Abstract
The hallmark of Multiple Sclerosis (MS) pathophysiology is the damage to the myelin sheath around axons. The cerebellum is a predilection site for demyelination with a well-recognized role in motor and a rather understudied contribution to cognitive functions. The aim of this study is to investigate patterns of cerebellar grey and white matter pathology, expressed as reduced volume, as well as cortical thickness and their potential contribution to cognitive performance and disability status of patients with MS. 24 patients with MS underwent extensive neuropsychological assessment using paper and pencil tests and the Brain Health Assessment (BHA) tablet-based battery. Cerebellar lobular volumes and thickness were calculated using a volumetric analysis with automated segmentation of the cerebellum and its lobules. The main findings are a reduction of cerebellar grey matter (CGMV) and white matter volumes (CWMV) in lobule X and a widespread cerebellar cortical thinning in patients. Overall disease severity and neurological disability, assessed with the Expanded Disability Status Severity Scale, was correlated with fatigue and information processing speed tasks, but not with CGMV and CWMV. CWMV and CGMV of lobule I-II was negatively correlated with information processing speed, as well as visuospatial memory tests and, finally, inverse cortical thinning associations were noted between the whole cerebellum, lobule I-II, lobule III, lobule VI, Crus I, lobule VIIIA and information processing speed and verbal fluency tasks. The inverse associations observed may represent a compensatory mechanism activated in MS engaging additional high-level cortical areas functionally interconnected with the damaged cerebellum, in order to cope with the cognitive demands of a task.
Highlights
Multiple Sclerosis (MS) is a heterogeneous, neurodegenerative disease, characterized by the presence of inflammation, demyelination and loss of axons and neurons in the Central Nervous System (CNS) that leads to progressive physical disability and cognitive impairment
Given the limited information on the cerebellar pathology expressed as cerebellar atrophy in MS and the much-disputed role of the cerebellum in cognitive functioning our aim was twofold: first, we wanted to determine the extent of cerebellar atrophy in patients with MS using a novel automatic magnetic resonance imaging (MRI) segmentation analysis, and second to investigate if cerebellar atrophy is related to cognitive deficits-measured with widely used neuropsychological procedures and experimental computerized tasks – and to the disability status of persons with Multiple Sclerosis (PwMS), assessed with the Expanded Disability Status Scale (EDSS)
No significant differences in either cerebellar grey matter volume (CGMV) or cerebellar WM volume (CWMV) were observed between patients with relapsingremitting Multiple Sclerosis (RRMS), secondary progressive Multiple Sclerosis (SPMS) and primary- progressive Multiple Sclerosis (PPMS)
Summary
Multiple Sclerosis (MS) is a heterogeneous, neurodegenerative disease, characterized by the presence of inflammation, demyelination and loss of axons and neurons in the Central Nervous System (CNS) that leads to progressive physical disability and cognitive impairment. Cognitive impairment is estimated to affect 40%–65% of PwMS [1] and may be present even in the absence of physical disability. The mechanisms contributing to cerebellar atrophy in PwMS include demyelination, axonal/neuronal loss [5] and synaptic reduction [4]. The few available MRI studies have demonstrated a significant reduction in cerebellar GM and WM volume in PwMS compared to healthy controls, which is related to impaired motor function, and impaired performance on cognitive tests. Posterior cerebellar volume loss is mainly associated with cognitive impairment, whereas anterior cerebellar volume loss is associated with motor dysfunction [6, 7]
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