Multiple sclerosis relapses are periods when new symptoms suddenly appear or existing ones worsen, lasting at least 24 hours due to inflammation attacking the nervous system. Understanding what triggers these episodes, how to recognize them, and what treatment options are available can help patients and their healthcare teams manage the condition more effectively and potentially reduce future disability.

Understanding What Happens During a Relapse and How to Manage Symptoms

When someone lives with multiple sclerosis, their journey often involves periods of relative stability interrupted by episodes called relapses. These episodes represent moments when the immune system becomes particularly active against the brain and spinal cord, causing inflammation that disrupts normal nerve function. A relapse, also known as an exacerbation, attack, flare-up, episode, or bout, occurs when inflammation develops along the nerves and the myelin sheath—the protective covering that insulates nerve fibers in the central nervous system.^[1]

During a relapse, inflammation causes temporary worsening or recurrence of existing symptoms, or the appearance of completely new ones. The experience varies greatly from person to person. Some individuals might notice vision changes, including blurred vision, double vision, or painful eye movement. Others may experience tingling or numbness in various parts of their body, electrical sensations down the back when bending the neck forward, or a squeezing sensation around the chest or abdomen that feels like a hug. Additional symptoms can include difficulty walking, muscle weakness or stiffness, fatigue, bladder or bowel problems, and cognitive difficulties that some describe as brain fog.^[2]

The way symptoms develop during a relapse follows a typical pattern. They usually evolve over 24 to 48 hours and reach their worst point within several days. Symptoms that appear much more suddenly or develop gradually over weeks might suggest something other than a typical MS relapse and should prompt further medical evaluation. Most relapses last anywhere from a few days to several weeks, though some can persist for months. Following the active phase, patients may experience complete or partial recovery during what doctors call remission.^[3]

Not every worsening of symptoms represents a true relapse. Healthcare professionals use specific criteria to determine whether symptoms constitute an actual relapse. The symptoms must be present for at least 24 hours, though in practice, relapse symptoms generally last much longer. They must occur at least 30 days after the start of any previous relapse, meaning MS symptoms should have been relatively stable for about one month before new symptoms appear or existing ones worsen. Importantly, there must be no other explanation for the symptoms, such as fever, infection, heat exposure, or other external factors.^[4]

Understanding these patterns helps patients and healthcare providers distinguish between normal day-to-day symptom fluctuations and genuine relapses requiring medical attention. For those newly diagnosed with MS, this distinction can be challenging at first. However, with time and experience, most people develop a better sense of their own MS patterns and can more readily recognize when they’re experiencing a true relapse versus temporary symptom variations caused by other factors.^[4]

Standard Treatment Approaches for Managing Multiple Sclerosis Relapses

When a relapse occurs and treatment is deemed necessary, healthcare providers typically turn to corticosteroids as the first line of therapy. These powerful medications work by reducing inflammation in the central nervous system, helping to shorten the duration and lessen the severity of relapse symptoms. However, it’s important to understand that while corticosteroids can provide significant symptomatic relief during an acute episode, they do not appear to affect the long-term progression of multiple sclerosis or prevent future relapses.^[8]

The standard corticosteroid treatment involves high-dose administration over a period of three to five days. The most commonly prescribed medication is methylprednisolone (brand name Solu-Medrol), typically given by intravenous infusion at a dose of 1 gram per day. This method delivers the drug directly into the bloodstream for a quicker response. The infusion can be performed in various settings, including hospitals, infusion centers, or sometimes even at home, depending on the healthcare system and patient circumstances.^[8]

Another corticosteroid option is dexamethasone (brand name Decadron), also given by intravenous infusion. Research has established the optimal dosing for these treatments. Important evidence came from the Optic Neuritis Treatment Trial, a large study that compared different treatment approaches for optic neuritis, which is a common manifestation of MS relapses. This trial demonstrated that high-dose intravenous methylprednisolone followed by an oral prednisone taper accelerated visual recovery compared to placebo. Interestingly, the study also showed that low-dose oral prednisone alone was no better than placebo and was actually associated with an increased risk of recurrent optic neuritis, which is why standard-dose oral prednisone alone is not recommended for relapse treatment.^[14]

However, an equivalent high-dose oral regimen of corticosteroids has emerged as an alternative to intravenous therapy. An oral prednisone dose of 1,250 milligrams is considered equivalent to 1 gram of intravenous methylprednisolone. This option has become appealing to many patients because of its convenience and potentially lower cost. Studies examining the bioavailability of high-dose oral prednisone compared to intravenous methylprednisolone have shown similar absorption levels between the two routes of administration. For moderate to severe relapses, this high-dose oral option can be just as effective as intravenous therapy.^[14]

