Multiple Sclerosis (MS)

Multiple sclerosis is caused by an abnormal immune response in people who carry a genetic susceptibility to the disease, triggered by one or more environmental factors—most importantly, prior infection with the Epstein-Barr virus (EBV). MS is not directly inherited, but genes play a significant role in determining who is at risk. It is not contagious, and it cannot be passed from one person to another.

In MS, immune cells that are supposed to defend the body against infection instead turn against the body’s own tissues. T-cells—a type of white blood cell—become abnormally activated, cross from the bloodstream into the central nervous system, and attack the myelin sheath around nerve fibers. This immune attack causes inflammation and demyelination. The exact trigger that causes immune cells to turn on myelin is not fully understood, but the leading hypothesis is called molecular mimicry—the idea that a previous infection, particularly with Epstein-Barr virus, trains the immune system to recognize a viral protein that is structurally similar to a protein in the myelin sheath, causing the immune system to mistakenly attack myelin even after the infection is gone. B-cells—another type of immune cell—also play an important role in MS by producing inflammatory proteins, activating harmful T-cells, and forming clusters in the membranes surrounding the brain that drive ongoing damage in progressive disease.

No single gene causes MS. Instead, MS risk is influenced by a combination of genetic variants—particularly variants in genes that regulate the immune system. The HLA-DRB1*15:01 variant is the strongest known genetic risk factor and is carried by a significant proportion of MS patients of northern European ancestry. Having a parent or sibling with MS increases an individual’s lifetime risk to approximately 2–3%, compared to about 0.3% in the general population. Identical twins have roughly a 25% rate of both being affected, which demonstrates that genetics alone does not determine whether MS develops—environmental factors are also essential.

A number of environmental exposures are associated with MS risk and help explain why the disease is far more common in some regions and populations than others. Key environmental contributors include:

• Epstein-Barr virus (EBV) infection: the single strongest environmental risk factor identified. A landmark 2022 study of over 10 million U.S. military personnel showed that the risk of MS increased 32-fold following EBV infection. EBV is the virus that causes infectious mononucleosis (mono). Nearly everyone is infected with EBV at some point in life, but those who acquire it as adolescents or young adults—getting symptomatic mono—appear to be at the highest risk of later developing MS.
• Low vitamin D levels: —Vitamin D plays an important role in regulating the immune system. People with low vitamin D levels—including those who live at high latitudes with less sunlight—have a higher risk of MS. This is one factor thought to contribute to the well-established north-south gradient in MS prevalence.
• Geographic latitude: MS is significantly more common in regions farther from the equator. Countries at high northern and southern latitudes have substantially higher rates than equatorial regions, a pattern linked to sunlight exposure and vitamin D.
• Smoking: Cigarette smoking increases the risk of developing MS and accelerates its progression once the disease has started. The mechanism likely involves immune dysregulation and direct toxic effects on the central nervous system.
• Obesity in childhood and adolescence: Higher body weight during the teen years has been associated with an increased risk of developing MS, potentially through effects on immune function and vitamin D metabolism.

Multiple sclerosis can develop in anyone, but certain factors significantly increase a person’s likelihood of developing the condition. Understanding these factors is important for early vigilance and may eventually inform preventative strategies.

• Sex: Women are two to three times more likely to develop relapsing MS than men. The sex gap in MS prevalence has been widening over recent decades and is thought to reflect hormonal and immunological differences between sexes.
• Age: MS most commonly begins in people between the ages of 20 and 40. It can occur outside this range, including in children (pediatric MS) and older adults, but the peak onset is in the third decade of life.
• Ethnicity: MS is most prevalent in people of northern European descent, but it affects people of all racial backgrounds. Black Americans with MS tend to have a more aggressive disease course on average. Hispanic and Asian populations generally have lower prevalence but are not immune. The incidence of MS in Black and Hispanic Americans has been increasing.
• Family history: Having a first-degree relative (parent, sibling, or child) with MS increases lifetime risk to approximately 2–3%. The risk is higher with an affected identical twin (approximately 25%).

