Myelocortical MS, New Disease Subtype Marked by Nerve Cell But Not Myelin Loss, Identified in Study

Myelocortical MS, New Disease Subtype Marked by Nerve Cell But Not Myelin Loss, Identified in Study

Researchers have identified a new subtype of multiple sclerosis (MS), one marked by nerve cell degeneration that occurs independently of immune system attacks against myelin, a process known as demyelination and considered a hallmark of MS.

The new subtype — called myelocortical MS — is indistinguishable from others in the MS spectrum using conventional magnetic resonance imaging (MRI), highlighting the need for more sensitive MRI imaging techniques.

This finding unmasks a previously unknown heterogeneity within MS, and may make possible more personalized therapies for patients.

“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,” Bruce Trapp, PhD, chair of the Cleveland Clinic’s Lerner Research Institute Department of Neurosciences and the study’s lead author, said in a press release.

“This information highlights the need for combination therapies to stop disability progression in MS,” Trapp added.

The study, “Cortical neuronal densities and cerebral white matter demyelination in multiple sclerosis: a retrospective study,” was published in The Lancet Neurology journal.

White matter makes up half the human brain and is the prime target for the immune system attacks in MS. It contains nerve fibers (axons) — the long extensions of neurons — which are surrounded by a protective coat of myelin, the insulating substance that works to speed signals, or communication, between nerve cells. This coating is the particular target of attacks by certain immune system cells in a process known as demyelination.

In myelocortical MS, the newly discovered subtype, nerve cells die but there is no evidence of demyelination in the brain’s white matter.

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In their study, Cleveland Clinic researchers looked at brain tissue samples from 100 MS patients who had donated their brains upon death. In 12 of these patients, they found no traces of white matter demyelination.

They then did a deeper analysis, comparing brain tissue from these 12 patients with 12 tissue samples from those known to have MS, and with brain samples from individuals free of any neurological disease.

The team found MS demyelinated lesions  in the spinal cord and cerebral cortex — the cerebrum’s outer layer, a gray matter part of the brain responsible for memory  and information processing — in both myelocortical and typical MS patient samples. But demyelinated lesions affecting the brain’s white matter were detected in MS patients only.

Brains of patients with myelocortical MS nonetheless showed signs of degeneration, detected by a lower number of neurons and a reduction in the brain’s thickness, a feature also known to MS. For instance, brains from healthy controls showed a mean neuronal density of 419 nerve cells per square millimeter (mm2) in layer 3 of the cerebral cortex (a layer that receives input from other cortical areas), while those with myelocortical MS had 349.8 neurons per mm2 in this layer, a significant decrease. Similar and significant decreases in cortical nerve cell densities between these two groups were also seen in other cerebral cortex layers.

Altogether, these results show that, contrary to what was previously believed, the death of neurons in MS can occur without signs of white matter demyelination.

“We propose that myelocortical multiple sclerosis is a subtype of multiple sclerosis that is characterised by demyelination of spinal cord and cerebral cortex but not of cerebral white matter,” the researchers wrote, adding that the “identification of a new subtype of multiple sclerosis supports the concept that multiple sclerosis is a complex disease with multiple underlying disease mechanisms.”

Daniel Ontaneda, MD, clinical director of the brain donation program at Cleveland Clinic’s Mellen Center for MS and a study author, added: “The importance of this research is two-fold. The identification of this new MS subtype highlights the need to develop more sensitive strategies for properly diagnosing and understanding the pathology of MCMS [myelocortical MS]. We are hopeful these findings will lead to new tailored treatment strategies for patients living with different forms of MS.”

The team emphasized that identifying signs of myelocortical MS in patients will require “sensitive brain imaging modalities that reliably delineate myelinated and demyelinated cerebral white matter.”

The study was supported by the National Multiple Sclerosis Society and the National Institute of Neurological Disorders and Stroke.

9 comments

  1. Dale Degraffenreid says:

    Are there companies doing studies as of now? My daughter has PPMS and none of the Meds are helping with her nerve disorder. The nerves in her feet, legs, and pelvic area are very painful. She may be considered for a research program.

  2. Terry says:

    I haven’t had new lesions in years. But my MS just keeps progressing, my walking becomes worse, numbness becomes worse, fatigue becomes worse. But They keep telling me I must be stable because I don’t have any new lesions. Those DMDs Must be working.

    • Stefanie Woodrick says:

      Terry, I just came across this information. I’m in the exact same situation as you! I’m calling my neurologist tomorrow!

  3. Christina Aivazoglou says:

    I was diagnosed 12 years ago. I have been on countless amounts of the DMD’s including stem cell transplant with chemotherapy and nothing has worked. This is beginning to make sense. all I do is research and I cannot find anything to make sense until now. Could you please tell me what are the different types of medication that you are researching for this subtype of MS? I am so ready to throw the towel in and totally give up. Having MS and not finding a medication that works,, is worst, way worse than having cancer.

  4. Christina Aivazoglou says:

    I was diagnosed with Ms 12 years ago. I have been on a countless amount of DMD’s including stem cells with chemotherapy. I had stem cells 2 years after diagnosis. My MRI does not change but I continue to have progression. I feel as if happened this type of MS is worse than having cancer. At least with cancer you have either a positive or negative outcome. There is no trial and error.

  5. Christina Aivazoglou says:

    I was diagnosed with MS 12 years ago. I have been on a countless amount of DMD’s including stem cells with chemotherapy. I had stem cells 2 years after diagnosis. My MRI does not change but I continue to have progression. I feel as if having this type of MS is worse than having cancer. At least with cancer you have either a positive or negative outcome. There is no trial and error.

  6. Marcia Baker says:

    I’m on my 2nd neurologist since I was diagnosed with MS over 28 years ago.

    My MRI scans show very little if any changes in the past 15 years and before that, few lesions (I don’t think they have ever found an active one either).

    But where I did have a couple of lesions in my cervical spine (neck area) are now black holes. Literally nothing.

    Hook me up to wires and my body isn’t talking with my brain either.

    This is quite interesting and seems to be me to a tee.

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