMS, the atrophy rate of the posterior superior lobe (VI + Crus I) was a significant predictor of future PASAT performance deterioration. Regional cerebellar volume reduction is associated with motor and cognitive disability in MS and may serve as a predictor for future disease progression, especially of dexterity and impaired processing speed.
Highlights
Measures of central nervous system (CNS) atrophy are increasingly recognized as viable biomarkers of disease burden in multiple sclerosis (MS) [1, 2]
Cerebellar volumes (TCV, anterior lobe and posterior superior lobe volume (CGV), CWV, anterior lobe, posterior superior lobe, posterior inferior lobe — see Fig. 1) and their change over time were evaluated with respect to demographic and clinical metrics using Linear mixed-effects regression (LMER) (Table 3)
In men, volume loss progressed faster compared to women in total cerebellar volume (TCV), CGV, posterior superior lobe and posterior inferior lobe volume
Summary
Measures of central nervous system (CNS) atrophy are increasingly recognized as viable biomarkers of disease burden in multiple sclerosis (MS) [1, 2]. In MS patients, both cerebellar signs and symptoms are significant contributors to the development of disability and often progress despite disease-modifying treatment [6, 7]. Further cross-sectional neuroimaging studies have confirmed cerebellar volume reductions in patients with MS when compared to healthy controls [9,10,11,12,13]. While correlation with the expanded disability status scale (EDSS) was at best modest [10] or non-existing [11, 15, 16], more convincing correlations were observed between cerebellar volumes and clinical measures, which directly reflect fine-motor skills, locomotion or cognition [9, 12,13,14, 17]. The high variability between studies may be explained by the application of different techniques (semiautomated versus automated segmentation, voxel based morphometry, whole versus lobule-wise analyses etc.), heterogeneity in patient cohorts (disease duration, disease types, number of patients) and the fact that mainly cross-sectional study designs were used
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