Motor neuron disease comprises a group of severe disorders of the nervous system characterized by progressive degeneration of motor neurons (neurons are the basic nerve cells that combine to form nerves). Motor neurons control the behavior of muscles. Motor neuron diseases may affect the upper motor neurons, nerves that lead from the brain to the medulla (a part of the brain stem) or to the spinal cord, or the lower motor neurons, nerves that lead from the spinal cord to the muscles of the body, or both. Spasms and exaggerated reflexes indicate damage to the upper motor neurons. A progressive wasting (atrophy) and weakness of muscles that have lost their nerve supply indicate damage to the lower motor neurons.
Generally, a motor neuron disease is characterized by muscle weakness and wasting (atrophy) that occurs with normal intellectual functioning. For specific symptoms, see each of the forms of motor neuron diseases in the section showing the Disorder Constituents.. The different forms affect certain motor neurons, and consequently certain symptoms are associated with each of them. Also, there may be an overlap among the different forms and there may be an overlap of their associated symptoms.
Debate still exists on whether there are distinct forms of motor neuron disease or if they are all variants of amyotrophic lateral sclerosis. Symptoms of the different forms may overlap.
Amyotrophic Lateral Ssclerosis (Lou Gehrig’s Disease) or ‘ALS’ is the most well known MND. It affects both the upper and lower motor neurons. Clumsy hands, weakness in the legs, or difficulty in swallowing and slow speech may be the first signs. The disease progresses to involve muscles all over the body. Coughing, difficulty in breathing, progressive wasting and weakness, and spasticity or stiffness of muscles may occur. ALS affects adults, men more than women, usually between the ages of 40 and 70. (For more information on this disorder, choose “ALS” as your search term in the Rare Disease Database).
Primary Lateral Sclerosis affects adults. It is characterized by progressive degeneration of the upper motor neurons. Difficulty in speech and swallowing, semi- or complete paralysis of the legs and/or arms, and muscle twitching and spasticity may occur. Males and females are affected equally by this rare disease. (For more information on this disorder, choose “Primary Lateral Sclerosis” as your search term in the Rare Disease Database.)
Werdnig-Hoffman Disease (Infantile Spinal Muscular Atrophy) is a severe motor neuron disease that affects infants. It is characterized by weakness, twitching, and wasting of the muscles of the body. Breathing, excretory, and feeding difficulties may occur. It is a hereditary form of MND. The more serious and progressive form of Werdnig-Hoffmann disease becomes evident within the first few months of life. This rare disease is estimated to occur in 1 out of every 1,000,000 live births per year. It affects males and females equally. (For more information on this disorder, choose “Werdnig-Hoffmann” as your search term in the Rare Disease Database).
Kugelberg-Welander Syndrome (Juvenile Spinal Muscular Atrophy) is a serious disorder usually appearing in the first ten to twenty years of life. It is characterized by muscle wasting, weakness in the arms and legs, twitching, difficulties in walking, and eventual loss of reflexes. The muscles of the eye, heart, and anal sphincter (ring of muscles that prevents passage of feces) may be affected causing vision problems, irregular heartbeat, and loss of bowel control. Kugelberg-Welander is a hereditary form of motor neuron disease. This rare disease tends to have a higher incidence and severity in males than in females. (For more information on this disorder, choose “Kugelberg-Welander” as your search term in the Rare Disease Database).
Progressive Spinal Muscular Atrophy is a slowly progressive MND. Muscle weakness and wasting may begin in the hands and eventually affect the arms, shoulders, legs, and the rest of the body. Muscle twitching may occur in the limbs and tongue.
Progressive Bulbar Palsy is a severe motor neuron disease usually occurring in childhood. It affects the muscles of the tongue, lips, palate, pharynx (back of the throat), and larynx (‘voice-box’). Weakness and wasting of these muscles may cause difficulties in chewing, swallowing, and talking. Respiratory problems may also occur.
The exact cause of most types of motor neuron disease is not known. Most, perhaps all, are genetically transmitted. However, the genetics of some of these disorders is extremely complex. For example, at least five genes have been identified as active in the development of ALS. Spinal muscular atrophy itself has at least eight and perhaps twelve different forms. Progressive bulbar palsy is inherited as an autosomal recessive trait. The location of the altered gene has not been established. Amyotrophic lateral sclerosis appears to be inherited as an autosomal dominant trait. Genes at gene map loci 22q12.2, 21q22.1, 14q11, 12q11-q12, and 2p13. Spinal muscular atrophy, All Types. SMA1 is transmitted as an autosomal dominant trait and the gene has been traced to a site at 5q12.2-q13.3. Kugelberg-Welander syndrome appears to be transmitted as an autosomal dominant trait. Werdnig- Hoffmann disease appears to be transmitted as an autosomal recessive trait. Juvenile spinal muscular atrophy, benign focal amyotrophy and infantile spinal muscular atrophy are transmitted as autosomal dominant traits.
Chromosomes, which are present in the nucleus of human cells, carry the genetic information for each individual. Human body cells normally have 46 chromosomes. Pairs of human chromosomes are numbered from 1 through 22 and the sex chromosomes are designated X and Y. Males have one X and one Y chromosome and females have two X chromosomes. Each chromosome has a short arm designated “p” and a long arm designated “q”. Chromosomes are further sub-divided into many bands that are numbered. For example, “chromosome 11p13” refers to band 13 on the short arm of chromosome 11. The numbered bands specify the location of the thousands of genes that are present on each chromosome.
