Overview

Multiple sclerosis affects around 2.5 million people worldwide; it is one of the most common neurological disorders and cause of disability of young adults, especially in Europe and North America.

Multiple Sclerosis is an unpredictable disease of the central nervous system; marked by weakness, numbness, a loss of muscle coordination, and problems with vision, speech, and bladder control. Multiple sclerosis (MS) can range from relatively benign to somewhat disabling to devastating, as communication between the brain and other parts of the body is disrupted.

Multiple sclerosis (MS) involves an immune-mediated process in which an abnormal response of the body’s immune system is directed against the central nervous system (CNS), which is made up of the brain, spinal cord and optic nerves. The exact antigen — or target that the immune cells are sensitized to attack — remains unknown, which is why MS is considered by many experts to be “immune-mediated” rather than “autoimmune.”

• Within the CNS, the immune system attacks myelin — the fatty substance that surrounds and insulates the nerve fibers — as well as the nerve fibers themselves.
• The damaged myelin forms scar tissue (sclerosis), which gives the disease its name.
• When any part of the myelin sheath or nerve fiber is damaged or destroyed, nerve impulses traveling to and from the brain and spinal cord are distorted or interrupted, producing a wide variety of symptoms.
• The disease is thought to be triggered in a genetically susceptible individual by a combination of one or more environmental factors.
• People with MS typically experience one of four disease courses, which can be mild, moderate or severe.

Types of Multiple Sclerosis

Clinically Isolated Syndrome (CIS)

Clinically isolated syndrome (CIS) is one of the MS disease courses. CIS refers to a first episode of neurologic symptoms that lasts at least 24 hours and is caused by inflammation or demyelination (loss of the myelin that covers the nerve cells) in the central nervous system (CNS). CIS can be either monofocal or multifocal:

• Monofocal episode: The person experiences a single neurologic sign or symptom — for example, an attack of optic neuritis — that’s caused by a single lesion.
• Multifocal episode: The person experiences more than one sign or symptom — for example, an attack of optic neuritis accompanied by numbness or tingling in the legs — caused by lesions in more than one place.

The episode usually has no associated fever or infection and is followed by a complete or partial recovery.

• High risk of developing MS: When CIS is accompanied by magnetic resonance imaging (MRI)-detected brain lesions that are similar to those seen in MS, the person has a 60 to 80 percent chance of a second neurologic event and diagnosis of MS within several years.
• Low risk of developing MS: When CIS is not accompanied by MRI-detected brain lesions, the person has about a 20 percent chance of developing MS over the same period of time.

Like MS, CIS is two to three times more common in women than men. Seventy percent of people diagnosed with CIS are between the ages of 20 and 40 years (average 30 years) but people can develop CIS at older or younger ages.

Relapsing-remitting MS (RRMS)

RRMS – the most common disease course – is characterized by clearly defined attacks of new or increasing neurologic symptoms. These attacks – also called relapses or exacerbations – are followed by periods of partial or complete recovery (remissions). During remissions, all symptoms may disappear, or some symptoms may continue and become permanent. However, there is no apparent progression of the disease during the periods of remission.

At different points in time, RRMS can be further characterized as either active (with relapses and/or evidence of new MRI activity) or not active, as well as worsening (a confirmed increase in disability over a specified period of time following a relapse) or not worsening. An increase in disability is confirmed when the person exhibits the same level of disability at the next scheduled neurological evaluation, typically 6 to 12 months later.Approximately 85 percent of people with MS are initially diagnosed with RRMS.

Relapsing-remitting MS is defined by inflammatory attacks on myelin (the layers of insulating membranes surrounding nerve fibers in the central nervous system (CNS)), as well as the nerve fibers themselves. During these inflammatory attacks, activated immune cells cause small, localized areas of damage which produce the symptoms of MS. Because the location of the damage is so variable, no two people have exactly the same symptoms.

