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Amyotrophic Lateral Sclerosis

ALS

Amyotrophic lateral sclerosis (ALS) is one of the most common forms of motor neuron diseases. It is also known as “Lou Gehrig's disease”, after a well-known baseball player in New York.

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Presentation

The hallmark of the disease is a mixed upper and lower motor neuropathy that is progressive over time. The upper motor signs include spasticity, hyperreflexia and weakness. The lower motor signs include amyotrophy, weakness and fasciculations. The diagnosis is suspected when there is insidious loss of function in more than one parts of the body. The lower motor neuron signs tend to appear first usually in the tongue and limbs. 80% of patients present with predominately limb symptoms with the rest presenting with bulbar symptoms.

The limb disease may present with altered gate such a foot drag while upper limb involvement usually begins with loss of dexterity and wasting of muscles over time. Eventually the function deteriorates and mobility reduces with spasticity and subsequent contractures.

Patients who present with bulbar symptoms usually present with speech abnormalities and dysphagia. Most patient will tend to preserve ocular movements and bladder control [9].

Dyspnea
  • As the disease progresses the patient has difficulty swallowing and talking, with dyspnea as the accessory muscles of respiration are affected. Eventually muscles atrophy and the patient becomes a functional quadriplegic.[medical-dictionary.thefreedictionary.com]
  • Individuals may develop problems with moving, swallowing (dysphagia), speaking or forming words (dysarthria), and breathing (dyspnea).[medicinenet.com]
Hoarseness
  • Damage to the medulla can cause: slurred speech hoarseness difficulty swallowing emotional lability, which is characterized by excessive emotional reactions such as laughing or crying a loss of tongue muscle contour, or tongue atrophy excess saliva difficulty[healthline.com]
  • Other symptoms include hoarseness, dysphagia, and slurred speech; because swallowing is difficult, salivation appears to increase, and patients tend to choke on liquids.[merckmanuals.com]
  • A person with bulbar weakness may become hoarse or tired after speaking at length, or speech may become slurred. In addition to weakness, the other cardinal signs of ALS are muscle wasting and persistent twitching (fasciculation).[encyclopedia.com]
  • Weakness of these muscle groups usually cause problems such as slurred speech, difficulty with conversation and hoarseness of the voice.[encyclopedia.com]
Weakness
  • Symptoms vary in severity and may include muscle weakness and atrophy, fasciculations, emotional lability, and respiratory muscle weakness.[merckmanuals.com]
  • A person with bulbar weakness may become hoarse or tired after speaking at length, or speech may become slurred. In addition to weakness, the other cardinal signs of ALS are muscle wasting and persistent twitching (fasciculation).[medical-dictionary.thefreedictionary.com]
  • Weakness in swallowing muscles may cause choking, and greater difficulty eating and managing saliva. Weakness in breathing muscles can cause respiratory insufficiency, especially when lying down.[mda.org]
  • Degeneration here can cause: limp muscles, or flaccid weakness muscle wasting twitching breathing problems caused by weakness in the diaphragm and other respiratory muscles Early signs of ALS may include problems performing everyday tasks.[healthline.com]
Fatigue
  • Physical effects The person may experience fatigue, poor balance, slurred words, a weak grip, tripping when walking or other minor symptoms. Sometimes this stage occurs before a diagnosis is made.[mda.org]
  • Typical Presentation: Gradual onset, progressive muscle failure weakness, fatigue, problems with swallowing, abnormal reflexes, cramping, fasciculations[athenadiagnostics.com]
  • Later on, other treatments may be need to help with feeding and breathing problems, fatigue, and sleeplessness. Wheelchairs, lifts, computer-based communication tools, tube feeding and breathing machines may be needed.[aapmr.org]
  • As symptoms spread throughout the body, weight loss, fatigue, exaggerated reflexes, and decreased coordination become common. Ultimately, patients cannot walk, stand, eat, or breathe without assistance.[neurodiscovery.harvard.edu]
  • Other early symptoms vary but can include tripping, dropping things, abnormal fatigue of the arms and/or legs, slurred speech, muscle cramps and twitches, and/or uncontrollable periods of laughing or crying.[alsa.org]
Weight Loss
  • Clinical presentations of this fatal disease include weakness, loss of ambulation, oropharyngeal dysfunction, weight loss, and ...[centerwatch.com]
  • Other symptoms include: Difficulty breathing Difficulty swallowing Muscle cramps and weakness Speech problems Voice changes Weight loss Diagnosis ALS is diagnosed through a combination of physical exams and medical tests, including blood tests, breathing[mercyhealth.com]
