Amyotrophic lateral sclerosis

Definition

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that attacks the nerve cells (neurons) in the brain and spinal cord responsible for controlling voluntary muscles.

Description

ALS, also called Lou Gehrig's disease, is classified in a group of disorders called motor neuron diseases, characterized by the gradual deterioration and death of motor neurons. Neurons are cells that send and receive electrical signals over long distances within the body. Motor neurons convey impulses to control muscle contraction, and link the nervous system to the voluntary muscles of the body. Upper motor neurons located in the brain transmit signals to lower motor neurons located in the spinal cord which in turn send messages to specific muscles. In persons afflicted with ALS, one or both types of neurons degenerate or die, impairing the propagation of nervous system messages to muscles. The muscles gradually weaken, and eventually waste away (atrophy), with the result that the brain loses the ability to start and control voluntary movement.

Types of ALS

ALS occurs in five major forms:

• Classical ALS ALS characterized by a deterioration of both upper and lower motor neurons.
• Primary Lateral Sclerosis (PLS) ALS in which only the upper motor neurons deteriorate. This is the rarest form of the disease.
• Progressive Bulbar Palsy (PBP) ALS that starts with difficulties in speaking, chewing and swallowing due to lower motor neuron deterioration. PBP affects about 25% of people suffering from ALS.
• Progressive Muscular Atrophy (PMA) ALS in which only the lower motor neurons deteriorate.
• Familial (hereditary) ALS ALS that affects more than one member of the same family. This type of ALS accounts for a very small number of people with ALS in the United States (5–10%).

Demographics

According to the ALS Association, some 5,600 people in the United States are diagnosed with ALS each year. It is estimated that as many as 30,000 Americans have the disease at any given time. Most people develop ALS between the ages of 40 and 70, with an average age of 55 at the time of diagnosis. ALS is 20% more common in men than in women. However with increasing age, the incidence of ALS is more equal between genders. ALS has a worldwide incidence of about 2 per 100,000 persons and a prevalence of 4–7 per 100,000. As is the case for both Parkinson's and Alzheimer's disease, the incidence of ALS is increasing along with the increasing longevity of the population. Information concerning the specific incidence of ALS in the elderly (aged 75 years and older) is sparse and the apparent decrease in ALS incidence in patients older than 70 years is thought to reflect mortality from competing diseases in later life.

Causes and symptoms

Causes

The cause and development of ALS is complex and appears to involve many factors. ALS is increasingly considered as a neurodegeneration of the aging nervous system, a consequence of aging promoting the formation of free radicals, or reactive oxygen species (ROS), which damage the genetic material found in the mitochondria that generate energy for the cell. This injury is greatest in cells such as neurons. The neurons that are particularly likely to be affected are those that use high levels of oxygen, such as the motor neurons of the brain and the spinal cord, both of which are known to be damaged by ALS. About 5–10% of ALS cases are hereditary with 20% of these having a mutation of the superoxide-dismutase-1 (SOD1) gene. Other candidate genes relevant to ALS are currently the object of active research. Autoimmune responses, occurring when the body's immune system attacks its own cells, have also been proposed as a possible cause for motor neuron degeneration in ALS. Researchers have also studied environmental factors such as exposure to toxic or infectious agents, and other research has examined the possible role of dietary deficiency or trauma.

Symptoms

At the onset of ALS, symptoms are often mild to the point of being frequently overlooked. They may include:

• Muscle weakness in one or more of the following: hands, arms, legs, or muscles of speech, swallowing or breathing.
• Cramping or twitching (fasciculation) of muscles, especially in the hands and feet.
• Impairment of the use of the arms and legs.
• Difficulty in projecting the voice.
• Shortness of breath, difficulty in breathing and swallowing in later stages.

Initial ALS symptoms may be quite varied in different people and depending on the type of ALS, but muscle weakness is considered a characteristic initial sign, occurring in approximately 60% of all ALS patients. Early ALS signs usually include tripping, dropping things, abnormal fatigue of the arms and legs, slurred speech, muscle cramps and twitches, and uncontrollable fits of laughing or crying.

Diagnosis

The ALS diagnosis is difficult to establish and depends upon the recognition of characteristic symptoms supported by electrophysiological findings, since no ALS biological marker is yet available. To confirm a diagnosis of ALS, the recording of the electrical activity in muscles (electromyography, EMG) which includes conduction studies of various types, needle EMG, and tests that use transcranial magnetic stimulation of the motor cortex, are used. Nerve conduction velocity (NCV) tests are also used to exclude some of the disorders that mimic ALS. The diagnostic workup may also include a spinal tap, X-rays, magnetic resonance imaging (MRI), blood and urine studies, muscle and/or nerve biopsy, and complete neurological examination.

