What is multiple sclerosis?

Causes and Symptoms

Multiple sclerosis (MS) is a chronic and disabling disease of the nervous system. Symptoms can be mild, such as limb numbness, or severe, such as paralysis and loss of vision. How the disease will progress and its severity in specific individuals are difficult to predict because it progresses differently in each of its victims.

Multiple sclerosis is caused by degeneration of the nervous system. A fatty substance called myelin surrounds and protects many nerve fibers of the brain and spinal cord. Myelin is important because it speeds up signals that move along the nerve fibers. In MS, the body undergoes an autoimmune reaction in which it attacks its own tissues, causing a breakdown in the myelin layer along the nerves. When any part of the myelin sheathing is destroyed, nerve impulses to and from the brain are slowed, distorted, or interrupted. The disease is called “multiple” because it affects many areas of the brain. Sclerosis refers to the hardening and scarring of tissue over the damaged areas of myelin.

The initial symptoms of MS may include tingling, numbness, slurred speech, blurred or double vision, loss of coordination, and muscle weakness. Later manifestations include unusual fatigue, muscle tightness, bowel and bladder control difficulties, sexual dysfunction, and paralysis. The most common cognitive functions influenced are short-term memory, abstract reasoning, verbal fluency, and speed of information processing. All the mental and physical symptoms listed may come or go in any combination. The symptoms may also vary in intensity from mild to severe throughout the course of the disease.

The symptoms of MS vary not only from person to person but also, on occasion, within the same person. This makes the prognosis of the disease difficult to foresee. Although the general course of the disease may be anticipated, the symptoms and their severity seem to be quite unpredictable in most individuals. In the “classic” course of MS, as time progresses, chronic problems gradually accumulate over many years, slowly worsening the sufferer’s quality of life. The total level of disability will vary from patient to patient.

The typical pattern of MS is marked by active periods of the disease during which the nerves are being ravaged by the immune system. These periods are called attacks, relapses, or exacerbations. The active periods of the disease are followed by calm periods called remissions. The cycle of attack and remission will differ from sufferer to sufferer. Some people have few attacks, and their MS disabilities slowly accumulate over time; in these cases, it takes decades for the sufferer to become truly debilitated. Most people with MS have what is known as the relapsing-remitting form of the disease. They suffer many attacks over time, and these attacks occur unpredictably; the attacks are then followed by complete remission, which may last months or years. Again, the injuries may take many years to accumulate to complete disability.

The most aggressive form of the disease is primary progressive MS. In this type of MS, the disease follows a rapid course that steadily worsens from its first onset. Although there are still attacks and partial remission, the attacks are quite severe and occur more regularly. Full paralysis may develop in primary progressive MS in three to five years. Secondary progressive MS occurs in patients who initially have the relapsing-remitting type and later develop the more aggressive form.

Both genetic and environmental factors have been implicated in inducing the onset of MS. While viral infection has been suggested as a cause, no single virus has ever been proved to be associated with MS, although Epstein-Barr virus and the human herpesvirus 6 (HHV-6) are considered likely candidates to be involved in some way. Infections such as influenza, the common cold, and gastroenteritis increase the risk of relapse, but flu vaccination is perfectly safe for patients with MS. Risk may be conferred by exposure to a specific environment during adolescence, but that environment and the genetic risk factors have not yet been characterized. Support for a genetic component comes from examining identical twins. The likelihood of MS in the second identical twin, when the first twin has MS, is 30 percent.

Researchers Sharon Lynch and John Rose suggested that certain racial and geographic populations are less susceptible than others to the disease. MS is uncommon in Japanese people and among American Indians. The disease is more common among northern European Caucasians and North Americans of higher latitudes. There is an additional sexual dimorphism in the epidemiology of MS; the disease is found more frequently in women, by a ratio of 2 to 1.

The disease usually begins its first manifestations in late adolescence (around age eighteen) to early middle age (around age thirty-five). It is not clear how the interaction between the genetics of the sufferer and the environment may trigger onset. The progressive type of MS is more common over the age of forty, so those with late-onset MS often have the quickest deterioration of motor function. The reason that an older age predisposes someone to primary chronic progressive MS is still not clear.

Studies by Swiss researcher Avinoam Safran have shown that occasionally MS manifests after the age of fifty. This condition has been named late-onset multiple sclerosis. Nearly 10 percent of MS patients demonstrate their first symptom after the age of fifty. This type of MS is often not recognized by physicians, who do not expect it in the aged.

Treatment and Therapy

Scientists have been encouraged by advancements in MS diagnosis using magnetic resonance imaging (MRI) brain scans. In 2002 it was announced that these scans appeared to detect damage around nerve fibers in patients with possible early signs of MS. This apparent damage helps doctors predict who will eventually develop MS and how severe one’s experience with the disease might be, which in turn allows the patient to begin a drug regimen earlier. In the past, doctors did not officially diagnose MS or start treatment until patients had two episodes of nerve problems in different areas of the body—recurrences that could come years apart while damage nonetheless continued silently. New research has found that putting patients on MS drugs at the first sign of nerve inflammation drastically slows the chances of developing MS within a few years, although most will eventually still develop the disease.

