Citizendia

Amyotrophic lateral sclerosis
Classification and external resources
ICD-10G12.2
ICD-9335.20
OMIM105400
DiseasesDB29148
MedlinePlus000688
eMedicineneuro/14  emerg/24 pmr/10
MeSHD000690
Stephen Hawking, a physicist who has ALS.
Stephen Hawking, a physicist who has ALS. The International Statistical Classification of Diseases and Related Health Problems (most commonly known by the abbreviation ICD) provides codes to classify Diseases The International Statistical Classification of Diseases and Related Health Problems 10th Revision ( ICD -10) is a coding of diseases and signs symptoms abnormal findings G00-G99 - Diseases of the Nervous system (G00-G09 Inflammatory diseases of the Central nervous system ( Bacterial meningitis The International Statistical Classification of Diseases and Related Health Problems (most commonly known by the abbreviation ICD) provides codes to classify Diseases The following is a list of codes for International Statistical Classification of Diseases and Related Health Problems. The Mendelian Inheritance in Man project is a Database that catalogues all the known Diseases with a genetic component, and—when possible—links them The Diseases Database is a free Website that provides information about the relationships between medical conditions Symptoms, and Medications. MedlinePlus, with the MedlinePlus Medical Encyclopedia, is a website network containing Health information from the world's largest medical Library eMedicine is an online clinical medical knowledge base that was founded in 1996 by Scott Plantz and Richard Lavely two medical doctors Medical Subject Headings ( MeSH) is a huge Controlled vocabulary (or metadata system for the purpose of indexing journal articles and books Stephen William Hawking CH, CBE, FRS, FRSA (born 8 January 1942 is a British theoretical physicist. A physicist is a Scientist who studies or practices Physics. Physicists study a wide range of physical phenomena in many branches of physics spanning

Amyotrophic Lateral Sclerosis (ALS, sometimes called Maladie de Charcot, or Lou Gehrig's Disease (US)) is a progressive, usually fatal, neurodegenerative disease caused by the degeneration of motor neurons, the nerve cells in the central nervous system that control voluntary muscle movement. Jean-Martin Charcot ( 29 November 1825 – 16 August 1893) was a French Neurologist and professor of Anatomical pathology Henry Louis "Lou" Gehrig ( June 19 1903  – June 2 1941) born Ludwig Heinrich Gehrig, was an American Neurodegenerative Disease ( Greek νέυρο- néuro-, "nerval" and Latin dēgenerāre, "to decline" or "to In Vertebrates the term motor neuron (or motoneuron) classically applies to Neurons located in the Central nervous system (or CNS that project Skeletal muscle is a type of Striated muscle, which usually attaches to tendons As a motor neuron disease, the disorder causes muscle weakness and atrophy throughout the body as both the upper and lower motor neurons degenerate, ceasing to send messages to muscles. The motor neurone diseases (or motor neuron diseases) (MND are a group of progressive neurological disorders that destroy Motor neurones the cells that control voluntary Upper motor neurons are Motor neurons that originate in motor region of the Cerebral cortex or the Brain stem and carry motor information down Lower motor neurons ( LMNs) are the Motor neurons connecting the Brainstem and Spinal cord to Muscle fibers, bringing the nerve Unable to function, the muscles gradually weaken, develop fasciculations (twitches) because of denervation, and eventually atrophy because of that denervation. A fasciculation (or "muscle Twitch " is a small local involuntary Muscle contraction (twitching visible under the skin arising from the spontaneous discharge Atrophy is the partial or complete Wasting away of a part of the Body. The patient may ultimately lose the ability to initiate and control all voluntary movement except of the eyes.

Cognitive function is generally spared except in certain situations such as when ALS is associated with frontotemporal dementia. Frontotemporal dementia (FTD is a clinical Syndrome caused by degeneration of the Frontal lobe of the Brain and may extend back to the Temporal lobe [1] However, there are reports of more subtle cognitive changes of the frontotemporal type in many patients when detailed neuropsychological testing is employed. Sensory nerves and the autonomic nervous system, which controls functions like sweating, generally remain functional. &trade The autonomic nervous system ( ANS) (or visceral nervous system) is the part of the Peripheral nervous system that acts as a Control

Contents

History

Epidemiology, causes and risk factors

ALS is one of the most common neuromuscular diseases worldwide, and people of all races and ethnic backgrounds are affected. One to 2 people per 100,000 develop ALS each year. [2] ALS most commonly strikes people between 40 and 60 years of age, but younger and older people can also develop the disease. Men are affected slightly more often than women.

