ALS - Knowledge

2313:. Worldwide the number of people who develop ALS yearly is estimated to be 1.9 people per 100,000 per year, while the number of people who have ALS at any given time is estimated to be about 4.5 people per 100,000. In Europe, the number of new cases a year is about 2.6 people per 100,000, while the number affected is 7–9 people per 100,000. The lifetime risk of developing ALS is 1:350 for European men and 1:400 for European women. Men have a higher risk mainly because spinal-onset ALS is more common in men than women. The number of those with ALS in the United States in 2015 was 5.2 people per 100,000, and was higher in whites, males, and people over 60 years old. The number of new cases is about 0.8 people per 100,000 per year in east Asia and about 0.7 people per 100,000 per year in south Asia. About 80% of ALS epidemiology studies have been conducted in Europe and the United States, mostly in people of northern European descent. There is not enough information to determine the rates of ALS in much of the world, including Africa, parts of Asia, India, Russia, and South America. There are several geographic clusters in the Western Pacific where the prevalence of ALS was reported to be 50–100 times higher than the rest of the world, including 915:(ALSFRS-R), a 12-item instrument survey administered as a clinical interview or self-reported questionnaire that produces a score between 48 (normal function) and 0 (severe disability). The ALSFRS-R is the most frequently used outcome measure in clinical trials and is used by doctors to track disease progression. Though the degree of variability is high and a small percentage of people have a much slower progression, on average people with ALS lose about 1 ALSFRS-R point per month. Brief periods of stabilization ("plateaus") and even small reversals in ALSFRS-R score are not uncommon, due to the fact the tool is subjective, can be affected by medication, and different forms of compensation for changes in function. However, it is rare (<1%) for these improvements to be large (i.e. greater than 4 ALSFRS-R points) or sustained (i.e. greater than 12 months). A survey-based study among clinicians showed that they rated a 20% change in the slope of the ALSFRS-R as being clinically meaningful, which is the most common threshold used to determine whether a new treatment is working in clinical trials. 576: 2149: 1865:(NIV) is the main treatment for respiratory failure in ALS. In people with normal bulbar function, it prolongs survival by about seven months and improves quality of life. One study found that NIV is ineffective for people with poor bulbar function while another suggested that it may provide a modest survival benefit. Many people with ALS have difficulty tolerating NIV. Invasive ventilation is an option for people with advanced ALS when NIV is not enough to manage their symptoms. While invasive ventilation prolongs survival, disease progression and functional decline continue. It may decrease the quality of life of people with ALS or their caregivers. Invasive ventilation is more commonly used in Japan than in North America or Europe. 2329: 2180:

suggest devices such as ramps, braces, walkers, bathroom equipment (shower chairs, toilet risers, etc.), and wheelchairs that help people remain mobile. Occupational therapists can provide or recommend equipment and adaptations to enable ALS people to retain as much safety and independence in activities of daily living as possible. Since respiratory insufficiency is the primary cause of mortality, physical therapists can help improve respiratory outcomes in people with ALS by implementing pulmonary physical therapy. This includes inspiratory muscle training, lung volume recruitment training, and manual assisted cough therapy aimed at increasing respiratory muscle strength as well as increasing survival rates.

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spread next to either the opposite arm or to the leg on the same side. Bulbar-onset patients most typically get their next symptoms in their arms rather than legs, arm-onset patients typically spreads to the legs before the bulbar region, and leg-onset patients typically spread to the arms rather than the bulbar region. Over time, regardless of where symptoms began, most people eventually lose the ability to walk or use their hands and arms independently. Less consistently, they may lose the ability to speak and to swallow food. It is the eventual development of weakness of the respiratory muscles, with the loss of ability to cough and to breathe without support, that is ultimately life-shortening in ALS.

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normal or only moderately impaired bulbar function, NIV prolongs survival by about seven months and significantly improves the quality of life. For those with poor bulbar function, NIV neither prolongs survival nor improves the quality of life, though it does improve some sleep-related symptoms. Despite the clear benefits of NIV, about 25–30% of all people with ALS are unable to tolerate it, especially those with cognitive impairment or bulbar dysfunction. Results from a large 2015 cohort study suggest that NIV may prolong survival in those with bulbar weakness, so NIV should be offered to all people with ALS, even if it is likely that they will have difficulty tolerating it.

84: 1505: 2377:(other diseases they have), difficulty seeing a neurologist, or dying quickly from an aggressive form of ALS. In the United States in 2015, the lowest prevalence was in the 18–39 age group, while the highest prevalence was in the 70–79 age group. Sporadic ALS usually starts around the ages of 58 to 63 years, while genetic ALS starts earlier, usually around 47 to 52 years. The number of ALS cases worldwide is projected to increase from 222,801 in 2015 to 376,674 in 2040, an increase of 69%. This will largely be due to the aging of the world's population, especially in developing countries. 734:(PLS) is a subtype of the overall ALS category which accounts for about 5% of all cases and only affects the upper motor neurons in the arms, legs, and bulbar region. However, more than 75% of people with apparent PLS go on to later develop lower motor neuron signs within four years of symptom onset, meaning that a definitive diagnosis of PLS cannot be made until several years have passed. PLS has a better prognosis than classical ALS, as it progresses slower, results in less functional decline, does not affect the ability to breathe, and causes less severe weight loss than classical ALS. 2337:

had the highest prevalence of the four US Census regions with 5.5 people per 100,000, followed by the Northeast (5.1), the South (4.7), and the West (4.4). The Midwest and Northeast likely had a higher prevalence of ALS because they have a higher proportion of whites than the South and West. Ethnically mixed populations may be at a lower risk of developing ALS; a study in Cuba found that people of mixed ancestry were less likely to die from ALS than whites or blacks. There are also differences in the genetics of ALS between different ethnic groups; the most common ALS gene in Europe is

2281:, or palliative care at the end of life, is especially important in ALS because it helps to optimize the management of symptoms and increases the likelihood of a peaceful death. It is unclear exactly when the end-of-life phase begins in ALS, but it is associated with significant difficulty moving, communicating, and, in some cases, thinking. Although many people with ALS fear choking to death (suffocating), they can be reassured that this occurs rarely, less than 1% of the time. Most patients die at home, and in the final days of life, opioids can be used to treat pain and 2204: 2099:(FVC), but it is a poor detector of early respiratory failure and is not a good choice for those with bulbar symptoms, as they have difficulty maintaining a tight seal around the mouthpiece. Measuring FVC while the person is lying on their back (supine FVC) is a more accurate measure of diaphragm weakness than upright FVC. Sniff nasal inspiratory pressure (SNIP) is a rapid, convenient test of diaphragm strength that is not affected by bulbar muscle weakness. If someone with ALS has signs and symptoms of respiratory failure, they should undergo daytime 740:(PMA) is another subtype that accounts for about 5% of the overall ALS category and affects lower motor neurons in the arms, legs, and bulbar region. While PMA is associated with longer survival on average than classical ALS, it is still progressive over time, eventually leading to respiratory failure and death. As with PLS developing into classical ALS, PMA can also develop into classical ALS over time if the lower motor neuron involvement progresses to include upper motor neurons, in which case the diagnosis might be changed to classic ALS. 766: 2140:, in which they are completely paralyzed except for their eye muscles. About half of the people with ALS who choose to undergo invasive ventilation report a decrease in their quality of life but most still consider it to be satisfactory. However, invasive ventilation imposes a heavy burden on caregivers and may decrease their quality of life. Attitudes toward invasive ventilation vary from country to country; about 30% of people with ALS in Japan choose invasive ventilation, versus less than 5% in North America and Europe. 2087:(NIV) is the primary treatment for respiratory failure in ALS and was the first treatment shown to improve both survival and quality of life. NIV uses a face or nasal mask connected to a ventilator that provides intermittent positive pressure to support breathing. Continuous positive pressure is not recommended for people with ALS because it makes breathing more difficult. Initially, NIV is used only at night because the first sign of respiratory failure is decreased gas exchange ( 2275:) and cognitive dysfunction may impair their ability to communicate their wishes regarding care. Continued failure to solicit the preferences of the person with ALS may lead to unplanned and potentially unwanted emergency interventions, such as invasive ventilation. If people with ALS or their family members are reluctant to discuss end-of-life issues, it may be useful to use the introduction of gastrostomy or noninvasive ventilation as an opportunity to bring up the subject. 2091:) during sleep; symptoms associated with this nocturnal hypoventilation include interrupted sleep, anxiety, morning headaches, and daytime fatigue. As the disease progresses, people with ALS develop shortness of breath when lying down, during physical activity or talking, and eventually at rest. Other symptoms include poor concentration, poor memory, confusion, respiratory tract infections, and a weak cough. Respiratory failure is the most common cause of death in ALS. 2229:

People with ALS are often instructed to avoid dry or chewy foods in their diet and instead have meals that are soft, moist, and easy to swallow. Switching to thick liquids (like fruit nectar or smoothies) or adding thickeners (to thin fluids like water and coffee) may also help people facing difficulty swallowing liquids. There is tentative evidence that high-calorie diets may prevent further weight loss and improve survival, but more research is still needed.