  • As symptoms spread throughout the body, weight loss, fatigue, exaggerated reflexes, and decreased coordination become common. Ultimately, patients cannot walk, stand, eat, or breathe without assistance.[neurodiscovery.harvard.edu]
  • Muscle decline and weight loss can be slowed with nutritional supplements called branched-chain amino acids (BCAAs). Phenytoin and carbamazepine may ease cramps. Medication can help control excess saliva production, one of the symptoms of ALS.[webmd.boots.com]
  • Symptoms of ALS include progressive muscle weakness beginning in the limbs, muscle twitching and cramping, slowed speech becoming progressively harder to understand, difficulty in breathing and swallowing; persistent fatigue, weight loss resulting from[brainfoundation.org.au]
Epilepsy
  • The most common manifestations are ataxia, vertigo (dizziness) and neuropathy, followed by epilepsy (seizures) , ALS and multiple sclerosis-like symptoms.[glutenfreesociety.org]
  • Gluten sensitivity induces a inflammatory reaction in the small intestine mucosa, but it can also cause neurologic manifestations, such as ataxia (impaired coordination, balance and speech), neuropathy, dizziness, epilepsy, and cortical calcifications[brainblogger.com]
  • Topamax is already FDA approved for the adjunctive treatment of partial epilepsy and therefore is available by prescription.[medicine.yale.edu]
  • […] following medical societies: American Academy of Neurology , American Academy of Sleep Medicine , American Association of Neuromuscular and Electrodiagnostic Medicine , American Clinical Neurophysiology Society , American College of Physicians , American Epilepsy[emedicine.medscape.com]
Nocturnal Leg Cramp
  • FDA bans quinine for nocturnal leg cramps. Drug Utilization Rev . 1995; Oct:150. 26. Moss AH, Casey P, Stocking CB, Roos RP, Brooks BR, Siegler M.[aafp.org]
Choking
  • Weakness in swallowing muscles may cause choking, and greater difficulty eating and managing saliva. Weakness in breathing muscles can cause respiratory insufficiency, especially when lying down.[mda.org]
  • Because choking is common as ALS progresses, patients may need a tube called a percutaneous endoscopic gastrostomy (PEG) tube or feeding tube to be placed into the stomach for feeding.[ucsfhealth.org]
  • The complications of ALS include: choking pneumonia malnutrition bed sores What Is the Long-Term Outlook for People with ALS? The typical life expectancy for a person with ALS is two to five years.[healthline.com]
  • The complications of ALS include: choking pneumonia malnutrition bed sores The typical life expectancy for a person with ALS is two to five years. Approximately 20 percent of patients live with ALS for over five years.[healthline.com]
  • To avoid choking or inhaling food and saliva into the lungs, a feeding tube might need to be placed into the stomach. People with difficulty breathing will eventually have to go on a respirator.[chealth.canoe.com]
Dysphagia
  • Patients usually present with facial weakness, dysphagia, and dysarthria.[merckmanuals.com]
  • Patients with bulbar onset ALS usually present with dysarthria and dysphagia for solids or liquids. Limb symptoms can develop almost simultaneously with bulbar symptoms, and in the vast majority of cases will occur within 1-2 years.[orpha.net]
  • Symptoms include progressive weakness, atrophy, fasciculation, dysphagia, and eventual paralysis of respiratory function.[patientslikeme.com]
  • Patients who present with bulbar symptoms usually present with speech abnormalities and dysphagia. Most patient will tend to preserve ocular movements and bladder control.[symptoma.com]
Gagging
  • Progressive bulbar palsy The muscles innervated by cranial nerves and corticobulbar tracts are predominantly affected, causing progressive difficulty with chewing, swallowing, and talking; nasal voice; reduced gag reflex; fasciculations and weak movement[merckmanuals.com]
  • Frequent tripping or falls Difficulty with fine hand motions such as buttoning, writing, turning a key in a lock Atrophy of hand muscles Atrophy of tongue Difficulty chewing food Difficulty swallowing ( dysphagia ) Difficulty speaking Oversensitive gag[emedicinehealth.com]
  • Symptoms of upper motor neuron involvement include tight and stiff muscles ( spasticity ) and exaggerated reflexes ( hyperreflexia ) including an overactive gag reflex.[en.m.wikipedia.org]
Drooling
  • […] hands Impaired speech Difficulty swallowing As the ALS progresses, symptoms may include: A weakening of other limbs, perhaps accompanied by twitching, muscle cramping, and exaggerated, faster reflexes Problems with chewing, swallowing, and breathing; drooling[webmd.boots.com]
  • Patients may notice increase in their saliva and drooling. Insomnia can occur because of difficulty turning in bed, anxiety and depression.[med.unc.edu]
  • ALS progression, lending support to anecdotal reports by some patients that cannabinoids may be efficacious in moderating the disease’s development and in alleviating certain ALS-related symptoms such as pain, appetite loss, spasticity, depression and drooling[norml.org]