"Familial ALS" accounts for approximately 5%-10% of all ALS cases and is caused by genetic factors. Of these, approximately 1 in 10 are linked to a mutation in copper/zinc superoxide dismutase (SOD1), an enzyme responsible for scavenging free radicals. Copper (ˈkɒpɚ is a Chemical element with the symbol Cu (cuprum and Atomic number 29 Zinc (ˈzɪŋk from Zink is a Metallic Chemical element with the symbol Zn and Atomic number 30 The enzyme superoxide dismutase ( SOD,) catalyzes the Dismutation of Superoxide into Oxygen and Hydrogen peroxide. Enzymes are Biomolecules that catalyze ( ie increase the rates of Chemical reactions Almost all enzymes are Proteins In Chemistry, radicals (often referred to as free radicals) are atoms molecules or ions with Unpaired electrons on an otherwise Open shell An antisense drug trial is underway using a small interfering RNA molecule (siRNA) that inhibits the production of this mutant SOD1 protein. Sense, when applied in a Molecular biology context is a general concept used to compare the polarity of Nucleic acid molecules such as DNA or RNA Ribonucleic acid ( RNA) is a Nucleic acid that consists of a long chain of Nucleotide units [3]

Although the incidence of ALS is thought to be regionally uniform, there are three regions in the West Pacific where there has in the past been an elevated occurrence of ALS. This seems to be declining in recent decades. The largest is the area of Guam inhabited by the Chamorro people, who have historically had a high incidence (as much as 143 cases per 100,000 people per year) of a condition called Lytico-Bodig disease which is a combination of ALS, Parkinsonism, and dementia. Guam ( Chamorro: cha Guåhån) officially the Territory of Guam, is an island in the western Pacific Ocean and is an organized unincorporated Lytico-Bodig disease, sometimes spelt Lytigo-bodig is a neurological disease that exists on the Island of Guam. [4] Two more areas of increased incidence are the Kii peninsula of Japan and West Papua. [5][6]

Although there have been reports of several "clusters" including three American football players from the San Francisco 49ers, three soccer-playing friends in the south of England,[7] and reports of conjugal (husband and wife) cases in the south of France,[8][9][10][11][12] these are statistically plausible chance events. American football, known in the United States and Canada simply as football, is a competitive Team sport known for mixing strategy with The San Francisco 49ers are a professional American football team Association football, more commonly known as football or soccer, is a Team sport played between two teams of eleven players and is widely considered Although many authors consider ALS to be caused by a combination of genetic and environmental risk factors, so far the latter have not been firmly identified, other than a higher risk with increasing age.

Cause and risk factors

Scientists have not found a definitive cause for ALS and the onset of the disease has been linked to several factors, including: a virus; exposure to neurotoxins or heavy metals; DNA defects; immune system abnormalities; and enzyme abnormalities. There is a known hereditary factor in familial ALS (FALS); however, there is no known hereditary component in the 90-95% cases diagnosed as sporadic ALS. An inherited genetic defect linked to a defect on chromosome 21 is believed to cause approximately 40% of familial cases of ALS. This mutation is believed to be autosomal dominant. The children of those diagnosed with familial ALS have a higher risk factor for developing the disease; however, those who have close family members diagnosed with sporadic ALS have no greater a risk factor than the general population [1].

Some causative factors have been suggested for the increased incidence in the western Pacific. Prolonged exposure to a dietary neurotoxin is one suspected risk factor in Guam; the neurotoxin is a compound found in the seed of the cycad Cycas circinalis,[13] a tropical plant found in Guam, which was used in the human food supply during the 1950s and early 1960s. Cycads are a group of Seed plants characterized by a large crown of compound leaves and a stout trunk. Cycas circinalis, also known as the Queen Sago, is a type of Cycad that was thought to be linked with the degenerative disease Lytico-Bodig disease

According to the ALS Association, military veterans are at an increased risk of contracting ALS. The ALS Association is the only national not-for-profit health organization dedicated solely to lead the fight against Amyotrophic Lateral Sclerosis commonly known as Lou Gehrig's Disease In its report ALS in the Military,[14] the group pointed to an almost 60% greater chance of the disease in military veterans than the general population. For Gulf War veterans, the chance is seen as twice that of the general population in a joint study by the Veterans Affairs Administration and the DOD. The United States Department of Veterans Affairs ( VA) is a government-run military Veteran benefit system with Cabinet -level status

Symptoms

Initial symptoms

The onset of ALS may be so subtle that the symptoms are frequently overlooked. A symptom' (from Greek σύμπτωμα, "accident misfortune that which befalls" from συμπίπτω, "I befall" from The earliest symptoms are obvious weakness and/or muscle atrophy. This is followed by twitching, cramping, or stiffness of affected muscles; muscle weakness affecting an arm or a leg; and/or slurred and nasal speech. The twitching, cramping, etc. associated with ALS is a result of the dying muscle, therefore these symptoms without clinical weakness or atrophy of affected muscle is likely not ALS.

