Myelocortical MS (MCMS)

[frodo]

Researchers discover new subtype of multiple sclerosis (The Lancet)

https://www.ms-uk.org/researchers-disco ... -sclerosis

Cleveland Clinic researchers have discovered a new subtype of multiple sclerosis (MS), providing a better understanding of the individualised nature of the disease.

MS has long been characterised as a disease of the brain's white matter, where immune cells destroy myelin - the fatty protective covering on nerve cells. The destruction of myelin (called demyelination) was believed to be responsible for nerve cell (neuron) death that leads to irreversible disability in patients with MS.

However, in the new findings, a research team led by Bruce Trapp, Ph.D., identified for the first time a subtype of the disease that features neuronal loss but no demyelination of the brain's white matter. The findings, published in Lancet Neurology, could potentially lead to more personalised diagnosis and treatments.

This new subtype of MS, called myelocortical MS (MCMS), was indistinguishable from traditional MS on MRI. 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 disease was only diagnosed in post-mortem tissues.

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,” said Trapp, chair of Cleveland Clinic's Lerner Research Institute Department of Neurosciences. “This information highlights the need for combination therapies to stop disability progression in MS.”

In the study of brain tissue from 100 MS patients who donated their brains after death, the researchers observed that 12 brains did not have white matter demyelination. They compared microscopic tissue characteristics from the brains and spinal cords of 12 MCMS patients, 12 traditional MS patients 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 having no typical MS lesions in the white matter, MCMS brains did have reduced neuronal density and cortical thickness, which are hallmarks of brain degeneration also observed in traditional MS. Contrary to previous belief, these observations show that neuronal loss can occur independently of white matter demyelination.

“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,” said Daniel Ontaneda, M.D., clinical director of the brain donation program at Cleveland Clinic's Mellen Center for Treatment and Research in MS. “We are hopeful these findings will lead to new tailored treatment strategies for patients living with different forms of MS.”

[frodo]

These are big news. First of all, because 12% of patients have damage in the WM without demyelination. So much for the autoimmune demyelination theories.

In this review (https://reliawire.com/myelocortical-ms/) they explain it: "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".

Only two days after publication there are already several reactions to the article:

• https://newsroom.clevelandclinic.org/20 ... sclerosis/
  https://www.neurologylive.com/clinical- ... plications
  http://practicalneurology.com/news/?id=52293&center=36
  https://www.radiologybusiness.com/topic ... ic-imaging
  https://www.sciencedaily.com/releases/2 ... 185244.htm
  https://www.genengnews.com/gen-news-hig ... d/81256158
  https://www.medpagetoday.com/neurology/ ... osis/74721
  https://www.medicalnewstoday.com/articles/322859.php
  https://multiplesclerosisnewstoday.com/ ... -in-study/
  https://www.raredr.com/news/new-subtype ... discovered

By the way, this is not the first time they report it. They found it in 2013.

http://onlinelibrary.ectrims-congress.e ... tiple.html

This has enormous consequences for pathogenesis theories. In 2016 a review said: "Furthermore, this study supports the concept that MS may be a neurodegenerative disease with a secondary aberrant immune response"

https://etd.ohiolink.edu/pg_10?0::NO:10 ... BID:114418

It is also interesting an interview with Bruce Trapp, leader of the team who found it.

https://www.neurologylive.com/clinical- ... -sclerosis

[NHE]

Thanks. New paradigms are finally replacing outdated modes of thinking.

I've added MCMS to the Forums FAQ list of acronyms.
http://www.thisisms.com/forum/site-supp ... ml#p210825

[Kheuer]

These are big news. First of all, because 12% of patients have damage in the WM without demyelination. So much for the autoimmune demyelination theories.

Your statement is not scientifically supportable.

This subset of patients may be able to re-myelinate white matter more efficiently.

And AI demyelination has been proven to be a causative agent in MS.

From your link

"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."

