Amyotrophic Lateral Sclerosis

This progressive disorder strikes approximately 5,600 Americans annually, with an average survival time of just two to five years from symptom onset.

It is the most common disorder within a group of diseases affecting motor neurons. Typically, 30,000 Americans have the disease at any given time. The costs of both care and treatment for ALS are expensive, and they continue to rise as the disease progresses. In the final stages, ALS can cost as much as $200,000 a year per family, and costs Americans some $300 million annually.

Commonly known as Lou Gehrig’s disease, ALS affects neurons that control voluntary muscle movements such as walking. For reasons that are not completely understood, motor neurons in the brain and spinal cord begin to disintegrate. Because signals from the brain are not carried by these damaged nerves to the body, the muscles begin to weaken and deteriorate from the lack of stimulation and resulting disuse.

The first signs of progressive paralysis are usually seen in the hands and feet or in the muscles of speech and swallowing. Early symptoms include weakness in the legs, difficulty walking, clumsiness of the hands when washing and dressing, and slurred speech. Eventually, almost all muscles under voluntary control, including those of the respiratory system, are affected. Despite the paralysis, however, the mind and the senses remain intact. Death is usually caused by respiratory failure or pneumonia.
No specific test identifies ALS, but electrical tests of muscle activity, muscle biopsies, blood studies, computed tomography (CT), and magnetic resonance imaging (MRI) scans help diagnose the disease and rule out other disorders.

In more than 90 percent of cases, ALS is sporadic, arising in individuals with no known family history of the disorder. Potential causes or contributors to the disease include an excess amount of the neurotransmitter glutamate, which becomes toxic; oxygen in a dangerous form in the body, resulting in what is called oxidative distress; environmental factors; and an autoimmune response in which the body’s defenses turn against body tissue. In the other 5 to 10 percent of cases, ALS is familial — transmitted to family members because of a gene defect.

Scientists have now identified several genes that are responsible for some forms of ALS. The most common and well-studied of these are mutations in the gene that codes for superoxide dismutase, a defense against oxidative distress. Scientists believe that whatever they learn from studying this and other genes will have relevance for understanding the more common, sporadic form of this motor neuron disease.

Once ALS is diagnosed, there is little that can be done to slow its progression. Various drugs can ease specific problems, such as muscle cramping and neurological stiffness, but there is no cure. An anti-glutamate drug slows the disease’s progression modestly. Additional drugs are now under study. Protecting or regenerating motor neurons using nerve growth factors, other more potent drugs, and stem cells may someday provide additional benefits for patients.