The parts of the body affected by early symptoms of ALS depend on which motor neurons in the body are damaged first. About 75% of people experience "limb onset" ALS. In some of these cases, symptoms initially affect one of the legs, and patients experience awkwardness when walking or running or they notice that they are tripping or stumbling more often. Other limb onset patients first see the effects of the disease on a hand or arm as they experience difficulty with simple tasks requiring manual dexterity such as buttoning a shirt, writing, or turning a key in a lock. Occasionally the symptoms remain confined to one limb; this is known as monomelic amyotrophy. Monomelic amyotrophy (also known as MMA, Hirayama's disease, Sobue disease or Juvenile nonprogressive amyotrophy) is an untreatable focal

About 25% of cases are "bulbar onset" ALS. These patients first notice difficulty speaking clearly. Speech becomes garbled and slurred. Nasality and loss of volume are frequently the first symptoms. Difficulty swallowing, and loss of tongue mobility follow. Eventually total loss of speech and the inability to protect the airway when swallowing are experienced. In Medicine, aspiration is the entry of secretions or foreign material into the trachea and Lungs The patient may either inhale the material

Regardless of the part of the body first affected by the disease, muscle weakness and atrophy spread to other parts of the body as the disease progresses. Patients experience increasing difficulty moving, swallowing (dysphagia), and speaking or forming words (dysarthria). Dysphagia should not be confused with the similarly pronounced Dysphasia, a language disorder Dysarthria is a motor Speech disorder resulting from neurological injury, characterised by poor articulation (cf Symptoms of upper motor neuron involvement include tight and stiff muscles (spasticity) and exaggerated reflexes (hyperreflexia) including an overactive gag reflex. Spasticity or muscular hypertonicity is a disorder of the body Motor system, and especially the central nervous system (CNS in which certain Muscles continually Hyperreflexia is defined as overactive or overresponsive Reflexes. An abnormal reflex commonly called Babinski's sign (the large toe extends upward as the sole of the foot is stimulated) also indicates upper motor neuron damage. In Medicine and Neurology, the Babinski response to the plantar reflex is a Reflex, named after Joseph Babinski ( 1857 - 1932) (a French Symptoms of lower motor neuron degeneration include muscle weakness and atrophy, muscle cramps, and fleeting twitches of muscles that can be seen under the skin (fasciculations). Around 15–45% of patients experience pseudobulbar affect, also known as "emotional lability", which consists of uncontrollable laughter, crying or smiling, attributable to degeneration of bulbar upper motor neurons resulting in exaggeration of motor expressions of emotion. Labile affect or pseudobulbar affect refers to the pathological expression of Laughter, Crying or smiling.

To be diagnosed with ALS, patients must have signs and symptoms of both upper and lower motor neuron damage that cannot be attributed to other causes.

Emerging symptoms

Although the sequence of emerging symptoms and the rate of disease progression vary from person to person, eventually patients will not be able to stand or walk, get in or out of bed on their own, or use their hands and arms. Difficulty swallowing and chewing impair the patient's ability to eat normally and increase the risk of choking. Maintaining weight will then become a problem. Because the disease usually does not affect cognitive abilities, patients are aware of their progressive loss of function and may become anxious and depressed. A small percentage of patients go on to develop frontotemporal dementia characterized by profound personality changes; this is more common among those with a family history of dementia. Frontotemporal dementia (FTD is a clinical Syndrome caused by degeneration of the Frontal lobe of the Brain and may extend back to the Temporal lobe A larger proportion of patients experience mild problems with word-generation, attention, or decision-making. Cognitive function may be affected as part of the disease process or could be related to poor breathing at night (nocturnal hypoventilation). Health care professionals need to explain the course of the disease and describe available treatment options so that patients can make informed decisions in advance.

As the diaphragm and intercostal muscles (rib cage) weaken, forced vital capacity and inspiratory pressure diminish. Intercostal muscles are several groups of Muscles that run between the Ribs, and help form and move the Chest wall. In bulbar onset ALS, this may occur before significant limb weakness is apparent. Bilevel positive pressure ventilation (frequently referred to by the tradename BiPAP) is frequently used to support breathing, first at night, and later during the daytime as well. It is recommended that long before BiPAP becomes insufficient, patients (with the eventual help of their families) must decide whether to have a tracheostomy and long term mechanical ventilation. Tracheotomy and tracheostomy are Surgical procedures on the neck to open a direct airway through an incision in the trachea (the windpipe Most patients do not elect this route, and instead choose palliative hospice care at this point. Palliative care (from Latin palliare to cloak is any form of medical care or treatment that concentrates on reducing the severity of Disease Symptoms Most people with ALS die of respiratory failure or pneumonia, not the disease itself. Pneumonia is an inflammatory illness of the Lung. Frequently it is described as lung Parenchyma / alveolar inflammation and abnormal