Both the Cerebral Cortex AND Spinal Cord have myelin sheathing, and the MCMS persons showed lesions on the spinal cord and in the cerebral cortex so they had demyelination just not in the white matter.

Perhaps you should research the scientific correctness of statements that you make before you post things on the board.

[frodo]

Perhaps you should research the scientific correctness of statements that you make before you post things on the board.

That statement is not mine. I was just quoting the source I gave:

https://reliawire.com/myelocortical-ms/

I will quote it completely:

"In the study of brain tissue from 100 MS patients who donated their brains after death, the researchers observed that 12 brains did not have white matter demyelination. They compared microscopic tissue characteristics from the brains and spinal cords of 12 MCMS patients, 12 traditional MS patients and also individuals without neurological disease"

The sentence "so much for the autoimmune demyelination theories" is mine and I could be wrong. Anyway I was referring to an "only autoimmune" model. Sorry if that was inacurate.

Thanks for your comment anyway.

[frodo]

Maybe related to myelocortical MS: A report about Optic-Spinal MS (OSMS)

OSMS reports are old and they were found to be mostly NMO, but some cases are AQP4-negative and therefore inside MS.

Thus, OSMS still exists and could be related to Myelocortical MS (MCMS)

In this paper the researchers do not state clearly if they have tested their patients for AQP4, but let's hope they have.

Cytokine–chemokine and cognitive profile of multiple sclerosis patients with predominant optic nerve and spinal cord involvement

https://www.tandfonline.com/doi/abs/10. ... 19.1666238

Conclusion: Neuropsychological and motor function test performances of CMS (conventional MS) and MS-SCON patients (MS presenting predominantly with spinal cord and optic nerve attacks) were highly comparable.

CMS and MS-SCON present with similar clinical, neuropsychological and immunological features.

Therefore, optic nerve and spinal cord-dominant form of MS does not necessarily establish a distinct entity in our region.

Cognitive networks of the central nervous system may be damaged during the disease course of MS, despite the absence of cerebral or cerebellar clinical attacks.

[frodo]

The cortical pathology is associated to a specific CSF profile:

Inflammatory intrathecal profiles and cortical damage in multiple sclerosis

https://onlinelibrary.wiley.com/doi/ful ... /ana.25197

Abstract
Objective

Gray matter (GM) damage and meningeal inflammation have been associated with early disease onset and a more aggressive disease course in multiple sclerosis (MS), but can these changes be identified in the patient early in the disease course?

Methods

To identify possible biomarkers linking meningeal inflammation, GM damage, and disease severity, gene and protein expression were analyzed in meninges and cerebrospinal fluid (CSF) from 27 postmortem secondary progressive MS and 14 control cases. Combined cytokine/chemokine CSF profiling and 3T magnetic resonance imaging (MRI) were performed at diagnosis in 2 independent cohorts of MS patients (35 and 38 subjects) and in 26 non‐MS patients.

Results

Increased expression of proinflammatory cytokines (IFNγ, TNF, IL2, and IL22) and molecules related to sustained B‐cell activity and lymphoid‐neogenesis (CXCL13, CXCL10, LTα, IL6, and IL10) was detected in the meninges and CSF of postmortem MS cases with high levels of meningeal inflammation and GM demyelination. Similar proinflammatory patterns, including increased levels of CXCL13, TNF, IFNγ, CXCL12, IL6, IL8, and IL10, together with high levels of BAFF, APRIL, LIGHT, TWEAK, sTNFR1, sCD163, MMP2, and pentraxin III, were detected in the CSF of MS patients with higher levels of GM damage at diagnosis.

Interpretation

A common pattern of intrathecal (meninges and CSF) inflammatory profile strongly correlates with increased cortical pathology, both at the time of diagnosis and at death. These results suggest a role for detailed CSF analysis combined with MRI as a prognostic marker for more aggressive MS. Ann Neurol 2018 Ann Neurol 2018;83:739–755