Multiple sclerosis relapse represents one of the most challenging aspects of living with this chronic autoimmune disease. Understanding what triggers these episodes, recognizing their symptoms, and knowing how to manage them can significantly improve quality of life for people affected by this condition.
Understanding Multiple Sclerosis Relapses
A multiple sclerosis relapse, also called an exacerbation, attack, flare-up, episode, or bout, is a period when new symptoms appear or existing symptoms become significantly worse. During a relapse, inflammation occurs along the nerves and myelin, which is the protective covering that insulates the nerves of the central nervous system consisting of the brain, spinal cord, and optic nerves. This inflammation disrupts the normal communication between the brain and the body, leading to various neurological symptoms.[1][3]
The symptoms of a relapse usually appear very quickly, developing over a period of hours or days. For a flare-up to be considered a true relapse, specific criteria must be met. The symptoms must be present for at least 24 hours without any signs of infection or fever. Additionally, the symptoms must occur at least 30 days from the start of the previous relapse, meaning that MS symptoms should have been stable for about one month before new symptoms appear or existing ones worsen.[4][8]
Relapses can last anywhere from a few days to several weeks or even months. Following a relapse, there is typically a period of complete or partial recovery, known as remission. During remission, some people may have no symptoms at all, while others may continue to experience some symptoms that healthcare providers can usually manage with appropriate interventions.[3][4]
It’s important to distinguish between a true relapse and what healthcare professionals call a pseudoexacerbation. A pseudoexacerbation is a temporary worsening of symptoms without actual myelin inflammation or damage. These episodes are brought on by other influences such as infection, fever, heat exposure, exercise, exhaustion, stress, or depression. Once the underlying cause is addressed and resolved, the symptoms typically improve.[8][12]
Epidemiology and Prevalence
Multiple sclerosis affects approximately 2.3 million people worldwide, with significant variation in prevalence across different regions and populations. The disease has resulted in approximately 18,900 deaths globally, showing an increase from 12,000 deaths recorded in 1990. These statistics highlight the serious nature of this chronic autoimmune condition and its impact on global health.[1]
In the United States alone, approximately 1 million people are living with multiple sclerosis. Among those diagnosed with the disease, an estimated 80% to 85% have relapsing-remitting multiple sclerosis, making it the most common form of MS. This type of MS is characterized by the pattern of relapses followed by periods of remission, which sets it apart from other forms of the disease.[2][5]
Multiple sclerosis typically presents between the ages of 20 and 50 years, affecting people during their most productive years. The disease shows a clear gender preference, being twice as common in women as in men. This gender disparity is consistent across different populations and geographical regions, although the reasons for this difference are not completely understood.[1]
While multiple sclerosis can affect anyone, certain ethnic groups show different rates of the disease. People of Northern European descent represent a large percentage of MS patients, though the disease can occur in individuals of any ethnicity. The variation in prevalence across different populations suggests that both genetic and environmental factors play important roles in disease development.[7]
Relapses tend to happen most often in the first few years after someone is diagnosed with MS, although they can occur at any time during the disease course. The frequency of relapses varies considerably among individuals, ranging from less than one relapse per year to more than two relapses per year. Understanding these patterns helps healthcare providers develop appropriate management strategies for each patient.[4][5]
Causes and Mechanisms
The exact cause of multiple sclerosis and its relapses remains unknown, but research has revealed important insights into what triggers these episodes. Multiple sclerosis is classified as an autoimmune disorder, meaning the body’s immune system mistakenly attacks its own healthy tissues. In the case of MS, the immune system targets the myelin sheath that protects nerve fibers in the central nervous system.[1][5]
During a relapse, self-reactive immune T cells wrongly attack the myelin sheath that surrounds nerves in the brain and spinal cord. This immune attack causes inflammation and damage to both the myelin and the underlying nerves. The damage interrupts the messages the brain sends through the nervous system to different parts of the body, leading to the various symptoms people experience during a relapse.[5][13]
The inflammatory process during a relapse involves an acute demyelinating reaction within the central nervous system. This means that the protective myelin covering is being stripped away from the nerve fibers, exposing them to potential damage. This demyelination creates areas of scarring, also called plaques or lesions, which can be seen on brain imaging studies. These lesions primarily form in the white matter of the brain and spinal cord, particularly in the periventricular regions, optic nerve, brainstem, and spinal cord.[1]
