Multiple sclerosis in detail - non-technical article.
Multiple sclerosis (MS) is a chronic autoimmune disorder affecting movement, sensation, and bodily functions. It is caused by destruction of the myelin insulation covering nerve fibers (neurons) in the central nervous system (brain and spinal cord).
In 2008, multiple sclerosis affected about 400,000 people in the United States, with 10,000 new cases being diagnosed each year. Worldwide, MS affects between 1.5 and 2.5 million people. Most people have their first symptoms between the ages of 20 and 40; symptoms rarely begin before age 15 or after age 60. Women are almost twice as likely to get MS as men, especially in their early years. People of northern European ancestry are more likely to be affected than people of other racial backgrounds, and MS rates are higher in the United States, Canada, and Northern Europe than other parts of the world. The disorder is unknown among certain native peoples such as the Inuit (native people of the Arctic) and Maori (Native people of New Zealand).
Multiple sclerosis is a slowly progressive disease of the central nervous system (CNS), which is comprised of the brain and spinal cord. In 1868, French physician Jean-Martin Charcot (1825-1893) provided the first detailed clinical description of the disease. Today researchers know that MS is an autoimmune disorder that causes the destruction of myelin, the insulating material that surrounds nerve fibers (neurons).Myelin helps electrical signals pass quickly and smoothly between the brain and the rest of the body.
When the myelin layer is destroyed, nerve messages are sent more slowly and less efficiently. Patches of scar tissue, called plaques, form over the affected areas, further disrupting nerve communication. The symptoms of MS occur when the brain and spinal cord nerves no longer communicate properly with other parts of the body. MS causes a wide variety of symptoms and can affect vision, balance, strength, sensation, coordination, and bodily functions.
The risk of developing MS is slightly higher if another family member is affected, suggesting the influence of genetic factors. If one person in a family has MS, then that person’s close family relatives (parents, children, siblings) have about a 5% greater chance of developing MS than people who do not have family members with the disorder. In addition, the higher prevalence of MS among people of northern European background suggests some genetic susceptibility.
Causes and symptoms
Multiple sclerosis is an autoimmune disorder, meaning it is caused by the body’s own immune system. For unknown reasons, immune cells attack and destroy the myelin sheath that insulates neurons in the brain and spinal cord. This myelin sheath speeds transmission of nerve impulses and prevents electrical activity in one cell from short-circuiting to another cell. Disruption of communication between the brain and other parts of the body prevents normal passage of sensations and control messages, leading to the symptoms of MS. The demyelinated areas appear as plaques, small round areas of gray neuron without the white myelin covering. The progression of symptoms in MS is correlated with development of new plaques in the portion of the brain or spinal cord controlling the affected areas. Because there appears to be no pattern in the appearance of new plaques, the progression of MS can be unpredictable.
Despite considerable research, the trigger for this autoimmune destruction is still unknown. At various times, evidence has pointed to genes, environmental factors, viruses, or a combination of these.
The fact that the risk of developing MS is slightly higher if another family member is affected, suggests that there is a genetic susceptibility to the disease.
The role of an environmental factor is suggested by studies of the effect of migration on the risk of developing MS. Age plays an important role in determining this change in risk—young people in low-risk groups who move into countries with higher MS rates display the risk rates of their new surroundings, while older migrants retain the risk rate of their original home country. One interpretation of these studies is that an environmental factor, either protective or harmful, is acquired in early life; the risk of disorder later in life reflects the effects of the early environment.
These same data can be used to support the involvement of a slow-acting virus, one that is acquired early in live but begins its destructive effects much later. Slow viruses are known to cause other disorders, including AIDS. In addition, viruses have been implicated in other autoimmune disorders. Many claims have been made for the role of viruses, slow or otherwise, as the trigger for MS, but as of 2014 no strong candidate has emerged.
How a virus could trigger the autoimmune reaction is also unclear. There are two main models of virally induced autoimmunity. The first suggests the immune system is actually attacking a virus (one too well-hidden for detection in the laboratory), and the myelin damage is an unintentional consequence of fighting the infection. The second model suggests the immune system mistakes myelin for a viral protein, one it encountered during a prior infection. Primed for the attack, it destroys myelin because it resembles the previously recognized viral invader.