Multiple sclerosis affects the brain and spinal cord—the pathways through which all nerve signals travel—so it can potentially affect almost any function in the body. Symptoms vary enormously depending on where in the central nervous system the damage is located. No two people with MS have exactly the same symptom profile. Some people have only one or two symptoms throughout their lives; others develop a wider range over time. Symptoms during a relapse typically appear over hours to days, plateau, and then partially or fully recover over weeks to months. In progressive MS, some level of function is lost with each flare and may not return.

• Fatigue: This is the most commonly reported symptom in MS, affecting up to 80% of people. MS-related fatigue is different from ordinary tiredness—it is often described as a profound, disabling exhaustion that is not proportional to activity level and is frequently worse in the afternoon. It is one of the leading causes of work disability.
• Difficulty walking (gait problems): Weakness, spasticity (muscle stiffness and spasms), balance problems, and sensory changes in the legs can all impair walking. This is among the most impactful symptoms for daily function.
• Numbness or tingling: often one of the first symptoms. Numbness, tingling, or pins-and-needles sensations can affect the face, arms, legs, or trunk. They may appear in one limb and spread, or occur in both legs simultaneously.
• Muscle weakness: MS causes weakness most commonly in the legs and, less often, the arms. Weakness may be subtle early on and worsen during relapses or heat exposure.
• Spasticity: involuntary muscle stiffness, tightness, or spasms in the limbs. Spasticity can cause significant pain and can make walking and daily tasks more difficult.
• Vision problems: Optic neuritis—inflammation of the optic nerve—is one of the most common initial presentations of MS. It typically causes pain with eye movement and blurring or loss of vision in one eye. Double vision (diplopia) can also occur when the nerves controlling eye movement are affected.
• Bladder dysfunction: Urgency, frequency, incomplete emptying, and incontinence are among the most common and impactful MS symptoms, affecting a majority of people with the disease over its course.
• Pain: MS causes several types of pain: neuropathic pain (burning, stabbing, or electric-shock sensations from nerve damage), musculoskeletal pain from altered movement patterns, and Lhermitte’s sign: a brief electric-shock sensation down the spine triggered by bending the neck forward.
• Cognitive changes: Problems with memory, attention, processing speed, and word-finding affect a substantial proportion of people with MS, even those with otherwise mild physical symptoms.
• Depression and anxiety: MS is associated with significantly elevated rates of depression and anxiety, both as direct neurological effects of the disease and as responses to living with a chronic, unpredictable illness.
• Heat sensitivity (Uhthoff’s phenomenon): Many people with MS experience temporary worsening of symptoms when body temperature rises—from exercise, hot weather, fever, or hot baths. This is not a true relapse and reverses when body temperature normalizes.
• Bowel dysfunction: Constipation is very common. Less frequently, people may experience urgency or incontinence.
• Sexual dysfunction: Reduced libido, erectile dysfunction, and changes in sensation are common and often underreported.
• Tremor and coordination problems: These can affect the hands, head, or voice; tremor can interfere with writing, eating, and other fine motor tasks.
• Speech and swallowing difficulties: Dysarthria (slurred speech) and dysphagia (difficulty swallowing) can occur when the brainstem is involved.

A neurologist, a doctor who specializes in diseases of the brain and nervous system—diagnoses MS. The diagnostic process requires demonstrating that demyelinating lesions have occurred in more than one location in the central nervous system (dissemination in space) and at more than one point in time (dissemination in time). This framework is formalized in the McDonald Criteria, the internationally accepted diagnostic standard, which was most recently revised in 2017 and updated in 2024 to incorporate newer biomarker evidence. Reaching a diagnosis of MS requires ruling out other conditions that can cause similar symptoms and MRI findings—MS has no single definitive test, and the diagnosis is made by integrating clinical history, examination, imaging, and laboratory results.

A thorough neurological examination assesses reflexes, muscle strength, coordination, balance, sensation, vision, speech, and cognitive function. The findings help the neurologist identify which parts of the nervous system are affected and assess whether disability can be measured using a standardized scale called the Expanded Disability Status Scale (EDSS), which ranges from 0 (normal neurological exam) to 10 (death due to MS).