Primary-Progressive Multiple Sclerosis (PPMS)

PPMS is characterized by worsening neurologic function (accumulation of disability) from the onset of symptoms, without early relapses or remissions. PPMS can be further characterized at different points in time as either active (with an occasional relapse and/or evidence of new MRI activity) or not active, as well as with progression (evidence of disease worsening on an objective measure of change over time, with or without relapse or new MRI activity) or without progression. Approximately 15 percent of people with MS are diagnosed with PPMS.

Although there is a lot of variability among people with PPMS, we know that as a group, they differ in several ways from people with relapsing forms of MS:

• Relapsing forms of MS (including relapsing-remitting MS, and secondary progressive in those individuals who continue to experience relapses) are defined by inflammatory attacks on myelin. PPMS involves much less inflammation of the type seen in relapsing MS. As a result, people with PPMS tend to have fewer brain lesions (also called plaques) than people with relapsing MS and the lesions tend to contain fewer inflammatory cells. People with PPMS also tend to have more lesions in the spinal cord than in the brain. Together, these differences make PPMS more difficult to diagnose and treat than relapsing forms of MS.
• In the relapsing forms, women are affected two to three times as often as men; in PPMS, the numbers of women and men are approximately equal.
• The average age of onset is approximately 10 years later in PPMS than in relapsing MS.
• People with PPMS tend to experience more problems with walking and more difficulty remaining in the workforce.
• In general, people with PPMS may also require more assistance with their everyday activities.

Secondary-progressive MS (SPMS)

SPMS follows an initial relapsing-remitting course. Most people who are diagnosed with RRMS will eventually transition to a secondary progressive course in which there is a progressive worsening of neurologic function (accumulation of disability) over time. SPMS can be further characterized at different points in time as either active (with relapses and/or evidence of new MRI activity) or not active, as well as with progression (evidence of disease worsening on an objective measure of change over time, with or without relapses) or without progression.

SPMS occurs in people who initially had a relapsing-remitting disease course. In other words, SPMS occurs as a second phase of the disease for many individuals. Primary progressive MS (PPMS) is the first — and only — phase of the illness for approximately 15 percent of people with MS.

In SPMS, people may or may not continue to experience relapses caused by inflammation; the disease gradually changes from the inflammatory process seen in RRMS to a more steadily progressive phase characterized by nerve damage or loss.

Symptoms of Multiple Sclerosis

Common Symptoms

• Fatigue; occurs in about 80% of people, can significantly interfere with the ability to function at home and work, and may be the most prominent symptom in a person who otherwise has minimal activity limitations.
• Vision Problems; the first symptom of MS for many people. Onset of blurred vision, poor contrast or color vision, and pain on eye movement can be frightening — and should be evaluated promptly.
• Bladder Problems; occurs in at least 80% of people with MS, can usually be managed quite successfully with medications, fluid management, and intermittent self-catheterization.
• Depression; studies have suggested that clinical depression — the severest form of depression — is among the most common symptoms of MS. It is more common among people with MS than it is in the general population or in persons with many other chronic, disabling conditions.
• Numbness or Tingling; numbness of the face, body, or extremities (arms and legs) is often the first symptom experienced by those eventually diagnosed as having MS.
• Weakness; that results from deconditioning of unused muscles or damage to nerves that stimulate muscles, can be managed with rehabilitation strategies and the use of mobility aids and other assistive devices.
• Bowel Problems; constipation is a particular concern among people with MS, as is loss of control of the bowels. Bowel issues can typically be managed through diet, adequate fluid intake, physical activity and medication.
• Pain; is very common in MS. In one study, 55% of people with MS had “clinically significant pain” at some time, and almost half had chronic pain.
• Cognitive Changes; refers to a range of high-level brain functions affected in more than 50% of people with MS, including the ability to process incoming information, learn and remember new information, organize and problem-solve, focus attention and accurately perceive the environment.
• Spasticity; refers to feelings of stiffness and a wide range of involuntary muscle spasms; can occur in any limb, but it is much more common in the legs.
• Dizziness and Vertigo; people with MS may feel off balance or lightheaded, or — much less often — have the sensation that they or their surroundings are spinning (vertigo).
• Emotional Changes; can be a reaction to the stresses of living with MS as well as the result of neurologic and immune changes. Significant depression, mood swings, irritability, and episodes of uncontrollable laughing and crying pose significant challenges for people with MS and their families.
• Sexual Problems; very common in the general population including people with MS. Sexual responses can be affected by damage in the central nervous system.