Research suggests that the development of MS involves a complex interaction between genetic predisposition and environmental factors. While genetics play a role in making someone more susceptible to MS, the risk of passing the condition to children is relatively low. Environmental factors such as exposure to certain bacteria or viruses, particularly the Epstein-Barr virus, may trigger the disease in genetically susceptible individuals.[2][7]
Risk Factors for Relapses
Evidence suggests that multiple sclerosis relapses are influenced by various factors including age, sex, pregnancy, serum levels of vitamin D, interactions between genetic and environmental factors, and infectious diseases. Many of these factors are modifiable, which means that patients and healthcare providers can take steps to reduce the risk of relapses and improve outcomes.[1]
Infections represent one of the most significant triggers for MS relapses. Even mild infections such as sinus infections or urinary tract infections can cause old MS symptoms to reappear or trigger new symptoms. The relationship between infection and relapse is so strong that healthcare providers routinely check for occult infections when evaluating patients with potential relapses.[2][12]
Heat and certain temperatures can worsen MS symptoms or trigger pseudoexacerbations. This phenomenon, sometimes called Uhthoff’s phenomenon, occurs when elevated body temperature temporarily impairs the ability of demyelinated nerves to conduct electrical signals. Sources of heat that may affect symptoms include hot weather, fever, hot baths, saunas, or strenuous exercise. However, it’s important to note that heat does not cause actual MS attacks or relapses, and exposure to heat doesn’t create permanent damage.[2][12]
Stress has been identified as a potential trigger for MS symptoms and possibly relapses. Both physical and mental stress can affect the immune system and may contribute to disease activity. Chronic diseases like MS can cause immense emotional stress, which can lead to secondary symptoms such as fatigue, confusion, and depression. Managing stress through activities such as meditation and yoga has been shown to help people living with MS.[1][2]
Smoking tobacco products has been associated with worsening MS symptoms and may increase the risk of relapses. The harmful effects of smoking on the immune system and vascular health may contribute to more active disease. People with MS who smoke are encouraged to quit as part of their overall disease management strategy.[2]
Vitamin D deficiency has been linked to increased risk of MS relapses. Adequate vitamin D levels appear to play a protective role in the immune system and may help reduce disease activity. Healthcare providers often monitor vitamin D levels in patients with MS and recommend supplementation when levels are low.[1][2]
Symptoms of MS Relapses
The symptoms experienced during an MS relapse vary considerably from person to person, reflecting the different areas of the central nervous system that may be affected. Common relapse syndromes include unilateral optic neuritis affecting one eye, focal brainstem or cerebellar syndromes affecting balance and coordination, or partial myelitis affecting the spinal cord.[12]
Vision changes are among the most common symptoms during MS relapses. These can include blurry vision, impaired color vision, painful eye movement, double vision, or temporary vision loss. When the optic nerve is affected, people may experience these visual disturbances that can range from mild to severe. Some individuals may notice that objects moving across their visual field appear to travel along a curved trajectory, a phenomenon known as the Pulfrich phenomenon.[2][5]
Sensory symptoms frequently occur during relapses. People may experience tingling or numbness in various parts of the body, often in the arms or legs. Some individuals describe a squeezing sensation around the chest or abdomen that feels like a tight hug, known as a sensory level. Another characteristic symptom is an electrical tingling sensation or shocks that run down the back when bending the neck forward, called Lhermitte’s sign.[2][12]
Motor symptoms affecting movement and strength are common during relapses. These can include muscle weakness, difficulty walking, problems maintaining balance, or muscle stiffness and spasticity. The severity of these symptoms can range from mild difficulty with fine motor tasks to significant impairment in walking or performing daily activities.[2][5]
Fatigue is one of the most frequent and debilitating symptoms experienced by people with MS, and it often worsens during relapses. This fatigue is different from normal tiredness and doesn’t necessarily improve with rest. It can significantly impact a person’s ability to work, socialize, and perform daily activities.[2][5]
Bladder and bowel problems can emerge or worsen during relapses. These may include difficulty or hesitation when trying to urinate, a feeling of urgency where one must go immediately, constipation, or loss of bladder or bowel control. These symptoms can significantly affect quality of life and often require specific management strategies.[2][5]
Cognitive difficulties, sometimes described as brain fog, can occur during relapses. People may experience problems with memory, concentration, information processing, or multitasking. These cognitive changes can be subtle or more pronounced, affecting work performance and daily functioning.[2][5]
Vertigo, or the sensation of spinning or dizziness, can be a particularly distressing symptom during relapses, especially when the brainstem is affected. This can make it difficult to maintain balance and may increase the risk of falls.[5][13]
Prevention Strategies