Magnetic resonance imaging (MRI) of the brain and spinal cord is the most important diagnostic test for MS. It detects MS plaques (areas of myelin damage) with high sensitivity. Different MRI sequences are used for different purposes. T2-weighted and fluid-attenuated inversion recovery (FLAIR) sequences show all areas of white matter damage, both old and new. T1-weighted images with gadolinium contrast reveal actively inflaming lesions—called enhancing lesions—that represent areas of current blood-brain barrier breakdown and active inflammation. Lesions that appear bright on T2 but dark on T1 (called T1 black holes) represent areas of more severe, permanent tissue destruction. MRI also allows quantification of brain volume loss (atrophy), which correlates with long-term disability and cognitive decline. Serial MRI over time tracks disease activity and treatment response.

A lumbar puncture (spinal tap) collects a small sample of the fluid surrounding the brain and spinal cord. In MS, the cerebrospinal fluid (CSF) often contains elevated levels of immunoglobulins (immune proteins) produced within the central nervous system, visible as distinctive patterns called oligoclonal bands on protein electrophoresis. The presence of two or more oligoclonal bands in the CSF—when they are not present in the blood—supports a diagnosis of MS. Elevated levels of the immunoglobulin G (IgG) and a protein called kappa free light chains in the CSF are additional supportive findings. CSF analysis is most useful when MRI findings are insufficient to confirm dissemination in time and space.

Evoked potential studies measure how long it takes the brain to respond to sensory stimulation—visual, auditory, or somatosensory (touch/vibration). A visual evoked potential (VEP) test is the most commonly used: the patient watches a flashing checkerboard pattern while electrodes on the scalp measure the brain’s electrical response. A delayed response indicates slowed nerve conduction due to myelin damage in the visual pathway, even if the person has never had symptomatic optic neuritis. Evoked potentials can provide evidence of a demyelinating lesion in a location not yet visible on MRI.

Multiple sclerosis cannot be cured, but it is highly treatable. Treatment for MS falls into three broad categories: disease-modifying therapies (DMTs) that reduce the frequency of relapses and slow disability accumulation, treatments for acute relapses, and symptomatic treatments that address the individual effects of MS on daily function and quality of life. Your neurologist will tailor a treatment plan to your specific disease type, level of activity on MRI and clinically, your lifestyle, and your personal priorities. The earlier treatment is started, the better the long-term outcomes—decades of data consistently show that early, effective treatment reduces disability accumulation over time.

A true relapse—new or worsening neurological symptoms lasting more than 24 hours in the absence of fever or infection—can be treated with a short course of high-dose corticosteroids. Intravenous methylprednisolone (typically 1,000 mg per day for three to five days) reduces inflammation at the site of the active lesion, shortening the duration of the relapse and speeding recovery. Corticosteroids do not change the final degree of recovery or the long-term course of the disease—they simply accelerate the resolution of the acute episode. For relapses that do not respond to steroids, plasmapheresis (plasma exchange)—a procedure that filters inflammatory proteins out of the blood—may be used.

More than 20 FDA-approved disease-modifying therapies are available for relapsing forms of MS. They are organized into three general tiers based on efficacy and risk profile. Neurologists and patients work together to choose among them based on disease activity, patient preferences, family planning considerations, and safety monitoring requirements. No DMT is approved for CIS or RIS as a primary indication, though several are approved for CIS and can delay conversion to clinically definite MS.

Lower-efficacy first-line therapies are the most established and are often the starting point for people with mild-to-moderate relapsing MS. They include the injectable interferon beta medications—interferon beta-1a (Avonex®, Rebif®), interferon beta-1b (Betaseron®, Extavia®), and the pegylated form peginterferon beta-1a (Plegridy®)—which reduce relapse rates by roughly 30% compared to placebo. Glatiramer acetate (Copaxone®, Glatopa®), also injectable, works differently by altering the immune response and achieves similar efficacy. These therapies have long safety records spanning decades. Oral options in this tier include dimethyl fumarate (Tecfidera®), diroximel fumarate (Vumerity®), and teriflunomide (Aubagio®).

Moderate-to-high-efficacy therapies offer greater relapse reduction and may be used as initial treatment in people with more active disease, or when first-line therapies have not been sufficiently effective. Oral options in this tier include fingolimod (Gilenya®)—the first oral MS therapy, approved in 2010—and its successors siponimod (Mayzent®, also approved for active SPMS) and ozanimod (Zeposia®). These sphingosine-1-phosphate receptor modulators work by trapping lymphocytes in the lymph nodes and preventing them from entering the central nervous system. Cladribine tablets (Mavenclad®) provide two short annual treatment courses that produce durable immune cell reduction.