Following the high-dose treatment course, physicians may prescribe an oral corticosteroid like prednisone to help ease the patient off the treatment gradually. This tapering process typically occurs over one to two weeks. The tapering helps minimize potential side effects associated with suddenly stopping corticosteroid therapy and allows the body to readjust its own cortisol production, which can be suppressed during high-dose corticosteroid treatment.^[8]

Not every relapse requires treatment with corticosteroids. Healthcare providers generally reserve steroid treatment for more severe flare-ups that significantly impact function or quality of life. Less severe relapses may be managed with watchful waiting, allowing the natural recovery process to occur without pharmaceutical intervention. This decision depends on multiple factors, including the severity of symptoms, which parts of the nervous system are affected, the patient’s functional status, and individual patient preferences after discussion with their healthcare team.^[8]

For individuals who cannot tolerate the side effects of corticosteroids, who have found previous steroid treatments ineffective, or who may have difficulty accessing timely medical support for intravenous infusions, alternative treatments exist. One such alternative involves highly purified forms of adrenocorticotropic hormone (ACTH) in gelatin, available under brand names Acthar Gel and Purified Cortrophin Gel. These medications act similarly to corticosteroids in reducing inflammation. Studies suggest that purified forms of ACTH are comparable in effectiveness to corticosteroids and have received approval from the U.S. Food and Drug Administration specifically for treating MS relapses. This medication is typically given once daily through intramuscular or subcutaneous injection over a period of three to five days.^[8]

Corticosteroid therapy can produce various side effects that patients should be aware of. Common side effects include increased appetite, weight gain, fluid retention, mood changes or emotional instability, difficulty sleeping, elevated blood sugar levels, and increased blood pressure. Some patients experience stomach upset or gastrointestinal discomfort. More serious but less common side effects can include increased risk of infection due to immune suppression, bone density loss with prolonged use, and eye problems such as cataracts or glaucoma. Most side effects are temporary and resolve once the treatment course is completed, but patients should report any concerning symptoms to their healthcare provider.^[9]

When corticosteroids and ACTH prove ineffective or inappropriate, healthcare providers may consider second-line therapies. Intravenous immunoglobulin (IVIg) represents one such option. This treatment involves administering antibodies collected from thousands of healthy donors. IVIg helps modulate the immune system and reduce inflammation through multiple mechanisms. Another advanced therapy is therapeutic apheresis, also known as plasma exchange or plasmapheresis. This procedure physically removes antibodies and inflammatory factors from the blood. These second-line therapies are typically reserved for severe relapses that don’t respond to standard corticosteroid treatment or for patients who cannot receive corticosteroids due to contraindications.^[14]

Factors That Influence Relapse Risk and Prevention Strategies

Understanding what influences the likelihood of experiencing a relapse can help patients and healthcare teams develop strategies to potentially reduce relapse frequency. Research has identified several factors that appear to play a role in MS relapse risk, though the complex interplay between these factors means that relapse prediction remains imperfect.^[1]

Age and sex significantly influence relapse patterns. Multiple sclerosis typically presents between ages 20 and 50 years, and the condition is approximately twice as common in women compared to men. This gender difference extends to relapse patterns, with hormonal factors potentially playing a role. Pregnancy represents a particularly interesting period in terms of relapse risk. Many women experience a reduction in relapse activity during pregnancy, particularly in the third trimester, possibly due to immune system changes that help the body tolerate the developing baby. However, relapse risk may increase somewhat in the first few months after delivery as hormone levels shift and the immune system readjusts.^[1]

Vitamin D levels have emerged as an important modifiable factor in MS relapse risk. Research suggests that low serum levels of vitamin D may be associated with increased relapse frequency. This connection has led many healthcare providers to monitor vitamin D levels in their MS patients and recommend supplementation when levels are insufficient. The mechanism behind this association likely involves vitamin D’s role in immune system regulation, though the exact details continue to be studied.^[1]

Infections represent another significant trigger for relapses. Even relatively mild infections, such as urinary tract infections or upper respiratory infections, can precipitate symptom worsening or trigger a true relapse. The immune system activation that occurs during infection may inadvertently increase autoimmune activity against the nervous system in people with MS. This is why prompt treatment of infections is particularly important for individuals with multiple sclerosis, and why some patients notice symptom changes during viral illnesses.^[2]

Stress has been identified as a potential relapse trigger, though the relationship is complex and not fully understood. Both physical and emotional stress may contribute to relapse risk. Many patients report experiencing relapses during or shortly after particularly stressful life events. While it’s impossible to eliminate all stress from life, stress management techniques such as meditation, yoga, regular exercise, and adequate sleep may help reduce overall stress burden and potentially contribute to better MS management.^[1]