ALS predominantly affects the motor neurons, and in the majority of cases the disease does not impair a patient's mind, personality, intelligence, or memory. Nor does it affect a person's ability to see, smell, taste, hear, or feel touch. Control of eye muscles is the most preserved function, although some patients with an extremely long duration of disease (20+ years) may lose eye control too. Unlike multiple sclerosis, bladder and bowel control are usually preserved in ALS, although as a result of immobility and diet changes, intestinal problems such as constipation can require intensive management. Multiple sclerosis (abbreviated MS also known as disseminated sclerosis or encephalomyelitis disseminata) is an autoimmune condition in which the

Diagnosis

No test can provide a definite diagnosis of ALS, although the presence of upper and lower motor neuron signs in a single limb is strongly suggestive. Instead, the diagnosis of ALS is primarily based on the symptoms and signs the physician observes in the patient and a series of tests to rule out other diseases. Physicians obtain the patient's full medical history and usually conduct a neurologic examination at regular intervals to assess whether symptoms such as muscle weakness, atrophy of muscles, hyperreflexia, and spasticity are getting progressively worse.

Because symptoms of ALS can be similar to those of a wide variety of other, more treatable diseases or disorders, appropriate tests must be conducted to exclude the possibility of other conditions. One of these tests is electromyography (EMG), a special recording technique that detects electrical activity in muscles. Electromyography (EMG is a technique for evaluating and recording the activation signal of muscles Certain EMG findings can support the diagnosis of ALS. Another common test measures nerve conduction velocity (NCV). A nerve conduction study (NCS is a test commonly used to evaluate the function especially the ability of Electrical conduction, of the motor and Sensory nerves Specific abnormalities in the NCV results may suggest, for example, that the patient has a form of peripheral neuropathy (damage to peripheral nerves) or myopathy (muscle disease) rather than ALS. Peripheral neuropathy is the term for damage to Nerves of the Peripheral nervous system, which may be caused either by diseases of the Nerve or from the In Medicine, a myopathy is a neuromuscular Disease in which the Muscle fibers do not function for any one of many reasons resulting in Muscular weakness The physician may order magnetic resonance imaging (MRI), a noninvasive procedure that uses a magnetic field and radio waves to take detailed images of the brain and spinal cord. Although these MRI scans are often normal in patients with ALS, they can reveal evidence of other problems that may be causing the symptoms, such as a spinal cord tumor, multiple sclerosis, a herniated disk in the neck, syringomyelia, or cervical spondylosis. Multiple sclerosis (abbreviated MS also known as disseminated sclerosis or encephalomyelitis disseminata) is an autoimmune condition in which the A hernia is a protrusion of a tissue, structure or part of an organ through the muscular tissue or the membrane by which it is normally contained Syringomyelia (sɪˌrɪŋgoʊmaɪˈiːliə is a generic term referring to a disorder in which a Cyst or cavity forms within the Spinal cord. Not to be confused with Spondylitis, Spondylolysis or Spondylolisthesis.

Based on the patient's symptoms and findings from the examination and from these tests, the physician may order tests on blood and urine samples to eliminate the possibility of other diseases as well as routine laboratory tests. Blood is a specialized Bodily fluid that delivers necessary substances to the body's cells such as nutrients and oxygen—and transports Waste products Urine is a liquid waste product of the body secreted by the Kidneys by a process of filtration from Blood and Excreted through the Urethra. In some cases, for example, if a physician suspects that the patient may have a myopathy rather than ALS, a muscle biopsy may be performed.

Infectious diseases such as human immunodeficiency virus (HIV), human T-cell leukaemia virus (HTLV), Lyme disease, syphilis[15] and tick-borne encephalitis[16] viruses can in some cases cause ALS-like symptoms. Human immunodeficiency virus ( HIV) is a Lentivirus (a member of the Retrovirus family that can lead to acquired immunodeficiency syndrome Human T-lymphotropic virus (HTLV is a Human, single-stranded RNA Retrovirus that causes T-cell Leukemia and T-cell Lymphoma Lyme disease, or borreliosis, is an Emerging infectious disease caused by at least three Species of Bacteria belonging to the Genus Syphilis is a Sexually transmitted disease caused by the spirochetal Bacterium Treponema pallidum pallidum. Tick-borne meningoencephalitis or Tick-borne encephalitis is a tick-borne Viral infection of the Central nervous system affecting humans as well Neurological disorders such as multiple sclerosis, post-polio syndrome, multifocal motor neuropathy, and spinal muscular atrophy also can mimic certain facets of the disease and should be considered by physicians attempting to make a diagnosis. Multiple sclerosis (abbreviated MS also known as disseminated sclerosis or encephalomyelitis disseminata) is an autoimmune condition in which the Post-polio syndrome ( PPS) sometimes termed Middle age onset Post-polio syndrome is a condition that affects survivors of Poliomyelitis, a viral Spinal Muscular Atrophy ( SMA) is a term applied to a number of different disorders all having in common a genetic cause and the manifestation of weakness due to loss There have been documented cases of a patient presenting with ALS-like symptoms, having a positive Lyme titer, and responding to antibiotics. [17] Lyme disease is particularly difficult to diagnose.