1869: 2386: 1387:(in men more than women). Overall these effects are small, with each exposure in isolation only increasing the likelihood of a very rare condition by a small amount. For instance an individual's lifetime risk of developing ALS might go from "1 in 400" without an exposure to between "1 in 300" and "1 in 200" if they were exposed to heavy metals. A range of other exposures have weaker evidence supporting them and include participation in 2402: 1906: 1163:. Those with a bulbar onset have a worse prognosis than limb-onset ALS; a population-based study found that bulbar-onset ALS patients had a median survival of 2.0 years and a 10-year survival rate of 3%, while limb-onset ALS patients had a median survival of 2.6 years and a 10-year survival rate of 13%. Those with respiratory-onset ALS had a shorter median survival of 1.4 years and 0% survival at 10 years. While 9458: 1713: 2679: 1664: 2592: 2074: 1342:(4% of familial cases, 1% sporadic), with the remaining genes mostly accounting for fewer than 1% of either familial or sporadic cases. ALS genes identified to date explain the cause of about 70% of familial ALS and about 15% of sporadic ALS. Overall, first-degree relatives of an individual with ALS have a ~1% risk of developing ALS themselves. 895:), including an overactive gag reflex. While the disease does not cause pain directly, pain is a symptom experienced by most people with ALS caused by reduced mobility. 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 ( 1587:

increase the binding affinity of the low-complexity domain, causing their respective proteins to aggregate in the cytoplasm. Once these mutant RNA-binding proteins are misfolded and aggregated, they may be able to misfold normal proteins both within and between cells in a prion-like manner. This also

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While they appear identical clinically and pathologically, ALS can be classified as being either familial or sporadic, depending on whether there is a known family history of the disease and/or whether an ALS-associated genetic mutation has been identified via genetic testing. Familial ALS is thought

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for ALS proposes that cellular damage accumulates over time due to genetic factors present at birth and exposure to environmental risks throughout life. ALS can strike at any age, but its likelihood increases with age. Most people who develop ALS are between the ages of 40 and 70, with an average age

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are the most frequently reported behavioral features of ALS. ALS and FTD are now considered to be part of a common disease spectrum (ALS–FTD) because of genetic, clinical, and pathological similarities. Genetically, repeat expansions in the C9orf72 gene account for about 40% of genetic ALS and 25% of

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ALS can affect people at any age, but the peak incidence is between 50 and 75 years and decreases dramatically after 80 years. The reason for the decreased incidence in the elderly is unclear. One thought is that people who survive into their 80s may not be genetically susceptible to developing ALS;

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connected to a ventilator. It is an option for people with advanced ALS whose respiratory symptoms are poorly managed despite continuous NIV use. While invasive ventilation prolongs survival, especially for those younger than 60, it does not treat the underlying neurodegenerative process. The person

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ALS must be differentiated from the "ALS mimic syndromes", which are unrelated disorders that may have a similar presentation and clinical features to ALS or its variants. Because the prognosis of ALS and closely related subtypes of motor neuron disease are generally poor, neurologists may carry out

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People of all races and ethnic backgrounds may be affected by ALS, but it is more common in whites than in Africans, Asians, or Hispanics. In the United States in 2015, the prevalence of ALS in whites was 5.4 people per 100,000, while the prevalence in blacks was 2.3 people per 100,000. The Midwest

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Physical therapy can promote functional independence through aerobic, range of motion, and stretching exercises. Occupational therapy can assist with activities of daily living through adaptive equipment. Speech therapy can assist people with ALS who have difficulty speaking. Preventing weight loss

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repeats are deposition of RNA transcripts in the nucleus, translation of the RNA into toxic dipeptide repeat proteins in the cytoplasm, and decreased levels of the normal C9orf72 protein. Mitochondrial bioenergetic dysfunction leading to dysfunctional motor neuron axonal homeostasis (reduced axonal

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is the most commonly mutated gene in ALS and causes motor neuron death through a number of mechanisms. The pathogenic mutation is a hexanucleotide repeat expansion (a series of six nucleotides repeated over and over); people with up to 30 repeats are considered normal, while people with hundreds or

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that was approved for medical use in the United States in April 2023, for the treatment of SOD1-associated ALS. In a study of 108 patients with SOD1-associated ALS there was a non-significant trend towards a slowing of progression, as well as a significant reduction in neurofilament light chain, a

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There is considerable variation among clinicians on how to approach genetic testing in ALS, and only about half discuss the possibility of genetic inheritance with their patients, particularly if there is no discernible family history of the disease. In the past, genetic counseling and testing was

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can ease problems with breathing and prolong survival, it does not affect the progression rate of ALS. Most people with ALS die between two and four years after the diagnosis. Around 50% of people with ALS die within 30 months of their symptoms beginning, about 20% live between five and ten years,

2252:(RCTs) have yet been conducted to indicate whether enteral tube feeding has benefits compared to continuation of feeding by mouth. Nevertheless, PEG tubes are still offered with the intent of improving the person's quality of life by sustaining nutrition, hydration status, and medication intake. 1849:

may also, occasionally, mimic some of the early symptoms of ALS. Nonetheless, the absence of other neurological features that develop inexorably with ALS means that, over time, the distinction will not present any difficulty to the experienced neurologist; where doubt remains, EMG may be helpful.

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appear remarkably common among patients with ALS, it remains open whether personality can increase susceptibility to ALS directly. Instead, genetic factors giving rise to personality might simultaneously predispose people to developing ALS, or the above personality traits might underlie lifestyle

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The start of ALS may be so subtle that the symptoms are overlooked. The earliest symptoms of ALS are muscle weakness or muscle atrophy, typically on one side of the body. Other presenting symptoms include trouble swallowing or breathing, cramping, or stiffness of affected muscles; muscle weakness

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and shortening (contracture) of muscles. Physical and occupational therapists can recommend exercises that provide these benefits without overworking muscles because muscle exhaustion can lead to a worsening of symptoms associated with ALS, rather than providing help to people with ALS. They can

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Non-invasive ventilation prolongs survival longer than riluzole. A 2006 randomized controlled trial found that NIV prolongs survival by about 48 days and improves the quality of life; however, it also found that some people with ALS benefit more from this intervention than others. For those with

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is a symptom in which patients cry, smile, yawn, or laugh, either in the absence of emotional stimuli, or when they are feeling the opposite emotion to that being expressed; it is experienced by about half of ALS patients and is more common in those with bulbar-onset ALS. While relatively benign

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is characterized by lower motor neuron damage affecting the arm muscles, typically starting with the upper arms symmetrically and progressing downwards to the hands. Flail leg syndrome is characterized by lower motor neuron damage leading to asymmetrical weakness and wasting in the legs starting

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Isolated variants of ALS have symptoms that are limited to a single region for at least a year; they progress more slowly than classical ALS and are associated with longer survival. These regional variants of ALS can only be considered as a diagnosis should the initial symptoms fail to spread to

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develops in about 85% of people with ALS at some point over the course of their disease. Therefore, regular periodic assessment of the weight and swallowing ability in people with ALS is very important. Dysphagia is often initially managed via dietary changes and modified swallowing techniques.

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Although the initial site of symptoms and subsequent rate of disability progression vary from person to person, the initially affected body region is usually the most affected over time, and symptoms usually spread to a neighbouring body region. For example, symptoms starting in one arm usually

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ALS. Limb-onset ALS begins with weakness in the hands, arms, feet, and/or legs and accounts for about two-thirds of all classical ALS cases. Bulbar-onset ALS begins with weakness in the muscles of speech, chewing, and swallowing and accounts for about 25% of classical ALS cases. A rarer type of

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may help maintain weight and nutrition. Death is usually caused by respiratory failure. The disease can affect people of any age, but usually starts around the age of 60. The average survival from onset to death is two to four years, though this can vary, and about 10% of those affected survive

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plays a large role in rehabilitation for individuals with ALS. Specifically, physical, occupational, and speech therapists can set goals and promote benefits for individuals with ALS by delaying loss of strength, maintaining endurance, limiting pain, improving speech and swallowing, preventing

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It is important to monitor the respiratory function of people with ALS every three months because beginning NIV soon after the start of respiratory symptoms is associated with increased survival. This involves asking the person with ALS if they have any respiratory symptoms and measuring their

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should begin shortly after someone is diagnosed with ALS. Discussion of end-of-life issues gives people with ALS time to reflect on their preferences for end-of-life care and can help avoid unwanted interventions or procedures. Hospice care can improve symptom management at the end of life and

