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Is it an MS Relapse, or is it Something Else?

With MS Relapses, the answers may not always be black and white. But it’s important to get to the bottom of what’s happening.

They’ve been called attacks, exacerbations, flare-ups, relapses and more. If you’re living with MS, you’re likely familiar them, whatever name you happen to use.
MS relapses are periods of MS activity that often manifest outwardly as an increase in the severity of existing symptoms, or the first experience with new symptoms altogether. They can be annoying, frightening, frustrating, debilitating — and sometimes they might even turn out to be not what you think.

What exactly is an MS relapse, and what’s the difference between a true relapse and a pseudo-relapse? In this issue, we’ll delve into this sometimes gray subject and provide some guidance to getting black and white answers.

MS causes inflammatory damage in the Central Nervous System (CNS), including the spine. While MS impacts the CNS in various ways, one of the main targets of this autoimmune inflammation is the myelin, a protective sheath that wraps around normal nerve fibers and helps ensure they can conduct nerve impulses efficiently.
When that myelin is damaged, the nerve impulse is slowed or even completely blocked, resulting in a variety of different symptoms. When these symptoms occur for the first time — the initial attack on that specific area of the nervous system —we call it a relapse.

For the rest of this article, we’ll use the term “relapse,” but remember what we’re talking about might commonly be called an attack, an exacerbation, a flare, and possibly other terms. The important distinction is whether you’re experiencing new MS damage, or a recurrence of old symptoms that feels a lot like it.

Defining a Relapse

Now, let’s get specific — what exactly do we mean when we talk about MS relapses?

Clinically, your physician might describe a relapse as:

“An isolated clinical episode with patient-reported symptoms and objective findings typical of MS, reflecting a focal or multifocal inflammatory demyelinating event in the central nervous system (CNS), developing acutely or subacutely, with a duration of at least 24 hours, with or without recovery, and in the absence of fever or infection. Attack, relapse, exacerbation, and (when it is the first episode) clinically isolated syndrome (CIS) are synonyms.” (Source: Thompson AJ, et al. Diagnosis of multiple sclerosis: 2017 revisions Of the McDonald Criteria. Lancet Neurology 2018; 17: 162-173).

In plain English, we have a few criteria to meet in order to classify an event as an MS relapse:

  • New neurologic symptoms lasting more than 24 hours;
  • Subacute (less rapid) or acute (very rapid) onset of those symptoms; and
  • Should be associated with a new Gadolinium-enhanced (Gd+) lesion on an MRI scan (gadolinium is a chemical element that’s administered before an MRI scan and allows doctors to better see MS lesions, which appear as white spots on scan results).

The key here is that what we’re seeing in a relapse is new MS activity, as measured not only by symptoms, but also by exam and the presence of new MRI lesions. New MS attacks may occur in any MS patient, but are most common when people are younger and/or relatively more newly diagnosed.

Types of MS Relapses

When we think of MS relapses, they tend to follow a specific pattern or affect a particular part of the CNS. Several examples of relapses include:

  • Optic neuritis – A common form of relapse that can manifest with blurred vision, typically in one eye, but occasionally in both eyes at the same time. This is also often associated with pain or soreness with eye movement.
  • Brainstem attack – This might include numbness or weakness on the face, double vision, or other types of symptoms of the head and face.
  • Transverse myelitis – Attack of the spinal cord which can lead to numbness or weakness in one or both arms or legs, or perhaps from the waist or chest down, and possibly associated with bowel or bladder dysfunction. Sometimes there can be pain in these areas as well.
  • Cerebellar attack – The cerebellum is the posterior (back part of the brain) which is responsible for balance and coordination. This type of relapse can present with balance issues, vertigo, loss of motor function, and other related symptoms.
  • Cerebral attack – This might affect things like language, cognition, or impaired mobility usually only on one side of the body.

All of the above may also have more general symptoms such as fatigue, and all have one thing in common: all represent a new autoimmune attack damaging the myelin around our nerves. When viewed with an MRI scan, these damaged areas show up as characteristic spots or “plaques” in the brain and on the spinal cord.

However, MRI’s don’t only show us active or recent damage — we can also look into a patient’s history with MS, by comparing several MRIs over time. Doctors look for changes from one MRI to the next, to be able to determine which spots might indicate new MS activity, and which spots are showing us areas where MS has caused damage in the past.

This MRI history becomes particularly important as our bodies deal with each individual MS relapse. This is where the concept of neurologic reserve comes into play (for more on neurologic reserve, please see Neurologic Reserve — Countering the Impacts of Relapses).


We’ve addressed relapses and how our body reacts to them, now it’s time to examine their troublesome cousin, the pseudo-relapse.

