Amyotrophic Lateral Sclerosis Health Article

Definition

Amyotrophic lateral sclerosis (ALS) is a disease that breaks down tissues in the nervous system (a neurodegenerative disease) of unknown cause that affects the nerves responsible for movement. It is also known as motor neuron disease and Lou Gehrig's disease, after the baseball player whose career it ended.

Description

ALS is a disease of the motor neurons, those nerve cells reaching from the brain to the spinal cord (upper motor neurons) and the spinal cord to the peripheral nerves (lower motor neurons) that control muscle movement. In ALS, for unknown reasons, these neurons die, leading to a progressive loss of the ability to move virtually any of the muscles in the body. ALS affects "voluntary" muscles, those controlled by conscious thought, such as the arm, leg, and trunk muscles. ALS, in and of itself, does not affect sensation, thought processes, the heart muscle, or the "smooth" muscle of the digestive system, bladder, and other internal organs. Most people with ALS retain function of their eye muscles as well. However, various forms of ALS may be associated with a loss of intellectual function (dementia) or sensory symptoms.

"Amyotrophic" refers to the loss of muscle bulk, a cardinal sign of ALS. "Lateral" indicates one of the regions of the spinal cord affected, and "sclerosis" describes the hardened tissue that develops in place of healthy nerves. ALS affects approximately 30, 000 people in the United States, with about 5, 000 new cases each year. It usually begins between the ages of 40 and 70, although younger onset is possible. Men are slightly more likely to develop ALS than women.

ALS progresses rapidly in most cases. It is fatal within three years for 50% of all people affected, and within five years for 80%. Ten percent of people with ALS live beyond eight years.

Causes

The symptoms of ALS are caused by the death of motor neurons in the spinal cord and brain. Normally, these neurons convey electrical messages from the brain to the muscles to stimulate movement in the arms, legs, trunk, neck, and head. As motor neurons die, the muscles they enervate cannot be moved as effectively, and weakness results. In addition, lack of stimulation leads to muscle wasting, or loss of bulk. Involvement of the upper motor neurons causes spasms and increased tone in the limbs, and abnormal reflexes. Involvement of the lower motor neurons causes muscle wasting and twitching (fasciculations).

Although many causes of motor neuron degeneration have been suggested for ALS, none has yet been proven responsible. Results of recent research have implicated toxic molecular fragments known as free radicals. Some evidence suggests that a cascade of events leads to excess free radical production inside motor neurons, leading to their death. Why free radicals should be produced in excess amounts is unclear, as is whether this excess is the cause or the effect of other degenerative processes. Additional agents within this toxic cascade may include excessive levels of a neurotransmitter known as glutamate, which may over-stimulate motor neurons, thereby increasing free-radical production, and a faulty detoxification enzyme known as SOD-1, for

superoxide dismutase type 1. The actual pathway of destruction is not known, however, nor is the trigger for the rapid degeneration that marks ALS. Further research may show that other pathways are involved, perhaps ones even more important than this one. Autoimmune factors or premature aging may play some role, as could viral agents or environmental toxins.

Two major forms of ALS are known: familial and sporadic. Familial ALS accounts for about 10% of all ALS cases. As the name suggests, familial ALS is believed to be caused by the inheritance of one or more faulty genes. About 15% of families with this type of ALS have mutations in the gene for SOD-1. SOD-1 gene defects are dominant, meaning only one gene copy is needed to develop the disease. Therefore, a parent with the faulty gene has a 50% chance of passing the gene along to a child.

Sporadic ALS has no known cause. While many environmental toxins have been suggested as causes, to date no research has confirmed any of the candidates investigated, including aluminum and mercury and lead from dental fillings. As research progresses, it is likely that many cases of sporadic ALS will be shown to have a genetic basis as well.

A third type, called Western Pacific ALS, occurs in Guam and other Pacific islands. This form combines symptoms of both ALS and Parkinson's disease.