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ALS can also be classified based on the age of onset. While the peak age of onset is 58 to 63 for sporadic ALS and 47 to 52 for genetic ALS, about 10% of all cases of ALS begin before age 45 ("young-onset" ALS), and about 1% of all cases begin before age 25 ("juvenile" ALS). People who develop

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published the first EMG/NCS diagnostic criteria for ALS, consisting of four findings he considered to strongly support the diagnosis. Since then a number of diagnostic criteria have been developed, which are mostly in use for research purposes for inclusion/exclusion criteria, and to stratify

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Brooks BR (July 1994). "El Escorial World Federation of Neurology criteria for the diagnosis of amyotrophic lateral sclerosis. Subcommittee on Motor Neuron Diseases/Amyotrophic Lateral Sclerosis of the World Federation of Neurology Research Group on Neuromuscular Diseases and the El Escorial

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As a disease, ALS itself can be classified in a few different ways: by which part of the motor neurons are affected; by the parts of the body first affected; whether it is genetic; and the age at which it started. Each individual diagnosed with the condition will sit at a unique place at the

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There is no cure for ALS. Management focuses on treating symptoms and providing supportive care, with the goal of improving quality of life and prolonging survival. This care is best provided by multidisciplinary teams of healthcare professionals; attending a multidisciplinary ALS clinic is

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In bulbar-onset ALS, the first symptoms are difficulty speaking or swallowing. Speech may become slurred, nasal in character, or quieter. There may be difficulty with swallowing and loss of tongue mobility. A smaller proportion of people experience "respiratory-onset" ALS, where the

1239:. Though its exact cause is unknown, genetic and environmental factors are thought to be of roughly equal importance. The genetic factors are better understood than the environmental factors; no specific environmental factor has been definitively shown to cause ALS. A multi-step 779:

young-onset ALS are more likely to be male, less likely to have bulbar onset of symptoms, and more likely to have a slower progression of the disease. Juvenile ALS is more likely to be genetic in origin than adult-onset ALS; the most common genes associated with juvenile ALS are

1295:, meaning that a patient's ancestors carried the gene but did not express the disease in their lifetimes. The lack of positive family history may be caused by lack of historical records, having a smaller family, older generations dying earlier of causes other than ALS, genetic 2621:(who notably lived longer than any other known person with the condition), a number of other notable individuals have or have had ALS. Several books have been written and films have been made about patients of the disease as well. American sociology professor and ALS patient 2594: 2599: 2597: 2593: 2459:

patients for analysis in trials. Research diagnostic criteria for ALS include the "El Escorial" in 1994, revised in 1998. In 2006, the "Awaji" criteria proposed using EMG and NCV tests to help diagnose ALS earlier, and most recently the "Gold Coast" criteria in 2019.

2244:, in which a tube is placed through the nose and down the esophagus into the stomach. A gastrostomy tube is more appropriate for long-term use than a nasogastric tube, which is uncomfortable and can cause esophageal ulcers. The feeding tube is usually inserted by a 2598: 1525:(normal) SOD1 protein are common in sporadic ALS. It is thought that misfolded mutant SOD1 can cause misfolding and aggregation of wild-type SOD1 in neighboring neurons in a prion-like manner. Other protein degradation genes that can cause ALS when mutated include 1970:

putative ALS biomarker thought to indicate neuronal damage. A follow-up study and open-label extension suggested that earlier treatment initiation had a beneficial effect on slowing disease progression. Tofersen is available as an intrathecal injection into the

2263:, which relieves symptoms and improves the quality of life without treating the underlying disease, should begin shortly after someone is diagnosed with ALS. Early discussion of end-of-life issues gives people with ALS time to reflect on their preferences for 1959:, which was initially shown to prolong the survival of patients by an average of six months. Relyvrio was withdrawn by the manufacturer in April 2024 following the completion of the Phase 3 PHOENIX trial which did not show substantial benefit to ALS patients. 2421:

was the first to describe a disorder he named "progressive muscular atrophy", a form of ALS in which only the lower motor neurons are affected. In 1869, the connection between the symptoms and the underlying neurological problems were first described by

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Providing individual patients with a precise prognosis is not currently possible, though research is underway to provide statistical models on the basis of prognostic factors including age at onset, progression rate, site of onset, and presence of

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and inspiratory pressure diminish. In respiratory-onset ALS, this may occur before significant limb weakness is apparent. Individuals affected by the disorder may ultimately lose the ability to initiate and control all voluntary movement, known as

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of the brain) and lower motor neurons (located in the brainstem and spinal cord). In ALS with frontotemporal dementia, neurons throughout the frontal and temporal lobes of the brain die as well. The pathological hallmark of ALS is the presence of

1311:) should be considered significant when determining a family history. There have been calls in the research community to routinely counsel and test all diagnosed ALS patients for familial ALS, particularly as there is now a licensed gene therapy ( 1315:) specifically targeted to carriers of SOD-1 ALS. A shortage of genetic counselors and limited clinical capacity to see such at-risk individuals makes this challenging in practice, as does the unequal access to genetic testing around the world. 1015:, ALS has staging systems numbered between 1 and 4 that are used for research purposes in clinical trials. Two very similar staging systems emerged around a similar time, the King's staging system and Milano-Torino (MiToS) functional staging. 2596: 4665:

Cedarbaum JM, Stambler N, Malta E, Fuller C, Hilt D, Thurmond B, Nakanishi A (October 1999). "The ALSFRS-R: a revised ALS functional rating scale that incorporates assessments of respiratory function. BDNF ALS Study Group (Phase III)".

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There are a number of ALS genes that encode for RNA-binding proteins. The first to be discovered was TDP-43 protein, a nuclear protein that aggregates in the cytoplasm of motor neurons in almost all cases of ALS; however, mutations in

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samples to eliminate the possibility of other diseases, as well as routine laboratory tests. In some cases, for example, if a physician suspects the person may have a myopathy rather than ALS, a muscle biopsy may be performed.

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around the feet. Isolated bulbar palsy is characterized by upper or lower motor neuron damage in the bulbar region (in the absence of limb symptoms for at least 20 months), leading to gradual onset of difficulty with speech (

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No single test can provide a definite diagnosis of ALS. Instead, the diagnosis of ALS is primarily made based on a physician's clinical assessment after ruling out other diseases. Physicians often obtain the person's full

1000:. Most ALS patients die at home after a period of worsening difficulty breathing, a decline in their nutritional status, or a rapid worsening of symptoms. Sudden death or acute respiratory distress are uncommon. Access to 2223:

in people with ALS improves both survival and quality of life. Weight loss in ALS is often caused by muscle wasting and increased resting energy expenditure. Weight loss may also be secondary to reduced food intake since

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In limb-onset ALS, the first symptoms are in the arms or the legs. If the legs are affected first, people may experience awkwardness, tripping, or stumbling when walking or running; this is often marked by walking with a

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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

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which connects to the muscle itself. Damage to either the upper or lower motor neuron, as it makes its way from the brain to muscle, causes different types of symptoms. Damage to the upper motor neuron typically causes

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A Phase III, Randomized, Double-Blind, Placebo-Controlled, Multicenter Trial to Evaluate the Safety and Efficacy of AMX0035 Versus Placebo for 48-week Treatment of Adult Patients With Amyotrophic Lateral Sclerosis

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Classical ALS accounts for about 70% of all cases of ALS and can be subdivided into where symptoms first appear as these are usually focussed to one region of the body at initial presentation before later spread.

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is thought to involve many different cellular and molecular processes. The genes known to be involved in ALS can be grouped into three general categories based on their normal function: protein degradation, the

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online. Participants filmed themselves filling a bucket full of ice water and pouring it onto themselves; they then nominated other individuals to do the same. Many participants donated to ALS research at the

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in 1933 to reflect his belief that ALS, progressive bulbar palsy, and progressive muscular atrophy were all different forms of the same disease. In some countries, especially the United States, ALS is called

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The multi-step hypothesis suggests the disease is caused by some interaction between an individual's genetic risk factors and their cumulative lifetime of exposures to environmental factors, termed their

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leads to decreased levels of RNA-binding protein in the nucleus, which may mean that their target RNA transcripts do not undergo normal processing. Other RNA metabolism genes associated with ALS include

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relative to other symptoms, it can cause increased stigma and social isolation as people around the patient struggle to react appropriately to what can be frequent and inappropriate outbursts in public.

2187:. These health professionals can teach people adaptive strategies such as techniques to help them speak louder and more clearly. As ALS progresses, speech-language pathologists can recommend the use of 7975: 868:" that drags gently on the ground. If the arms are affected first, they may experience difficulty with tasks requiring manual dexterity, such as buttoning a shirt, writing, or turning a key in a lock. 10938: 9375: 6626: 1227:

Cognitive and behavioral issues are associated with poorer prognosis as they may reduce adherence to medical advice, and deficits in empathy and social cognition which may increase caregiver burden.