  • Some PALS experience sialorrhea, drooling. Some PALS experience problems with thinking (which is referred to as cognitive impairment ), and/or changes in behavior.[caregiver.org]
  • There are medicines that can help with many of the symptoms you might have, such as muscle problems (stiffness, cramps , twitching), drooling and extra saliva , depression and mood swings, and pain.[webmd.com]
Fasciculation of the Tongue
  • Within a month, the patient had slurred speech, difficulty in swallowing liquids and fasciculations of the tongue.[aafp.org]
Tongue Atrophy
  • Damage to the medulla can cause: slurred speech hoarseness difficulty swallowing emotional lability, which is characterized by excessive emotional reactions such as laughing or crying a loss of tongue muscle contour, or tongue atrophy excess saliva difficulty[healthline.com]
Muscle Cramp
  • cramping urinary frequency or incontinence (late findings) sensory remains normal Physical exam neck ptosis (neck drop) due to neck extensor weakness manual muscle testing elicits muscle cramping upper motor neuron (UMN) signs spasticity hyperreflexia[orthobullets.com]
  • Other symptoms include: Difficulty breathing Difficulty swallowing Muscle cramps and weakness Speech problems Voice changes Weight loss Diagnosis ALS is diagnosed through a combination of physical exams and medical tests, including blood tests, breathing[mercyhealth.com]
  • Early signs of ALS Most people with ALS first feel muscle cramps, spasms or twitching ( fasciculations ) in one of their arms or legs. Other signs include weakness in the hands and feet or loss of balance.[alstdi.org]
  • Other early symptoms vary but can include tripping, dropping things, abnormal fatigue of the arms and/or legs, slurred speech, muscle cramps and twitches, and/or uncontrollable periods of laughing or crying.[alsa.org]
Muscular Atrophy
  • atrophy and related syndromes G12.0 Infantile spinal muscular atrophy, type I [Werdnig-Hoffman] G12.1 Other inherited spinal muscular atrophy G12.2 Motor neuron disease G12.21 Amyotrophic lateral sclerosis G12.22 Progressive bulbar palsy G12.23 Primary[icd10data.com]
  • Two rare subtypes of ALS are progressive muscular atrophy and progressive bulbar palsy. Progressive muscular atrophy is a variety of ALS in which the neuron degeneration is most pronounced in the spinal cord .[britannica.com]
  • Progressive muscular atrophy In many cases, especially those with childhood onset, inheritance is autosomal recessive. Other cases are sporadic. The disorder can develop at any age.[merckmanuals.com]
  • Amyotrophic Lateral Sclerosis (ALS), Progressive Muscular Atrophy (PMA), Progressive Bulbar Palsy (PBP) and Primary Lateral Sclerosis (PLS) are all subtypes of motor neurone disease.[alsmndalliance.org]
  • atrophy weakness clinical fasciculations clumsiness Evaluation Diagnosis dependent on demonstration of both UMN and LMN involvement combination of UMN and LMN in the same extremity, in the absence of pain or sensory symptoms, and cranial nerve findings[orthobullets.com]
Muscle Twitch
  • These persistent muscle twitches are generally not painful, but can be annoying or interfere with sleep. They are the result of the ongoing disruption of signals from the nerves to the muscles that occurs in ALS.[mda.org]
  • Symptoms of ALS include progressive muscle weakness beginning in the limbs, muscle twitching and cramping, slowed speech becoming progressively harder to understand, difficulty in breathing and swallowing; persistent fatigue, weight loss resulting from[brainfoundation.org.au]
  • Muscle twitching is almost always present. Serious complications arise when the disease affects the swallowing muscles which can lead to aspiration pneumonia or when it affects the respiratory muscles.[med.unc.edu]
  • ALS often begins with muscle twitching and weakness in a limb, or slurred speech. Eventually, ALS affects control of the muscles needed to move, speak, eat and breathe. There is no cure for ALS, and eventually the disease is fatal.[mayoclinic.org]
Muscle Spasticity
  • This is a progressive and fatal disease, with initial complaints about muscle spasticity followed by progressively worsening muscle weakness.[fusfoundation.org]
  • ALS symptoms The first symptoms usually include weakness or tight and stiff muscles (spasticity) in a particular area, said Dr. Jaydeep Bhatt, a neurologist NYU Langone Medical Center in New York City.[livescience.com]
  • (spasticity) Muscle cramps Muscle twitching visible under skin (fasciculations) There may be evidence for frontal lobe dysfunction in patients with ALS.[emedicinehealth.com]
  • Some of the early symptoms include: fasciculations (muscle twitches) in the arm, leg, shoulder, or tongue muscle cramps tight and stiff muscles ( spasticity ) muscle weakness affecting an arm, a leg, neck or diaphragm. slurred and nasal speech difficulty[medicinenet.com]
Emotional Lability
  • Emotional lability can occur in all ALS sufferers, even those without dementia. Inattention and slowed thinking are the most common cognitive symptoms of ALS. ALS-related dementia can also occur if there’s cell degeneration in the frontal lobe.[healthline.com]
