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Inside An MS Exacerbation

By Devin Garlit ·

Exacerbation, relapse, flare-up, attack: these are all names for the same thing with regard to Multiple Sclerosis. The general definition of this event is the occurrence of new or worsening of old symptoms lasting for more than 24 hours and taking place at least 30 days after a similar event. While this can be a standard occurrence for those with Multiple Sclerosis, not everyone actually understands what’s going during this period. Understanding what is happening during an exacerbation is critical for those with MS. With that in mind, I’ll do my best to help break it down as simply as I can.

What’s happening to the body during an MS exacerbation?

During one of these moments, the disease has caused your own immune system to attack your body. Specifically, your immune system begins to assault your central nervous system. Its weapon of choice? Inflammation (caused by various immune cells). This inflammation damages myelin, a fatty substance that surrounds and helps insulate our nerves. This insulating layer makes sure our nerves properly conduct the electrical signals that our brain sends to the other parts of our body (think of it as the plastic covering on an electrical wire). When this layer is damaged, those signals don’t move fast enough or at all, which is where we start to see our symptoms. Can’t lift your leg fast enough or at all? The myelin around a nerve between your brain and leg has been compromised and the signal isn’t traveling as efficiently as it should be. Not only does our immune system damage the myelin, but it also damages the cells needed to regrow it.

When the immune system attacks

These moments that we call exacerbations (or whichever term you like) are when the immune system is making its attack. It’s when the immune system has created a lot of inflammation in your central nervous system, and it’s damaging that myelin layer. Not only does this inflammation damage that protective coating, but it also has an effect on those signals that are traveling through that part of the central nervous system. We use steroids to fight exacerbations as they help to reduce this inflammation.

When a relapse is over: the aftermath

When an exacerbation is over, these damaged areas of myelin develop some scar tissue (that’s where we get the term sclerosis in multiple sclerosis, we are left with multiple scars; these scars are also referred to as plaques or lesions). Once all that inflammation is gone or significantly reduced, some of that myelin can regrow, but it never grows back completely or strong enough due to the scarring and because the cells needed to facilitate regrowth have been damaged. This regrowth, coupled with the reduction in inflammation, is why people can seem to bounce back after an exacerbation. They may even seem like they are completely well again. That’s why people often use the term “relapse,” because they seem to improve or go back to the way they were. This is a pattern that is extremely common in people diagnosed with the Relapsing-Remitting form of the disease. However, the more exacerbations you have, the more your ability to bounce back becomes hindered.

Accumulating damage over time

The more scars you have and the more cells that help regrow myelin are damaged, the less you are able to recover. In the past, maybe a damaged nerve could still get the brain’s signal where it needed to go, even if not the most efficiently (unless an outside influence temporarily triggered an issue). As more damage occurs over time though, the ability of that nerve to do its job, no matter the situation, becomes compromised. Basically, that’s how people with MS can worsen over time. That’s why doctors try to not only shorten the length of exacerbations through steroids but to minimize the overall number of them with disease-modifying drugs.

What Type of MS Do You Have? Experts Clarify How to Describe MS to Improve Care and Clinical Trials

An international committee of MS experts has published a statement that clarifies how to describe the different courses of multiple sclerosis and disease activity. The statement was prompted by inconsistencies in the way MS descriptors are used by the MS community. These clarifications can improve care and access to treatments, and refine the selection of clinical trial participants so that trial outcomes can be better applied to clinical care.

The statement was an effort by the International Advisory Committee on Clinical Trials in Multiple Sclerosis, which is jointly supported by the US National MS Society and the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS). The Committee provides perspective and guidance in areas of interest to planning and implementing clinical trials for new agents for the treatment of MS.

“With this published statement, we’re encouraging the healthcare and regulatory community to use the terms as described for the different subtypes of MS and for describing disease activity,” noted Fred Lublin, MD (Icahn School of Medicine at Mount Sinai), who is senior author of the statement and two previous papers defining MS subtypes that were published in 1996 and 2013 under the auspices of the committee. “It’s critical not just for improving patient care, but also for selecting participants for clinical trials, so you are comparing apples to apples.”

Inconsistent use of the terms: The 2013 paper defined four categories of MS based on current clinical course: clinically isolated syndrome (an initial episode of neurological symptoms), relapsing-remitting MS, secondary progressive MS, and primary progressive MS. The paper also recommended adding terms to describe an individual’s current disease state, such as “active” (shown by relapse or changes on MRI) and “progression” (shown by worsening of disability independent of relapse activity). While the time period for the activity was not specified, it was recommended that an assessment be performed at least annually.

Since the 2013 paper was published, there has been confusion in the use of the terms describing a person’s current disease state and the terms have been used without reference to a timeframe. For example, in the prescription indications for recent MS therapy approvals, neither the European Medicines Agency nor the U.S. Food and Drug Administration specified a timeframe for determining disease activity. Moreover, the agencies defined activity differently; the European Medicines Agency defined “activity” as either clinical relapse or MRI-detected inflammation, whereas the U.S. Food and Drug Administration defined “activity” only in terms of relapses.

Clarifying definitions: The recently published statement reiterates the definition of “activity” as clinical relapses or imaging features of inflammatory activity, evaluated annually or over another specified interval. The definition of “progression” is reiterated as clinical evidence of disability worsening, independent of relapses, in individuals in a progressive phase, evaluated annually or over another specified interval. Also, the more general term “worsening” refers to any increase in impairment or disability as the result of residual deficits caused by relapses, or increasing disability during progressive phases of MS.

Future work: “As part of its ongoing activities, the committee plans to continue to reevaluate and refine course descriptors, especially when new evidence-based methods enable pathological distinctions between MS phenotypes, said Professor Alan Thompson, Chair of the International Advisory Committee on Clinical Trials in MS and Dean of University College London’s Faculty of Brain Sciences. “This would vastly improve prognosis, treatment choices, and the development of more selective therapies.”

Read the recently published open access statement, “The 2013 clinical course descriptors for multiple sclerosis: A clarification” by Fred D. Lublin, Timothy Coetzee, Jeffrey A. Cohen, Ruth Ann Marrie, Alan J. Thompson. Published online in Neurology on May 29, 2020.

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