Amyotrophic lateral sclerosis (ALS) is a fatal disease that affects nerve cells in the brain and spinal cord that are responsible for movement. The motor neurons (nerve cells which send an impulse to illicit muscular contraction or movement) in an ALS patient die as a result of rapid degeneration. Voluntary muscles, controlled by motor neurons, lack proper nourishment and will weaken and atrophy (shrink) as a result. Examples of voluntary movement include stepping off of a curb or reaching for the top shelf. These activities rely on the muscles of the arms and legs. Paralysis sets in at the endstages of ALS and leaves the patient unable to function physically, despite remaining mentally intact. There are no known causes or cures for amyotrophic lateral sclerosis, and the disease can afflict anyone. The usual cause of death is paralysis of the respiratory muscles which control breathing.
Description
Amyotrophic lateral sclerosis is a progressive disease of the central nervous system. "A" means "no," "myo" implies muscle cells, and "trophic" refers to nourishment. The nerve cells that extend from the brain to the spinal cord (upper motor neurons), and from the spinal cord to the peripheral nerves (lower motor neurons), for unexplained reasons, degenerate and die. "Lateral" refers to the areas of the spinal cord that are affected, and "sclerosis" occurs as hard tissue replaces the previously originally healthy nerve.
The parts of the body that are not affected by ALS are those areas not involved in the use of motor neurons. The mind remains very sharp and in control of sight, hearing, smell, touch and taste. Bowel and bladder functions are generally not affected. Amyotrophic lateral sclerosis rarely causes pain, yet leaves patients dependent on the care of others during advanced stages.
At any given time there are about 30,000 people in the United States with amyotrophic lateral sclerosis, and about 5,000 new cases are reported each year. ALS progresses rapidly and paralyzed patients are usually under the intensive care of nursing facilities or loved ones. This can have a devastating psychological effect on the family members and the patient. In most cases, ALS is fatal within two to five years, although approximately 10% live eight years or more.
Amyotrophic lateral sclerosis is not a rare disease. ALS affects approximately seven people out of every 100,000. Most people with ALS are between 40 and 70 years of age. Approximately 5–10% of cases show a heredity pattern.
ALS, or Lou Gehrig's disease, is named after the great New York Yankee's first basemen. Lou Gehrig, known as the "Ironman" of baseball, died two years after he was diagnosed with amyotrophic lateral sclerosis.
Genetic profile
In 1991 a team of ALSA researchers linked familial ALS to chromosome 21. In 1993 it was found that there were structural defects in the SOD1 (superoxide dismutase) gene on chromosome 21. The SOD1 gene is an enzyme that protects the motor neurons from free radical damage. There is a high incidence of ALS on the island of Guam, in the Western New Guinea and on Kii peninsula of Japan leading some theorists to believe that genetic makeup may be susceptible to an environmental cause, such as the high levels of mercury and lead in these areas.
The inheritance pattern is autosomal dominant, which means that children of an affected parent have a 50% chance of inheriting the disorder. The majority of cases are due to a sporadic gene mutation, which means the mutation ocurrs only in the affected person. It is thought that sporadic mutations result from both biological and environmental causes. In rare cases, a mutation in NFH, the gene encoding for neurofilament (a structure that maintains cell shape) is apparent. Familial amyotropic lateral sclerosis has been linked to other chromosomal locations but the exact genes involved have not been identified. The Institutional Review Board at Thomas Jefferson University in Philadelphia recently approved the ALS gene therapy project. The goal of the project is to inject an adeno-associated virus carrying a normal copy of an EAAT2 gene into an ALS patient's spinal cord where the motor neurons are dying. The hope is that the cells in that area will not die off.
Demographics
Amyotrophic lateral sclerosis affects anyone and both men and women are at equal risk. ALS may occur at any age, and the odds of developing it increase with age. There have been reported cases of teenagers with ALS. A person only needs to inherit a defective gene from one parent to cause the disease.
Signs and symptoms
The disease starts slowly, affecting just one limb, such as the hands or feet, and steadily progresses to more limbs and muscles. When muscles lack the proper nourishment they require, they begin to thin and deteriorate. This condition is the hallmark of amyotrophic lateral sclerosis. Muscle wasting is due to the inability of degenerating motor neurons to elicit a signal to the muscles that allow them to function and grow. Common examples of symptoms for ALS are muscle cramps and twitching, weakness in the hands, feet, or ankles, speech slurring, and swallowing difficulties. Other early symptoms include arm and leg stiffness, foot drop, weight loss, fatigue, and difficulty making facial expressions.
