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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].

Weakness
  • Here, we report a patient who presented with progressive left arm weakness and was found to have bilateral MRI plexus abnormalities.[ncbi.nlm.nih.gov]
  • An 82-year-old woman developed neck weakness and dysarthria with antibodies against acetylcholine receptor (AChR) and low-density lipoprotein receptor-related protein 4 (LRP4).[ncbi.nlm.nih.gov]
  • Patient 1: A 58-year-old Japanese man developed progressive weakness and subsequent myasthenic symptoms including oculomotor disturbance.[ncbi.nlm.nih.gov]
  • The false-positive diagnoses were related to: early age, clinical presentation of symmetry, weakness greater than atrophy, symptomatic exacerbation.[ncbi.nlm.nih.gov]
  • Flail arm (FA) syndrome, a minor subtype of amyotrophic lateral sclerosis (ALS), is characterized by progressive weakness and upper girdle wasting, but the associated pathological changes remain unclear.[ncbi.nlm.nih.gov]
Fatigue
  • All studies assessed fatigue using the Fatigue Severity Scale (FSS; scale from 9 to 63, higher scores indicate more fatigue).[ncbi.nlm.nih.gov]
  • Individual muscle strength, fatigue and spasticity must all be taken into account when discussing exercise with persons with ALS. It can be concluded that physical and occupational therapy intervention is beneficial to persons with ALS.[ncbi.nlm.nih.gov]
  • The emotional burden for health-care professionals caring for people with terminal neurological disease should be recognised, with structures and procedures developed to address compassion, fatigue, and the moral and ethical challenges related to providing[ncbi.nlm.nih.gov]
  • Fatigue and weakness of the respiratory muscles eventually induce respiratory insufficiency, which is one of the main causes of death in patients with ALS. In ALS patients with respiratory insufficiency, application of a ventilator is indispensable.[ncbi.nlm.nih.gov]
  • Typical Presentation: Gradual onset, progressive muscle failure weakness, fatigue, problems with swallowing, abnormal reflexes, cramping, fasciculations[athenadiagnostics.com]
Weight Loss
  • ALS with respiratory onset has some common clinical features: male predominance, frequent camptocormia or dropped head, frequent widespread fasciculations, limb mobility fairly well preserved and significant weight loss in the early stages.[ncbi.nlm.nih.gov]
  • Enteral feeding (tube feeding) is offered to many people with amyotrophic lateral sclerosis/motor neuron disease experiencing difficulty swallowing (dysphagia) and maintaining adequate nutritional intake leading to weight loss.[ncbi.nlm.nih.gov]
  • Complications of ALS include: Breathing in food or fluid ( aspiration ) Loss of ability to care for self Lung failure Pneumonia Pressure sores Weight loss Call your provider if: You have symptoms of ALS, particularly if you have a family history of the[nlm.nih.gov]
Epilepsy
  • The most common manifestations are ataxia, vertigo (dizziness) and neuropathy, followed by epilepsy (seizures), ALS and multiple sclerosis-like symptoms.[glutenfreesociety.org]
  • […] treatment of diseases of the nervous system. 2016 PROSE Award winner of the Best Textbook Award in Biological & Life Sciences Provides a focused tutorial introduction to the core diseases of the nervous system Includes comprehensive introductions to Stroke, Epilepsy[books.google.com]
  • 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]
Hoarseness
  • […] climbing stairs, and walking Difficulty breathing Difficulty swallowing -- choking easily, drooling, or gagging Head drop due to weakness of the neck muscles Speech problems, such as a slow or abnormal speech pattern (slurring of words) Voice changes, hoarseness[nlm.nih.gov]
  • 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]
Dyspnea
  • CASE PRESENTATION: A 65-year-old Caucasian man with advanced amyotrophic lateral sclerosis presented with progressive dyspnea and palpitations.[ncbi.nlm.nih.gov]
  • We report a 65-year-old man who presented with a progressive exertional dyspnea. He was subsequently found to have a diaphragmatic paralysis that was felt to be secondary to spinal cord stenosis.[ncbi.nlm.nih.gov]
  • We have now validated a revised version of the ALSFRS, which incorporates additional assessments of dyspnea, orthopnea, and the need for ventilatory support.[ncbi.nlm.nih.gov]
