Motor neurone disease (MND) is a term used to cover a number of illnesses of the motor neurone: amyotrophic lateral sclerosis (ALS), progressive muscular atrophy (PMA), progressive bulbar palsy (PBP) and progressive lateral sclerosis (PLS). MND is the term used internationally while ALS is often used in the United States (where it is also known as Lou Gehrig's disease, after a famous patient) to cover all forms of MND. It was first described by Jean-Martin Charcot, a French neurologist, in 1869 and in France the disease is therefore known as Maladie de Charcot (Charcot's disease). In vertebrates, motoneurons (also called motor neurons) are efferent neurons that originate in the spinal cord and synapse with muscle fibers to facilitate muscle contraction and with muscle spindles to modify proprioceptive sensitivity. ... Henry Louis Gehrig, born Ludwig Heinrich Gehrig (June 19, 1903 – June 2, 1941), was an American first baseman in Major League Baseball who played his entire career for the New York Yankees and was elected to the Baseball Hall of Fame in 1939. ... Categories: People stubs | French physicians | 1825 births | 1893 deaths | History of medicine ... The French Republic or France (French: République française or France) is a country whose metropolitan territory is located in western Europe, and which is further made up of a collection of overseas islands and territories located in other continents. ... 1869 is a common year starting on Friday (link will take you to calendar). ... A disease is any abnormal condition of the body or mind that causes discomfort, dysfunction, or distress to the person affected or those in contact with the person. ...

Signs and symptoms

The onset of symptoms is usually between 40-70 years of age (average 55). The disorder is characterized by the progressive loss of voluntary muscle contraction due to the destruction of nerve cells in the brain and the spinal cord that are responsible for the stimulation of the voluntary muscles. Structure of a skeletal muscle A muscle contraction (also known as a muscle twitch or simply twitch) occurs when a muscle cell (called a muscle fiber) shortens. ... Neurons (also called nerve cells) are the primary cells of the nervous system. ... In the anatomy of animals, the brain, or encephalon, is the supervisory center of the nervous system. ... The spinal cord is a part of the vertebrate nervous system that is enclosed in and protected by the vertebral column (it passes through the spinal canal). ... Structure of a skeletal muscle Skeletal muscle is a type of striated muscle, attached to the skeleton. ...

While the initial symptoms are subtle, the disease causes progressive physical disability. Mental functioning and physical sensation is spared, although many patients exhibit depression as their symptoms worsen. In ordinary conversation, nearly any mood with some element of sadness may be called depressed. However, for depression to be termed clinical depression it must reach criteria which are generally accepted by clinicians; it is more than just a temporary state of sadness. ...

Diagnosis

The diagnosis is established on both clinical grounds and an electromyography (EMG) examination, which is obligatory to demonstrate the diffuse loss of nervous stimulation of muscles of extremities, face and abdomen. Electromyography (EMG) is a medical technique for measuring muscle response to nervous stimulation. ...

Clinically, upper motor neuron signs such as spasticity, lively reflexes and Babinski signs can be found, while the lower motor neurones demonstrate weakness and muscle atrophy. Weakness of bulbar musculature can also be seen (difficulty breathing, swallowing, coughing or speaking). Spasticity is a disorder of the bodys motor system in which certain muscles are continuously contracted. ... A reflex action or reflex is a biological control system linking stimulus to response and mediated by a reflex arc. ... In medicine (neurology), the Babinski reflex or Babinski sign is a reflex that can identify disease of the spinal cord and brain. ... For the play Breath by Samuel Beckett, see Breath (play). ... Swallowing, known scientifically as deglutition is the reflex in the human body that makes something pass from the mouth, through the esophagus. ... Cough is also the name of a band, see Cough (band) A cough is a sudden, often repetitive, spasmodic contraction of the thoracic cavity, resulting in violent release of air from the lungs, and usually accompanied by a distinctive sound. ...

Neuroimaging examinations are usually performed to rule out alternative causes, such as a mass lesion of upper parts of spinal cord.

Causes

Most cases of MNS are "sporadic", although there is a suggestion that the onset is triggered by a viral infection. At least 4 genes are known to be linked to ALS, these are, SOD1, ALS2, NEFH and VAPB. Only ~10% of cases are identified as genetic/hereditary, the causes for the remaining 90% are unknown.