Less Common Symptoms

• Speech Problems; including slurring (dysarthria) and loss of volume (dysphonia) occur in approximately 25-40% of people with MS, particularly later in the disease course and during periods of extreme fatigue. Stuttering is occasionally reported as well.
• Swallowing Problems; referred to as dysphagia — result from damage to the nerves controlling the many small muscles in the mouth and throat.
• Tremor; or uncontrollable shaking, can occur in various parts of the body because of damaged areas along the complex nerve pathways that are responsible for coordination of movements.
• Seizures; which are the result of abnormal electrical discharges in an injured or scarred area of the brain — have been estimated to occur in 2-5% people with MS, compared to the estimated 3% of the general population.
• Breathing Problems; respiration problems occur in people whose chest muscles have been severely weakened by damage to the nerves that control those muscles.
• Itching; Pruritis (itching) is one of the family of abnormal sensations — such as “pins and needles” and burning, stabbing or tearing pains — which may be experienced by people with MS.
• Hearing Loss; about 6% of people who have MS complain of impaired hearing. In very rare cases, hearing loss has been reported as the first symptom of the disease.
• Headache; although headache is not a common symptom of MS, some reports suggest that people with MS have an increased incidence of certain types of headache.

Secondary Symptoms that results from the primary symptoms

• Bladder dysfunction can cause repeated urinary tract infections.
• Inactivity can result in loss of muscle tone and disuse weakness (not related to demyelination), poor postural alignment and trunk control, decreased bone density (and resulting increased risk of fracture), and shallow, inefficient breathing.
• Immobility can lead to pressure sores.

Tertiary Symptoms

Tertiary symptoms are the “trickle down” effects of the disease on your life. These symptoms include social, vocational and psychological complications. For example, if you are no longer able to drive or walk, you may not be able to hold down your usual job. The stress and strain of dealing with MS often alters social networks and sometimes fractures relationships. Problems with bladder control, tremor or swallowing may cause people to withdraw from social interactions and become isolated.

Causes for Multiple Sclerosis

The worldwide distribution of MS can be only an indirect refl ection of its cause, implicating some environmental factor that varies with latitude, and can be interpreted in at least three different ways in the search for clues to a specific etiology. a), an environmental risk factor may be more common in temperate than tropical climates, b), such a factor may be more common in tropical climates, where it is acquired at an earlier age and consequently has less impact c), this factor may be equally common in all regions, but the chance of its acquisition or of the manifestation of symptoms is either increased by some enhancing factor present in temperate climates or reduced by a protective factor present in tropical areas.

Among those factors that have been most closely scrutinized are:

• infections, including a number of viral infections such as measles and Epstein–Barr virus;
• climate and solar conditions;
• living conditions;
• diet and trace elements.

It is now generally accepted that the etiology of MS involves some interplay of genetic and environmental factors. Evidence of racial or ethnic resistance, the increased risk among MS family members, and elevated monozygotic twin concordance rate all favor a genetic contribution to acquisition of the disease. The studies from which this evidence is derived, however, also indicate that heredity cannot entirely explain the occurrence of MS. This is underlined by the fact that no population-based study of monozygotic twins has found a concordance rate in excess of 30%. Some environmental factor, such as a virus or toxin, must still play a role.

Regardless of any factor, the demyelination occurs in all subjects suffering from Multiple Sclerosis.

The latest research identifies that the chloride-channel protein anoctamin 2 (ANO2) as a new target for autoantibody production in multiple sclerosis (MS) patients.

Diagnosing MS

Your doctor will need to perform a neurological exam, a clinical history, and a series of other tests to determine if you have MS.