Dry Cough
  • If patients report dry cough, this should prompt further diagnostic steps.[dx.doi.org]
Stridor
  • This case demonstrates that this occurs because amyotrophic lateral sclerosis patients' upper motor neuron reflex laryngeal closure and stridor cause upper airway collapse that renders mechanical insufflation-exsufflation (MIE) ineffective in expulsing[ncbi.nlm.nih.gov]
Dysphagia
  • BACKGROUND: Dysphagia is a critical symptom of Neuromuscular Diseases and is often associated with considerable morbidity and mortality.[ncbi.nlm.nih.gov]
  • Not all participants presented correlation between severity of dysphagia and SWAL-QOL level of impairment, with impact on the quality of life observed even in cases of mild dysphagia severity.[ncbi.nlm.nih.gov]
  • The patients exhibited dropped head syndrome or dysphagia as initial symptoms. Although their clinical findings were compatible with the revised El Escorial Criteria for ALS, their progression appeared to be more rapid than that of ALS.[ncbi.nlm.nih.gov]
  • We report the case of a 61-year-old man who presented with progressively worsening limb weakness and dysphagia. His examination showed mixed upper and lower motor neuron signs without sensory impairment.[ncbi.nlm.nih.gov]
  • It is a lethal and progressive neurodegenerative disease, principally affecting motor neurons; patient clinical characteristics are muscle weakness, dysphagia and respiratory failure.[ncbi.nlm.nih.gov]
Choking
  • In addition, the symptoms of choking on liquids are improved, and the utility of 30 mL water swallow test was improved with grade 2. The symptoms of muscle fibrillations of limbs are also reduced. However, muscle strength worsened slowly.[ncbi.nlm.nih.gov]
  • Choking - lorazepam sublingually can quickly relieve choking episodes. Dyspnoea - if severe and prolonged, is an indication for subcutaneous morphine. Complications Respiratory failure and death. Pneumonia due to infection or aspiration.[patient.info]
  • At the same time, problems with choking and swallowing make it hard to eat enough. To help with feeding, a tube may be placed into the stomach. A dietitian who specializes in ALS can give advice on healthy eating.[nlm.nih.gov]
Gagging
  • Muscle weakness starts in one body part, such as the arm or hand, and slowly gets worse until it leads to the following: Difficulty lifting, climbing stairs, and walking Difficulty breathing Difficulty swallowing -- choking easily, drooling, or gagging[nlm.nih.gov]
  • One year after onset, there were fasciculations in the 4 limbs, a left extensor plantar response, and an exaggerated gag reflex. There was amyotrophy of the intrinsic muscles in both hands.[dx.doi.org]
  • Symptoms of upper motor neuron involvement include spasticity and exaggerated reflexes ( hyperreflexia ) including an overactive gag reflex.[web.archive.org]
Drooling
  • Patients may notice increase in their saliva and drooling. Insomnia can occur because of difficulty turning in bed, anxiety and depression.[med.unc.edu]
  • The disease can also affect the muscles of the face, leading to problems such as incomplete eye closure and drooling.[mda.org]
  • Muscle weakness starts in one body part, such as the arm or hand, and slowly gets worse until it leads to the following: Difficulty lifting, climbing stairs, and walking Difficulty breathing Difficulty swallowing -- choking easily, drooling, or gagging[nlm.nih.gov]
  • Other symptoms are difficulty eating, drooling, dysarthria, dysphonia, choking events with meals, nasal regurgitation of fluids or pulmonary aspiration. Respiratory onset can present with: Dyspnoea and orthopnoea.[patient.info]
Fasciculation of the Tongue
  • In July 1995, she had amyotrophy and fasciculations of the tongue together with an exaggeration of the gag reflex. She had weakness of the cervical spine muscles and fasciculations of the upper limbs.[dx.doi.org]
  • Wasting and fasciculation of the tongue. Dysphagia (usually a late feature with significant speech difficulties). Accompanying emotional lability (inappropriate laughing or crying) - as with pseudobulbar palsies.[patient.info]
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]
Muscular Atrophy
  • Excluding lower motor neuron FA and FL cases, progressive muscular atrophy comprised 4% of the sample and had a prognosis similar to typical limb onset ALS.[ncbi.nlm.nih.gov]