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Gautier G, Verschueren A, Monnier A, Attarian S, Salort-Campana E, Pouget J (August 2010). "ALS with respiratory onset: clinical features and effects of non-invasive ventilation on the prognosis".

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Carlesi C, Pasquali L, Piazza S, Lo Gerfo A, Caldarazzo Ienco E, Alessi R, et al. (March 2011). "Strategies for clinical approach to neurodegeneration in Amyotrophic lateral sclerosis".

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can be used for anxiety. There are no medications to treat cognitive impairment/frontotemporal dementia (FTD); however, SSRIs and antipsychotics can help treat some of the symptoms of FTD.

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and malnutrition in people with ALS improves both survival and quality of life. Initially, difficulty swallowing (dysphagia) can be managed by dietary changes and swallowing techniques. A

1655:, a drug that modestly prolongs survival in ALS, inhibits glutamate release from pre-synaptic neurons; however, it is unclear if this mechanism is responsible for its therapeutic effect. 3157: 1872:

A person with late-stage ALS with a range of assistive technologies to support movement (power wheelchair), breathing (invasive ventilation), and communication (eye tracker and computer)

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are the most commonly reported cognitive symptoms in ALS. Cognitive impairment is found more frequently in patients with C9orf72 gene repeat expansions, bulbar onset, bulbar symptoms,

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is often feasible, albeit slow, and needs may change over time. Despite these challenges, many people in an advanced state of disease report satisfactory wellbeing and quality of life.

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Illustration showing the range of upper and lower motor neuron involvement in the two most common types of ALS (top row) and three of the most common rare subtypes of ALS (bottom row)

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Yang T, Hou Y, Li C, Cao B, Cheng Y, Wei Q, et al. (July 2021). "Risk factors for cognitive impairment in amyotrophic lateral sclerosis: a systematic review and meta-analysis".

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Luna J, Logroscino G, Couratier P, Marin B (May 2017). "Current issues in ALS epidemiology: Variation of ALS occurrence between populations and physical activity as a risk factor".

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can strengthen unaffected muscles, improve cardiovascular health, and help people fight fatigue and depression. Range of motion and stretching exercises can help prevent painful

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Clinical diagnosis of exclusion based on progressive symptoms of upper and lower motor neuron degeneration in which no other explanation can be found. Supportive evidence from

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Creemers H, Grupstra H, Nollet F, van den Berg LH, Beelen A (June 2015). "Prognostic factors for the course of functional status of patients with ALS: a systematic review".

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affecting an arm or a leg; or slurred and nasal speech. The parts of the body affected by early symptoms of ALS depend on which motor neurons in the body are damaged first.

1935:). People with ALS should begin treatment with riluzole as soon as possible following their diagnosis. Riluzole is available as a tablet, liquid, or dissolvable oral film. 1892:

increases the likelihood of a peaceful death. In the final days of life, opioids can be used to treat pain and dyspnea, while benzodiazepines can be used to treat anxiety.

1472:(abnormal aggregations of protein) known as Bunina bodies in the cytoplasm of motor neurons. In about 97% of people with ALS, the main component of the inclusion bodies is 1244:

of 55 at the time of diagnosis. ALS is 20% more common in men than women, but this difference in sex distribution is no longer present in patients with onset after age 70.

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indicating their attitude toward noninvasive ventilation, invasive ventilation, and feeding tubes. Late in the disease course, difficulty speaking due to muscle weakness (

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Beeldman E, Raaphorst J, Klein Twennaar M, de Visser M, Schmand BA, de Haan RJ (June 2016). "The cognitive profile of ALS: a systematic review and meta-analysis update".

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Al-Chalabi A, Hardiman O, Kiernan MC, Chiò A, Rix-Brooks B, van den Berg LH (October 2016). "Amyotrophic lateral sclerosis: moving towards a new classification system".

413:. Motor neuron loss typically continues until the abilities to eat, speak, move, and, lastly, breathe are all lost. While only 15% of people with ALS also fully develop 1881:

should be considered if someone with ALS loses 5% or more of their body weight or if they cannot safely swallow food and water. The feeding tube is usually inserted by

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Ahmed RM, Newcombe RE, Piper AJ, Lewis SJ, Yee BJ, Kiernan MC, Grunstein RR (April 2016). "Sleep disorders and respiratory function in amyotrophic lateral sclerosis".

6484:""Patients with amyotrophic lateral sclerosis (ALS) are usually nice persons"-How physicians experienced in ALS see the personality characteristics of their patients" 2191:

such as voice amplifiers, speech-generating devices (or voice output communication devices) or low-tech communication techniques such as head-mounted laser pointers,

1746:(EMG), a special recording technique that detects electrical activity in muscles. Certain EMG findings can support the diagnosis of ALS. Another common test measures 2267:

and can help avoid unwanted interventions or procedures. Once they have been fully informed about all aspects of various life-prolonging measures, they can fill out

9722: 575: 10652: 5269:

Corcia P, Pradat PF, Salachas F, Bruneteau G, Forestier N, Seilhean D, et al. (1 January 2008). "Causes of death in a post-mortem series of ALS patients".

591:

ALS can be classified by the types of motor neurons that are affected. To successfully control any voluntary muscle in the body, a signal must be sent from the

8731:

Zou ZY, Zhou ZR, Che CH, Liu CY, He RL, Huang HP (July 2017). "Genetic epidemiology of amyotrophic lateral sclerosis: a systematic review and meta-analysis".

8432:

Checkoway H, Lundin JI, Kelada SN (2011). "Chapter 22: Neurodegenerative diseases". In Rothman N, Hainaut P, Schulte P, Smith M, Boffetta P, Perera F (eds.).

7971: 4247:"Amyotrophic Lateral Sclerosis Regional Variants (Brachial Amyotrophic Diplegia, Leg Amyotrophic Diplegia, and Isolated Bulbar Amyotrophic Lateral Sclerosis)" 1762:(MRI) is often normal in people with early-stage ALS, it can reveal evidence of other problems that may be causing the symptoms, such as a spinal cord tumor, 9383: 6590: 2236:

should be considered if someone with ALS loses 5% or more of their body weight or if they cannot safely swallow food and water. This can take the form of a

8005: 2863: 8340:

Macpherson CE, Bassile CC (July 2016). "Pulmonary Physical Therapy Techniques to Enhance Survival in Amyotrophic Lateral Sclerosis: A Systematic Review".

7233: 8997:

Brooks BR, Miller RG, Swash M, Munsat TL (December 2000). "El Escorial revisited: revised criteria for the diagnosis of amyotrophic lateral sclerosis".

4538: 807:

that are associated with a poor prognosis. Late onset (after age 65) is generally associated with a more rapid functional decline and shorter survival.

6435:"Are people with amyotrophic lateral sclerosis (ALS) particularly nice? An international online case-control study of the Big Five personality factors" 6100:"A survey of current practice in genetic testing in amyotrophic lateral sclerosis in the UK and Republic of Ireland: implications for future planning" 1941:

has been shown to modestly slow the decline in function in a small group of people with early-stage ALS. It may work by protecting motor neurons from

1613:

thousands of repeats can have familial ALS, frontotemporal dementia, or sometimes sporadic ALS. The three mechanisms of disease associated with these

935:

can develop, and maintaining a healthy weight can become a significant problem that may require the insertion of a feeding tube. As the diaphragm and

10885: 3576: 1814: 8910:

Wilbourn AJ (October 1998). "Clinical neurophysiology in the diagnosis of amyotrophic lateral sclerosis: the Lambert and the El Escorial criteria".

7830:"Safety and efficacy of edaravone in well defined patients with amyotrophic lateral sclerosis: a randomised, double-blind, placebo-controlled trial" 4450:

Tard C, Defebvre L, Moreau C, Devos D, Danel-Brunaud V (May 2017). "Clinical features of amyotrophic lateral sclerosis and their prognostic value".

9918: 7193:

Silani V, Messina S, Poletti B, Morelli C, Doretti A, Ticozzi N, Maderna L (March 2011). "The diagnosis of Amyotrophic lateral sclerosis in 2010".

3553: 1275:

only offered to those with obviously familial ALS. But it is increasingly recognized that cases of sporadic ALS may also be due to disease-causing

5683:

Raaphorst J, Beeldman E, De Visser M, De Haan RJ, Schmand B (October 2012). "A systematic review of behavioural changes in motor neuron disease".