Either of these models allows a role for genetic factors, since certain genes can increase the likelihood of autoimmunity, and it seems likely that more than one gene is involved in a person’s susceptibility to MS. Environmental factors as well might change the sensitivity of the immune system or interact with myelin to provide the trigger for the secondary immune response. Possible environmental triggers that have been invoked in MS include viral infection, trauma, electrical injury, and chemical exposure, although controlled studies do not support a causative role.
MS is a diverse disease. No two affected persons are the same and each will experience different combinations of symptoms with differing severity. The symptoms of multiple sclerosis may occur in one of three patterns:
- The most common pattern is the relapsing-remitting pattern, in which there are clearly defined symptomatic attacks lasting 24 hours or more, followed by complete or almost complete improvement. The period between attacks may be a year or more at the beginning of the disorder, but may shrink to several months later on. About three-quarters of all people diagnosed with MS have this version of the disorder. This pattern is especially common in younger people who developMS.
- In the primary progressive pattern, the disorder progresses without remission or with only occasional plateaus or slight improvements. This pattern is more common in older people. About 10% of people with the disorder have this pattern.
- In the secondary progressive pattern, the person with MS begins with relapses and remissions, followed by more steady progression of symptoms. In some people, what begins as a relapsing-remitting pattern develops into a secondary progressive pattern.
Between 10–20% of people have a benign type of MS, meaning their symptoms progress very little over the course of their lives.
Because plaques may form in any part of the central nervous system, the symptoms of MS vary widely from person-to-person and from stage-to-stage of the disorder. Initial symptoms often include:
- muscle weakness, causing difficulty walking
- loss of coordination or balance
- numbness, ‘‘pins and needles,’’ (paresthesias) or other abnormal sensations
- visual disturbances, including blurred or double vision.
Later symptoms may include:
- muscle spasticity and stiffness
- speech or swallowing difficulty
- loss of bowel and bladder control
- incontinence, constipation
- sexual dysfunction
- cognitive changes.
Weakness in one or both legs is common, and may be the first symptom noticed by a person with MS. Muscle spasticity, where muscles are excessive and continuously contracted, is also common and may be more disabling than weakness.
Double vision or eye tremor (nystagmus) may result from involvement of the nerve pathways controlling movement of the eye muscles. Visual disturbances result from involvement of the optic nerves (optic neuritis) and may include development of blind spots in one or both eyes, changes in color vision, or blindness. Optic neuritis usually involves only one eye at a time and is often associated with movement of the effected eye.
More than half of all people affected by MS have pain during the course of their disorder, and many experience chronic pain, including pain from spasticity. Acute pain occurs in about 10% of cases. This pain may be a sharp, stabbing pain especially in the face, neck, or down the back. Facial numbness and weakness are also common.
Cognitive changes, including memory disturbances, depression, and personality changes, are found in people affected by MS, although it is not entirely clear whether these changes are due primarily to the disorder or to the psychological reaction to it. Depression may be severe enough to require treatment in up to 25% of those with MS. A smaller number of people experience disorder-related euphoria, or abnormally elevated mood, usually after a long disorder duration and in combination with other psychological changes.
Symptoms of MS may be worsened by heat or increased body temperature, including fever, intense physical activity, or exposure to sun, hot baths, or showers.
There is no single test that confirms the diagnosis of multiple sclerosis, and there are a number of other disorders with similar symptoms. While one person’s diagnosis may be immediately suggested by symptoms and history, another’s may not be confirmed without multiple tests and prolonged observation. The distribution of symptoms is important: MS affects multiple areas of the body over time. The pattern of symptoms is also critical, especially as evidence of the relapsing-remitting pattern, so a detailed medical history is one of the most important parts of the diagnostic process. A thorough search to exclude other causes of a patient’s symptoms is especially important if the following features are present:
- family history of neurologic disorder,
- symptoms and findings attributable to a single anatomic location,
- persistent back pain,
- age of onset over 60 or under 15 years of age, or
- progressively worsening disorder.
In addition to the medical history and a standard neurological exam, several lab tests are used to help confirm or rule out a diagnosis of MS:
- Magnetic resonance imaging (MRI) can reveal plaques on the brain and spinal cord. Gadolinium enhancement can distinguish between old and new plaques, allowing a correlation of new plaques with new symptoms. Plaques may be seen in several other disorders as well, including encephalomyelitis, neurosarcoidosis, and cerebral lupus. Plaques on MRI may be difficult to distinguish from small strokes, areas of decreased blood flow, or changes seen with trauma or normal aging.