A quick side-note: Few people are particularly satisfied with the term “pseudo” relapse, as it indicates something that’s not real. You may hear medical professionals call it “recrudescence.” Whatever the terminology, a pseudo-relapse is VERY real, as anyone who’s experienced one can tell you. It’s just not indicative of new or worsening MS activity, as we’ll get into shortly. We’re using the term in this issue to avoid confusion, because it’s in such common usage in the MS community.

After a relapse, our neurologic reserve comes into play, helping our nervous system to avoid or bypass areas of damage. But it’s important to understand that even in the best of circumstances, that’s not always a perfect system.

The fact of the matter is MS lesions are still areas of damaged neurons, even though they may mostly work well enough to not impact your daily life. A number of factors can lead to periods of dysfunction in those damaged cells, even when they’ve been managing to work relatively well for a long period of time.

So, previously-damaged areas or existing lesions from an MS relapse long ago, which might be working just fine for you on a daily basis, can suddenly stop working so well. When this happens, and the dysfunction is severe enough to cause symptoms, you may be experiencing a pseudo-relapse.

Pseudo-relapses can trigger some or all of the same symptoms that a prior relapse may have caused. This can make them nearly indistinguishable from a true MS relapse. And, of course, when you’re in the midst of experiencing symptoms, whether it’s a true relapse or a pseudo-relapse doesn’t really matter to you — your symptoms are very real, regardless of what’s causing them.

However, it is important to understand the difference, so we can better determine the next steps in treating whichever possibility is happening with you.

Are You Having a Relapse or Pseudo-Relapse?

The difference between a true MS relapse and a pseudo-relapse may not be immediately evident to you, and that’s a problem because treating the two possibilities can look very different.

This is especially true if the symptoms are very similar to what you’ve experienced during a previous relapse. Slight changes in location or increases in severity can be a sign of new MS activity occurring near existing lesions. For example, a prior attack may have caused numbness in your hand, and the new event is numbness in the same hand but also now extending up your arm to the shoulder.

Thankfully, there are a number of diagnostic strategies to help your MS care team determine if you’re having a relapse or a pseudo-relapse.
Your care team or neurologist will likely start by taking a look at your symptoms and comparing them to symptoms you’ve had in the past, particularly during periods known to be associated with MS activity that’s been confirmed in an MRI scan. Symptoms that typically present in a pseudo-relapse can include:

  • Recurrence of old symptoms in the same area as before
  • Sleep issues
  • Worsening of other medical conditions
  • Generalized weakness, fatigue, exhaustion
  • Cognitive slowing

If your symptoms are identical to a previous relapse, or similar but perhaps less severe, that’s a good indication that you may be experiencing a pseudo-relapse. Most relapses occur in new parts of the nervous system, so when you have the same or very similar fluctuation of symptoms over and over (for example, “my relapses are always leg weakness in my bad leg”), these are almost always pseudo-relapses.

Your team will ask about other things that may be going on with you, as there are a number of factors not directly related to MS that are known to contribute to pseudo-relapses. Some of these factors may include:

  • Infection, even simple ones like upper respiratory symptoms such as cough, sneezing, etc.
  • Fever
  • Overheating
  • Physical or emotional stress
  • Changes to other medications you may be taking, possibly prescribed by another physician and for reasons unrelated to MS

Pseudo-relapses also commonly clear up rather quickly, especially when and if the contributing factors associated with the recurrence of the old symptoms are resolved quickly. They may be quite severe, especially if someone had a severe attack from which they previously recovered. Pseudo-relapses may occur in any MS patient, but are more likely the cause of recurrent symptoms as people age with MS, as true relapses become less common, an individual may have accumulated more areas that could present as pseudo-relapses, and stresses such as infections are more common.

Conversely, new symptoms you haven’t had before, or symptoms that are significantly worse than what you’ve previously experienced but in a similar location, can be indicators that new MS activity is be underway — a true MS relapse.

New relapses and pseudo-relapses may be extremely difficult to distinguish. In almost all cases your doctor will want to do a relapse history, perform a neurological exam, and order one or more MRI scans looking for new MS lesions, or evidence of new MS activity in the area of existing lesions. MS activity visible on an MRI is the most definitive way to determine if you’re experiencing a true MS relapse, but it is the constellation of history, exam and MRI together that is most helpful.
If you’re experiencing symptoms that seem related to your MS and you have any question as to whether you may be having an MS relapse or pseudo-relapse, contact your

MS care team so they can help you determine the best course of treatment for what you’re dealing with.

Treatment of Relapses and Pseudo-relapses

Whether you’re having an MS relapse or a pseudo-relapse, your care team can treat the symptoms themselves, to control and relieve your immediate issues.

Treating a Pseudo-relapse

Treating a pseudo-relapse, depending on its severity, usually starts by identifying and treating the underlying cause of the symptoms, followed by treating those symptoms directly.