Because of the prognosis carried by this diagnosis and the variety of diseases or disorders that can resemble ALS in the early stages of the disease, patients should always obtain a second neurological opinion.

A study by researchers from Mount Sinai School of Medicine identified three proteins that are found in significantly lower concentration in the cerebral spinal fluid of patients with ALS than in healthy individuals. This finding was published in the February 2006 issue of Neurology. Neurology is a Scientific journal published by the American Academy of Neurology. Evaluating the levels of these three proteins proved 95% accurate for diagnosing ALS. The three protein markers are TTR, cystatin C, and the carboxyl-terminal fragment of neuroendocrine protein 7B2). These are the first biomarkers for this disease and may be first tools for confirming diagnosis of ALS. With current methods, the average time from onset of symptoms to diagnosis is around 12 months. Improved diagnostic markers may provide a means of early diagnosis, allowing patients to receive relief from symptoms years earlier. [18]

Etiology

SOD1

The cause of ALS is not known, though an important step toward answering that question came in 1993 when scientists discovered that mutations in the gene that produces the Cu/Zn superoxide dismutase (SOD1) enzyme were associated with some cases (approximately 20%) of familial ALS. The enzyme superoxide dismutase ( SOD,) catalyzes the Dismutation of Superoxide into Oxygen and Hydrogen peroxide. This enzyme is a powerful antioxidant that protects the body from damage caused by superoxide, a toxic free radical. Superoxide is the Anion O2&minus It is important as the product of the one-electron reduction of Dioxygen, which occurs widely in nature Free radicals are highly reactive molecules produced by cells during normal metabolism. In Chemistry, radicals (often referred to as free radicals) are atoms molecules or ions with Unpaired electrons on an otherwise Open shell Metabolism is the set of Chemical reactions that occur in living Organisms in order to maintain Life. Free radicals can accumulate and cause damage to DNA and proteins within cells. Although it is not yet clear how the SOD1 gene mutation leads to motor neuron degeneration, researchers have theorized that an accumulation of free radicals may result from the faulty functioning of this gene. Current research, however, indicates that motor neuron death is not likely a result of lost or compromised dismutase activity, suggesting mutant SOD1 induces toxicity in some other way (a gain of function). [19][20]

Studies involving transgenic mice have yielded several theories about the role of SOD1 in mutant SOD1 familial amyotrophic lateral sclerosis. This article is about organisms which have been genetically modified Mice lacking the SOD1 gene entirely do not customarily develop ALS, although they do exhibit an acceleration of age-related muscle atrophy (sarcopenia) and a shortened lifespan (see article on superoxide dismutase). Sarcopenia (from the Greek meaning "poverty of flesh" is the degenerative loss of Skeletal muscle mass and strength associated with Senescence. The enzyme superoxide dismutase ( SOD,) catalyzes the Dismutation of Superoxide into Oxygen and Hydrogen peroxide. This indicates that the toxic properties of the mutant SOD1 are a result of a gain in function rather than a loss of normal function. In addition, aggregation of proteins has been found to be a common pathological feature of both familial and sporadic ALS (see article on proteopathy). Proteopathy (Proteo- protein -pathy disease proteopathies pl. Interestingly, in mutant SOD1 mice, aggregates (misfolded protein accumulations) of mutant SOD1 were found only in diseased tissues, and greater amounts were detected during motor neuron degeneration. [21] It is speculated that aggregate accumulation of mutant SOD1 plays a role in disrupting cellular functions by damaging mitochondria, proteasomes, protein folding chaperones, or other proteins. In Cell biology, a mitochondrion (plural mitochondria) is a membrane-enclosed Organelle found in most eukaryotic cells. Proteasomes are large Protein complexes inside all Eukaryotes and Archaea, as well as in some Bacteria. This article is about the protein For other uses see Chaperone, a disambiguation page [22] Any such disruption, if proven, would lend significant credibility to the theory that aggregates are involved in mutant SOD1 toxicity. However, it is important to remember that SOD1 mutations cause only 10% or so of overall cases and the etiological mechanisms may be distinct from those responsible for the sporadic form of the disease. Yet, the ALS-SOD1 mice remain the best model of the disease thus far.