  • Symptoms vary in severity and may include muscle weakness and atrophy, fasciculations, emotional lability, and respiratory muscle weakness.[msdmanuals.com]
  • Emotional lability can cause fluctuations in mood and emotional response. Treatment and prevention There is no cure for ALS, so treatment aims to alleviate symptoms, prevent unnecessary complications, and slow the rate of disease progression.[medicalnewstoday.com]
Slurred Speech
  • ALS often begins with muscle twitching and weakness in a limb, or slurred speech. Eventually, ALS affects control of the muscles needed to move, speak, eat and breathe. There is no cure for ALS, and eventually the disease is fatal.[mayoclinic.org]
  • Other early symptoms vary but can include tripping, dropping things, abnormal fatigue of the arms and/or legs, slurred speech, muscle cramps and twitches, and/or uncontrollable periods of laughing or crying.[alsa.org]
  • Damage to the medulla can cause: slurred speech hoarseness difficulty swallowing emotional lability, which is characterized by excessive emotional reactions such as laughing or crying a loss of tongue muscle contour, or tongue atrophy excess saliva difficulty[healthline.com]
Dysarthria
  • Patients with bulbar onset ALS usually present with dysarthria and dysphagia for solids or liquids. Limb symptoms can develop almost simultaneously with bulbar symptoms, and in the vast majority of cases will occur within 1-2 years.[orpha.net]
  • […] incontinence (late findings) sensory remains normal Physical exam neck ptosis (neck drop) due to neck extensor weakness manual muscle testing elicits muscle cramping upper motor neuron (UMN) signs spasticity hyperreflexia ( ) Hoffman's ( ) Babinski's spastic dysarthria[orthobullets.com]
  • Clinical manifestations include progressive weakness, atrophy, fasciculation, hyperreflexia, dysarthria, dysphagia, and eventual paralysis of respiratory function.[icd10data.com]
  • Patients usually present with facial weakness, dysphagia, and dysarthria.[merckmanuals.com]
  • Difficulty with fine hand motions such as buttoning, writing, turning a key in a lock Atrophy of hand muscles Atrophy of tongue Difficulty chewing food Difficulty swallowing ( dysphagia ) Difficulty speaking Oversensitive gag reflex Difficulty forming words (dysarthria[emedicinehealth.com]
Hyperreflexia
  • […] difficulty muscle cramping urinary frequency or incontinence (late findings) sensory remains normal Physical exam neck ptosis (neck drop) due to neck extensor weakness manual muscle testing elicits muscle cramping upper motor neuron (UMN) signs spasticity hyperreflexia[orthobullets.com]
  • The upper motor signs include spasticity, hyperreflexia and weakness. The lower motor signs include amyotrophy, weakness and fasciculations. The diagnosis is suspected when there is insidious loss of function in more than one parts of the body.[symptoma.com]
  • The diagnostic process consists of a history and physical examination, repeated at regular intervals, to document progressive hyperreflexia, fasciculations, and upper and lower motor neuron involvement.[aafp.org]
  • Clinical manifestations include progressive weakness, atrophy, fasciculation, hyperreflexia, dysarthria, dysphagia, and eventual paralysis of respiratory function.[icd10data.com]
Abnormal Reflex
  • Typical Presentation: Gradual onset, progressive muscle failure weakness, fatigue, problems with swallowing, abnormal reflexes, cramping, fasciculations[athenadiagnostics.com]
  • Signs of the former include muscle tightness or stiffness and abnormal reflexes; signs of the latter include muscle weakness, cramps, twitches and atrophy. [ Related: Nervous System: Facts, Functions & Diseases ] Eventually, individuals with ALS lose[livescience.com]
  • Involvement of the upper motor neurons causes spasms and increased tone in the limbs, and abnormal reflexes. Involvement of the lower motor neurons causes muscle wasting and twitching (fasciculations).[encyclopedia.com]
Ataxia
  • Gluten-associated ataxia had already been linked to the presence of serum transglutaminase 6 antibodies; these had been reported to be present in 62% of patients with gluten ataxia.[brainblogger.com]
  • G11.3 Cerebellar ataxia with defective DNA repair G11.4 Hereditary spastic paraplegia G11.8 Other hereditary ataxias G11.9 Hereditary ataxia, unspecified G12 Spinal muscular atrophy and related syndromes G12.0 Infantile spinal muscular atrophy, type[icd10data.com]
  • The most common manifestations are ataxia, vertigo (dizziness) and neuropathy, followed by epilepsy (seizures) , ALS and multiple sclerosis-like symptoms.[glutenfreesociety.org]
  • MDA addresses the muscular dystrophies, spinal muscular atrophy, ALS, Charcot-Marie-Tooth disease, myasthenia gravis, Friedreich's ataxia, metabolic diseases of muscle, and inflammatory diseases of muscle, for a total of more than 40 neuromuscular diseases[patients.aan.com]
  • Examples: HIV, syphilis, myelitis, poliomyelitis, Lyme disease Endocrine disorders Examples: hyperthyroidism, hyperparathyroidism, diabetic radiculopathy Toxins Examples: lead, mercury Other Examples: postpolio syndrome, Huntington's disease, Friedreich's ataxia[aafp.org]

