Multiple Sclerosis Relapse

Multiple sclerosis relapses are episodes when new symptoms suddenly appear or existing symptoms get worse. These attacks are a key feature of the disease, especially in the relapsing-remitting form that affects most people with MS. Understanding what causes relapses and how to manage them can help you work with your healthcare team to maintain stability and quality of life.

Table of contents

• What Is a Multiple Sclerosis Relapse?
• Common Symptoms During a Relapse
• How Is a Relapse Defined?
• Understanding Pseudorelapses
• What Causes Relapses and Common Triggers
• Factors That Influence Relapse Risk
• Diagnosing a Relapse
• Treatment Options for Relapses
• Reducing Your Risk of Relapses

What Is a Multiple Sclerosis Relapse?

A relapse in multiple sclerosis is a period when new symptoms appear or existing symptoms become significantly worse. These episodes are also called exacerbations, attacks, flare-ups, episodes, or bouts.^[1] During a relapse, inflammation occurs along the nerves and the myelin (the protective covering that insulates the nerves of the central nervous system, which includes the brain, spinal cord, and optic nerves).^[3]

Relapses are experienced by most people diagnosed with multiple sclerosis. They occur with relapsing-remitting MS, progressive-relapsing MS, and sometimes secondary-progressive forms of MS. Relapses do not occur with primary-progressive MS, although individuals may experience day-to-day fluctuations in how they feel.^[3]

The symptoms during a relapse can range from a few days in duration to a few months, followed by a complete or partial recovery, which is called remission.^[3] Most people who have MS—approximately 80% to 85%—are initially diagnosed with relapsing-remitting MS, making it the most common form of the disease.^[2] In this form, periods of remission can last from months to years until they are interrupted by a relapse.^[4]

Common Symptoms During a Relapse

The symptoms of a multiple sclerosis relapse vary from person to person. During a relapse, you may experience new symptoms or an increase in existing symptoms.^[3] Common symptoms that can occur during relapses include:

• Vision changes, including blurry vision, impaired color vision, painful eye movement, double vision, or temporary vision loss^[2]
• Tingling or numbness in various parts of your body^[2]
• Numbness, weakness, or tingling in the arms or legs^[5]
• A squeezing sensation around your chest or abdomen that feels like a hug^[2]
• Fatigue^[2]
• Difficulty walking or maintaining balance^[5]
• Muscle weakness or stiffness^[2]
• Vertigo^[5]
• Bladder or bowel problems, including difficulty when trying to urinate or a feeling of urgency^[2]
• Electrical tingling or shocks down your back when you bend your neck forward^[2]
• Cognitive difficulties, sometimes described as brain fog or difficulty with memory and concentration^[2]

It is common to have a combination of symptoms during a relapse or attack.^[2]

How Is a Relapse Defined?

To be considered a true multiple sclerosis relapse, certain criteria must be met. A clinical relapse is defined as a sudden episode with patient-reported symptoms and objective findings typical of MS. The episode reflects inflammation and damage to myelin in the central nervous system that develops quickly.^[12]

The specific criteria for a relapse include:^[4]

• Old MS symptoms must have become worse or new symptoms appeared
• Symptoms must last for at least 24 hours (though relapse symptoms generally last for days, weeks, or even months)^[3]
• Symptoms must occur at least 30 days from the start of the last relapse (MS symptoms should have been stable for about one month before symptoms become worse or new symptoms appear)
• There must be no other explanation for the symptoms, such as fever or infection

A typical MS relapse evolves over 24 to 48 hours and reaches its worst point in several days. More sudden or gradual symptoms should prompt evaluation of alternative diagnoses.^[12] If you’re not sure whether you’re having a relapse, you could wait a day or two to see if your symptoms improve before contacting a health professional.^[4]

Understanding Pseudorelapses

Not all worsening of symptoms represents a true relapse. A pseudorelapse (also called a pseudoexacerbation) is a temporary worsening of symptoms without actual myelin inflammation or damage, brought on by other influences.^[8] Common triggers for pseudorelapses include:

• Infection or fever^[8]
• Exercise^[8]
• A warm environment or heat exposure^[2]
• Depression^[8]
• Exhaustion^[8]
• Stress^[8]

A pseudorelapse is a temporary recurrence of prior neurological problems, usually in the setting of certain stressors. When these factors are resolved, your symptoms should improve.^[12] For example, if a patient presents with reemergence of remote neurological problems concerning for a pseudorelapse, they should undergo basic laboratory testing before considering treatment for a relapse, including a urinalysis with culture since occult urinary tract infections are common in MS.^[12]

What Causes Relapses and Common Triggers

During MS relapses, the immune system mistakenly attacks the myelin sheath that surrounds nerves in the brain and spinal cord. This causes inflammation and harm to the myelin and the nerves. The damage interrupts messages the brain sends through the nervous system to different parts of the body and causes scars called lesions in the brain and spinal cord.^[5]

The exact cause of MS is unknown. Research suggests it relates to a genetic predisposition (changes in your DNA) that make you more likely to have an autoimmune condition like MS. Environmental factors can also cause MS, like exposure to bacteria or viruses such as Epstein-Barr virus.^[2]

You might notice certain things in your environment trigger MS symptoms. These could include:^[2]

• Stress
• Heat or certain temperatures
• Infections (even mild infections such as a sinus infection or urinary tract infection can cause old MS symptoms to reappear)
• Smoking tobacco products
• Vitamin D deficiency

It’s important to note that triggers for one person diagnosed with MS may not affect another person with the same condition.^[2]