6317:"Identification of risk factors associated with onset and progression of amyotrophic lateral sclerosis using systematic review and meta-analysis" 3928:"Discussing Personalized Prognosis Empowers Patients with Amyotrophic Lateral Sclerosis to Regain Control over Their Future: A Qualitative Study" 483:

There is no known cure for ALS. The goal of treatment is to slow the disease progression, and improve symptoms. Treatments that slow ALS include

1885:(PEG). There is weak evidence that PEG tubes improve survival. PEG insertion is usually performed with the intent of improving quality of life. 1651:), which is the main transporter that removes glutamate from the synapse; this leads to increased synaptic glutamate levels and excitotoxicity. 1579:

codes for FUS, another RNA-binding protein with a similar function to TDP-43, which can cause ALS when mutated. It is thought that mutations in

9913: 9462: 3149: 9040:

de Carvalho M, Dengler R, Eisen A, England JD, Kaji R, Kimura J, et al. (March 2008). "Electrodiagnostic criteria for diagnosis of ALS".

3809:

Pupillo E, Messina P, Logroscino G, Beghi E (February 2014). "Long-term survival in amyotrophic lateral sclerosis: a population-based study".

1945:. The most common side effects are bruising and gait disturbance. Edaravone is available as an intravenous infusion or as an oral suspension. 3297: 8256:

Pinto S, Carvalho M (2014). "Breathing new life into treatment advances for respiratory failure in amyotrophic lateral sclerosis patients".

6360: 5919: 1318:

More than 40 genes have been associated with ALS, of which four account for nearly half of familial cases, and around 5% of sporadic cases:

1211:

In addition to mild changes in cognition that may only emerge during neuropsychological testing, around 10–15% of individuals have signs of

9715: 3210:

van Es MA, Hardiman O, Chio A, Al-Chalabi A, Pasterkamp RJ, Veldink JH, van den Berg LH (November 2017). "Amyotrophic lateral sclerosis".

1709:, and spasticity are worsening. A number of biomarkers are being studied for the condition, but as of 2023 are not in general medical use. 10645: 6200:

McNeill A, Amador MD, Bekker H, Clarke A, Crook A, Cummings C, et al. (International Alliance of ALS/MND Associations) (June 2022).

5434: 4902:

Castrillo-Viguera C, Grasso DL, Simpson E, Shefner J, Cudkowicz ME (2010). "Clinical significance in the change of decline in ALSFRS-R".

1521:, and RNA processing. Mutant SOD1 protein forms intracellular aggregations that inhibit protein degradation. Cytoplasmic aggregations of 5726:

Couratier P, Corcia P, Lautrette G, Nicol M, Marin B (May 2017). "ALS and frontotemporal dementia belong to a common disease spectrum".

2692: 10933: 9183: 7469:

Lewis M, Rushanan S (2007). "The role of physical therapy and occupational therapy in the treatment of amyotrophic lateral sclerosis".

6288: 5001:"A systematic review of the effect of moderate intensity exercise on function and disease progression in amyotrophic lateral sclerosis" 2188: 1181:

or behavioral dysfunction is present in 30–50% of individuals with ALS, and can appear more frequently in later stages of the disease.

973: 651:(PMA) involves only the lower motor neurons. There is debate over whether PLS and PMA are separate diseases or simply variants of ALS. 295: 10675: 10541: 9218: 1253: 7592:"Systematic review of the effectiveness of occupational therapy-related interventions for people with amyotrophic lateral sclerosis" 7044:"Mitochondrial bioenergetic deficits in C9orf72 amyotrophic lateral sclerosis motor neurons cause dysfunctional axonal homeostasis" 2608: 1948: 488: 316: 17: 5365: 3861:

Rowland LP (March 2001). "How amyotrophic lateral sclerosis got its name: the clinical-pathologic genius of Jean-Martin Charcot".

1781:

Based on the person's symptoms and findings from the examination and from these tests, the physician may order tests on blood and

1355:. The most consistent lifetime exposures associated with developing ALS (other than genetic mutations) include heavy metals (e.g. 1004:

is recommended from an early stage to explore options, ensure psychosocial support for the patient and caregivers, and to discuss

511:. In 1869, the connection between the symptoms and the underlying neurological problems was first described by French neurologist 10531: 9708: 6024: 5962: 10958: 10918: 10680: 10638: 10511: 10184: 2018: 567:

intersection of these complex and overlapping subtypes, which presents a challenge to diagnosis, understanding, and prognosis.

7513: 797:. Although most people with juvenile ALS live longer than those with adult-onset ALS, some of them have specific mutations in 10536: 10168: 1838: 912: 9153: 3011: 1488:-like propagation of misfolded proteins from cell to cell may explain why ALS starts in one area and spreads to others. The 720:

classical ALS affecting around 3% of patients is respiratory-onset, in which the initial symptoms are difficulty breathing (

10374: 10362: 9824: 8027: 2637: 1982:

Other medications may be used to help reduce fatigue, ease muscle cramps, control spasticity, and reduce excess saliva and

7690:"EFNS guidelines on the clinical management of amyotrophic lateral sclerosis (MALS)--revised report of an EFNS task force" 4487:"Deciphering amyotrophic lateral sclerosis: what phenotype, neuropathology and genetics are telling us about pathogenesis" 9567: 9275:"Amyotrophic Lateral Sclerosis: An update for 2013 Clinical Features, Pathophysiology, Management and Therapeutic Trials" 3926:

van Eenennaam RM, Koppenol LS, Kruithof WJ, Kruitwagen-van Reenen ET, Pieters S, van Es MA, et al. (November 2021).

2520: 2245: 1882: 1672: 1627: 8818:

Visser J, de Jong JM, de Visser M (February 2008). "The history of progressive muscular atrophy: syndrome or disease?".

3705:

Connolly S, Galvin M, Hardiman O (April 2015). "End-of-life management in patients with amyotrophic lateral sclerosis".

10593: 10526: 10081: 9257: 8441: 2111:(too much carbon dioxide in the blood). If their daytime blood gas analysis is normal, they should then have nocturnal 1920:

has been found to modestly prolong survival by about 2–3 months. It may have a greater survival benefit for those with

1822: 1697:

and conduct neurologic examinations at regular intervals to assess whether signs and symptoms such as muscle weakness,

10742: 10701: 10296: 10099: 2666: 2658: 1549:. Three genes implicated in ALS that are important for maintaining the cytoskeleton and for axonal transport include 5247: 2136:

with ALS will continue to lose motor function, making communication increasingly difficult and sometimes leading to

1636:, or nerve cell death caused by high levels of intracellular calcium due to excessive stimulation by the excitatory 10948: 3365: 5873:

Al-Chalabi A, Hardiman O (November 2013). "The epidemiology of ALS: a conspiracy of genes, environment and time".

4296:"Disease duration of progression is helpful in identifying isolated bulbar palsy of amyotrophic lateral sclerosis" 10415: 7423:

Eisen A, Krieger C (November 2013). "Ethical considerations in the management of amyotrophic lateral sclerosis".

2328: 7997: 5202:"Palliative care in amyotrophic lateral sclerosis: a review of current international guidelines and initiatives" 1647:) that is more permeable to calcium. In ALS, there are decreased levels of excitatory amino acid transporter 2 ( 10923: 10711: 9930: 9906: 9736: 3392:"The heritability of amyotrophic lateral sclerosis in a clinically ascertained United States research registry" 2148: 1789:

A number of infectious diseases can sometimes cause ALS-like symptoms, including human immunodeficiency virus (

1623: 37:"Motor neuron disease" and "Motor neurone disease" redirect here. For a group of muscle-wasting disorders, see 7255: 7229: 6385:

Grossman AB, Levin BE, Bradley WG (March 2006). "Premorbid personality characteristics of patients with ALS".

5099:

Kuzma-Kozakiewicz M, Andersen PM, Ciecwierska K, Vázquez C, Helczyk O, Loose M, et al. (September 2019).

3896: 10943: 10661: 10609: 10494: 10410: 10352: 10122: 9901: 1842: 249: 3449: 468:(hereditary). About half of these genetic cases are due to disease-causing variants in one of four specific 10953: 10578: 9952: 8076: 2568: 2531:

was the first to connect the clinical symptoms with the pathology seen at autopsy. The British neurologist

1928: 1846: 1005: 737: 648: 548: 7287:"Characteristics of fasciculations in amyotrophic lateral sclerosis and the benign fasciculation syndrome" 6693:"Axonal Transport and Neurodegeneration: How Marine Drugs Can Be Used for the Development of Therapeutics" 5986:"Amyotrophic Lateral Sclerosis Genetic Studies: From Genome-wide Association Mapping to Genome Sequencing" 10859: 10088: 2632: 2249: 1810: 1750:(NCV). Specific abnormalities in the NCV results may suggest, for example, that the person has a form of 241: 9679: 4616:

Gromicho M, Figueiral M, Uysal H, Grosskreutz J, Kuzma-Kozakiewicz M, Pinto S, et al. (July 2020).

3545: 1504: 10566: 10116: 9788: 8861:

Wijesekera LC, Mathers S, Talman P, Galtrey C, Parkinson MH, Ganesalingam J, et al. (March 2009).