Treatment

Currently, there is no cure for ALS and treatment seeks to relieve symptoms and make the patient comfortable. Medications are available to relieve painful muscle cramps, control spasticity, and reduce excess saliva. Only one medication, riluzole (Rilutek), has been approved by the FDA for ALS. It is believed to reduce the level of ALS-induced injury to motor neurons and to have a modest effect on prolonging survival. Riluzole does not heal the damage already done to motor neurons, and patients must be monitored for liver damage while taking it.

As of 2008, seven new clinical trials for the treatment of ALS were being sponsored by the National Institutes of Health (NIH). One trial seeks to investigate the medication memantine when used in combination with riluzole. Other trials aim to study the effect of drugs such as Thalidomide, Tamoxifen, and the antibiotic Ceftriaxone, in patients with ALS .

QUESTIONS TO ASK YOUR DOCTOR

• What ALS research is being done?
• What are the medication options?
• What are the side effects of medications?
• How many ALS cases have you treated with riluzole?

Nutrition/Dietetic concerns

Nutritional counselling can offer ALS patients good nutrition advice while offering other dietary options when swallowing becomes difficult, following weakening of the muscles involved in chewing and moving food toward the back of the mouth. These may include meal plans that provide enough calories, fiber, and fluid, and which show patients how to avoid foods that are hard to swallow. When patients can no longer obtain sufficient nourishment from eating, a feeding tube may be inserted into the stomach. The feeding tube also prevents choking and pneumonia resulting from inhaling liquids into the lungs.

Therapy

Several types of therapies, even if not ALS-specific, are considered beneficial for ALS patients, including:

• Heat or whirlpool therapy to relieve muscle cramping.
• Physical therapy to maintain mobility while easing the discomfort of muscle stiffness, cramps and fluid retention.
• Speech therapy and communication training to maintain as many verbal communication skills as possible.

Devices such as splints, corrective braces, grab bars, or reach-extenders, can also assist the performance of daily activities such as dressing, eating, and using the bathroom. Special equipment such as wheelchairs, electric beds or mattresses are also available to help provide functional independence .

Prognosis

The rate at which ALS develops can be quite variable from one person to another. The average survival time of people with ALS is three to five years, but many live five, ten or more years. In a small number of people, ALS is known to stop or halt its progression, although there is no understanding as to how this can occur.

KEY TERMS

Atrophy —A wasting or decrease in size of a body organ, tissue, or part owing to disease, injury, or lack of use.

Autoimmune response —A condition in which a person's immune system fails to recognize its own cells as being “self” and attacks its own body.

Biological marker —Measurable and quantifiable biological parameters that can be used to diagnose a disease accurately.

Electromyography (EMG) —The recording of the electrical activity in the muscle.

Fasciculation —Visible involuntary contraction or twitching of muscle fibers.

Immune system —The organs and cells that defends the body against infections and other diseases.

Magnetic resonance imaging (MRI) —An imaging method used to look inside the body without using surgery, harmful dyes or X—rays.

Motor neuron —A neuron that conveys impulses for muscle contraction or glandular secretion.

Motor neuron disease —Group of progressive neurological disorders that destroy motor neurones, the cells that control voluntary muscle activity such as speaking, walking, breathing, and swallowing.

Needle EMG —During an EMG test, a fine needle is inserted into the muscle to be tested. Recordings are made while the muscle is at rest, and then during the contraction to test muscle response.

Nerve conduction velocity (NCV) test —A test measuring the speed of signals through a nerve.

Nervous system —The system of cells, tissues and organs that regulates the body's responses to internal and external stimuli.

Neurodegeneration —Progressive loss of structure or function of neurons, including death of neurons.

Neurological disease —Disease of the nervous system.

Neuron —A nerve cell that sends and receives electrical signals over long distances within the body.

Progressive disease —Disease that increases in scope and severity, from bad to worse.

Reactive oxygen species (ROS) —Damaging molecules, including oxygen radicals and other highly reactive forms of oxygen that can harm cells.

Spasticity —Increased muscle tone that results in a tightening and shortening of a muscle.

Spinal tap —A procedure used to isolate cerebrospinal fluid for evaluation or diagnosis of disease.

Superoxide—dismutase (SOD) —An enzyme that catalyzes the decomposition of a superoxide into hydrogen peroxide and oxygen.