Other factors

Studies also have focused on the role of glutamate in motor neuron degeneration. Glutamic acid (abbreviated as Glu or E) is one of the 20 Alpha Amino acids It is not among the human Essential amino acids Its Glutamate is one of the chemical messengers or neurotransmitters in the brain. See Chemical synapse for an introduction to concepts and terminology used in this article Scientists have found that, compared to healthy people, ALS patients have higher levels of glutamate in the serum and spinal fluid. Blood plasma is the Liquid component of Blood, in which the Blood cells are suspended Laboratory studies have demonstrated that neurons begin to die off when they are exposed over long periods to excessive amounts of glutamate (excitotoxicity). Excitotoxicity is the pathological process by which nerve cells are damaged and killed by glutamate and similar substances Now, scientists are trying to understand what mechanisms lead to a buildup of unneeded glutamate in the spinal fluid and how this imbalance could contribute to the development of ALS. Failure of astrocytes to sequester glutamate from the extracellular fluid surrounding the neurones has been proposed as a possible cause of this glutamate-mediated neurodegeneration. Astrocytes (also known collectively as astroglia) are characteristic star-shaped glial cells in the Brain and Spinal cord.

Riluzole is currently the only FDA approved drug for ALS and targets glutamate transporters. Riluzole is a drug used to treat Amyotrophic Its very modest benefit to patients has bolstered the argument that glutamate is not a primary cause of the disease. The antibiotic ceftriaxone has demonstrated an unexpected effect on glutamate and appears to be a beneficial treatment for ALS in animal models. Ceftriaxone ( INN) (ˌsɛftraɪˈæksoʊn/ /ˌkɛf- is a third-generation Cephalosporin Antibiotic. Ceftriaxone is currently being tested in clinical trials.

Autoimmune responses which occur when the body's immune system attacks normal cells have been suggested as one possible cause for motor neuron degeneration in ALS. Some scientists theorize that antibodies may directly or indirectly impair the function of motor neurons, interfering with the transmission of signals between the brain and muscles. More recent evidence indicates that the nervous system's immune cells, microglia, are heavily involved in the later stages of the disease. Microglia are a type of Glial cell that acts as the first and main form of active immune defense in the Central nervous system (CNS

In searching for the cause of ALS, researchers have also studied environmental factors such as exposure to toxic or infectious agents. Other research has examined the possible role of dietary deficiency or trauma. However, as of yet, there is insufficient evidence to implicate these factors as causes of ALS.

Future research may show that many factors, including a genetic predisposition, are involved in the development of ALS.

Treatment

No cure has yet been found for ALS. However, the Food and Drug Administration (FDA) has approved the first drug treatment for the disease: Riluzole (Rilutek). Riluzole is a drug used to treat Amyotrophic Riluzole is believed to reduce damage to motor neurons by decreasing the release of glutamate. Clinical trials with ALS patients showed that riluzole lengthens survival by several months, and may have a greater survival benefit for those with a bulbar onset. The drug also extends the time before a patient needs ventilation support. Riluzole does not reverse the damage already done to motor neurons, and patients taking the drug must be monitored for liver damage and other possible side effects. However, this first disease-specific therapy offers hope that the progression of ALS may one day be slowed by new medications or combinations of drugs. A small, open-label study recently suggested that the drug lithium which traditionally is used for the treatment of bipolar affective disorder may slow progression in both animal models and the human form of the disease. Lithium (ˈlɪθiəm is a Chemical element with the symbol Li and Atomic number 3 [23] However, further research is needed to establish whether the effect is real or not.

Other treatments for ALS are designed to relieve symptoms and improve the quality of life for patients. This supportive care is best provided by multidisciplinary teams of health care professionals such as physicians; pharmacists; physical, occupational, and speech therapists; nutritionists; social workers; and home care and hospice nurses. Working with patients and caregivers, these teams can design an individualized plan of medical and physical therapy and provide special equipment aimed at keeping patients as mobile and comfortable as possible.

Physicians can prescribe medications to help reduce fatigue, ease muscle cramps, control spasticity, and reduce excess saliva and phlegm. Spasticity or muscular hypertonicity is a disorder of the body Motor system, and especially the central nervous system (CNS in which certain Muscles continually For the band see Saliva (band; for the village in Azerbaijan see Səliva. Phlegm ( is sticky Fluid secreted by the Mucous membranes of Humans and other Animals. Drugs also are available to help patients with pain, depression, sleep disturbances, and constipation. Major depressive disorder, also known as major depression, unipolar depression, unipolar disorder, clinical depression, or simply depression Constipation, costiveness, or irregularity, is a condition of the Digestive system in which a person (or animal experiences hard Feces that Pharmacists can give advice on the proper use of medications and monitor a patient's prescriptions to avoid risks of drug interactions. Pharmacists are Health professionals who practice the art and science of Pharmacy.