8459:"Global epidemiology of amyotrophic lateral sclerosis: a systematic review of the published literature" 2240:

tube, in which a tube is placed through the wall of the abdomen into the stomach, or (less commonly) a

1794: 1759: 1527: 1400: 750: 324: 253: 10890: 10768: 10706: 10516: 10484: 10458: 10436: 10285: 9864: 8073:"FDA approves treatment of amyotrophic lateral sclerosis associated with a mutation in the SOD1 gene" 2583:

only refers to "classical" ALS, meaning the form with both upper and lower motor neuron involvement.

2572: 2451: 2447: 2302: 2248:

procedure (PEG). While there is weak evidence that PEG tubes improve survival in people with ALS, no

2184: 2127:

Invasive ventilation bypasses the nose and mouth (the upper airways) by making a cut in the trachea (

1995: 1966: 1956: 1747: 1484:

mutations, the main component of the inclusion bodies is SOD1 protein or FUS protein, respectively.

1240: 1198: 731: 644: 544: 461: 382: 9205:

Goetz CG (March 2000). "Amyotrophic lateral sclerosis: early contributions of Jean-Martin Charcot".

10583: 10357: 9771: 9668: 9578: 7688:

Andersen PM, Abrahams S, Borasio GD, de Carvalho M, Chio A, Van Damme P, et al. (March 2012).

5150:"The optimisation of noninvasive ventilation in amyotrophic lateral sclerosis: a systematic review" 5148:

O'Brien D, Stavroulakis T, Baxter S, Norman P, Bianchi S, Elliott M, et al. (September 2019).

3296:

Hardiman O, Al-Chalabi A, Chio A, Corr EM, Logroscino G, Robberecht W, et al. (October 2017).

2564: 2167:

can also enhance people's independence and safety throughout the course of ALS. Gentle, low-impact

2084: 2077: 2060:

is safe and effective for treating cramps in ALS based on a randomized controlled trial from 2016.

1862: 985: 828: 625: 552: 492: 287: 5200:

Bede P, Oliver D, Stodart J, van den Berg L, Simmons Z, O Brannagáin D, et al. (April 2011).

3495:"Emerging insights into the complex genetics and pathophysiology of amyotrophic lateral sclerosis" 2418: 1685: 460:

are believed to be involved. The remaining 5–10% of cases have a genetic cause, often linked to a

10588: 10521: 10277: 10095: 9947: 9937: 9781: 6316: 6251:"The importance of offering early genetic testing in everyone with amyotrophic lateral sclerosis" 2512:

means "scarring" or "hardening" and refers to the death of the motor neurons in the spinal cord.

1818: 1300: 1212: 1160: 414: 161: 154: 9700: 9248:

Gordon PH (2006). "Chapter 1: History of ALS". In Mitsumoto H, Przedborski S, Gordon PH (eds.).

2152:

A man with ALS communicates by pointing to letters and words using a head-mounted laser pointer.

10928: 10453: 10445: 10400: 10076: 10048: 9896: 9083:

Shefner JM, Al-Chalabi A, Baker MR, Cui LY, de Carvalho M, Eisen A, et al. (August 2020).

8506:

Hardiman O, Al-Chalabi A, Brayne C, Beghi E, van den Berg LH, Chio A, et al. (July 2017).

5505:

Crockford C, Newton J, Lonergan K, Chiwera T, Booth T, Chandran S, et al. (October 2018).

3493:

Goutman SA, Hardiman O, Al-Chalabi A, Chió A, Savelieff MG, Kiernan MC, Feldman EL (May 2022).

3051:

Goutman SA, Hardiman O, Al-Chalabi A, Chió A, Savelieff MG, Kiernan MC, Feldman EL (May 2022).

2310: 2306: 2192: 1830: 1407: 1396: 1264: 496: 236: 9618: 9516: 8102:

Miller TM, Cudkowicz ME, Genge A, Shaw PJ, Sobue G, Bucelli RC, et al. (September 2022).

6648:

Okamoto K, Mizuno Y, Fujita Y (April 2008). "Bunina bodies in amyotrophic lateral sclerosis".

5430: 5101:"An observational study on quality of life and preferences to sustain life in locked-in state" 10737: 10468: 10342: 10160: 10138: 10053: 9976: 9886: 9873: 9798: 7972:"FDA Approves Oral Form for the treatment of adults with amyotrophic lateral sclerosis (ALS)" 6531:

Robberecht W, Philips T (April 2013). "The changing scene of amyotrophic lateral sclerosis".

5312:

Fang T, Al Khleifat A, Stahl DR, Lazo La Torre C, Murphy C, Young C, et al. (May 2017).

2662: 2524: 2468: 2298: 2096: 1952: 1751: 1508:

This figure shows ten proposed disease mechanisms for ALS and the genes associated with them.

1268: 1186: 532: 528: 457: 394: 38: 9175: 8155:

Lu CH, Macdonald-Wallis C, Gray E, Pearce N, Petzold A, Norgren N, et al. (June 2015).

6250: 6249:

Salmon K, Kiernan MC, Kim SH, Andersen PM, Chio A, van den Berg LH, et al. (May 2022).

5507:"ALS-specific cognitive and behavior changes associated with advancing disease stage in ALS" 10763: 10405: 10222: 10111: 8649: 6328: 3403: 2645: 2627: 2508: 2455: 2203: 2183:

People with ALS who have difficulty speaking or swallowing may benefit from working with a

2164: 1676: 1441: 1260: 957: 932: 928: 840: 560: 245: 31: 9646: 9546: 210:; heavy metals; organic chemicals; smoking; electric shock; physical exercise; head injury 8: 10758: 10334: 9981: 9836: 9776: 9556: 7093:

Verber NS, Shepheard SR, Sassani M, McDonough HE, Moore SA, Alix JJ, et al. (2019).

4853:

Bedlack RS, Vaughan T, Wicks P, Heywood J, Sinani E, Selsov R, et al. (March 2016).

3765:

Kiernan MC, Vucic S, Cheah BC, Turner MR, Eisen A, Hardiman O, et al. (March 2011).

2528: 2430:

in his 1874 paper. Flail arm syndrome, a regional variant of ALS, was first described by

2423: 2390: 2325:. The incidence in these areas has decreased since the 1960s; the cause remains unknown. 1931:

from pre-synaptic neurons. The most common side effects are nausea and a lack of energy (

1806: 1449: 1445: 1388: 1296: 1204: 993: 965: 823:

throughout the body due to the degeneration of the upper motor and lower motor neurons.

512: 425:. Depending on which of the aforementioned symptoms develops first, ALS is classified as 261: 257: 170: 150: 146: 72: 8653: 8508:"The changing picture of amyotrophic lateral sclerosis: lessons from European registers" 8457:

Chiò A, Logroscino G, Traynor BJ, Collins J, Simeone JC, Goldstein LA, White LA (2013).

8209:"Comprehensive rehabilitative care across the spectrum of amyotrophic lateral sclerosis" 7660: 7635: 7042:

Mehta AR, Gregory JM, Dando O, Carter RN, Burr K, Nanda J, et al. (February 2021).

6332: 6049:

McNeill A, Amador MD, Bekker H, Clarke A, Crook A, Cummings C, et al. (June 2022).

3649:

Soriani MH, Desnuelle C (May 2017). "Care management in amyotrophic lateral sclerosis".

3407: 2409:. In some countries, especially the United States, ALS is called "Lou Gehrig's disease". 1829:

investigations to evaluate and exclude other diagnostic possibilities. Disorders of the

10834: 10504: 10489: 10477: 10227: 10178: 10015: 9878: 9766: 9561: 9436: 9356: 9299: 9274: 9230: 9124: 9065: 9022: 8979: 8935: 8887: 8878: 8862: 8843: 8831: 8756: 8670: 8637: 8610: 8585: 8584:

Mehta P, Kaye W, Raymond J, Punjani R, Larson T, Cohen J, et al. (November 2018).

8545: 8483: 8458: 8414: 8365: 8317: 8292: 8233: 8208: 8181: 8156: 8137: 7906: 7879: 7770: 7745: 7719: 7448: 7355: 7330: 7170: 7145: 7121: 7094: 7070: 7043: 7019: 6994: 6919: 6894: 6870: 6843: 6819: 6794: 6770: 6743: 6719: 6692: 6673: 6618: 6556: 6508: 6483: 6459: 6434: 6410: 6352: 6275: 6226: 6201: 6177: 6148: 6129: 6075: 6050: 6016: 5898: 5848: 5800: 5767: 5708: 5665: 5622: 5579: 5531: 5506: 5479: 5452: 5396: 5338: 5313: 5294: 5239: 5179: 5125: 5100: 5076: 5049: 5030: 4976: 4949: 4927: 4879: 4854: 4827: 4802: 4783: 4735: 4711:"Clinical trials in amyotrophic lateral sclerosis: a systematic review and perspective" 4710: 4691: 4642: 4617: 4598: 4572: 4534: 4511: 4486: 4424: 4397: 4373: 4346: 4322: 4295: 4271: 4246: 4227: 4157: 4105: 4020: 3993: 3954: 3927: 3834: 3730: 3604: 3519: 3494: 3426: 3391: 3328: 3235: 3126: 3101: 3077: 3052: 3003: 2914: 2805: 2780: 2739: 2712: 2322: 2172: 2137: 2100: 1859:

associated with longer survival, fewer hospitalizations, and improved quality of life.