- A lumbar puncture, or spinal tap, is done to measure levels of immune system proteins, which are usually elevated in the cerebrospinal fluid of a person with MS. This test may not be necessary if other tests are diagnostic.
- Evoked potential tests are electrical tests of conduction speed in the nerves that can reveal reduced speeds consistent with the damage caused by plaques. These tests may be done with small electrical charges applied to the skin (somatosensory evoked potential), with light patterns flashed on the eyes (visual evoked potential), or with sounds presented to the ears (auditory evoked potential).
The clinician making the diagnosis, usually a neurologist, may classify the disorder as ‘‘definite MS,’’ meaning the symptoms and test results all point toward MS as the cause. ‘‘Probable MS’’ and ‘‘possible MS’’ reflect less certainty and may require more time to pass to observe the progression of the disorder and the distribution of symptoms.
As of 2014, there was no cure for MS. Nevertheless, several drugs may slow progression of the disorder and moderate some symptoms in many patients, especially if started early.
MS causes a wide variety of symptoms, and the treatments for these are equally diverse. Most symptoms can be treated and complications avoided with good care and attention from medical professionals. Good health and nutrition remain important preventive measures. Vaccination against influenza can prevent respiratory complications. Preventing complications such as pneumonia, bedsores, injuries from falls, or urinary infection requires attention to the primary problems that may cause them. Shortened life spans with MS are almost always due to complications rather than primary symptoms themselves.
Drug treatment of MS must be individualized. Not all drugs are appropriate for all patients. In the United States as of 2009, MS was most often treated with four drugs known as the ABCR drugs. These drugs are interferon beta-1a (Avonex), interferon beta-1b (Betaseron and Rebif) and glatiramer acetate (Copaxone). These drugs, on average, reduce relapses in the relapsing remitting form of MS by about one-third. Different measurements from tests of each have demonstrated other benefits as well: Avonex may slow the progress of physical impairment, Betaseron and Rebif may reduce the severity of symptoms, and Copaxone may decrease disability. All four drugs are administered by injection, some into muscle (IM), and some under the skin (SC). Some controversy exists on the most effective dose and the frequency with which these drugs should be administered.
Although the ABCR drugs reduce relapses and may keep patients in relatively good health for the short-term, their long-term success has not been proven and they do not work well for patients who have reached a steadily progressive stage of MS. Individuals with progressive forms of MS may be treated with mitoxantrone (Novantrone), cyclophosphamide (Cytoxan, Neosar), azathioprine (Imuran), or methotrexate (Rheumatrex). All these drugs suppress the immune system. None is ideal, and all have potentially serious side effects. Corticosteroid drugs such as methylprednisolone (Medrol) also may be used to reduce inflammation. Long-term use of corticosteroids also causes serious side effects.
Training in bowel and bladder care may be needed to prevent or compensate for incontinence. If the urge to urinate becomes great before the bladder is full, some drugs may be helpful, including propantheline bromide (Probanthine), oxybutynin chloride (Ditropan), or imipramine (Tofranil). Baclofen (Lioresal) may relax the sphincter muscle, allowing full emptying. Intermittent catheterization is effective in controlling bladder dysfunction. In this technique, a catheter is used to periodically empty the bladder.
Spasticity can be treated with oral medications, including baclofen and diazepam (Valium), or by injection with botulinum toxin (Botox). Spasticity relief may also bring relief from chronic pain. More acute types of pain may respond to carbamazepine (Tegretol) or diphenylhydantoin (Dilantin). Low back pain is common from increased use of the back muscles to compensate for weakened legs. Physical therapy and over-the-counter pain relievers may help.
Fatigue may be partially avoidable with changes in the daily routine to allow more frequent rests. Amantadine (Symmetrel) and Modafinil (Provigil), although not specifically approved for use with MS, are often used to treat fatigue and improve alertness. Pemoline (Cylert), a drug formerly used to treat fatigue in MS patients, was withdrawn from sale in the United States in October 2005 because of potentially fatal liver complications. Visual disturbances often respond to corticosteroids. Other symptoms that may be treated with drugs include seizures, vertigo, and tremor.
Clinical trials of new drugs and drug combinations to treat MS are ongoing.
