A New MS Subtype Discovered

Researchers at the Cleveland Clinic have identified a new subtype of Multiple Sclerosis (MS). MS has traditionally been defined as an inflammatory, demyelinating condition that affects the brain and spinal cord and causes neurological change. This new study published in The Lancet Neurology suggests that the new subtype is characterized by neuronal loss – damage or death of neurons, but no demyelination of the brain’s white matter.1

The research, carried out on postmortem brain tissue upon autopsy, recognizes new dimensions of this disease and offers promise that more specific diagnostic techniques might be identified to improve the diagnosis, care and potential treatments for people with MS.1

Multiple sclerosis, the basics

Multiple sclerosis is a neurodegenerative disorder that affects the brain and spinal cord. There is no known cause or cure of MS, an autoimmune disease in which communication defects result in the immune system attacking its own tissues, destroying the myelin coat, a fatty sheath that protects the nerve fibers of the brain and spinal cord.2 Until now, it was thought that demyelination of the brain’s white matter causes interruptions in the electrical conduction messages and leads to degeneration, cell death and permanent neurological disability.1

MS affects people differently. There are physical, cognitive and emotional aspects of the disease that impact not only the person diagnosed with MS, but their family and caregivers as well. Some benefit from treatments that can reduce episodes and flare-ups (in those with relapsing-remitting MS), modifying the course of the disease as well as ability to manage symptoms. Others will suffer from chronic deterioration (progressive types of MS).

New subtype explained

The new subtype myelocortical multiple sclerosis, MCMS, identified by Bruce Trapp Ph.D. and colleagues, suggests that nerve cell death can occur independently of white matter demyelination.1 In MS and MCMS there are lesions in the spinal cord and cerebral cortex; but in MCMS there are no lesions in the brain’s white matter. On MRI scans, MCMS looks the same as typical MS. This is because the nerve cells can become swollen and appear on the image as the loss of the myelin nerve coating. The difference was only identified upon autopsy.

Daniel Ontaneda, M.D., clinical director of the brain donation program at Cleveland Clinic’s Mellen Center confirms that the identification of this new MS subtype will help science to better understand the underlying pathology that may result in individualized disease treatment strategies for different forms of MS.

The study

The team at The Cleveland Clinic examined 100 brains and spinal cords that were donated for the purpose of advancing MS research as well as control subjects without evidence of neurological disease.1,3 The retrospective study conducted between 2011 and 2018 considered findings collected over nearly 15 years between 1998 and 2012.

Autopsied brains were examined for evidence of any discoloration of the cerebral white matter that characterize demyelinated lesions, using myelin protein immunocytochemistry. Those without discoloration were identified as having MCMS and those with discoloration identified as typical MS. The evaluation matched individuals with MCMS by age, gender, MRI protocol, MS subtype, disease duration, and disability scale assessments, with individuals with typical multiple sclerosis.


12 brains classified with myelocortical multiple sclerosis were compared with 12 typical brains having multiple sclerosis. There were similar demyelinated lesions in the spinal cord and cerebral cortex, but not in the brain’s white matter, in those with MCMS. The cortical demyelinated lesion areas were similar in both types.

Both types of MS brains were compared with control brains. Cortical neuronal loss was greater in the MCMS cortex than in the typical MS cortex. The demyelinated area of the spinal cord was significantly greater in typical MS than in MCMS. Even without demyelination of the brain white matter in MCMS, cortical neuronal densities were significantly decreased when compared with control brains.3

The future

MS is a complex condition with physical, social and psychological components. Improvements in understanding the intricacies of differences in the brain have led to the breakthrough that neurodegeneration and demyelination can occur independently in MS.1 There is a need to further investigate the pathology of degeneration in both types of MS. Evaluation of molecular mechanisms may help to identify future treatment protocols and disease modifying therapies.

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