While there is no cure for MS, there are many effective treatments. In most cases, steroidal drugs are used to treat relapses or attacks of the disease. Adrenocorticotropic hormone (ACTH), or corticotropin, was the first steroidal immunosuppressant to be used widely in MS treatment. The primary effect of the drug is to shorten the duration of an attack, although it does not appear to reduce the attack's severity. While it is still used with patients who respond well to it, corticotropin has been supplanted by other drugs. Methylprednisolone is an immunosuppressant and steroid that has replaced corticotropin. It has been shown to control the inflammation that accompanies demyelination. These steroids seem to work by sealing leaking blood vessels in the brain and reducing the responsiveness of the white blood cells of the immune system so that they cannot attack the myelin as easily.

Several federally approved drugs can slow the rate of attacks. Avonex, Rebif, and Betaseron are preparations of interferon (proteins regulating the immune system), and Copaxone is a mixture of small peptides that protects myelin. Although these drugs do not stop MS entirely, they do limit the level of myelin destruction, as observed in MRI scans of the brain. Avonex slows down the rate of progression to disability, and all four slow down the natural course of MS. University of Western Ontario researcher George Ebers was the first to perform experimental treatments on MS patients with interferons. The myelin sheath is actually produced by a special nerve cell called an oligodendrocyte; presumably the oligodendrocytes are stimulated to protect themselves by exposure to interferons. Patients treated with human interferons demonstrated a 34 percent reduction in frequency of attacks that was sustained over five years of treatment. More impressive was the 80 percent reduction of MS activity detected in their brains. Steroid treatment was rarely required in these patients.

In 2002, researchers announced that preliminary studies using mice and a class of statin drugs used to lower cholesterol in heart patients showed an improvement and some reversal of the debilitating symptoms of MS. The animal data was encouraging: the statin drugs appeared to reprogram the immune cells that attack myelin so they instead protect nerve coatings. Also in 2002, a parallel study using MS patients and the drug sold as Zocor—part of the statin class—showed early positive signs of similar anti-inflammatory effects in humans. Another strategy using a monoclonal antibody, Natalizumab, was approved in 2006 for the treatment of the relapsing form of MS. In 2010, the US Food and Drug Administration (FDA) approved fingolimod, the first oral drug for MS treatment.

During the 1990s, in a study supported by the National Institutes of Health and conducted at the Mayo Clinic, plasma exchange, also called plasmapheresis, was proven to be an effective treatment for certain patients suffering from severe symptoms of multiple sclerosis who were not responsive to conventional methods of treatment. Plasma exchange involves removing the patient’s blood; eliminating the plasma-containing antibodies that target myelin; replacing the plasma with a fluid with similar properties, usually containing albumin; and returning the blood to the patient. This procedure has been used for treatment of other autoimmune diseases, such as myasthenia gravis and Guillain-Barré syndrome, in the past.

Investigators concluded that plasma exchange might contribute to recovery from an acute attack in people with MS who have not responded to standard steroid treatment. Therefore, they recommended that this treatment only be considered for individuals experiencing a severe, acute attack that is not responding to high-dose steroids. Since the vast majority (90 percent) of people experiencing acute attacks respond well to the standard steroid treatment, plasma exchange would be considered a treatment alternative only for the approximately 10 percent who do not. Because the exact reasons for the effectiveness of plasmapheresis are not known, researchers feel that further studies are warranted based on the idea that some people may have antibodies in their plasma that are instrumental in certain disease activities that allow disabilities to occur.

As additional therapy, patients with MS should participate in a regular exercise program. Exercise is vital to the maintenance of functional ability in MS sufferers. It strengthens muscles, benefits gait, and generally improves coordination. The best type of exercise is aquatic in nature. Sufferers are often heat intolerant, and participation in a regular aerobic program would be unpleasant. Also, aquatic exercise is a low-impact activity that puts less stress on chronically sore muscles. Exercise programs also encourage socialization of patients and engender peer support.

Perspective and Prospects

The first written report of MS was published in 1400 when the famed Dutch skater Lydwina of Schieden was diagnosed. It was recognized initially as a wasting disease of unknown origin. The disease was described clinically by Jean-Martin Charcot in 1877. Charcot initially characterized the clinical signs and symptoms of MS. He recognized that the disease affects the nervous system and tried many remedies, without success. In 1890, the cause of MS was thought to be suppression of sweat; the treatment was electrical stimulation and bed rest. At the time, life expectancy for a sufferer was five years after diagnosis. By 1910, MS was thought to be caused by toxins in the blood, and purgatives were alleged to be the best treatment. In the 1930s, poor circulation was believed to cause MS, and blood-thinning agents became the treatment of choice. From the 1950s through the 1970s, MS was thought to be caused by severe allergies; treatments included antihistamines. Not until the 1980s was the basis of MS understood and effective treatment developed.

By the early twenty-first century, it was estimated that thousands of people had this disorder of the brain and spinal cord, which causes disruption in the smooth flow of electrical messages from brain and nerves to the body. The progress of the disease is slow and may take decades to achieve complete nerve degeneration and paralysis. Although often considered a disease of youth, MS has the potential to become an increasing problem in aging populations. More cases of late-onset MS have come to light in individuals over forty years of age, including such celebrities as comedian Richard Pryor, entertainer Annette Funicello, and talk-show host Montel Williams.

Several novel therapies that have been under investigation are sphingosine receptor modulator (fingolimod), vitamin D, inosine (Axosine), and antimicrobial agents. Various combinations of drugs are also being examined, including mitoxantrone (an immunosuppressant) and Copaxone. Ongoing clinical trials are likely to reveal treatment strategies that will further facilitate control of the symptoms and progression of MS.

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