Physical therapy helps the person with MS to strengthen and retrain affected muscles, maintain range of motion, prevent muscle stiffening, learn to use assistive devices such as canes and walkers, and to learn safer and more energy-efficient ways of moving, sitting, and transferring. Exercise and stretching programs are usually designed by the physical therapist and taught to the patient and caregivers for use at home. Exercise is an important part of maintaining function for the person with MS. Swimming is often recommended, not only for its low-impact workout, but also because it allows strenuous activity without overheating.
Occupational therapy helps the person with MS adapt to her environment and adapt the environment to her. The occupational therapist suggests alternate strategies and assistive devices for activities of daily living, such as dressing, feeding, and washing, and evaluates the home and work environment for safety and efficiency improvements that may be made.
Bee venom has been suggested as a treatment for MS, but no studies or objective reports support this claim.
In several studies, marijuana has been shown to have variable effects on the symptoms ofMS. Improvements have been documented for tremor, pain, and spasticity, and worsening for posture and balance. Side effects have included weakness, dizziness, relaxation, and incoordination, as well as euphoria.
Some studies support the value of high doses of vitamins, minerals, and other dietary supplements for controlling disorder progression or improving symptoms. Alpha-linoleic and linoleic acids, as well as selenium and vitamin E, have shown effectiveness in the treatment of MS. Selenium and vitamin E act as antioxidants. In addition, a diet low in saturated fats, maintained over a long period, may retard the disorder process. Studies have also shown that t’ai chi can be an effective therapy for MS because it works to improve balance and increase strength. There are conflicting views about the herb Echinacea and its benefit to MS.
Some alternative practitioners recommend Echinacea for people with MS. However, Echinacea appears to stimulate different parts of the immune system, particularly immune cells known as macrophages. In MS these cells are very active already and further stimulation could worsen the disorder.
It is difficult to predict how multiple sclerosis will progress in any one person. Most people with MS will be able to continue to walk and function at their work for many years after their diagnosis. The factors associated with the mildest course of MS are being female, having the relapsing-remitting form, having the first symptoms at a younger age, having longer periods of remission between relapses, and initial symptoms of decreased sensation or vision rather than of weakness or incoordination.
Fewer than 5% of people with MS have a severe progressive form, leading to death from complications within five years. At the other extreme, 10–20% have a benign form, with a very slow or no progression of their symptoms. Studies have shown that about seven out of 10 people with MS are still alive 25 years after their diagnosis, compared to about nine out of 10 people of similar age without disorder. On average, MS shortens the lives of affected women by about six years, and men by 11 years. Suicide is a significant cause of death in MS, especially in younger patients. Suicide is completed 7.5 times more often in patients with MS than in those without the disorder.
The degree of disability a person experiences five years after onset is, on average, about three-quarters of the expected disability at 10–15 years. A benign course for the first five years usually indicates the disorder will not cause marked disability.
There is no known way to prevent multiple sclerosis. Until the cause of the disorder is discovered, this is unlikely to change. Good nutrition, adequate rest, avoidance of stress, heat, and extreme physical exertion, and good bladder hygiene may improve quality of life and reduce symptoms.
Blackstone, Margaret. The First Year: Multiple Sclerosis: An Essential Guide for the Newly Diagnosed. New York: Marlowe, 2007.
Clinical trial—All new drugs undergo clinical trials before approval. Clinical trials are carefully conducted tests in which effectiveness and side effects are studied, with the placebo effect eliminated.
Evoked potentials—Tests that measure the brain’s electrical response to stimulation of sensory organs (eyes or ears) or peripheral nerves (skin). These tests may help confirm the diagnosis of multiple sclerosis.
Myelin—A layer of insulation that surrounds the nerve fibers in the brain and spinal cord.
Plaque—Patches of scar tissue that form where the layer of myelin covering the nerve fibers is destroyed by the multiple sclerosis disorder process.
Primary progressive—A pattern of symptoms of multiple sclerosis in which the disorder progresses without remission, or with occasional plateaus or slight improvements.
Relapsing-remitting—A pattern of symptoms of multiple sclerosis in which symptomatic attacks occur that last 24 hours or more, followed by complete or almost complete improvement.
Secondary progressive—A pattern of symptoms of multiple sclerosis in which there are relapses and remissions, followed by more steady progression of symptoms.