Multiple Sclerosis: Causes and symptoms

Multiple sclerosis is an autoimmune disease, meaning its cause is an attack 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, created by other brain cells called glia, speeds transmission 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 prevent 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 risk of developing MS is higher if another family member is affected, suggesting the influence of genetic factors. In addition, the higher prevalence of MS among people of northern European background suggests some genetic susceptibility.

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 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 disease 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 on but begins its destructive effects much later. Slow viruses are known to cause other diseases, including AIDS. In addition, viruses have been implicated in other autoimmune diseases. Many claims have been made for the role of viruses, slow or otherwise, as the trigger for MS, but as of 2001 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. 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.

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 disease, but may shrink to several months later on. This pattern is especially common in younger people who develop MS.
• In the "primary progressive" pattern, the disease progresses without remission or with occasional plateaus or slight improvements. This pattern is more common in older people.
• In the "secondary progressive" pattern, the person with MS begins with relapses and remissions, followed by more steady progression of symptoms.

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 disease. Initial symptoms often include:

• muscle weakness, causing difficulty walking
• loss of coordination or balance
• numbness, "pins and needles," or other abnormal sensations
• visual disturbances, including blurred or double vision Later symptoms may include:
• fatigue
• muscle spasticity and stiffness
• tremors
• paralysis
• pain
• vertigo
• 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, or excessive tightness, 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 neutritis) 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 affected eye.

More than half of all people affected by MS have pain during the course of their disease, 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, though it is not entirely clear whether these changes are due primarily to the disease 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 diseaserelated euphoria, or abnormally elevated mood, usually after a long disease 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.

— Ruthan Brodsky