The SOD1 gene codes for the enzyme superoxide dismutase that reduces the oxidative stress of the nerve cells. So far over 100 different mutations in the SOD1 gene have been found, all of which cause some form of ALS. Superoxide dismutase The enzyme superoxide dismutase , or SOD (EC 1. ...

Similar findings led the researchers to assume that the nerve cell death was caused by an excess of free radicals in the cell. This hypothesis is one of many others developed to describe the etiology of ALS/MND and is waiting to be reliably proven. In chemistry free radicals are uncharged atomic or molecular species with unpaired electrons or an otherwise open shell configuration. ... Etiology (alternately aetiology, aitiology) is the study of causation. ...

Pathophysiology

Skeletal muscles are stimulated by a group of neurons located on the frontal portion of the spinal cord projecting to the muscle cells (lower motor neurons) and these nerve cells are stimulated by a group of nerve cells that project from a specific region called the motor area, located on the frontal lobe (upper motor neurons). The latter projection is called the corticospinal tract. In MNS, the nerve cells of both pathways shrink and die. On macroscopic pathology, there is a degeneration of the ventral horns of the spinal cord, as well as atrophy of the ventral roots (shrunken in appearance). Similarly, a degeneration of the motor neurons in the brainstem is seen. Neuronal loss and astrogliosis develops as well. Degeneration of the corticospinal tracts, as well as of the neurons in the motor strip of the cerebral cortex is known. Structure of a skeletal muscle Skeletal muscle is a type of striated muscle, attached to the skeleton. ... The frontal lobe is an area in the brains of vertebrates. ... The corticospinal or pyramidal tract is a massive collection of axons that travel between the cerebral cortex of the brain, and the spinal cord. ... Astrocytosis (astrogliosis) is an abnormal increase in the number of astrocytes due to the destruction of nearby neurons, typically because of hypoglycemia or oxygen deprivation. ...

There is a role in excitotoxicity and oxidative stress, presumably secondary to mitochondrial dysfunction. In animal models, death by apoptosis has also been identified (tranlocation of Bax to mitochondria, and translocation of cytochrome c to cytosol). In biology, apoptosis (from the Greek words apo = from and ptosis = falling, pronounced ap-a-tow-sis[1]) is one of the main types of programmed cell death (PCD). ...

Epidemiology

MND has three major subgroups called primary lateral sclerosis (only the first motor neurons are affected), spinal muscular atrophy (only the second motor neurons are affected) and ALS (both are affected).

The incidence of MND is approximately 1-5 out of 100,000 people, and men have a 20% higher rate of incidence than women. Approximately 5600 cases are diagnosed in the U.S. every year.

Prognosis

The disease has always a grave prognosis and 50% of patients die within the first 3 years, 20% will live 5 years or more, only 10% survive for 10 years or more. There are documented cases of people living 35 years or more after diagnosis; Stephen Hawking has lived for more than 40 years since his diagnosis. Stephen Hawking in his classroom. ...

Treatment

Treatment is essentially supportive and symptomatic. Many patients require modifications to their living environment as they become progressively physically impaired. Riluzole, an inhibitor of glutamate, may delay the progression of ALS in selected patients. Meanwhile, some experimental drugs are used in trial setting; many of these are intended to interfere with oxidative stress of the cells (a suspected mechanism); success has so far been limited. Riluzole is a drug used to treat amyotrophic lateral sclerosis. ... Glutamic acid or glutamate is one of the 20 most common natural amino acids. ...

Some current promising research towards a cure has focused on gene therapy and the use of stem cells, though the ethical and legal difficulties surrounding the harvesting of stem cells have slowed progress, particularly in the United States. Gene therapy is the insertion of genes into an individuals cells and tissues to treat a disease, and hereditary diseases in particular. ... Mouse embryonic stem cells. ...

