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Inflammation, permanent scarring and progressive disability in multiple sclerosis patients - Breakthrough
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Inflammation, permanent scarring and progressive disability in multiple sclerosis patients

A new study led by Mayo Clinic examined the role of inflammation in creating permanent scarring in multiple sclerosis.

Multiple sclerosis (MS), aptly named for the multiple scars it creates, is a complex neurological disorder. Recent research indicates that these scars within the brain and spinal cord of MS patients could hold the key to understanding why they develop progressive disabilities. Remarkably, similar immune system attacks on the central nervous system, as seen in related diseases, do not yield the same outcome. These revelations hint at the underlying processes that might be critical in determining the course of these diseases, and provide a foundation for improved patient care, including the need for an NDIS worker screening check in Victoria.

Breaking down the complexities of neurological scarring

A study published in Neurology, led by Mayo Clinic researchers, aimed to investigate the role of inflammation in creating permanent scarring in three diseases: MS, Aquaporin-4 antibody positive neuromyelitis optica spectrum disorder (AQP4-NMOSD), and Myelin oligodendrocyte glycoprotein antibody associated disorder (MOGAD). This groundbreaking research explored if scarring might be responsible for the absence of slow progressive disability in AQP4-NMOSD and MOGAD, compared to MS.

“The distinctions in scarring that we discovered could assist physicians in more readily differentiating these three diseases for more accurate diagnoses,” says Eoin Flanagan, M.B., B.Ch., a Mayo Clinic neurologist and senior author of the study. “However, more significantly, our findings enhance our understanding of the mechanisms causing nerve damage in these three diseases and suggest a crucial role of such scars in the development of long-term disability in MS.”

The role of the immune system and the course of MS, AQP4-NMOSD, and MOGAD

In all three conditions, the body’s immune system targets the myelin, the protective layer around nerves, causing inflammation and consequent removal of myelin (demyelination) within the brain and spinal cord. Common symptoms include visual problems, numbness, weakness, or bowel or bladder dysfunction. The body attempts to repair these lesions by reinsulating the nerves, but this effort can be incomplete, leading to residual scarring visible on future MRIs. The presence of these scars, akin to an electrical cable stripped of its insulation, leaves nerve fibres susceptible to further damage and deterioration over time.

Comparative analysis of scarring across MS, AQP4-NMOSD, and MOGAD

The study included 156 patients (67 with MS; 51 with AQP4-NMOSD, and 38 with MOGAD) who experienced a combined total of 172 attacks or relapses. In MS patients, areas of inflammation only modestly reduced in size, resulting in moderately sized scars. When these scars occur in regions controlling arm and leg muscles, nerve fibres can degenerate, leading to a slow worsening of disability in the secondary progressive course of MS.

However, AQP4-NMOSD and MOGAD differ from MS in that they don’t exhibit the same slow progression of disability. In AQP4-NMOSD, large areas of inflammation occur during attacks often leading to severe symptoms. While scarring is common, it is typically smaller and less critical than in MS, resulting in fewer long-term problems.

In contrast, despite MOGAD patients experiencing large areas of inflammation during an attack, the researchers found that lesions tended to vanish completely over time, leaving no scar. This aligns with the excellent recovery rate from episodes and overall favourable long-term prognosis without the slow worsening disability seen in MS. The exact reasons for this remarkable recovery in MOGAD patients remain unclear. It could indicate an enhanced capacity for remyelination, the process of restoring the protective myelin coating around nerves.

“We hope that the improved understanding of the ways MOGAD repairs its lesions so effectively may lead to novel treatment avenues to prevent scar formation in MS,” says Dr. Flanagan. This highlights the potential for breakthroughs in treating MS, utilising knowledge gleaned from studying related disorders.

An interdisciplinary approach and future implications

The research was a collective effort involving multiple researchers from Mayo Clinic, Medical University of South Carolina, and University of Verona. This interdisciplinary approach underscored the importance of collaborative work in complex fields like neurology. The research was generously funded by several institutions, including the Gianesini Research Grant from UniCredit Foundation and University of Verona, Mayo Clinic Center for Multiple Sclerosis and Autoimmune Neurology, and the National Institute of Health’s National Institute of Neurological Disorders and Stroke.

“Our study emphasises the importance of the currently available MS medications that can very effectively prevent attacks, new lesions and subsequent scar formation,” says Elia Sechi, M.D., a former Mayo Clinic fellow and first author of the study. Dr. Sechi is now based at the University of Sassari in Sardinia, Italy.

This ground-breaking research has fundamentally enhanced our understanding of multiple sclerosis and related disorders. It has illuminated the role of inflammation and scarring in these diseases and offered tantalising hints towards better treatment strategies for MS. This study serves as a stepping stone towards a future where progressive disability in MS could potentially be halted, significantly improving the quality of life for those affected by this debilitating disease.

Vey Law

Vey Law is a reporter at Breakthrough.

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