Amyotrophic Lateral Sclerosis: The Whys and Wherefores
By Carol Duff MSN, BA, RN
Amyotrophic lateral sclerosis (ALS) is the most common of the adult-onset motor neuron (nerve cells located in the brain, spinal cord, and brainstem) diseases and is often referred to as Lou Gehrig disease, named after the famous baseball player who died of ALS in 1941. ALS was first recognized in 1869 by French neurologist Jean-Martin Charcot. Other names used to identify this disease are motor neuron disease (MND), and Charcot’s disease.
Other people you may have heard of, who have also had this disease are theoretical physicist, cosmologist and author Stephen Hawking, Hall of Fame pitcher Jim “Catfish” Hunter, Toto bassist Mike Porcaro, Senator Jacob Javits, actor David Niven, boxing champion Ezzard Charles, musician Lead Belly (Huddie Ledbetter), photographer Eddie Adams, entertainer Dennis Day, jazz musician Charles Mingus, and former vice president of the United States Henry A. Wallace. Classically this disease affects motor neurons at two or more levels supplying many regions of the body and does not care who you are.
ALS is a progressive degeneration and loss of motor neurons which results in a progressive muscle atrophy, weakness, and muscle twitching. Specifically, the anterior horn cells and the neurons that are associated with them degenerate. Motor neurons in the brain (upper motor neurons) transmit messages to motor neurons in the spinal cord (lower motor neurons) and then to muscles.
With ALS, upper and lower motor neurons die and can not longer send messages to the muscles. The brain is eventually unable to start or to control voluntary muscle control. Muscles of the diaphragm and chest wall will be unable to move and the ability to breath on one’s own disappears. The cause of this devastating illness is not known. Not everyone who has ALS has the same set of symptoms.
The two types of ALS are the familial and the sporadic. Sporadic is the most common form and makes up 90 to 95% of cases while familial (FALS), inherited, makes up 5 to 10%. In families with FALS there is a 50% chance that each child will inherit the gene mutation and may develop ALS. Only one parent is needed to have the gene which causes ALS. For 20% of those with familial cases result from a genetic defect that leads to the mutation of the enzyme, superoxide dismutase 1 (SOD1). Not all of the genetic mutations are due to this enzyme and research goes on.
As of September 2008, the Department of Veterans Affairs has declared that ALS has become a presumptive compensable illness for veterans because there is a correlation between time spent in the military and the later development of this disease. Even those veterans who were previously denied compensation for ALS can receive compensation.
The entire regulation may be viewed at www.federalregister.gov/OFRUpload/OFRData/2008-21998 PI.pdf This decision was based on an Institute of Medicine (IOM) report that concluded that there was limited and suggestive evidence between military service and the development of ALS later in life. This is a weaker endorsement than if the term was sufficient evidence.
ALS mostly occurs in people between the ages of 40 and 70. Although the number fluctuates, there is more than 20,000 Americans who have this disease at any given time with 5,000 being diagnosed every year. Sixty percent are men and 93% are Caucasian. For reasons unknown, military veterans are about twice as likely to be diagnosed with ALS than the general public.
Worldwide there are about 1 to 2 cases of ALS for every 100,000 people. In the U.S. geographically the most cases occur in the western Pacific part of the U.S. where it is often associated with dementia and Parkinsonism. The ALS Association estimates that there are between 6 and 8 cases of ALS per every 100,000 people in the U.S.
Another area being looked at is the role of glutamate when motor neurons die. Glutamate is one of the several chemicals that carry messages or transmission between brain neurons. People with ALS have a higher level of glutamate in the serum and spinal fluid when compared to those without ALS. Neurons begin to die when they are exposed over long periods of time to glutamate. Research is ongoing into understanding the mechanism that leads to the buildup of excessive glutamate in the spinal fluid and why this excess leads to the development of ALS.
Autoimmune responses (occur when the body’s immune system attacks normal cells) is also being researched as a possible cause of the motor neuron disintegration seen in ALS. It is speculated that antibodies produced during this attack on the immune system may interfere with the transmission of healthy signals between the brain and muscles. The environment, with exposure to infectious or toxic agents, is being studied to determine if the cause lies there, perhaps trauma or dietary deficiencies are the cause, although as of now there is not clear case of this.
In the general population the cause or exact disease mechanism of ALS is unknown. There is the potential for many factors to be involved. Possible factors are it is in one’s genes (familial), programmed cell death, mitochondrial dysfunction and oxidative stress, inflammation of neurons, protein aggregation, exitotoxicity. The initial onset of ALS may be very discrete, so symptoms can be overlooked.