Workup

Due to it slow progression it may take a neurologist a few months to come to a diagnosis, unless there is a strong family history of the illness. Needle electromyography and nerve conduction studies and will aid in diagnosis and exclude any other conditions that may mimic the disease. Genetic testing is only performed if there is a suspicion that there may be a genetic or familial cause. If there is uncertainty a muscle biopsy may have to be done to exclude other courses.

Treatment

The treatment for this condition is totally supportive and includes, speech, physical and occupational therapy. It is very important that the patient and relatives are educated well on the condition and prognosis. There are also a number of support groups that help families and suffers deal with the condition. The only drug available currently is riluzole that has been shown to delay the time to tracheostomy by about 2 months [10].

Prognosis

As mentioned before, amyotrophic lateral sclerosis is a fatal disease with the median time to death from diagnosis being 3 years. The patients who survive long tend to get the disease at a younger age, with primary limb involvement. Most individuals succumb to secondary infections such a pneumonia [8].

Etiology

The underlying etiology is unknown. Most cases are sporadic with approximately 10% of the cases being familial or genetic. The genes in familial causes are numerous and no single gene has been identified that can explain the pathology. Many of the genes identified have been associated with other neurological diseases such as dementia and Alzheimer disease. In the families which have identified genes the mode of transmission is usually autosomal dominant. There is no clinical difference between the familial variant compared to the sporadic cases.

The only establish risk factor that has been identified is smoking. Studies have shown that smokers are at twice the risk of suffering from this disease as compared to non-smokers [2] [3].

Epidemiology

The annual incidence is approximately 2 per 100,000 population. Finland has the highest incidence in the world with rates almost twice that of other countries. It tends to affect whites more than other races and is higher in men as compared to women.
Amyotrophic lateral sclerosis may occur between teenager years to as high as the 80s. There is increasing risk with age [4] [5] [6].

