The field of multiple sclerosis (MS) has witnessed significant advancements over the past two decades. Our understanding of the disease has evolved and continues to do so. Interestingly, some old theories that were previously dismissed are now resurfacing. New scientific evidence, combined with recent technological advancements, have made it possible to visualize disease activity that was previously undetectable.
One of the key new insights in the field is the concept of MS as a disease continuum or spectrum, rather than a condition with distinct phases, a view that had been accepted until recently. Indeed, most current evidence suggests that MS can begin in a pre-clinical form, sometimes manifesting as brain changes detected incidentally on MRI scans performed for unrelated reasons. In some cases, a prodromal phase may occur without any involvement of the nervous system. This raises the possibility of identifying MS even earlier than its clinical onset, a prospect that may not be far off.
The new proposed criteria now allow for the diagnosis of MS without a clinical incident, which had been a necessary condition in all previous versions. This change could enable earlier intervention in individuals at risk. The value of early intervention has been supported by studies investigating disease-modifying therapies (DMTs) treatment of radiologically isolated syndrome. These studies have shown not only a reduction in overall disability but also an improvement in overall outcome measures.
This leads us to an important question: would identifying the disease at its very earliest biological stage, before the formation of brain lesions or clinical symptoms, be beneficial? Technological advancements have enabled the detection of various CSF and serum biomarkers that may become abnormal even before clinical symptoms appear. Imaging, one of our most powerful tools for assessing disease activity, continues to provide important biomarkers. Notable recent additions, such as the central vein sign and paramagnetic rim lesions, are expected to be included in the next iteration of diagnostic criteria.
The treatment paradigms and choices in MS have evolved in parallel with broader developments in the field. Notably, there has been a marked shift towards early and aggressive treatment of relapsing disease, alongside a growing focus on therapies targeting progressive MS. We are now seeing DMTs being studied that may not significantly reduce relapse rates but are more effective in slowing progression.
It is becoming increasingly evident that relapses are not the sole, and perhaps not even the primary driver of disability. Instead, there appears to be a subtle, progressive and degenerative process occurring in the background from the onset of the disease. This process is thought to be driven by a pathophysiology distinct from that of relapses.
Importantly, it is now unequivocally accepted that MS, in all its forms, is a chronic and continuous immune response to Epstein–Barr virus (EBV), with this viral infection lying at the core of the disease. It is also now recognized that infectious mononucleosis (mono), particularly when it occurs at a certain age, is associated with a higher risk of developing MS.
The question that has persisted for years is: if EBV is so ubiquitous, why don’t we see MS more frequently? We now understand that additional contributing factors, including genetics and certain environmental influences, must also be present. More importantly, recent studies have identified specific regions of the virus’s protein that are associated with a higher risk, suggesting that not all serotypes of EBV carry the same risk for developing multiple sclerosis.
The field of multiple sclerosis continues to be an exciting area of research. Although we have made significant strides in understanding the disease and improving our ability to detect and treat it, we are only beginning to uncover what lies beneath the surface of the iceberg tip we see. What was once a greater and more daunting challenge is now becoming increasingly navigable, yet much remains to be explored.
Dr Yasir Jassam is an internationally recognized neurologist and neuroimmunologist specializing in autoimmune and neuroinflammatory disorders, including multiple sclerosis, neuromyelitis optica, autoimmune encephalitis and other spinal cord conditions. Board-certified by the American Board of Psychiatry and Neurology, he is a Fellow of the Royal College of Physicians and the American Academy of Neurology. Dr Jassam completed a neurology residency at Tufts University, followed by a neuroimmunology fellowship at the NIH. He serves as Director of the Multiple Sclerosis & Neuroimmunology Program and Chair of the Department of Neurology and Psychiatry at Hoag. Dr Jassam is also Division Chief of Neurology in Hoag Specialty Clinic.
Citation: Jassam, Y. The Future of Multiple Sclerosis: A New Era. touchNEUROLOGY.com. 15 April 2025.
Disclosures: This short article was provided by Dr Jassam to touchNEUROLOGY. No funding or fees are associated with the publication of this article.
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