Infectious diseases such a human immunodeficiency virus (HIV), Lyme disease, human T-cell leukemia virus, syphilis, and tick born encephalitis can present with symptoms that mimic ALS symptoms. Neurological disorders such as multiple sclerosis, diabetic neuropathy, multifocal motor neuropathy, brain stem syndrome, cervical disk syndromes, brainstem gliomas, myasthenia gravis, spinal muscular atrophy, and post-polio syndrome can also imitate ALS.
This list does have all the diseases and illnesses that can mimic ALS symptoms, but is representable. These diseases should be considered when a healthcare provider is attempting to diagnose ALS. These various diseases, illnesses, and disorders can resemble early stage ALS, so this may prompt a second neurological opinion.
In the 1990s, after Desert Storm/Shield, the VA was seeing veterans only in their 30s and 40s being diagnosed with ALS when the typical onset age is 50s, 60s, or 70s. A VA/Department of Defense study showed a significantly increased rate of ALS disease in the veteran population versus the general population.
In December of 2001 full disability and survivor benefits was conferred on Gulf War Veterans with ALS. Studies by the Department of Veterans Affairs confirmed that veterans who had served during the Gulf War had double the chance of getting ALS than those who did not serve. The incidence of Air Force personnel getting ALS was even higher at 2.7 times more likely than Air Force personnel not deployed.
With ALS the larger motor neurons are more affected than the smaller ones. The death of the anterior horn cells causes breakdown of the motor axons. The covering of the axons are destroyed by Schwann cells. The axons then break into small parts.
The name of this disease if formed from the pathophysiological changes that occur in the body. Amyotrophic (no muscle nourishment) refers to atrophy of muscle fibers which lose the ability to respond due to the lack of nerve impulses due to the degeneration of the horn cells. Lateral sclerosis refers to the hardening of the anterior and lateral columns of the spinal cord again due to the degeneration of neurons in these particular areas. The healthy neurons are replaced by fibrous astrocytes. These areas of debris, caused by the degeneration, create small areas of debris which is then further destroyed by macrophages which come to the area to clean up the debris. Myelin or the protective covering of the nerves is also destroyed.
The average time from diagnosis to the necessity of a ventilator for breathing is between two and four years and once a ventilator is used there will be another five to ten years of life expectancy. This disease if more prevalent in males and can occur from teen years to the 80s with the average being 62 years with the peak age of onset between 55 and 75. For a diagnosis of ALS, the patient must have signs of both upper and lower motor neuron damage that is not explained by another cause.
ALS progresses with weakness and wasting of muscles, often not on both sides equally. In 75 to 80% of those affected will start with symptoms of the arms and or legs with equal involvement between upper and lower extremities. Those with lower extremity involvement will usually start with tripping, awkwardness when running, and stumbling.
Those who have symptoms beginning with the arms may experience difficulty in buttoning clothing; trouble picking up small objects, even turning a key can be problematic. There may be muscle twitching which can be embarrassing for the patient. Muscle cramping is common and repeated cramping associated with stress placed on the joints can cause aching of the arms, legs and back. Once the muscles are not strong enough to be used, there can be contractions or abnormal positioning of the limbs due to muscle disuse.
The 19 to 25% with bulbar involvement will have trouble with speech such a slurring or hoarseness, and the inability to increase the volume of their voice. There may be spastic movement or no movement (flaccid) of muscles involved in speech. The voice can develop a strained quality with a nasal sounding quality and someone with bulbar ALS will eventually lose the ability to speak.
At that time, they must rely on writing (if arms are still functional), communication boards, or other speech assistance devices. A speech therapist may be beneficial and nonverbal communication can be established. Speech synthesizers and computer-generated communication systems will be helpful.
Bulbar involvement may include difficulties with swallowing, with liquids presenting more of a problem than solids. Due to the lack of control of the lips drooling may be present. There may be an overactive gag reflex due to exaggeration of reflexes (hyperreflexia). The difficulties in swallowing can lead to weight loss.
A nutritionist can assist in developing foods that the patient will still be able to eat. Sometimes a stomach tube is inserted to assist in giving nutrition, but this does not interfere with regular eating measures. Pneumonia can result from aspirating fluids or food into the lungs during times when swallowing has become difficult.
Pseudobulbar symptoms may be another part of the disease. Patients with these types of symptoms may have exaggerated emotional responses and have frequent and rapid alterations in their emotional state. Intense laughter may be followed by tears; all the while an emotional response may not be totally responsive to the current social issue or psychosocial situation.
Usually the muscles which control the eye muscle movements, bowel and bladder control are normal. Later abdominal muscle weakness can cause the urge incontinence or severe constipation. Senses of the skin will be intact because the disease only involves motor neurons. Patients may have some numbness or feel tingling, pricking, burning, and itching. No matter where muscle weakness begins, muscle weakness and atrophy of muscles will spread to other parts of the body.
