BACKGROUND AND AIMS
Cerebellar involvement is common in multiple sclerosis (MS),1,2 with pathological evidence of extensive white matter (WM) and grey matter (GM) damage, especially in patients with progressive MS (PMS).3,4 MRI studies confirmed higher cortical lesion number and volume in PMS compared to patients with relapsing–remitting MS (RRMS)5 and more prominent GM atrophy with increasing disability.6 Atrophy of anterior cerebellar lobes correlated with physical disability and atrophy of posterior lobes correlated with cognitive impairment.7-9 However, the cerebellum is a highly interconnected structure, whose functioning is critically dependent onto input and output pathways. Using a multiparametric MRI approach (studying atrophy, lesions, and WM microstructural abnormalities), the authors aimed to quantify cerebellar damage and identify predictors of physical disability and cognitive dysfunction in patients with MS, and to characterise patients with cerebellar disability.
MATERIALS AND METHODS
One hundred and sixty-four patients with MS (89 RRMS and 75 PMS), and 68 age- and sex-matched healthy controls underwent brain and cervical spinal cord (CSC) 3T MRI with pulse sequences for assessing lesions and atrophy in the brain (separately for cerebellum, brainstem, and supratentorial areas) and CSC; and microstructural damage (with diffusion-tensor metrics) of the cerebellar peduncles. Subjects underwent neurological examination and neuropsychological assessment with the Brief Repeatable Battery. Domain-specific z-scores were averaged, yielding a cognitive z-score. MRI predictors of clinical variables were identified with random forest models.
According to random forest analysis, informative predictors of higher Expanded Disability Status Scale score were: lower cord GM and global areas, brain volume, GM volume (GMV), cortical GMV, cerebellum lobules I–IV and vermis GMV, and higher cord GM and brainstem lesion volume (LV) in patients with MS (out-of-bag [OOB]-R2=0.83); higher brainstem and CSC GM LV, lower CSC global area, higher MCP, and cerebellum WM LV in patients with RRMS (OOB-R2=0.35); lower CSC GM area, lower cerebellum lobules I–IV GMV, lower normalised brain volume, and lower brain GMV in patients with PMS (OOB-R2=0.31).
Informative predictors of lower cognition z-score were: higher supratentorial and superior cerebellar peduncle LV and lower brain, thalamus, and basal ganglia volumes, GMV, cerebellum lobule VIIIBm, and Crus II GMV in patients with MS (OOB-R2=0.25); lower thalamus volume, higher supratentorial and SCP LV, lower normalised brain volume, lower posterior cerebellum and cerebellum Crus II GMV, and higher cerebellum WM LV in patients with RRMS (OOB-R2=0.21); lower basal ganglia volume, lower brain GMV, lower cerebellum lobule VIIIb GMV, lower thalamus volume, higher supratentorial, and lower cerebellum Crus II GMV in patients with PMS (OOB-R2=0.22).
In patients with cerebellar disability, the authors found three clusters with homogenous MRI metrics: patients with high brain LV (including cerebellar peduncles), those with marked cerebellum GM atrophy, and patients with severe CSC damage.
In this multiparametric MRI study, the authors found that damage to cerebellum GM and connecting structures explains a significant proportion of physical disability and cognitive dysfunction in patients with MS. Among patients with cerebellar disability, the authors identified three homogeneous MRI-subgroups, which is a step forward in MRI-clinical correlations.