Researchers have discovered that reactivation of the dormant Epstein-Barr virus (EBV) in immune cells may trigger disease flares in multiple sclerosis, with the virus becoming detectable weeks to months before an MS relapse occurs. This finding could reshape how doctors approach MS treatment by pointing toward more precise, virus-targeted therapies instead of broadly suppressing the entire immune system.

What Is Epstein-Barr Virus and Why Does It Matter for MS?

Most people have been infected with Epstein-Barr virus by adulthood. The virus is best known for causing infectious mononucleosis, but after infection, it remains dormant in B-cells, a type of immune cell. In people with MS, this dormant virus can reactivate, and new research suggests that reactivation may be a key driver of disease flares.

A team of researchers analyzed blood samples from 114 people with MS and 21 healthy participants over decades as part of the Comprehensive Longitudinal Investigation of Multiple Sclerosis. They discovered that B-cells show notable changes in activity just before an MS relapse, with dormant EBV reactivating in the weeks and months prior to a flare. At the same time, there is an increase in a subset of B-cells called ABC-like B-cells, which are linked to chronic infection and autoimmune disease.

"We believe this work provides foundational insights into the cause of multiple sclerosis. This study puts all the pieces together, showing a timeline of how the reactivated virus interacts with risk genes to unleash inflammation before relapse occurs," said Tanuja Chitnis, MD, chief of the neuroimmunology division at Mass General Brigham.

Tanuja Chitnis, MD, Chief of Neuroimmunology Division at Mass General Brigham

How Could This Change MS Treatment?

The current standard approach to MS treatment relies on broadly suppressing the immune system to prevent flares. However, this new understanding of EBV's role opens the possibility of more targeted interventions. Instead of dampening the entire immune response, doctors could potentially develop therapies that specifically target EBV or the immune cells involved in relapse.

The researchers noted that their study does not definitively prove a cause-and-effect relationship between EBV reactivation and MS relapse. The study was limited to a relatively small number of patients, so further research is necessary to validate the results. However, the scientists are optimistic about the implications.

"These findings open a whole new avenue for targeted therapeutics. Currently, most MS treatments work by broadly suppressing the immune system. Our results suggest there's an opportunity to be more precise and develop approaches that target EBV or the immune cells involved in relapse," Chitnis explained.

Tanuja Chitnis, MD, Chief of Neuroimmunology Division at Mass General Brigham

Understanding the Three-Part Approach to MS Treatment

While this EBV discovery points toward future therapies, it's important to understand how MS treatment currently works. Multiple sclerosis is treated on three separate fronts, each with its own goal and timeline.

• Relapse Treatment: Short courses of corticosteroids shorten a relapse and speed recovery by blunting acute inflammation, though they do not change the long-term course of the disease. For severe relapses that do not respond to steroids, plasma exchange may be considered.
• Disease-Modifying Therapy: Long-term medicines that dial down the immune attack are judged by fewer relapses and stable MRI scans over months, not by how symptoms feel day to day. About 85 percent of people are diagnosed with relapsing-remitting MS, the form for which disease-modifying therapies have the strongest evidence.
• Symptom Management: Rehabilitation and targeted treatments address accumulated damage like fatigue, spasticity, pain, bladder urgency, and walking difficulty, one problem at a time.

Understanding which track a given medicine belongs to is crucial. People sometimes stop a disease-modifying therapy because their fatigue has not improved, when the medicine was never meant to touch fatigue. Others skip a steroid course, believing their long-term tablets should have prevented the relapse. Each track has its own goal, its own timeline, and its own way of being judged.

What Defines an MS Relapse?

A true MS relapse is defined by new or worsening neurological symptoms lasting at least 24 hours without fever or infection. Shorter flares are often pseudo-relapses triggered by heat or illness. Symptoms can include numbness, weakness, double vision, or loss of balance.

Recovery is rarely instant. Symptoms can take weeks or months to improve after a relapse, and rehabilitation often begins during this window. Whether or not steroids are used, every relapse is also a signal that the disease-modifying therapy track needs a second look.

How to Protect Your MS Treatment Plan

• Never Stop Therapy Without Consulting Your Neurologist: Stopping a disease-modifying therapy because you feel well can be followed by silent lesion formation or rebound activity. Any change to your treatment plan belongs with your neurologist, not with personal judgment about how you feel.
• Distinguish Between Relapse Treatment and Long-Term Therapy: Understand that corticosteroids for a relapse and disease-modifying therapies serve different purposes. Steroids address the fire burning right now, while disease-modifying therapies work on preventing future fires by calming the immune attack.
• Report Symptom Changes Promptly: New or worsening neurological symptoms lasting more than 24 hours should be reported to your healthcare team. Early confirmation of a relapse allows for timely treatment and recovery planning.
• Participate in Long-Term Monitoring: Disease-modifying therapies are judged by fewer relapses and stable MRI scans over months, not by immediate symptom relief. Regular imaging and follow-up appointments help track whether your treatment is working as intended.

What About Myelin Repair and Cognitive Function?

In a separate but related development, researchers at the University of Manitoba have identified a potential treatment for restoring cognitive function in people with chronic MS. The team found that restoring levels of the protein neuregulin-1 in the brains of mice with chronic MS improved mobility and cognition issues. The protein is significantly depleted from the brain in human MS samples and in animal models of the disease.

Chronic MS is the stage of the disease when the brain's natural ability to repair itself begins to fail. The replacement of neuregulin-1 compared favorably against existing treatment methods for MS and shows promise for treatment of early-stage MS as well. Previous tests that modeled relapsing-remitting MS with active inflammation show that the new method could potentially serve as both an immune-modulatory agent, restoring balance to an overactive immune system, and a regenerative therapy.

"Myelin is essential to effectively relay messages through the brain and spinal cord to the body and vice versa," said Soheila Karimi, head researcher and professor of physiology and pathophysiology at the Max Rady College of Medicine.

Soheila Karimi, Professor of Physiology and Pathophysiology at Max Rady College of Medicine, University of Manitoba

Karimi's team is now working on development of a molecule that could be injected into patients with chronic MS as a treatment, which would then be tested in a clinical trial. The team would also need to work out an ideal treatment schedule. While the findings are very promising, there is still more work ahead before this approach reaches patients.

The convergence of these discoveries, from EBV reactivation triggering flares to neuregulin-1 restoration improving cognitive function, suggests that MS treatment is moving toward more targeted, personalized approaches. Rather than one-size-fits-all immune suppression, future therapies may address the specific biological mechanisms driving disease in individual patients.