While relapses cannot be completely avoided, several strategies can help lower the risk and manage the impact of these episodes. A healthy lifestyle forms the foundation of relapse prevention. Regular exercise, a balanced diet, and adequate sleep strengthen the body and may help reduce inflammation. Exercise is strongly recommended and appears to be protective for the brain and spinal cord, despite concerns some people may have about exertion triggering symptoms.[16]
The Mediterranean diet has been shown to have neuroprotective properties for people with MS. This dietary approach is high in fish, vegetables, and nuts, while being low in red meat. Following this eating pattern may help support overall health and potentially reduce disease activity.[11]
Maintaining a healthy weight is important for people with MS. Research shows that people who are overweight have a higher chance of developing MS, and those with MS who are overweight tend to have more active disease and faster progression. Weight management through diet and exercise should be part of a comprehensive approach to MS care.[11]
Avoiding known triggers is crucial in preventing relapses. This includes staying away from smoking, managing stress through relaxation techniques, avoiding overheating, and promptly treating infections when they occur. Simple measures like staying hydrated, dressing appropriately for the weather, and using cooling strategies during hot weather can help prevent heat-related symptom flares.[2][16]
Disease-modifying therapies represent one of the most important tools in preventing relapses. These medications, prescribed by doctors or neurologists, work to slow disease progression and reduce the frequency and severity of relapses. Newer treatments, such as medications that deplete circulating B cells, have shown remarkable effectiveness. Some of these treatments can be up to 98% effective in preventing new relapses when used early in the course of the disease.[5][16]
Vitamin D supplementation may play a role in relapse prevention. Healthcare providers often recommend monitoring vitamin D levels and taking supplements to maintain adequate levels, as this vitamin appears to support immune system function and may help reduce disease activity.[1]
Pathophysiology of MS Relapses
The pathophysiology of MS relapses involves complex changes in normal bodily functions at the mechanical, physical, and biochemical levels. During a relapse, inflammation occurs along the nerves and myelin in the central nervous system, triggering a cascade of damaging events that disrupt normal nerve function.[3][8]
The central nervous system contains nerve cells called neurons, each having a covering that functions like a rubber coating around an electrical wire. This coating, known as the myelin sheath, protects the nerve inside and helps neurons send electrical signals to and from the brain, telling the body what to do. In people with MS, immune cells enter the central nervous system and attack the myelin sheath, interfering with the ability of neurons to send signals between the brain and the body.[7]
The immune attack during a relapse involves multiple mechanisms. High-dose corticosteroids, which are often used to treat relapses, work by suppressing the immune system and reducing inflammation through several pathways. These include suppressing the production of proinflammatory cytokines and chemokines, inducing the production of anti-inflammatory cytokines, reducing the migration of inflammatory cells such as leukocytes into the central nervous system, stabilizing mast cell membranes to prevent the release of inflammatory mediators, and inhibiting the production of prostaglandins and other inflammatory substances.[14]
Corticosteroids also act as immunosuppressants by inhibiting the proliferation and inducing the apoptosis (programmed cell death) of lymphocytes. This immunosuppressive action helps reduce the ongoing immune attack on the myelin and may help prevent further relapses in the short term.[14]
The damage caused by relapses results in the formation of scars or lesions in the brain and spinal cord. These lesions, which give multiple sclerosis its name (referring to the multiple scars or “sclerae”), represent areas where myelin has been damaged or destroyed. The disease is characterized by plaque formation in the white matter, axonal injury (damage to the nerve fibers themselves), and demyelination, mainly in the spinal cord, optic nerve, brainstem, and periventricular regions of the brain.[1][5]
These lesions can be visualized using magnetic resonance imaging (MRI). Some lesions show active inflammation detected on MRI using a dye containing the chemical element gadolinium, known as gadolinium-enhanced or Gd+ lesions. Other lesions show the long-term impact of inflammation on the brain. While the exact relationship between MRI findings and overall health is not entirely clear, MRIs are commonly used to monitor disease activity and help healthcare teams make treatment decisions.[7]
Between attacks, symptoms may disappear completely as some repair of the myelin occurs, but permanent neurological problems often remain, especially as the disease advances. The ability to recover from relapses varies and is affected by factors such as comorbidities, functional status prior to the relapse, and age. Most patients experience some spontaneous recovery, though the degree of recovery is variable.[1][12]
Even when relapses are not causing symptoms, underlying MS activity could be damaging the central nervous system. This means that the disease may be worsening and people might experience new symptoms later, even during periods when they feel fine. This understanding emphasizes the importance of disease-modifying therapies that work continuously to protect the nervous system, not just during symptomatic periods.[7]