Physical therapy and special equipment such as assistive technology can enhance patients' independence and safety throughout the course of ALS. Assistive technology (AT is a generic term that includes assistive adaptive and rehabilitative devices for people with disabilities and includes the process used in selecting Gentle, low-impact aerobic exercise such as walking, swimming, and stationary bicycling can strengthen unaffected muscles, improve cardiovascular health, and help patients fight fatigue and depression. Aerobic exercise refers to Exercise that involves or improves oxygen consumption by the body Swimming is the movement by humans or animals through Water, usually without artificial assistance Range of motion and stretching exercises can help prevent painful spasticity and shortening (contracture) of muscles. Physical therapists can recommend exercises that provide these benefits without overworking muscles. Occupational therapists can suggest devices such as ramps, braces, walkers, and wheelchairs that help patients remain mobile.

ALS patients who have difficulty speaking may benefit from working with a speech-language pathologist. These health professionals can teach patients adaptive strategies such as techniques to help them speak louder and more clearly. As ALS progresses, speech-language pathologists can recommend the use of augmentative and alternative communication such as voice amplifiers, speech-generating devices (or voice output communication devices) and/or low tech communication techniques such as alphabet boards or yes/no signals. Augmentative and alternative communication (AAC refers "to an area of research clinical and educational practice These methods and devices help patients communicate when they can no longer speak or produce vocal sounds. With the help of occupational therapists, speech-generating devices can be activated by switches or mouse emulation techniques controlled by small physical movements of, for example, the head, finger or eyes.

Patients and caregivers can learn from speech-language pathologists and nutritionists how to plan and prepare numerous small meals throughout the day that provide enough calories, fiber, and fluid and how to avoid foods that are difficult to swallow. Patients may begin using suction devices to remove excess fluids or saliva and prevent choking. When patients can no longer get enough nourishment from eating, doctors may advise inserting a feeding tube into the stomach. The use of a feeding tube also reduces the risk of choking and pneumonia that can result from inhaling liquids into the lungs. The tube is not painful and does not prevent patients from eating food orally if they wish.

When the muscles that assist in breathing weaken, use of nocturnal ventilatory assistance (intermittent positive pressure ventilation (IPPV) or bilevel positive airway pressure (BIPAP)) may be used to aid breathing during sleep. In Medicine, mechanical ventilation is a method to mechanically assist or replace spontaneous breathing when patients cannot do so on their own Such devices artificially inflate the patient's lungs from various external sources that are applied directly to the face or body. When muscles are no longer able to maintain oxygen and carbon dioxide levels, these devices may be used full-time.

Patients may eventually consider forms of mechanical ventilation (respirators) in which a machine inflates and deflates the lungs. To be effective, this may require a tube that passes from the nose or mouth to the windpipe (trachea) and for long-term use, an operation such as a tracheotomy, in which a plastic breathing tube is inserted directly in the patient's windpipe through an opening in the neck. The traceartes, or windpipe, is a tube that has an inner diameter of about 20-25 mm and a length of about 10-16 cm in humans Tracheotomy and tracheostomy are Surgical procedures on the neck to open a direct airway through an incision in the trachea (the windpipe Patients and their families should consider several factors when deciding whether and when to use one of these options. Ventilation devices differ in their effect on the patient's quality of life and in cost. Although ventilation support can ease problems with breathing and prolong survival, it does not affect the progression of ALS. Patients need to be fully informed about these considerations and the long-term effects of life without movement before they make decisions about ventilation support. It must be pointed out that some patients under long-term tracheostomy intermittent positive pressure ventilation with deflated cuffs or cuffless tracheostomy tubes (leak ventilation) are able to speak. This technique preserves speech in some patients with long-term mechanical ventilation.

Social workers and home care and hospice nurses help patients, families, and caregivers with the medical, emotional, and financial challenges of coping with ALS, particularly during the final stages of the disease. Social work is a discipline involving the application of Social theory and research methods to study and improve the lives of people groups and societies Palliative care (from Latin palliare to cloak is any form of medical care or treatment that concentrates on reducing the severity of Disease Symptoms Social workers provide support such as assistance in obtaining financial aid, arranging durable power of attorney, preparing a living will, and finding support groups for patients and caregivers. A power of attorney (POA or letter of attorney in Common law systems or Mandate in civil law systems is an authorization to Advance health care directives or advance directives are instructions given by individuals specifying what actions should be taken for their health in the event that they are Home nurses are available not only to provide medical care but also to teach caregivers about tasks such as maintaining respirators, giving feedings, and moving patients to avoid painful skin problems and contractures. Home hospice nurses work in consultation with physicians to ensure proper medication, pain control, and other care affecting the quality of life of patients who wish to remain at home. The home hospice team can also counsel patients and caregivers about end-of-life issues.