One of the earliest symptoms of ALS is weakness in the bulbar muscles. These muscles in the mouth and throat assist in chewing, swallowing, and speaking. Weakness of these muscle groups usually cause problems such as slurred speech, difficulty with conversation and hoarseness of the voice.
Another symptom of ALS that usually occurs after initial symptoms appear is persistent muscle twitching (fasciculation). Fasciculation is almost never the first sign of ALS.
As the disease progresses the respiratory muscles (breathing muscles) weaken, resulting in increased difficulty with breathing, coughing, and possibly inhaling food or saliva. The potential for lung infection increases and can cause death. Many patients find it more comfortable and extend their lives when assisted by ventilators at this stage of the disease. Communication becomes very difficult. One way to accomplish feedback with others is to make use of the eyes. Blinking is one mode that patients of amyotrophic lateral sclerosis will be forced to utilize, in order to continue communication.
As the disease progresses, victims gradually lose the use of their feet, hand, leg, and neck muscles, and paralysis results in affected muscle groups. They are able to speak and swallow only with great struggle. Sexual dysfunction is not affected. Breathing will become increasingly difficult and the patients of ALS may decide to prolong life with the use of assisted ventilation, which may decrease the risks of death from infections such as pneumonia.
Diagnosis
ALS is difficult to diagnose. There is no one set way to test for the disease. A series of diagnostic tests will rule out and exclude other possible causes and diseases that resemble ALS. Electro diagnostic tests such as electromyography (EMG) and nerve conduction velocity (NCV) are used to help diagnose ALS. Blood and urine tests, spinal taps, x rays, and muscle and/or nerve biopsy are performed, as well as magnetic resonance imaging (MRI), myelograms of the cervical spine and a complete neurological exam.
Currently, there is no treatment for ALS. Management aims to control the symptoms that patients experience. Emotional, psychological, and physical support are provided to ease the difficulty associated with this disorder.
Moderate activities are recommended in the early stages of the disease. Physical therapy can help muscles stay active and delay the resulting weakness. ALS patients are encouraged to maintain a healthy diet and exercise regularly for as long as possible. Education of ALS is very important in developing an understanding of the disease, and is vital for family members as well as patients.
Although there are no set treatments for ALS there are still many special considerations that can assist in the quality of lifestyle for the patient. Implementing a physical therapy program, providing a wheelchair or walker, assistance when bathing, and suction machines to help evacuate accumulated secretions all help the ALS patient. Other considerations include providing foods that are soft and easy to swallow, skin maintenance, feeding tubes, ventilation maintenance and emotional support.
Researchers have developed a drug approved by the Food and Drug Administration (FDA) called Rilutek (riluzole). The drug was the first to have a positive effect in that it appears to extend the life of ALS patients by about three months.
Another drug, Myotrophin (somatomedin C), appears to prevent neuron loss and enhance neuron generation in animal studies.
Prognosis
Amyotrophic lateral sclerosis normally progresses rapidly and leads to death from respiratory infection within three to five years. If the person involved is young and the initial symptoms appear in the limbs, the disease tends to develop more slowly. Improved medical care has prolonged the lives of ALS patients and shows promise for more effective treatments in the future.
BOOKS
Adams, Raymond D., Maurice Victor, and Allan H. Ropper. Adam's & Victor's Principles of Neurology, 6th ed. New York, McGraw Hill, 1997.
Brown, Robert H. "The motor neuron diseases." In Harrison's Principles of Internal Medicine, 14th ed., edited by Anthony S. Fauci, et al. New York: McGraw-Hill, 1998, pp. 2368-2372.
Feldman, Eva L. "Motor neuron diseases." In Cecil Textbook of Medicine, 21st ed., edited by Lee Goldman and J. Claude Bennett. Philadelphia: W.B. Saunders, 2000, pp. 2089-2092.
PERIODICALS
Foubistor, V. "Gene therapy fosters hope." American Medical News 43 (March 6, 2000).
ORGANIZATIONS
Association of America (ALSA). 27001 Agoura Rd., Suite150, Calabasas Hills, CA 91301-5104. (818) 800-9006. Fax: (818) 880-9006. <http://www.alsa.org>.
Center for Neurologic Study. 9850 Genesee Ave., Suite 320, Lajolla, CA 92037. (858) 455-5463. Fax: (858) 455-1713. cns@cts.org. <http://www.cnsonline.org>.
Forbes Norris ALS Research Center. Caifornia Pacific Medical Center, 2324 Sacramento St., San Francisco, CA 94115. (415) 923-3604. Fax: (415) 673-5184.