Environmental temperature and heat exposure can worsen MS symptoms, though this typically causes pseudoexacerbations rather than true relapses. The phenomenon known as Uhthoff’s phenomenon describes temporary symptom worsening with heat exposure or during exercise, particularly affecting vision in people with a history of optic neuritis. While heat doesn’t cause actual nerve damage or constitute a true relapse, avoiding excessive heat exposure and using cooling strategies can help maintain function and comfort.^[2]

Smoking tobacco products has been associated with increased MS activity and potentially increased relapse frequency. The harmful effects of smoking on the immune system and blood vessels may contribute to worse outcomes in MS. Smoking cessation is strongly encouraged for all people with MS as part of comprehensive disease management.^[2]

Genetic and environmental factors interact in complex ways to influence both MS susceptibility and disease course. While specific genetic variations can increase MS risk, genetics alone don’t determine whether someone will develop MS or experience frequent relapses. Environmental exposures, including past infection with certain viruses like Epstein-Barr virus, may also contribute to MS development and potentially to relapse patterns.^[2]

Disease-Modifying Therapies for Long-Term Relapse Prevention

While corticosteroids address acute relapses, long-term management of relapsing-remitting multiple sclerosis centers on disease-modifying therapies (DMTs). These medications are prescribed to be taken regularly—not just during relapses—with the goal of reducing the frequency of relapses, slowing disease progression, and decreasing the formation of new lesions in the brain and spinal cord. Unlike corticosteroids that treat symptoms during relapses, disease-modifying therapies work to alter the underlying disease course.^[5]

For many years, healthcare providers prescribed immunomodulatory medications as first-line disease-modifying therapies. These drugs work by adjusting immune system activity rather than broadly suppressing it. Examples include interferons and glatiramer acetate, which help reduce immune system attacks on myelin. While these medications provided some benefit in reducing relapse rates, they offered modest effectiveness and could cause uncomfortable side effects that affected treatment adherence.^[5]

More recent advances in MS treatment have brought highly effective therapies that significantly reduce relapse risk and slow disease progression. Medicines that deplete circulating B cells—a type of immune cell involved in the autoimmune attack on the nervous system—have shown particularly impressive results. Two such medications are ocrelizumab (brand name Ocrevus) and ofatumumab (brand name Kesimpta). Ocrelizumab received approval from the U.S. Food and Drug Administration in 2017, followed by ofatumumab approval in 2020. Research indicates that these B cell-depleting therapies can prevent relapses with remarkable effectiveness—studies suggest ocrelizumab may be 98 percent effective in preventing new relapses when used early in the disease course.^[5]

These newer medications represent a significant advancement in MS treatment capabilities. According to experts, when these highly effective treatments are initiated early in the disease course, they can dramatically alter the trajectory of multiple sclerosis, potentially preventing significant disability accumulation. The therapies work by targeting specific immune cells that drive the autoimmune process, thereby reducing both clinical relapses that patients can feel and silent disease activity that can only be detected through imaging studies.^[5]

The availability of multiple disease-modifying therapy options allows healthcare providers to tailor treatment to individual patient needs, considering factors such as disease severity, lifestyle considerations, tolerance for side effects, and personal preferences. Some DMTs are taken as pills, others as injections that patients can self-administer at home, and still others as intravenous infusions given periodically in healthcare facilities. Each approach has advantages and disadvantages that should be discussed thoroughly between patients and their healthcare teams.^[13]

Starting disease-modifying therapy early after diagnosis is generally recommended for most people with relapsing-remitting MS. Evidence suggests that early intervention can be more effective than delayed treatment in preventing long-term disability. However, the decision about which specific therapy to use involves careful consideration of the individual patient’s situation. Some patients may start with moderately effective therapies and escalate to more potent options if disease activity continues, while others may begin with highly effective therapies from the outset, particularly if they have aggressive disease features.^[16]

Regular monitoring is essential for patients taking disease-modifying therapies. This typically includes periodic magnetic resonance imaging (MRI) scans to detect new lesion formation, blood tests to monitor for side effects, and clinical assessments to evaluate disease activity and disability status. Some relapses are “silent,” meaning they cause new lesions visible on MRI without producing noticeable symptoms. Regular MRI surveillance, especially early in the disease course, helps detect this subclinical disease activity. Healthcare providers may adjust treatment strategies based on these monitoring results, switching to alternative therapies if breakthrough disease activity occurs despite treatment.^[5]