Etymology

Amyotrophic comes from the Greek language. A- means "no", myo refers to "muscle", and trophic means "nourishment"; amyotrophic therefore means "no muscle nourishment," which describes the characteristic atrophication of the sufferer's disused muscle tissue. Lateral identifies the areas in a person's spinal cord where portions of the nerve cells that are affected are located. As this area degenerates it leads to scarring or hardening ("sclerosis") in the region. The Greek language (Greek Ελληνικά, IPA – Hellenic) is an Indo-European language with a documented history of some 3,000 years. ... Atrophy is the partial or complete wasting away of a part of the body. ... Multiple sclerosis (MS) is a demyelinating disease, a non-contagious chronic autoimmune disorder of the central nervous system which can present with a variety of neurological symptoms occurring in attacks or slowly progressing over time. ...

History and prominent patients

Lou Gehrig brought national and international attention to the disease in 1939 when he abruptly retired from baseball after being diagnosed with ALS/MND. Theoretical physicist Stephen Hawking, ex-Celtic football player Jimmy Johnstone and former guitar virtuoso Jason Becker also suffer from the disease. Blues singer and guitarist Leadbelly, American soap opera veteran Michael Zaslow, Hollywood actor David Niven, jazz giant Charles Mingus, Rangers footballer Sam English, and Hall of Fame pitcher Jim "Catfish" Hunter died from the disease. Henry Louis Gehrig, born Ludwig Heinrich Gehrig (June 19, 1903 – June 2, 1941), was an American first baseman in Major League Baseball who played his entire career for the New York Yankees and was elected to the Baseball Hall of Fame in 1939. ... A view of the playing field at Busch Stadium in Saint Louis, Missouri. ... Theoretical physics attempts to understand the world by making a model of reality, used for rationalizing, explaining, predicting physical phenomena through a physical theory. There are three types of theories in physics; mainstream theories, proposed theories and fringe theories. ... Stephen Hawking in his classroom. ... ... The striker (wearing red jersey) has run past the defender (in white jersey) and is about to take a shot at the goal, while the goalkeeper positions himself to stop the ball. ... Jimmy Johnstone (born 30 September 1944) is a Scottish football legend. ... An amazingly agile neo-classical guitarist who achieved fame at 16 as a technical virtuoso and guitar prodigy, as part of the Mike Varney-produced duo Cacophony with Marty Friedman. ... Leadbelly (January 29, 1885 - December 6, 1949) was an influential blues singer and guitarist. ... The first TIME cover devoted to soap operas: Dated January 12, 1976, Bill Hayes and Susan Seaforth Hayes of Days of Our Lives are featured with the headline Soap Operas: Sex and suffering in the afternoon. A soap opera is an ongoing, episodic work of fiction, usually broadcast on television... Michael Joel Zaslow (November 1, 1942 - December 6, 1998) was an American actor. ... For other uses, see Hollywood (disambiguation) Greetings from Hollywood Hollywood is a district of the City of Los Angeles, California, U.S.A., that runs from about Vermont Avenue on the east to just beyond Laurel Canyon Boulevard above Sunset and Crescent Heights Boulevards on the west; the north to... David Niven was the second unofficial James Bond. ... Jazz is a musical art form characterized by blue notes, syncopation, swing, call and response, polyrhythms, and improvisation. ... Charles Mingus Stamp issued by the USPS on September 16, 1995. ... Rangers Football Club is among the worlds most successful football clubs. ... The term footballer is ambiguous, as there are several games known as football. ... The National Baseball Hall of Fame and Museum, located at 25 Main Street in Cooperstown, New York, United States, is a semi-official museum operated by private interests that serves as the central point for the study of the history of baseball in North America, the display of baseball-related... A baseball pitcher delivers the ball to home plate In baseball, pitching is the act of throwing the baseball from the pitchers mound toward the catcher with the goal of retiring a batter who attempts to make contact with it, or draw a walk. ... James Augustus Catfish Hunter (April 8, 1946 _ September 9, 1999) was a prolific Major League Baseball right-handed starting pitcher between 1965 and 1979. ...

References

• Some information gathered from Dr. M Norenberg, Oct 26th, 2004: University of Miami.

External links

• ALS Association (http://www.alsa.org/)
• ALS Online Database (http://www.alsod.org)
• ALS/MND Alliance (http://www.alsmndalliance.org/index.shtml)
• The ALS Association (http://www.alsa.org/)
• MND Association (http://www.mndassociation.org/full-site/home.shtml)