Both animal and human research suggest calorie restriction (CR) may be contraindicated for those with ALS. Calorie restriction, or caloric restriction (CR aims to improve health and slow the aging process by limiting dietary energy intake Research on a transgenic mouse model of ALS demonstrates that CR may hasten the onset of death in ALS. This article is about organisms which have been genetically modified [24] In that study, Hamadeh et al also note two human studies[25][26] that they indicate show "low energy intake correlates with death in people with ALS. " However, in the first study, Slowie, Paige, and Antel state: "The reduction in energy intake by ALS patients did not correlate with the proximity of death but rather was a consistent aspect of the illness. " They go on to conclude: "We conclude that ALS patients have a chronically deficient intake of energy and recommended augmentation of energy intake. " (PMID 8604660)

Previously, Pedersen and Mattson also found that in the ALS mouse model, CR "accelerates the clinical course" of the disease and had no benefits. [27] Suggesting that a calorically dense diet may slow ALS, a ketogenic diet in the ALS mouse model has been shown to slow the progress of disease. [28]

The new discovery of RNAi has some promise in treating ALS. RNA interference ( RNAi) is a mechanism that inhibits Gene expression at the stage of translation or by hindering the transcription of specific In recent studies, RNAi has been used in lab rats to shut off specific genes that lead to ALS. Cytrx Corporation has sponsored ALS research utilizing RNAi gene silencing technology targeted at the mutant SOD1 gene. CytRx Corp ( is a biopharmaceutical research and development company engaged in the development of products primarily in the area of Small molecules and ribonucleic acid [29] The mutant SOD1 gene is responsible for causing ALS in a subset of the 10% of all ALS patients who suffer from the familial, or genetic, form of the disease. Cytrx's orally-administered drug Arimoclomol is currently in clinical evaluation as a therapeutic treatment for ALS. Arimoclomol is an experimental drug compound developed by CytRx Corporation, a biopharmaceutical company based in Los Angeles California.

Insulin-like growth factor 1 has also been studied as treatment for ALS. Insulin-like growth factor 1 (IGF-1 that was once called somatomedin C is a Polypeptide Protein Hormone similar in Molecular structure Cephalon and Chiron conducted two pivotal clinical studies of IGF-1 for ALS, and although one study demonstrated efficacy, the second was equivocal, and the product has never been approved by the FDA. In January of 2007, the Italian Ministry of Health has requested INSMED corporation's drug, IPLEX, which is a recombinant IGF-1 with Binding Protein 3(IGF1BP3) to be used in a clinical trial for ALS patients in Italy. IPLEX (mecasermin rinfabate origin injection is a drug developed by INSMED corporation for the treatment of Growth failure in children with severe primary IGF-I

Methylcobalamin is being studied in Japan[30]: preliminary results show it significantly lengthens survival time of ALS patients. Methylcobalamin is a cobalamin (MeB12 used in Peripheral neuropathy, Diabetic neuropathy etc

Prognosis

Regardless of the part of the body first affected by the disease, it is usual for muscle weakness and atrophy to spread to other parts of the body as the disease progresses. It is important to remember that some patients with ALS have an arrested course with no progression beyond a certain point despite extensive follow-up. Such a pattern is particularly true for young males with predominant upper limb weakness especially on one side (so-called monomelic or Hirayama type motor neuron disease). Eventually people with ALS will not be able to stand or walk, get in or out of bed on their own, or use their hands and arms. In later stages of the disease, individuals have difficulty breathing as the muscles of the respiratory system weaken. Although ventilation support can ease problems with breathing and prolong survival, it does not affect the progression of ALS. Most people with ALS die from respiratory failure, usually within 3 to 5 years from the onset of symptoms. However, about 10 percent of those individuals with ALS survive for 10 or more years.

Resources

United States

International

United Kingdom

Canada

Australia

Awareness and fundraising events

Notable people affected by ALS

Notable people living with ALS include:

Notable people who have died of ALS include:

See also

References

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External links

General Muscular Dystrophy

This article incorporates in public domain text from The U.S. National Institute of Neurological Disorders and Stroke

Dictionary

amyotrophic lateral sclerosis

-noun

  1. (pathology, neurology) A chronic, progressive disease characterized by degeneration of the central nervous system and the loss of voluntary muscle control.
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