1763: 1236: 1178: 961: 953: 936: 873: 668: 662: 640: 636: 604: 596: 584: 580: 556: 477: 418: 269: 166: 116: 8923: 7846: 7829: 5985: 4679: 4586: 4205: 3783: 3766: 3718: 3510: 3223: 3068: 10267: 10233: 10205: 10196: 10128: 10104: 9971: 9819: 9589: 9440: 9428: 9348: 9304: 9253: 9222: 9128: 9116: 9057: 9014: 8971: 8967: 8927: 8892: 8835: 8800: 8748: 8713: 8675: 8615: 8537: 8488: 8437: 8406: 8401: 8384: 8357: 8322: 8273: 8238: 8186: 8141: 8129: 7952: 7911: 7851: 7810: 7775: 7711: 7706: 7689: 7665: 7613: 7567: 7486: 7440: 7402: 7360: 7308: 7210: 7175: 7126: 7075: 7024: 6975: 6970: 6924: 6875: 6824: 6775: 6724: 6665: 6661: 6622: 6610: 6548: 6513: 6464: 6402: 6344: 6280: 6231: 6182: 6133: 6121: 6080: 6008: 5954: 5890: 5840: 5805: 5743: 5700: 5657: 5614: 5610: 5583: 5571: 5536: 5484: 5388: 5366:"Phenotypic heterogeneity of amyotrophic lateral sclerosis: a population based study" 5343: 5286: 5231: 5183: 5171: 5130: 5081: 5022: 4981: 4931: 4919: 4884: 4832: 4801:

Atassi N, Berry J, Shui A, Zach N, Sherman A, Sinani E, et al. (November 2014).

4775: 4740: 4683: 4647: 4590: 4516: 4467: 4429: 4378: 4327: 4276: 4219: 4161: 4149: 4129: 4097: 4055: 4025: 3959: 3878: 3838: 3826: 3788: 3722: 3666: 3608: 3596: 3524: 3431: 3320: 3227: 3131: 3082: 2995: 2918: 2906: 2810: 2744: 2434:

in 1886. Flail leg syndrome, another regional variant of ALS, was first described by

2268: 2049:

may be prescribed when people with ALS begin having trouble swallowing their saliva (

1841:, may also mimic ALS, although this rarely presents diagnostic difficulty over time. 1834: 1513: 1489: 1463:

The defining feature of ALS is the death of both upper motor neurons (located in the

1453: 1415: 1372: 1360: 1182: 836: 279: 265: 215: 104: 9069: 9026: 8983: 8939: 8847: 8779:"What's in a name? Problems, facts and controversies regarding neurological eponyms" 8760: 8549: 8418: 8157:"Neurofilament light chain: A prognostic biomarker in amyotrophic lateral sclerosis" 7452: 7436: 6677: 6414: 6356: 6147:

Müller K, Oh KW, Nordin A, Panthi S, Kim SH, Nordin F, et al. (February 2022).

5902: 5852: 5712: 5669: 5626: 5597:

Wicks P (July 2007). "Excessive yawning is common in the bulbar-onset form of ALS".

5400: 5298: 4787: 4602: 4231: 4109: 3734: 3239: 1618:

length and fast axonal transport of mitochondrial cargo) has been shown to occur in

765: 10864: 10390: 10261: 10256: 10041: 10036: 9629: 9418: 9360: 9338: 9294: 9286: 9234: 9214: 9106: 9096: 9049: 9006: 8963: 8919: 8882: 8874: 8863:"Natural history and clinical features of the flail arm and flail leg ALS variants" 8827: 8790: 8740: 8705: 8665: 8657: 8605: 8597: 8527: 8519: 8478: 8470: 8396: 8369: 8349: 8312: 8304: 8265: 8228: 8220: 8176: 8168: 8119: 8028:"ALS drug will be pulled from US market after study showed patients didn't benefit" 7942: 7901: 7891: 7841: 7802: 7765: 7761: 7757: 7723: 7701: 7655: 7651: 7647: 7603: 7557: 7517: 7478: 7432: 7394: 7350: 7346: 7342: 7298: 7202: 7165: 7157: 7116: 7106: 7065: 7055: 7014: 7010: 7006: 6965: 6955: 6914: 6910: 6906: 6865: 6855: 6814: 6806: 6765: 6755: 6714: 6704: 6657: 6602: 6540: 6503: 6495: 6454: 6446: 6394: 6336: 6270: 6262: 6221: 6213: 6172: 6164: 6111: 6070: 6062: 6020: 6000: 5882: 5832: 5795: 5787: 5779: 5735: 5692: 5649: 5606: 5563: 5526: 5518: 5474: 5469: 5464: 5380: 5333: 5325: 5278: 5243: 5221: 5213: 5161: 5120: 5112: 5071: 5061: 5034: 5012: 4971: 4961: 4911: 4874: 4866: 4822: 4814: 4767: 4730: 4722: 4695: 4675: 4637: 4629: 4618:"Spreading in ALS: The relative impact of upper and lower motor neuron involvement" 4582: 4563:

Chiò A, Mora G, Lauria G (February 2017). "Pain in amyotrophic lateral sclerosis".

4506: 4498: 4485:

Ravits J, Appel S, Baloh RH, Barohn R, Brooks BR, Elman L, et al. (May 2013).

4459: 4419: 4409: 4368: 4358: 4317: 4307: 4266: 4258: 4209: 4201: 4141: 4089: 4015: 4005: 3949: 3939: 3870: 3818: 3778: 3714: 3658: 3588: 3514: 3506: 3421: 3411: 3332: 3312: 3219: 3121: 3113: 3072: 3064: 3007: 2987: 2898: 2800: 2792: 2734: 2724: 2649: 2264: 2241: 2168: 2156: 1942: 1925: 1921: 1743: 1725: 1717: 1668: 1637: 1469: 1276: 1190: 221: 96: 83: 8385:"Causes and place of death in Italian patients with amyotrophic lateral sclerosis" 7947: 7930: 7873: 7871: 7869: 7867: 7865: 6995:"There has been an awakening: Emerging mechanisms of C9orf72 mutations in FTD/ALS" 6560: 6116: 6099: 6098:

De Oliveira HM, Soma A, Baker MR, Turner MR, Talbot K, Williams TL (August 2023).

5329: 3925: 10829: 10824: 10814: 10696: 10312: 10003: 9583: 9423: 9406: 9343: 9326: 9145: 9101: 9084: 9053: 8709: 8353: 8172: 5739: 5696: 5522: 5116: 5017: 5000: 4870: 4818: 4726: 4709:

Wong C, Stavrou M, Elliott E, Gregory JM, Leigh N, Pinto AA, et al. (2021).

4502: 4463: 3662: 3416: 3117: 3053:"Recent advances in the diagnosis and prognosis of amyotrophic lateral sclerosis" 2972: 2654: 2622: 2618: 2260: 2088: 2022: 1888: 1694: 1433: 1392: 1167: 1001: 964:

are uncommon, although trouble getting to a toilet can lead to difficulties. The

621: 540: 406: 390: 225: 10630: 6340: 5166: 5149: 4010: 2002:) can be used for neuropathic pain, while nonsteroidal anti-inflammatory drugs ( 10799: 10369: 10318: 10146: 9855: 9732: 9632: 9594: 9010: 8054: 7862: 7398: 7331:"Mechanical ventilation for amyotrophic lateral sclerosis/motor neuron disease" 7161: 7060: 6760: 6217: 6066: 4312: 4047: 3592: 2889:

Kwan J, Vullaganti M (September 2022). "Amyotrophic lateral sclerosis mimics".

2477: 2431: 2286: 2112: 2046: 1971: 1767: 1706: 1698: 1633: 1457: 1437: 1012: 948: 887:). Symptoms of upper motor neuron involvement include tight and stiff muscles ( 824: 749:

other spinal cord regions for an extended period of time (at least 12 months).

410: 92: 9657: 9531: 9325:

Huynh W, Simon NG, Grosskreutz J, Turner MR, Vucic S, Kiernan MC (July 2016).

