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Cerebral White Matter Demyelination Not a Hallmark of Myelocortical MS

David Bai
Findings from a retrospective study comparing typical and myelocortical multiple sclerosis (MS) identified major pathological differences between the 2 MS subtypes and determined that demyelination and neuronal degeneration are independent processes. 
Findings from a study comparing typical and myelocortical multiple sclerosis (MS) identified major pathological differences between the 2 MS subtypes and determined that demyelination and neuronal degeneration are independent processes. 

Inflammation mediated by the immune system provokes demyelination of cerebral white matter, thought to be the major hallmark of MS, and the main monitoring parameter for accessing the effectiveness of disease-modifying therapies. However, only 55% of cerebral T2-weighted white-matter lesions are demyelinated, meaning other mechanisms may lead to neurological disability such as demyelination of the spinal cord or the cerebral cortex, or neurodegeneration independent of demyelination. To better understand the pathology of MS without cerebral white-matter demyelination, Trapp et al, in a retrospective study, compared postmortem brains from these individuals versus patients with MS and cerebral white-matter demyelination.

Postmortem brains with cerebral white-matter demyelination are identified as typical MS, while postmortem brains without cerebral white-matter demyelination was identified as myelocortical MS. When comparing the 2, the median number (P <.0001) and average size (P =.0068) of white-matter lesions was significantly larger in typical MS versus myelocortical MS. In both typical and myelocortical MS, demyelination of the spinal cord was evident, with a significantly greater occupation of demyelinated lesions occurring in typical MS (P =.0083). Subpial cortical demyelination was also detected in both groups.

When examining neuronal densities in the cortical layers, patients with myelocortical MS had significantly decreased densities in cortical layers III, V, and VI, while patients with typical MS had decreased neuronal densities in cortical layer V, but not in layers III or VI. Only layer V of the inferior frontal gyrus had significantly decreased neuronal density in myelocortical MS compared with typical MS. Cortical thickness was also decreased in both MS groups, with thinner cortical layers in the typical MS group.

Brain parenchymal fraction (P =.0006), white-matter fraction (P =.0211), and grey-matter fraction (P =.0129) were all significantly lower in typical MS than in myelocortical MS. Magnetic resonance imaging showed abnormal lesions in T2-weighted, T1-weighted, and total magnetization transfer ratio (MTR) imaging in both myelocortical and typical MS, with MTR lesions being significantly greater in typical MS than in myelocortical MS (P =.0388).

Findings from this retrospective study have shown that cerebral white-matter demyelination and cortical neuronal degermation can be independent factors in myelocortical MS. While cerebral white-matter demyelination was not identified in myelocortical MS, cortical neuronal density and cortical thickness were significantly decreased.

This study provides a much-needed analysis on the underlying mechanism of MS and suggests that monitoring parameters may not only need to access demyelination of cerebral white-matter, but also cortical neuronal degeneration, and other abnormalities detected in myelocortical MS.

Reference

Trapp BD, Vignos M, Dudman J, et al. Cortical neuronal densities and cerebral white matter demyelination in multiple sclerosis: a retrospective study [published online August 21, 2018]. Lancet Neurol. doi: 10.1016/S1474-4422(18)30245-X.

 
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