Ventilation will eventually become necessary for breathing but does not affect the progression of the disease which frequently ends in respiratory failure usually 3 to 5 years from the beginning of the symptoms. About 10% will survive for 10 or more years. Of course, it is impossible to determine what length of time someone will live when they are at the beginning of the disease course. The rate of progression of the disease will determine the potential amount of time for survivability.
ALS patients often have complications from pneumonia as they are unable to breath on their own. Someone with ALS will lose his or her independence as muscles can not longer work. Usually the patient’s ability to breath will define the progression of the disease and will also be what the healthcare provider will base patient’s level of disease on. Adequate respirations assisted by mechanical devices will alleviate sleep problems associated with decrease ability to breath during sleep go a long way toward improving the extension of life.
Other complications of ALS will be decreased ability to perform activities of daily living, inability to walk, aspiration pneumonia (inhaling liquids, secretions, or foods into lungs), breakdown of skin due to being in a wheelchair or bedridden, and deep vein thrombosis (blood clots, usually in leg veins) and pulmonary emboli (blood clots that go to lungs).
The Federal Drug Administration (FDA) has approved four drugs to treat ALS (Riluzole, Nuedexta, Radicava, and Tiglutik.) These drugs may reduce the motor neuron damage and extend life for several months. These drugs is particularly useful for those who have difficulty in swallowing. Other drugs which are used may be those to treat depression, pain, sleep disturbances, decrease the production of saliva, and constipation. Mechanical respirations (ventilators) will be needed when the patient can not longer breathe on his or her own.
Treatment for someone with ALS will usually be divided into the areas of supportive treatment, education, and treatments specific for the medical need of the patient. Local support groups are available for additional support. Consultations with other groups will greatly affect how a person with ALS can live the rest of his or her life. These consults may be with occupational and physical therapists, nutritionists, respiratory therapy, speech therapist, pulmonologist, gastroenterologist, visiting nurse for patient care at home, hospice, spiritual if patient wishes, alternative therapies which may give the patient some sense of being in control, genetic councilors, psychologists, and psychiatrists.
People with ALS are eligible for Medicare and Social Security benefits without the waiting period associated with other chronic diseases. With the eventual decreased ability to sign documents or to take care of their personal affairs, some may need legal advice. Three is an increased potential for falls as ALS progresses and many with ALS will have several falls before they will alter their independent activities.
Those who initially are able to drive will have to quit as the disease progresses and some states have a mandatory reporting policy for practitioners to the Department of Motor Vehicles Affairs. Local branches of the ALS Association and the Muscular Dystrophy Association have great resources to inform patients on what is available locally. The patient with ALS may wish to complete advance directives for what will happen if they become unable to make decisions (too ill, unconscious, end of life, etc) and documentation of this will go into medical records.
The ALS Association can be accessed at www.alsa.org. This helpful website offers information for those who require knowledge and assistance about this devastating disease. The ALS Association supports veterans and offers a great deal of assistance on their website. Go to http://www.alsa.org/policy/veterans.cfm to obtain help if you are a veteran.
Other areas for help are Living with ALS Manual http://www.alsa.org/resources/manuals.cfm
MDA ALS Caregiver’s Guide
ALS Lou Gehrig’s Disease
ALS 1996 and Beyond: New Hopes and Challenges
ALS Newsletter for the Muscular Dystrophy Association
ALS association. http://www.alsa.org/about-als/what-is-als.html, 2019.
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Department of Veterans Affairs, 2008. Va secretary establishes als as a presumptive compensable illness. Retrieved on November 9, 2009 from http://www1.va.gov/opa/pressrel/pressrelease.cfm?id=1583
Department of Veterans Affairs, 2003. News release:Gulf war service – ALS link confirmed. Retrieved on November 9, 2009 from http://www1.va.gov/opa/pressrel/docs/ALS_Neurology.doc
Meekins, Gregg, 2008. Amyotrophic lateral sclerosis and gulf war veterans. Retrieved on November 9, 2009 from http://www1.va.gov/gulfwaradvisorycommittee/docs/ALSMeekins.pdf
National Institute of Neurological Disorders and Stroke, (2009). NINDS amyotrophic lateral sclerosis information page. Retrieved on November 10, 2009 from
Shannon, P. & Bockeneck, W., 2009. Amyotrphic lateral sclerosis. Retrieved on November 9, 2009 from http://emedicine.medscape.com/article/306543-overview
Veterans Administration, 2000. Study will assess ALS among Gulf War Veterans. Retrieved on November 9, 2009 from http://www1.va.gov/opa/pressrel/docs/nrpgals.doc