8795: 8778: 7880:"Disease-modifying and symptomatic treatment of amyotrophic lateral sclerosis" 6960: 6943: 6398: 5886: 5653: 5282: 4915: 4771: 4262: 4145: 4093: 3874: 2991: 10912: 10869: 10819: 10789: 10784: 10395: 10347: 10217: 9986: 9942: 9793: 9635: 9290: 8744: 8523: 7896: 7746:"Riluzole for amyotrophic lateral sclerosis (ALS)/motor neuron disease (MND)" 7636:"Enteral tube feeding for amyotrophic lateral sclerosis/motor neuron disease" 7608: 7591: 7516:. American Speech-Language-Hearing Association, Rockville, MD. Archived from 7111: 6168: 6004: 5836: 5567: 5384: 5217: 4966: 4398:"Inherited Paediatric Motor Neuron Disorders: Beyond Spinal Muscular Atrophy" 3944: 2683: 2532: 2454:(NCV) testing began to be used to evaluate clinically suspected ALS. In 1969 2374: 2318: 2132: 2007: 1999: 1771: 1702: 1644: 1411: 1308: 1220: 1216: 1194: 896: 892: 629: 613: 402: 129: 9407:"The ALS ice bucket challenge – can a splash of water reinvigorate a field?" 7929:

Takei K, Watanabe K, Yuki S, Akimoto M, Sakata T, Palumbo J (October 2017).

7806: 7206: 6266: 6202:"Predictive genetic testing for Motor neuron disease: time for a guideline?" 6051:"Predictive genetic testing for Motor neuron disease: time for a guideline?" 10844: 10839: 10794: 9891: 9761: 9744: 9432: 9352: 9308: 9226: 9120: 9061: 9018: 8954:"Clinical limits of amyotrophic lateral sclerosis" workshop contributors". 8896: 8839: 8804: 8752: 8717: 8679: 8636:

Arthur KC, Calvo A, Price TR, Geiger JT, Chiò A, Traynor BJ (August 2016).

8619: 8601: 8541: 8492: 8410: 8361: 8326: 8277: 8242: 8190: 8133: 7956: 7915: 7855: 7814: 7779: 7715: 7669: 7617: 7571: 7490: 7482: 7444: 7406: 7380: 7378: 7376: 7374: 7364: 7312: 7303: 7286: 7214: 7179: 7130: 7079: 7028: 6979: 6928: 6879: 6828: 6779: 6728: 6669: 6614: 6552: 6517: 6468: 6406: 6348: 6284: 6235: 6186: 6125: 6084: 6012: 5894: 5844: 5809: 5747: 5704: 5661: 5618: 5575: 5540: 5488: 5392: 5347: 5290: 5235: 5175: 5134: 5098: 5085: 5026: 4985: 4923: 4888: 4836: 4779: 4744: 4687: 4651: 4594: 4520: 4471: 4433: 4414: 4382: 4331: 4280: 4223: 4153: 4101: 4059: 4029: 3963: 3882: 3830: 3792: 3726: 3670: 3600: 3528: 3435: 3324: 3231: 3135: 3086: 2999: 2910: 2814: 2748: 2506:

identifies the locations in the spinal cord of the affected motor neurons.

2435: 2414: 2278: 2233: 2220: 2128: 1878: 1798: 1729: 1518: 1493: 1464: 1164: 969: 831:

are generally unaffected, meaning the majority of people with ALS maintain

592: 536: 508: 500: 386: 291: 229: 178: 8975: 8931: 8124: 8103: 7931:"Edaravone and its clinical development for amyotrophic lateral sclerosis" 6606: 5640:

Sauvé WM (December 2016). "Recognizing and treating pseudobulbar affect".

5066: 4363: 2729: 2563:

in the US) refers to all forms of the disease, including "classical" ALS,

1170:

lived for 55 more years following his diagnosis, his was an unusual case.

10849: 10804: 10716: 9850: 9811: 9753: 9663: 9652: 9613: 7562: 7545: 7329:

Radunovic A, Annane D, Rafiq MK, Brassington R, Mustfa N (October 2017).

6744:"Defining novel functions for cerebrospinal fluid in ALS pathophysiology" 5201: 4803:"The PRO-ACT database: design, initial analyses, and predictive features" 4245:

Jawdat O, Statland JM, Barohn RJ, Katz JS, Dimachkie MM (November 2015).

3316: 2635:, and Stephen Hawking was the subject of the critically acclaimed biopic 2237: 2216: 2208: 2108: 2042: 2034: 1775: 1721: 1539: 1380: 1299:, and uncertainty over whether certain neuropsychiatric conditions (e.g. 201: 30:

This article is about the neurodegenerative disease. For other uses, see

9484: 9219:

10.1002/(SICI)1097-4598(200003)23:3<336::AID-MUS4>3.0.CO;2-L

8661: 8532: 7371: 6860: 5822: 4214: 3361: 2973:"Supportive and symptomatic management of amyotrophic lateral sclerosis" 2332:

Estimated prevalence of ALS in the United States by age group, 2012–2015

1825:

can also mimic certain aspects of the disease and should be considered.

10809: 10721: 9961: 9831: 9641: 9327:"Assessment of the upper motor neuron in amyotrophic lateral sclerosis" 9111: 8638:"Projected increase in amyotrophic lateral sclerosis from 2015 to 2040" 8383:

Spataro R, Lo Re M, Piccoli T, Piccoli F, La Bella V (September 2010).

8224: 7969: 7546:"Motor neuron disease: systematic reviews of treatment for ALS and SMA" 6895:"Mechanisms of FUS mutations in familial amyotrophic lateral sclerosis" 6810: 6709: 5791: 4633: 2614: 2549: 2498: 2406: 2272: 2176: 2080:

supports breathing with a face or nasal mask connected to a ventilator.

2057: 2050: 2030: 1991: 1987: 1590: 1533: 1332: 1292: 944: 888: 884: 879:

Over time, people experience increasing difficulty moving, swallowing (

820: 798: 781: 755: 609: 445: 434: 398: 336:

Life expectancy highly variable but typically 2–4 years after diagnosis

303: 283: 138: 125: 66: 9499: 8691: 8689: 8474: 8308: 8269: 6450: 5226: 3822: 2902: 2796: 2385: 2171:

such as performing activities of daily living, walking, swimming, and

1235:

It is not known what causes sporadic ALS, hence it is described as an

10854: 10071: 10022: 10010: 9993: 9925: 9624: 9541: 9376:"George Bush delivers possibly the best ALS ice bucket challenge yet" 7634:

Sulistyo A, Abrahao A, Freitas ME, Ritsma B, Zinman L (August 2023).

6795:"Modelling amyotrophic lateral sclerosis: progress and possibilities" 6499: 4901: 2225: 2104: 1938: 1640: 1522: 1364: 997: 924: 923:

Difficulties with chewing and swallowing make eating very difficult (

880: 865: 844: 759: 725: 473: 438: 331: 312: 174: 142: 109: 6544: 5783: 2095:

respiratory function. The most commonly used measurement is upright

1688:

around the center of the image, consistent with the diagnosis of ALS

1630:

gene-editing, and human post-mortem spinal cord tissue examination.

968:

responsible for eye movement are usually spared, meaning the use of

10546:

Spinal muscular atrophy with lower extremity predominance (SMALED)

10251: 10243: 10209: 10063: 9966: 9688: 9674: 8686: 8586:"Prevalence of Amyotrophic Lateral Sclerosis – United States, 2015" 7263: 6742:

Ng Kee Kwong KC, Mehta AR, Nedergaard M, Chandran S (August 2020).

6741: 5147: 4577: 4396:

Teoh HL, Carey K, Sampaio H, Mowat D, Roscioli T, Farrar M (2017).

2545: 2038: 2026: 1962: 1932: 1917: 1910: 1802: 1755: 1652: 1352: 1312: 1304: 940: 484: 453: 422: 320: 308: 7687: 5984:

He J, Mangelsdorf M, Fan D, Bartlett P, Brown MA (December 2015).

4757: 2401: 2373:

alternatively, ALS in the elderly might go undiagnosed because of

2033:

are the most commonly used oral drugs for treating spasticity; an

1512:

It is still not fully understood why neurons die in ALS, but this

587:, which go from the spinal cord to the muscles, highlighted teal. 10939:

Systemic atrophies primarily affecting the central nervous system

9730: 8436:. International Agency for Research on Cancer. pp. 408–409. 8293:"Rehabilitation in amyotrophic lateral sclerosis: why it matters" 6844:"The genetics of amyotrophic lateral sclerosis: current insights" 5682: 5311: 4615: 4079: 3102:"Lifetime Risk and Heritability of Amyotrophic Lateral Sclerosis" 2682:

This article incorporates text from this source, which is in the

2282: 1432:

Upon examination at autopsy, features of the disease that can be

1384: 1368: 1320: 1287: 832: 816: 721: 647:(PLS) involves degeneration of only the upper motor neurons, and 600: 9572: 7146:"Electrodiagnosis in persons with amyotrophic lateral sclerosis" 6941: 6792: 2211:

tube is placed through the wall of the abdomen into the stomach.

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