Typical treatments for a pseudo-relapse, in addition to any symptom-specific interventions, can include:

  • Antibiotics
  • Anti-fever medications (non-steroid anti-inflammatories, or acetaminophen)
  • Physical therapy and occupational therapy
  • Treating other possible causes (cooling down, stress management, etc.)

Generally, a pseudo-relapse does not warrant steroids, a common treatment for an active MS relapse. Nor do they warrant re-evaluating your current Disease Modifying Therapy (DMT), as long as you’ve been relatively stable on your DMT for some time.

There’s also very little concern that a pseudo-relapse is causing your MS itself to worsen — yes, your symptoms may be similar and the same part of your nervous system is being affected, but the prime characteristic of a pseudo-relapse is that there is no new MS activity going on.

In most cases, once those underlying causes are dealt with, a pseudo-relapse will begin to subside. In some patients, especially those who are older and may have accumulated more disability, however, even a pseudo-relapse may result in an apparent loss of function. One example is worsened walking that does not “go back” to the same level of walking as before a severe infection. Why this occurs is not exactly known, but it’s likely related to deconditioning that’s difficult to overcome in the face of the infection.

Treating an MS Relapse

Treating true MS relapses is of course more complicated, because we’re dealing both with the symptoms you’re experiencing at that moment and an increase in MS inflammatory activity in your CNS. Depending on your symptoms, their severity, your MS history, and other factors, treating the new inflammation of your relapse may involve any of the following:

  • High dose steroids daily for 3-5 days, which may be taken intravenously (IV) or orally. Some providers also use a slow taper over 7-10 days as well, but this can be associated with more steroid side effects.
  • Plasmapheresis (PLEX), which is used if there is a less than satisfactory response to the steroids.

Some providers may suggest the use Acthar gel, especially to treat relapses that have not responded to a first round of steroids. But this is extremely expensive, and studies have not yet shown that it works better than re-dosing with steroids, or use of PLEX. With advancements in treatments and modern DMTs, hospitalization is rare, noting PLEX is typically done in the hospital for severe relapses.

What should you expect from steroids? They typically will result in more rapid remission of symptoms than waiting for remission without steroids, so they are particularly used when someone has more disabling symptoms such as impaired vision or trouble walking. The effects of steroids usually begin to be seen 3-4 days after starting steroids, and there may be lingering symptoms that clear only incompletely, or take a long time to clear. Ultimately steroids will improve the speed of remission, but studies show that the outcomes at two years are usually about the same regarding degree of remission, with or without steroids.

And to be clear, steroids may result in improvement of pseudo-relapses, especially fatigue. But when steroids produce near instantaneous relief of symptoms, this is most likely a pseudo-relapse. Some might ask, “well, if steroids help me feel better, why not use them with pseudo-relapses also?” The main reason is that steroids have many potential short-term and long-term side effects, and multiple dosings over a lifetime can be quite harmful.

DMTs and Relapses

An MS relapse can be an indicator that your DMT may not be working as well for you as hoped, and any new relapse, or severity of an MS relapse, can be a reason to re-evaluate your course of treatment. Modern disease modifying therapies have changed the outlook for people living with MS, as many of them have proven to be effective at reducing both the frequency and severity of relapses, as well as the overall progression of MS over time.

While we can’t expect DMTs to completely prevent relapses in all patients, we do expect less relapses with more effective DMTs. However, not every patient will react to every drug in exactly the same way.

Your DMT should:

  • Reduce overall risk of relapses
  • Reduce severity of new relapses, including need for steroids
  • Prevent new MRI lesion formation
  • Reduce progression of disability as seen on the neurological exam

Your DMT should not impact occurrence of pseudo-relapses. A pesudorelapse is NOT a reason to consider a change in DMT.

If your experience tells you that your DMT may not be working as effectively as you and your doctor expects, it may be time to begin the discussion about whether or not there are other treatment strategies for you to try.


MS relapses are one of the manifestations of MS that are a common thread among most patients, and the variations may be very broad even within one individual over time, and between different people. Both symptoms and severity can make it difficult to determine whether or not you’re in the midst of a relapse or a pseudo-relapse.

It’s important for clinicians to try to distinguish between relapses and pseudo-relapses for both short- and long-term treatment decisions. Symptoms may be similar or even indistinguishable, but certain presenting features can help your MS care team determine what you’re experiencing. In addition, sometimes new symptoms are not from MS at all. For example, worsening walking could be due to arthritis in the knee or hip.

When you are unsure about symptoms you’re experiencing, please contact your MS care team right away.

The information in this article is largely based on a presentation given by Dr. Robert Gross at the MS Center’s Spring 2022 Education Summit, and reviewed by MS Center Medical Director Dr. John Corboy. You can find Dr. Gross’s original presentation in our Education Summit archive, at MSCenter.org/edsummit.

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