Factors That Influence Relapse Risk

Evidence suggests that MS relapse is influenced by several factors. Many of these factors are modifiable and require the attention of patients and healthcare providers if favorable outcomes are to be realized.^[1] Key factors that can influence relapse risk include:

Age and Sex: MS usually presents between the age of 20 and 50 years and is twice more common in women than men.^[1] MS relapse is influenced by age and sex.^[1]

Pregnancy: Pregnancy is one of the factors that influences MS relapse.^[1]

Vitamin D Levels: Serum levels of vitamin D can influence the occurrence of relapses.^[1] Vitamin D deficiency has been identified as a potential trigger for worsening MS symptoms.^[2]

Genetic and Environmental Interactions: Interactions between genetic and environmental factors play a role in MS relapse.^[1]

Infectious Diseases: Infectious diseases can influence the risk of experiencing a relapse.^[1]

Diagnosing a Relapse

When you’re first diagnosed with MS, it can be difficult to work out if you’re having a relapse or not. This is because many MS symptoms can fluctuate from day to day, so changes might be part of the everyday up and down pattern of MS, rather than the start of a relapse.^[4] With time, you will become an expert on your own MS and will develop a better feel for whether you’re having a relapse.^[4]

Patients with relapsing-remitting disease who experience common MS symptoms will likely know that they’re having a relapse based on how they’re feeling. However, some relapses are silent, especially early in the course of the disease. These relapses may damage the myelin and cause new lesions without perceived symptoms or disability.^[5]

Silent relapses can be detected by magnetic resonance imaging (MRI), which may be recommended periodically for patients who have recently been diagnosed with the disease. If you do MRIs looking for new lesions at the beginning of the disease, lesions are occurring all the time. You could go years with this happening and not have a clinical relapse. It’s only when you have a lesion in a part of the brain—like the optic nerve, the spinal cord, or the brainstem—where there’s a lot going on in a small area, that you have a clinical relapse with accompanying symptoms.^[5]

The evaluation of a relapse should be tailored to the clinical scenario. In the setting of an established diagnosis of MS, new neurological symptoms compatible with those caused by MS, and no symptoms or history suggesting another condition, no further testing may be needed. When symptoms are atypical of a relapse, a targeted work-up should be pursued to identify the cause.^[12]

Treatment Options for Relapses

When treatment is necessary, relapses are usually treated with a high-dose course of powerful corticosteroids (a type of steroid) over a period of three to five days.^[8] These powerful medications help reduce inflammation in the body and shorten the duration of flare-ups, but they do not have a long-term benefit for treating the disease itself.^[5]

Corticosteroid Treatment: Corticosteroids are approved by the United States Food and Drug Administration (FDA) for the treatment of MS relapses. They work by reducing inflammation in the central nervous system. While they usually lessen the severity and duration of a relapse, they do not appear to affect the long-term progression of the disease.^[8]

These medications are given by intravenous (IV) infusion, providing the drug directly into the bloodstream for a quicker response. Administration may be performed in a hospital, infusion center, or sometimes at home. As an alternative to IV steroids, treatment for a moderate to severe relapse also includes an equivalent, high-dose, oral regimen of steroids.^[8]

To treat relapses, physicians may prescribe corticosteroids such as methylprednisolone or dexamethasone, both given by IV infusion, or via an equivalent, high-dose, oral regimen of these steroids. An oral corticosteroid, prednisone, may be prescribed after the high-dose treatment to ease the patient off the treatment, tapered over one to two weeks.^[8]

Less-severe relapses are usually not treated with steroids, so their use may be reserved for more severe flare-ups.^[8]

Alternative Treatments: For individuals who are not able to tolerate the side effects of steroids, who have found that previous treatments were not effective, or who may have difficulty getting timely medical support for IV infusions, other options are available. An alternative to corticosteroids includes highly purified forms of adrenocorticotropin (ACTH) in gelatin, which act similarly to corticosteroids. Studies suggest that purified forms of ACTH in gelatin are similar in effectiveness to corticosteroids and are approved by the FDA specifically for the treatment of MS relapses.^[8]

Other Treatment Modalities: Several modalities are available for the treatment of multiple sclerosis relapse, including corticosteroids, intravenous immunoglobulins (IVIg), and therapeutic apheresis.^[14]

Reducing Your Risk of Relapses

While relapses cannot be completely avoided, there are strategies to lower the risk and manage the impact. Adopting a healthy lifestyle can help prevent relapses and support overall health. Regular exercise, a balanced diet, and adequate sleep strengthen the body and reduce inflammation. Avoiding triggers like smoking and excessive stress also helps maintain stability.^[16]

Disease-Modifying Therapies (DMTs): When patients with relapsing-remitting MS are diagnosed, they are prescribed medications to take regularly to decrease the risk of relapses.^[5] There are newer MS treatments that can help patients experience fewer relapses and less disability. Medicines that deplete circulating B cells, such as ocrelizumab and ofatumumab, can prevent relapses and are thought to slow the progression of the disease.^[5]

Minimizing Relapse Risk: Minimizing the risk of relapse is essential in multiple sclerosis. As none of the treatments currently available are capable of completely preventing relapses, treatment of these episodes remains a cornerstone of MS care.^[10] Identification of MS relapse risk factors can help in the development of therapies that could be used to manage MS and MS relapse.^[1]

It is important to remember that underlying MS activity could be damaging your central nervous system whether or not you are experiencing symptoms. So even if you’re feeling fine, your MS may be worsening and you might experience new symptoms later. Even infrequent or mild relapses can cause permanent damage to the central nervous system and may lead to future disability. That’s why it’s important to take every relapse seriously and talk to your healthcare team right away.^[7]