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ROCHESTER, Minnesota – Did you know that multiple sclerosis (MS) means multiple scars? New research shows that scars of the brain and spinal cord in people with MS may offer clues as to why they develop progressive disability, but not those with related diseases where the immune system attacks the nervous system central.
In a study published in Neurology, researchers and colleagues at the Mayo Clinic assessed whether inflammation leads to permanent scarring in these three conditions:
MRS.
Neuromyelitis optic spectrum disorder positive for anti-aquaporin-4 antibodies (AQP4-NMOSD).
Myelin Oligodendrocyte Glycoprotein Antibody Disorder (MOGAD).
They also investigated whether scarring could be a reason for the lack of slow progressive disability in AQP4-NMOSD and MOGAD, compared to MS.
“The differences in wound healing we found will help doctors more easily distinguish these three conditions for easier diagnosis,” says Eoin Flanagan, MB, B.Ch., neurologist at the Mayo Clinic and lead author of the study. “More importantly, our results improve our understanding of the mechanisms of nerve damage in these three diseases and may suggest an important role of these scars in the development of long-term disability in MS.”
In all three of these diseases, the body’s immune system targets myelin, isolating it around the nerves. This causes inflammation and leads to the removal of myelin, called demyelination, in the brain and spinal cord. Visual problems, numbness, weakness, or dysfunction of the bowel or bladder are common symptoms. Areas of demyelination, called lesions, appear as white spots on an MRI. Repair mechanisms in the body attempt to re-isolate nerves and repair damage, but this can be incomplete, leading to a scar that remains visible on future MRI scans. Much like an electrical cable without its insulation, this scar can leave nerve fibers vulnerable to further damage and degenerate over time.
The study included 156 patients, including 67 patients with MS; AQP4-NMOSD, 51; and MOGAD, 38. These patients presented 172 combined seizures or relapses.
With MS, researchers found that areas of inflammation only modestly reduced in size and resulted in a medium-sized scar. When the scars are in the areas of the brain and spinal cord that control the muscles of the arms and legs, the nerve fibers can degenerate and lead to the disability slowly worsening during the secondary progressive course of MS .
“Our study highlights the importance of currently available MS drugs that can very effectively prevent seizures, new lesions and subsequent scar formation,” says Elia Sechi, MD, former Mayo Clinic Fellow and lead author of the study. Dr Sechi is now at the University of Sassari in Sardinia, Italy.
But AQP4-NMOSD and MOGAD are different from MS in that they do not have the same slow worsening disability typical of the progressive course of MS.
With AQP4-NMOSD, large areas of inflammation occur during seizures, often resulting in severe symptoms. Scars are common, but they tend to be smaller and in less prominent places than in MS. Thus, fewer long-term problems result from these scars.
With MOGAD, despite having large areas of inflammation during an attack, the researchers found that the lesions tended to disappear completely over time and leave no scars. This fits well with the excellent recovery from the episodes and the good general long-term prognosis without the slow worsening of disability seen in MS.
The reasons for this recovery are unclear, the researchers note. This may suggest an increased ability to put the coating back on the nerves or remyelination.
“We hope that improving understanding of how MOGAD repairs its lesions so well may lead to new treatment pathways to prevent scar formation in MS,” said Dr. Flanagan.
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Other Mayo Clinic researchers involved in this study are Karl Krecke, MD; Steven Messina, MD; Sean Pittock, MD; John Chen, MD, Ph.D.; Brian Weinshenker, MD; A. Sebastian Lopez Chiriboga, MD; Claudia Lucchinetti, MD; Nicholas Zalewski, MD; Jan-Mendelt Tillema, MD; Amy Kunchok, MD; Padraig Morris, MBBCh .; James Fryer; Adam Nguyen; Tammy Greenwood; Stéphanie Syc-Mazurek, MD, Ph.D .; and B. Mark Keegan, MD Marina Buciuc, MD, formerly of the Mayo Clinic and now of the Medical University of South Carolina in Charleston, and Salvatore Monaco, MD, University of Verona, also contributed.
This research was funded by the Gianesini Research Grant from the UniCredit Foundation and the University of Verona, the Mayo Clinic Center for Multiple Sclerosis and Autoimmune Neurology, and the National Institute of Neurological Disorders and Stroke of the ‘National Institute of Health (R01NS113828).
Dr Flanagan reports research support as the site’s principal investigator in a randomized, placebo-controlled clinical trial of inebilizumab, a CD19 inhibitor, in neuromyelitis optic spectrum disorders funded by AstraZeneca and Horizon Therapeutics.
About the Mayo Clinic
Mayo Clinic is a non-profit organization committed to innovation in clinical practice, education, and research, and providing compassion, expertise, and answers to all in need of healing. Visit the Mayo Clinic News Network for more information on the Mayo Clinic. For more information on COVID-19, including the Mayo Clinic Coronavirus Map Tracker, which has 14-day forecasts of COVID-19 trends, visit the COVID-19 Resource Center at the Mayo Clinic.
Media contact:
Susan Barber Lindquist, Mayo Clinic Public Affairs, [email protected]
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