Sex distribution
Age distribution

Pathophysiology

The pathophysiology of amyotrophic lateral sclerosis is unknown, but a number of theories exist. The disease is named after the pathology is causes - amyotrophy - muscular atrophy, and lateral sclerosis refers to the changes seen in the lateral tracts.

It is thought that there are multiple mechanisms involved, few which have been noted include derangements in free radical scavenging, and derangements in cellular cytoskeletons. The most upcoming theory that has a lot of research focused on it is the theory that aggregation in mRNA processing may be a significant contributor, leading to neuronal dysfunction and death [7].

Prevention

The only risk factor identified is smoking so cessation or avoidance would assume to be beneficial. Suspected family cases should have testing and counselling when appropriate.

Summary

Amyotrophic lateral sclerosis (ALS) is overall a fatal disease with no active treatments. With good support, suffers may lead meaningful, but restricted lives. It is one of many motor neuron diseases, but what makes it stand out is that it presents with both upper and lower motor neuron signs [1].

Patient Information

  • Definition: Amyotrophic lateral sclerosis (ALS) is a disease that affects the nerves that control muscle movement. This causes the muscles to weaken and become shrunken. This makes it difficult for the person to do daily activates and eventually they may be unable to walk, talk or eat as the disease progresses. 
  • Cause: The cause of this disease is unknown, but there are some families that are known to pass it down generations. In these families a few genes have been affected. Most of the cases have no family links. There has been some information that smoking may contribute to its onset.
  • Symptoms: The will be weakness of the affected region of the body, with either rigid limbs or floppy limbs. Speech and swallowing may be the first to be affected in some individuals. 
  • Diagnosis: Most of the diagnosis is made by history and examination, with few tests being done to see if the nerves are functioning well.
  • Treatment: Treatment is very limited with only one drug available called riluzole that slows down the disease, briefly. Most of the other treatment is supportive to help the patient not to get stiffness in the joints and bedsores. They may require speech therapy and devices to aid in movement such as wheel chairs. As speech is also affected communication devices may be required to aid. They may also require breathing support and feeding tubes. 
  • Overall the disease has a poor outcome and family support is very important. There are groups that aid the families psychologically, helping them understand and process all the information.

References

Article

  1. Mitsumoto H, Chad DA, Pioro EP. Amyotrophic lateral sclerosis. In: Contemporary Neurology Series, 49, F.A. Davis Company, Philadelphia 1998.
  2. l-Chalabi A, Lewis CM. Modelling the effects of penetrance and family size on rates of sporadic and familial disease. Hum Hered. 2011;71(4):281-8. 
  3. Hanby MF, Scott KM, Scotton W, Wijesekera L, Mole T, Ellis CE, et al. The risk to relatives of patients with sporadic amyotrophic lateral sclerosis. Brain. Dec 2011;134:3454-7. 
  4. Chiò A, Mora G, Calvo A, Mazzini L, Bottacchi E, Mutani R. Epidemiology of ALS in Italy: a 10-year prospective population-based study. Neurology. Feb 24 2009;72(8):725-31. 
  5. Alonso A, Logroscino G, Jick SS, Hernán MA. Incidence and lifetime risk of motor neuron disease in the United Kingdom: a population-based study. Eur J Neurol. Jun 2009;16(6):745-51.
  6. Johnston CA, Stanton BR, Turner MR, Gray R, Blunt AH, Butt D, et al. Amyotrophic lateral sclerosis in an urban setting: a population based study of inner city London. J Neurol. Dec 2006;253(12):1642-3.
  7. Barber SC, Shaw PJ. Oxidative stress in ALS: key role in motor neuron injury and therapeutic target. Free Radic Biol Med. Mar 1 2010;48(5):629-41
  8. Visser J, van den Berg-Vos RM, Franssen H, et al. Disease course and prognostic factors of progressive muscular atrophy. Arch Neurol 2007; 64:522.
  9. Hirano A. Neuropathology of ALS: an overview. Neurology 1996; 47:S63.
  10. Miller RG, Jackson CE, Kasarskis EJ et al. Practice Parameter update: The care of the patient with amyotrophic lateral sclerosis: Drug, nutritional, and respiratory therapies (an evidence-based review). Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2009;73:1218-1226

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