Genetic diseases are determined by the combination of genes for a particular trait that are on the chromosomes received from the father and the mother.
Recessive genetic disorders occur when an individual inherits the same abnormal gene for the same trait from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk for two carrier parents to both pass the defective gene and, therefore, have an affected child is 25 percent with each pregnancy. The risk to have a child who is a carrier like the parents is 50 percent with each pregnancy. The chance for a child to receive normal genes from both parents and be genetically normal for that particular trait is 25 percent. The risk is the same for males and females.
All individuals carry 4-5 abnormal genes. Parents who are close relatives (consanguineous) have a higher chance than unrelated parents to both carry the same abnormal gene, which increases the risk to have children with a recessive genetic disorder.
Dominant genetic disorders occur when only a single copy of an abnormal gene is necessary for the appearance of the disease. The abnormal gene can be inherited from either parent, or can be the result of a new mutation (gene change) in the affected individual. The risk of passing the abnormal gene from affected parent to offspring is 50 percent for each pregnancy regardless of the sex of the resulting child.
The affected populations of the different forms of Motor Neuron Disease varies. In general, all forms are rare. For more information, see the specific forms in the Disorder Subdivisions section.
Treatment of motor neuron disease is symptomatic and supportive.
Certain drugs may be used to control muscle symptoms. baclofen for spasticity, quinine for cramps, diazepam for muscular contractions, and pyridostigmine to improve nerve-to-muscle message transmission.
Various respiratory aids can be used to help a patient breathe. When swallowing becomes difficult, nutrition can be maintained by the use of various devices or by the use of softer more nutritious foods. Methods that help control excess saliva if the patient has difficulty swallowing may also be used.
Devices that help the patient continue daily activities such as braces, hand splits, limb supports, or a wheelchair are important. Bedridden patients can be made more comfortable with sheepskins or water mattresses.
Genetic counseling may be of benefit to patients and their families with a hereditary form of motor neuron disease.
Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.
For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
Tollfree: (800) 411-1222
TTY: (866) 411-1010
For information about clinical trials sponsored by private sources contact:
There are 59 clinical trials involving various motor neuron diseases listed at the NIH website devoted to clinical trials.
Beers MH, Berkow R., eds. The Merck Manual. 17th ed. Whitehouse Station, NJ: Merck Research Laboratories; 1999:1485-88.
Kasper, DL, Fauci AS, Longo DL, et al. Eds. Harrison’s Principles of Internal Medicine. 16th ed. McGraw-Hill Companies. New York, NY; 2005:2424-27.
Adams RD, Victor M, Ropper AA. Eds. Principles of Neurology. 6th ed. McGraw-Hill Companies. New York, NY; 1997:1089-94.
Rowland LP. Ed. Merritt’s Neurology. 10th ed. Lippincott Williams & Wilkins. Philadelphia, PA. 2000: 708-14.
Hardy J, Orr H. The genetics of neurodegenerative diseases. J Neurochem. 2006;97:1690-99.
Sumner CJ. Therapeutics development for spinal muscular atrophy. NeuroRx. 2006;3:235-45.
Hervias I, Beal MF, Manfredi G. Mitochondrial dysfunction and amyotrophic lateral sclerosis. Muscle Nerve. 2006;33:598-608.
Monani UR. Spinal muscular atrophy: a deficiency in a ubiquitous protein; a motor neuron-specific disease. Neuron. 2005;48:885-96.
Goodyear-Smith FA. Palliative care service needs of motor neuron disease patients. J Palliat Care. 2005;21:117-25.
Umapathi T, Hughes RA, Nobile-Orazio E, Leger JM. Immunosuppressant and immunomodulatory treatments for multifocal motor neuropathy. Cochrane Database Syst Rev. 2005;:CD003217.
Winhammer JM, Rowe DB, Henderson RD. Kiernan JC. Assessment of disease progression in motor neuron disease. Lancet Neurol. 2005;4:229-38.
Holzbaur EL. Motor neurons rely on motor proteins. Trends Cell Biol. 2004;14:233-40.
Veldink JH, Van den Berg LH, Wokke JH. The future of motor neuron disease: the challenge is in the genes. J Neurol. 2004;251:491-500.
FROM THE INTERNET
Motor Neuron Diseases Fact Sheet. National Institutes of Neurological Disorders and Stroke (NINDS). Last Updated September 05, 2006. 10pp.
The information in NORD’s Rare Disease Database is for educational purposes only and is not intended to replace the advice of a physician or other qualified medical professional.
The content of the website and databases of the National Organization for Rare Disorders (NORD) is copyrighted and may not be reproduced, copied, downloaded or disseminated, in any way, for any commercial or public purpose, without prior written authorization and approval from NORD. Individuals may print one hard copy of an individual disease for personal use, provided that content is unmodified and includes NORD’s copyright.
National Organization for Rare Disorders (NORD)
55 Kenosia Ave., Danbury CT 06810 • (203)744-0100