Emerging Treatments in Clinical Trials

While current disease-modifying therapies have dramatically improved outcomes for many people with MS, research continues into even more effective and better-tolerated treatments. Clinical trials are investigating various innovative approaches to managing multiple sclerosis and preventing relapses. These investigations span different phases of research, each designed to answer specific questions about safety, effectiveness, and optimal use of potential new therapies.^[10]

Phase I clinical trials represent the first stage of testing new treatments in humans. These studies primarily focus on safety, determining what doses can be given safely and what side effects occur. Phase I trials typically involve small numbers of participants and provide initial information about how the human body processes the medication. While safety is the main concern, researchers also gather preliminary data on whether the treatment shows any signs of affecting the disease.^[10]

Phase II clinical trials expand the investigation to larger groups of participants and focus primarily on efficacy—whether the treatment actually works to reduce relapses, prevent new lesions, or slow disease progression. These studies also continue to monitor safety and side effects. Phase II trials help researchers determine the optimal dose and schedule for the medication. They provide crucial information about whether the treatment merits further investigation in larger, more definitive studies.^[10]

Phase III clinical trials are large-scale studies that compare the new treatment directly with standard therapies or placebo. These trials provide the most rigorous evidence about whether a treatment is effective and safe enough to warrant approval by regulatory agencies like the U.S. Food and Drug Administration. Phase III trials typically enroll hundreds or even thousands of participants across multiple countries and follow them for extended periods. Success in Phase III trials is generally required before a new treatment can be approved for widespread use.^[10]

Clinical trials for multiple sclerosis relapse treatment are conducted at medical centers around the world, including locations in the United States, Europe, and other regions. Patient eligibility for trials varies depending on the specific study requirements, but generally includes people with confirmed relapsing-remitting MS who meet certain disease activity criteria. Some trials specifically recruit patients who haven’t responded well to existing therapies, while others may include people newly diagnosed with MS. Interested patients should discuss clinical trial participation with their neurologist, who can help identify appropriate opportunities.^[10]

Various innovative treatment approaches are being explored in MS clinical trials. Researchers continue investigating new ways to modulate the immune system, targeting different immune cell types or signaling pathways involved in the autoimmune attack on myelin. Some studies examine whether combining different therapies might provide better results than single medications alone. Other research explores whether treatments can not only prevent relapses but also promote repair of existing damage to the myelin sheath—a process called remyelination. While these approaches remain experimental, they represent the future of MS treatment and hold promise for even better outcomes.^[10]

Most common treatment methods

• Corticosteroid therapy
  • High-dose intravenous methylprednisolone (1 gram daily for 3-5 days) administered in hospitals, infusion centers, or at home
  • Intravenous dexamethasone as an alternative corticosteroid option
  • Equivalent high-dose oral prednisone (1,250 mg) as a convenient alternative to intravenous therapy
  • Oral prednisone taper (1 mg/kg/day) for 1-2 weeks following high-dose treatment
  • Reduces inflammation in the central nervous system and shortens relapse duration
  • Does not prevent future relapses or affect long-term disease progression
  • Reserved for moderate to severe relapses that significantly impact function
• ACTH therapy
  • Highly purified adrenocorticotropic hormone in gelatin (brand names Acthar Gel and Purified Cortrophin Gel)
  • Given once daily by intramuscular or subcutaneous injection for 3-5 days
  • Acts similarly to corticosteroids in reducing inflammation
  • Alternative for patients who cannot tolerate corticosteroids or have difficulty accessing intravenous infusions
  • FDA-approved specifically for treating MS relapses
• Intravenous immunoglobulin (IVIg)
  • Antibodies collected from thousands of healthy donors
  • Helps modulate the immune system and reduce inflammation through multiple mechanisms
  • Second-line therapy for severe relapses that don’t respond to corticosteroids
  • Option for patients with contraindications to corticosteroid therapy
• Therapeutic apheresis
  • Also known as plasma exchange or plasmapheresis
  • Physically removes antibodies and inflammatory factors from the blood
  • Advanced therapy reserved for severe relapses unresponsive to standard treatments
  • Requires specialized equipment and trained personnel
• Disease-modifying therapies for long-term relapse prevention
  • Immunomodulatory medications such as interferons and glatiramer acetate that adjust immune activity
  • B cell-depleting therapies including ocrelizumab (Ocrevus) and ofatumumab (Kesimpta)
  • Highly effective at preventing relapses (up to 98% effective when started early in disease course)
  • Taken regularly to reduce relapse frequency, slow disease progression, and decrease new lesion formation
  • Available in various formulations including pills, self-administered injections, and periodic intravenous infusions
  • Early initiation after diagnosis generally recommended for most people with relapsing-remitting MS