Transcranial magnetic stimulation (TMS) —A procedure which uses a strong magnet held outside the head to influence brain activity.

Prevention

In cases there is a family history of ALS, genetic counselling may be provided.

Caregiver concerns

ALS home caregivers are likely to be family members. According to the National Family Caregivers Association (NFCA), more than 26.6% of the adult American population provided care for a chronically ill, disabled or aged family member or friend in 2006. In becoming caregivers, most people experience new roles and relationships that are different from the ones they had with their loved one before ALS onset. Depression can strike anyone, with caregivers being especially vulnerable—it is the most common healthcare condition reported by family caregivers. They should seek healthcare professional counselling should the emotional demands of caring for a family member become too overwhelming, so as to ensure that their needs are also taken into consideration, while making time to keep doing the activities that they consider important.

Resources

BOOKS

Abramovitz, Melissa. Diseases and Disorders—Lou Gehrig's Disease. Farmington Hills, MI: Lucent Books, 2006.

Bak, Richard. Lou Gehrig—An American Classic. Dallas, TX: Taylor Trade Publishing, 1995.

Brown, Robert H., Michael Swash, and Piera Pasinelli, eds. Amyotrophic Lateral Sclerosis, 2nd ed. Malden, MA: Blackwell Science, 2006.

Dodson Wade, Mary. ALS: Lou Gehrig's Disease. Berkeley Heights, NJ: Enslow Publishers, Inc., 2001.

Eisen, Andrew, and Charles Krieger. Amyotrophic Lateral Sclerosis: A Synthesis of Research and Clinical Practice. Cambridge, UK: Cambridge University Press, 2006.

Miller, Robert G., et al. Amyotrophic Lateral Sclerosis (American Academy of Neurology). New York, NY: Demos Medical Publishing, 2004.

Mitsumoto, Hiroshi, and Theodore L. Munsat. Amyotrophic Lateral Sclerosis: A Guide for Patients and Families. New York, NY: Demos Medical Publishing, 2001.

Scott, Donald W., and William L. C. Scott. Amytrophic Lateral Sclerosis. Ottawa, ON: Trafford Publishing, 2006.

PERIODICALS

Bensimon, G., et al. “A study of riluzole in the treatment of advanced stage or elderly patients with amyotrophic lateral sclerosis.” Journal of Neurology 249, no. 5 (May 2002): 609–615.

Forbes, R. B., et al. “The epidemiology of amyotrophic lateral sclerosis in people aged 80 or over.” Age and Ageing 33, no. 2 (2004): 131–134.

OTHER

ALS Breathing Difficulties. ALS Association Fact Sheet.(February 20, 2008) http://org/files/cms/Resources/Breathing_Difficulties.pdf

Amyotrophic Lateral Sclerosis. NINDS Fact Sheet. February 07, 2008. (February 20, 2008) http://www.ninds.nih.gov/disorders/amyotrophiclateralsclerosis/detail_amyotrophiclateralsclerosis.htm

Experts Suggest Promising Drugs for ALS Clinical Trials. ALS Association, In the News. July 11, 2006. (February 20, 2008) http://www.alsa.org/patient/article.cfm?id=987

Facts About Amyotrophic Lateral Sclerosis (ALS). MDA Publications. (February 20, 2008) http://www.als-mda.org/publications/fa-als.html

What is ALS ? ALS Association Fact Sheet. (February 20, 2008) http://www.alsa.org/als/what.cfm?CFID=5786425…CFTOKEN=44408c9-d7c9125d-afd6-40f8-98a8-c46323f4f8c5

ORGANIZATIONS

The ALS Association, 27001 Agoura Road, Suite 150, Calabasas Hills, CA, 91301–5104, (818) 880–9007, (818) 880–9006, http://www.alsa.org.

The ALS Society of Canada, 265 Yorkland Boulevard, Suite 300, Toronto, Ontario, Canada, M2J 1S5, (416) 497–2267, (800) 267–4ALS, (416) 497–1256, http://www.als.ca.

National Institute of Neurological Disorders and Stroke (NINDS), P.O. Box 5801, Bethesda, MD, 20824, (301) 496–5751, (800) 352–9424, http://www.ninds.nih.gov.

Robert Packard Center for ALS Researchat Johns Hopkins, 5801 Smith Avenue, McAuley Suite 110, Baltimore, MD, 21209–3652, (410) 735–7678, http://www.alscenter.org.

Monique Laberge Ph.D.