Diagnostic testing may include the following:

• MRI is the best imaging test for MS. Using a contrast dye allows the MRI to detect active and inactive lesions throughout the brain and spinal cord.
• Evoked potentials require stimulation of nerve pathways to analyze electrical activity in the brain. The three types of evoked potentials doctors use to help diagnose MS are visual, brainstem, and sensory.
• A spinal tap, or lumbar puncture, can help your doctor find abnormalities in your spinal fluid. It can help rule out infectious diseases.
• Doctors use blood tests to eliminate other conditions with similar symptoms.

The diagnosis of MS requires evidence of demyelination in more than one area of the brain, spinal cord, or optic nerves. That damage must have occurred at different times.

It also requires ruling out other conditions that have similar symptoms. This includes Lyme disease, lupus, and Sjogren’s syndrome.

Treatment for Multiple Sclerosis

No cure is available for MS, but multiple treatment options exist.

If you have relapsing-remitting MS (RRMS), you can choose one of the disease-modifying drugs. These medications are designed to slow disease progression and lower your relapse rate.

Self-injectable disease-modifying drugs include glatiramer (Copaxone, Glatopa) and beta interferons, such as:

• Avonex
• Betaseron
• Extavia
• Plegridy
• Rebif

Oral medications for RRMS include:

• dimethyl-fumarate (Tecfidera)
• fingolimod (Gilenya)
• teriflunomide (Aubagio)

Intravenous infusion treatments for RRMS include:

• alemtuzumab (Lemtrada)
• natalizumab (Tysabri)
• mitoxantrone (Novantrone), which is for severe MS only

Disease-modifying drugs aren’t effective in treating progressive MS.

Your doctor can prescribe corticosteroids, such as methylprednisolone (Medrol) and prednisone (Deltasone) to treat relapses.

Other treatments may ease your symptoms and improve your quality of life. Because the disease is different for everybody, treatment depends on your specific symptoms. For most people, a flexible approach is necessary.

Risk Factors

These factors may increase your risk of developing multiple sclerosis:

• Age. MS can occur at any age, but most commonly affects people between the ages of 15 and 60.
• Sex. Women are about twice as likely as men are to develop MS.
• Family history. If one of your parents or siblings has had MS, you are at higher risk of developing the disease.
• Certain infections. A variety of viruses have been linked to MS, including Epstein-Barr, the virus that causes infectious mononucleosis.
• Race. White people, particularly those of Northern European descent, are at highest risk of developing MS. People of Asian, African or Native American descent have the lowest risk.
• Climate. MS is far more common in countries with temperate climates, including Canada, the northern United States, New Zealand, southeastern Australia and Europe.
• Certain autoimmune diseases. You have a slightly higher risk of developing MS if you have thyroid disease, type 1 diabetes or inflammatory bowel disease.
• Smoking. Smokers who experience an initial event of symptoms that may signal MS are more likely than nonsmokers to develop a second event that confirms relapsing-remitting MS.

Complications

People with multiple sclerosis also may develop:

• Muscle stiffness or spasms
• Paralysis, typically in the legs
• Problems with bladder, bowel or sexual function
• Mental changes, such as forgetfulness or mood swings
• Depression
• Epilepsy

Statistics about MS

• MS is the most widespread neurological condition disabling young adults worldwide.
• About 400,000 people in the United States have MS, though that’s only an estimate. Doctors in the United States aren’t required to report MS to any agency. According to the National MS Society, there hasn’t been a scientifically sound, national study on the prevalence of MS in the United States since 1975.
• Most people are between the ages of 20 and 40 when their doctor diagnoses them with MS. Women develop MS 2 to 3 times more often than men, a difference that has grown steadily for five decades. MS is more common among Caucasians of northern European ancestry than other ethnic groups.
• Rates of MS tend to be lower in places that are closer to the equator. The rates of MS are higher in places farther away from the equator. This may have to do with sunlight and vitamin D. People who relocate to a new location before age 15 generally acquire the risk factors associated with the new location.
• Data from 1999-2008 showed that direct and indirect costs of MS were between $8,528 and $54,244 per year. Current disease-modifying drugs can cost up to $60,000 per year.