Sporadic ALS

Amyotrophic lateral sclerosis (ALS) is a progressive neurological disorder that is associated with a loss of motor neurons.

Depending on the cause, ALS is classified as sporadic ALS (SALS) or familial ALS (FALS). SALS accounts for about 90 percent of ALS cases where the cause of the disease is not well understood. Unlike FALS, SALS patients have no known family history of ALS. It is thought that a complex interaction between genetic and environmental factors leads to SALS.

Genetic factors involved in SALS

Genetic mutations that are known to cause FALS also can be seen in SALS patients, but less frequently. Only about 10 percent of SALS patients carry a genetic mutation that is known to cause ALS. In the remaining cases, the contribution of genes to the disease is unclear. It is thought that certain combinations of rare genetic mutations can cause SALS. Each individual mutation seems to have only a small effect, which makes it difficult to identify mutations that are linked to the development of the disease.

Environmental risk factors associated with SALS

Because SALS usually occurs late in adult life (during a person’s late 50s or early 60s), it is difficult to identify environmental risk factors associated with the disease because a person may have been exposed to them decades ago.

Men have a 1.5 times greater risk of developing SALS compared to women. One proposed contributing risk factor is the male sex hormone testosterone.

Smoking is another risk factor associated with an increased risk of developing SALS. It is, however, not known which of the toxic substances in tobacco smoke are involved.

Research has shown that U.S. military service personnel have a higher risk of developing SALS compared to the general population. Factors such as strenuous physical exertion, poor sleep, trauma, psychological stress, and lead exposure are common in military service and may play a role in the development of SALS. But the link between military service and SALS is not clear, because there is no association between military service and SALS in other countries.

Oxidative stress is one factor that is involved in the pathology of ALS. It has been proposed that agents that cause oxidative stress could be commonly involved in the development of SALS.


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