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Researchers Identify New Subtype of Multiple Sclerosis

Jaime Rosenberg

Researchers have discovered a new subtype of multiple sclerosis (MS), providing a better understanding of the disease and potentially opening the door to more personalized diagnosis and treatments.

Traditionally, demyelination of cerebral white matter is thought to stimulate neuronal degeneration and permanent neurological disability in patients with MS. However, brain magnetic resonance imaging (MRI) studies have indicated a possibility of demyelination and neuronal degeneration occurring independently. Now, new study findings have identified a subtype of MS—myelocortical MS (MCMS)—that has neuronal loss but no demyelination of the brain’s white matter.  

“This study opens up a new arena in MS research,” said Bruce Trapp, PhD, chair, Cleveland Clinic’s Lerner Research Institute, and lead researcher of the study, in a statement. “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.”
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He added that the findings highlight a need for combination therapies to stop disability progression in MS.

The study looked at the brains and spinal cords of 100 patients with MS through the Cleveland Clinic rapid autopsy protocol. They were collected between May 1998 and November 2012 and analyzed between September 6, 2011, and February 2, 2018. Of the brains, 12 did not show white matter lesions, representing MCMS.

The pathological features of the MCMS brains and corresponding spinal cords were compared with those from 12 traditional MS patients and from patients without neurological disease (controls). Despite the absence of cerebral white-matter demyelination in MCMS, cortical density and cortical thickness were significantly decreased when compared with controls.

“Cerebral white matter demyelination and cortical neuronal loss therefore seem to be independent events in MCMS,” noted the researchers.

Both traditional MS and MCMS showed lesions in the spinal cord and in the cerebral cortex. However, the authors noted that the average percentage area covered by demyelinated lesions was significantly greater in those with traditional MS. They added that the presence of spinal cord demyelination is likely the cause of the severe physical disability in patients with MCMS.

The findings led the authors to propose that MCMS is characterized by spinal cord demyelination, subpial cortical demyelination, and an absence of cerebral white-matter demyelination.

“The importance of this research is two-fold,” said Daniel Ontaneda, MD, clinical director of the brain donation program at the Cleveland Clinic’s Mellen Center for Treatment and Research in MS, in a statement. “The identification of this new MS subtype highlights the need to develop more sensitive strategies for properly diagnosing and understanding the pathology of MS.”

Reference
Trapp B, 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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