Why MS Patients Develop Progressive Disability

New research shows that the brain and spinal cord scars in people with MS may offer clues to why they develop progressive disability in comparison to related diseases that don’t develop them.

In a study researchers and colleagues assessed if inflammation leads to permanent scarring in MS, Aquaporin-4 antibody positive neuromyelitis optica spectrum disorder (AQP4-NMOSD) and Myelin oligodendrocyte glycoprotein antibody associated disorder (MOGAD).

They also studied whether scarring may be a reason for the absence of slow progressive disability in AQP4-NMOSD and MOGAD, compared with MS.

In all three of these diseases, the body’s immune system targets the myelin, the insulation around nerves. This causes inflammation and leads to removal of myelin, called demyelination, within the brain and spinal cord. Areas of demyelination, known as lesions, appear as white spots on an MRI. The repair mechanisms within the body try to reinsulate the nerves and repair the lesions, but this may be incomplete, leading to a scar that remains visible on future MRIs. 

The study included 156 patients, consisting of 67 patients with MS; AQP4-NMOSD, 51; and MOGAD, 38. 

With MS, the researchers found that areas of inflammation reduced only modestly in size and led to a moderately sized scar. When scars are in regions of the brain and spinal cord that control arm and leg muscles, nerve fibers can degenerate and lead to slow worsening of disability in the secondary progressive course of MS.

But AQP4-NMOSD and MOGAD are different from MS in that they do not have the same slow worsening of disability typical of the progressive course in MS.

With AQP4-NMOSD, large areas of inflammation occur during attacks, which often results in severe symptoms. Scars are common, but they tend to be smaller and in less important locations than in MS. Thus, less long-term problems result from those scars.

With MOGAD, despite having large areas of inflammation during an attack, the researchers found lesions tended to disappear completely over time and not leave any scar. This fits well with the excellent recovery from episodes and overall good long-term prognosis without the slow worsening disability seen in MS.

“We hope that the improved understanding on the ways MOGAD repairs its lesions so well may lead to novel treatment avenues to prevent scar formation in MS,” Dr. Flanagan says.


Elia Sechi, Karl N. Krecke, Steven A. Messina, Marina Buciuc, Sean J. Pittock, John J. Chen, Brian G. Weinshenker, A. Sebastian Lopez-Chiriboga, Claudia F. Lucchinetti, Nicholas L. Zalewski, Jan Mendelt Tillema, Amy Kunchok, Salvatore Monaco, Padraig P. Morris, James P. Fryer, Adam Nguyen, Tammy Greenwood, Stephanie B. Syc-Mazurek, B. Mark Keegan, Eoin P. Flanagan. Comparison of MRI Lesion Evolution in Different Central Nervous System Demyelinating Disorders. Neurology, 2021; 10.1212/WNL.0000000000012467 DOI: 10.1212/WNL.0000000000012467

Mayo Clinic. “Why MS patients develop progressive disability.” ScienceDaily. ScienceDaily, 19 July 2021. <www.sciencedaily.com/releases/2021/07/210719143410.htm>.

Images from:

Photo by Tim Mossholder