Neurology Central

Myelocortical multiple sclerosis: has a novel subtype been identified?

A team of researchers from Cleveland Clinic (OH, USA) have discovered a new subtype of multiple sclerosis (MS), termed myelocortical MS (MCMS). The researchers believe that their findings provide a better understanding of the individualized nature of the disease.

MS has long been characterized as a disease of the brain’s white matter, where immune cells destroy myelin. This demyelination was believed to be responsible for neuronal death, which leads to irreversible disability in individuals with MS.

However, for the first time, a team of researchers have identified a subtype of the disease (MCMS), which features neuronal loss but no demyelination of the brain’s white matter.

In the study, which was published in Lancet Neurology, the researchers observed that  in MCMS, part of the neurons become swollen and look like typical MS lesions indicative of white matter myelin loss on MRI.

The team’s findings support the concept that neurodegeneration and demyelination can occur independently in MS and underscore the need for more sensitive MRI imaging techniques for evaluating brain pathology in real time and monitoring treatment response in patients with the disease.

“This study opens up a new arena in MS research. It is the first to provide pathological evidence that neuronal degeneration can occur without white matter myelin loss in the brains of patients with the disease,” commented Bruce Trapp (Cleveland Clinic), lead investigator of the study. “This information highlights the need for combination therapies to stop disability progression in MS.”

Within the study, the researchers removed brains and spinal cords at autopsy from 100 individuals who had died with MS. According to the study, visual examinations of cerebral hemisphere slices were then carried out to identify brains without areas of cerebral white-matter discoloration that were indicative of demyelinated lesions (referred to as MCMS), and brains that had cerebral white-matter discolorations or demyelinated lesions (referred to as typical MS).

Their observations revealed that 12 brains did not have white matter demyelination. The researchers also compared microscopic tissue characteristics from the brains and spinal cords of individuals with MCMS (12), traditional MS (12) and also individuals without neurological disease.

Although both MCMS and traditional MS patients had typical MS lesions in the spinal cord and cerebral cortex, only the latter group had MS lesions in the brain white matter. Despite this, MCMS brains did have reduced neuronal density and cortical thickness, which are hallmarks of brain degeneration also observed in traditional MS.

“The importance of this research is twofold. The identification of this new MS subtype highlights the need to develop more sensitive strategies for properly diagnosing and understanding the pathology of MCMS,” said Daniel Ontaneda (Cleveland Clinic), co-author of the study.

Ontaneda concluded: “We are hopeful these findings will lead to new tailored treatment strategies for patients living with different forms of MS.”

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Sources: Trapp BD, Vignos M, Dudman J et al. Cortical neuronal densities and cerebral white matter demyelination in multiple sclerosis: a retrospective study. Lancet Neurology doi:10.1016/S1474-4422(18)30245-X (2018) (Epub ahead of print);