High-efficacy therapies produce the greatest reduction in relapse rates—often 50–70% or more compared to lower-efficacy agents—but require more intensive safety monitoring. This tier includes the infused anti-CD20 monoclonal antibodies: ocrelizumab (Ocrevus®)—approved for both relapsing MS and PPMS—ofatutumab (Kesimpta®), a self-injected anti-CD20 antibody, and ublituximab (Briumvi®). These drugs deplete B-cells from the bloodstream, reducing the B-cell-mediated inflammatory pathways central to MS activity. Natalizumab (Tysabri®) prevents immune cells from crossing the blood-brain barrier. Alemtuzumab (Lemtrada®) and cladribine work as immune reconstitution therapies—they produce profound, durable depletion of specific immune cell populations, with effects persisting years after treatment. These high-efficacy agents are associated with more significant safety considerations and require careful patient selection and monitoring.

For PPMS, ocrelizumab (Ocrevus®) is currently the only FDA-approved disease-modifying therapy. It has been shown to slow disability progression compared to placebo in clinical trials of PPMS patients. Other anti-CD20 agents and investigational neuroprotective therapies are being studied in progressive MS populations.

Managing the wide range of symptoms that MS can cause is an essential part of comprehensive MS care, often as important to daily quality of life as disease modification.

• Fatigue: managed with lifestyle strategies (pacing activities, good sleep hygiene, regular moderate exercise) and, when necessary, medications such as amantadine, modafinil, or methylphenidate. Treating contributing factors—depression, thyroid disease, anemia, poor sleep—is also important.
• Spasticity: treated with oral muscle relaxants, including baclofen and tizanidine, and with benzodiazepines for nighttime spasms. For severe or focal spasticity, intrathecal baclofen (delivered through a pump implanted under the skin directly into the spinal fluid space) or botulinum toxin injections into specific muscles can provide targeted relief.
• Pain: Neuropathic pain is treated with gabapentin (Neurontin®), pregabalin (Lyrica®), duloxetine, tricyclic antidepressants, and cannabinoids in some jurisdictions. Lhermitte’s sign and trigeminal neuralgia may respond to carbamazepine.
• Bladder dysfunction: Urinary urgency and frequency are treated with anticholinergic medicines (oxybutynin, solifenacin), beta-3 agonists (mirabegron), or botulinum toxin injections into the bladder wall. Incomplete emptying may require self-catheterization. Referral to a urologist experienced in neurogenic bladder is often helpful.
• Walking difficulty: Dalfampridine (Ampyra®), an oral potassium channel blocker, was FDA-approved in 2010 specifically to improve walking speed in MS. Physical therapy, bracing (ankle-foot orthoses), and assistive devices are also important components of walking management.
• Cognitive dysfunction: cognitive rehabilitation exercises, neuropsychological evaluation, treatment of contributing factors (depression, poor sleep, medications that impair cognition), and strategies such as memory aids are the primary tools. There are no FDA-approved medications for MS-related cognitive impairment.
• Depression: treated with antidepressant medications, psychotherapy, or both. Depression in MS responds to standard treatments and should be identified and treated actively, as it significantly affects quality of life and adherence to MS treatment.
• Tremor: Weighted devices, beta-blockers (propranolol), clonazepam, and occupational therapy strategies are used. Severe, disabling tremor may warrant consideration of deep brain stimulation.

Rehabilitation is a cornerstone of MS management at every stage of the disease. Physical therapy focuses on strength, balance, walking, and fall prevention. Occupational therapy addresses fine motor function, energy conservation, and home and workplace modifications. Speech therapy assists with dysarthria and dysphagia. Cognitive rehabilitation targets memory and attention strategies. Assistive devices commonly used by people with MS include canes, walkers, and wheelchairs or scooters for mobility; ankle-foot orthoses to improve foot drop; functional electrical stimulation (FES) devices that stimulate the nerve to lift the foot, and voice-activated or screen-magnification technology for cognitive and visual difficulties.