Widespread Demyelination in the Cerebellar Cortex in Multiple Sclerosis

TLDR

Neocortical demyelination in the forebrain is an important pathological feature of multiple sclerosis. The study reports that the cerebellar cortex is a major site of demyelination, especially in primary and secondary progressive MS. Cerebellar cortical lesions exhibit primary demyelination with preserved axons and neurons, occasional axonal spheroids, moderate Purkinje cell loss, and are frequently independent of white matter lesions. Cerebellar cortical demyelination affects on average 38.7 % of the cortex (up to 92 %), is band‑like across multiple folia, shows no correlation with white matter lesions, and may underlie cerebellar dysfunction in MS.

Abstract

Neocortical demyelination in the forebrain has recently been identified as an important pathological feature of multiple sclerosis (MS). Here we describe that the cerebellar cortex is a major predilection site for demyelination, in particular in patients with primary and secondary progressive MS. In these patients, on average, 38.7% of cerebellar cortical area is affected, reaching in extreme examples up to 92%. Cerebellar cortical demyelination occurs mainly in a band‐like manner, affecting multiple folia. The lesions are characterized by primary demyelination with relative axonal and neuronal preservation, although some axonal spheroids and a moderate reduction of Purkinje cells are present. Although cortical demyelination sometimes occurs together with demyelination in the adjacent white matter (leukocortical lesions), in most instances, the cortex was affected independently from white matter lesions. We found no correlation between demyelination in the cortex and the white matter, and in some cases, extensive cortical demyelination was present in the near absence of white matter lesions. Our data identify cortical demyelination as a potential substrate of cerebellar dysfunction in MS.