  • The patients were a 54-year-old man with progressive muscular atrophy who underwent removal of internal fixators in the arm and leg, and a 66-year-old woman with amyotrophic lateral sclerosis who underwent skin grafting in the left lower leg.[ncbi.nlm.nih.gov]
  • There is no curative treatment for the common motor neuron diseases, amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy. Nevertheless, there is an increasing volume of published studies.[ncbi.nlm.nih.gov]
  • She presented with muscular atrophy and increased tendon reflexes of the extremities as well as bulbar palsy, from which motor neuron disease was suspected.[ncbi.nlm.nih.gov]
  • 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]
Muscle Cramp
  • There is no evidence to support the use of any intervention for muscle cramps in ALS/MND. More and larger randomised controlled trials evaluating treatments for muscle cramps in ALS/MND are needed.[ncbi.nlm.nih.gov]
  • Evidence regarding secondary symptoms like spasticity, muscle cramps or sialorrhea remains generally scarce, but some new insights will also be discussed. Growing evidence suggests that multidisciplinary care in specialized clinics improves survival.[ncbi.nlm.nih.gov]
  • 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]
  • cramps and twitching in your arms, shoulders and tongue Eventually, ALS weakens muscles, including muscles used for breathing, until they become paralyzed.[disabled-world.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]
Muscle Twitch
  • twitching for 3 years.[ncbi.nlm.nih.gov]
  • 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]
  • Clinical Signs, Symptoms, and Diagnostics Symptoms and signs associated with these pathological changes include: Muscle fasciculation, more commonly known as muscle twitches Difficulty walking, moving your arms, speaking, and swallowing And, eventually[study.com]
  • 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]
  • Muscle twitches and cramps are common; they occur because degenerating axons (long fibers extending from nerve-cell bodies) become “irritable.” Symptoms may be limited to a single body region, or mild symptoms may affect more than one region.[web.archive.org]
Muscle Spasticity
  • This is a progressive and fatal disease, with initial complaints about muscle spasticity followed by progressively worsening muscle weakness.[fusfoundation.org]
  • The small muscles of the hands and feet are usually first affected, but muscle spasticity is absent. Primary lateral sclerosis - this is another rare type of MND. It mainly causes weakness in the leg muscles.[patient.info]
  • The earliest symptoms may include fasciculations, cramps, tight and stiff muscles ( spasticity ), muscle weakness affecting an arm or a leg, slurred and nasal speech, or difficulty chewing or swallowing.[web.archive.org]
Neck Weakness
  • An 82-year-old woman developed neck weakness and dysarthria with antibodies against acetylcholine receptor (AChR) and low-density lipoprotein receptor-related protein 4 (LRP4).[ncbi.nlm.nih.gov]
  • Evaluating a novel cervical orthosis, the Sheffield Support Snood, in patients with amyotrophic lateral sclerosis/motor neuron disease with neck weakness. Amyotroph. Lateral Scler. Frontotemporal Degener. 17, 436–442 (2016). 57.[doi.org]
Emotional Lability
  • Control of symptoms such as sialorrhoea, thick mucus, emotional lability, cramps, spasticity and pain should be attempted.[ncbi.nlm.nih.gov]
  • Symptoms vary in severity and may include muscle weakness and atrophy, fasciculations, emotional lability, and respiratory muscle weakness.[msdmanuals.com]
  • 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]
  • 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]
Dysarthria
  • An 82-year-old woman developed neck weakness and dysarthria with antibodies against acetylcholine receptor (AChR) and low-density lipoprotein receptor-related protein 4 (LRP4).[ncbi.nlm.nih.gov]
  • Two possible disease-modifying therapies that can slow disease progression are available for ALS, but patient management is largely mediated by symptomatic therapies, such as the use of muscle relaxants for spasticity and speech therapy for dysarthria[ncbi.nlm.nih.gov]
  • We report a 68-year-old man with moderate dysarthria, fasciculations, short neck, hearing deficit, and low posterior hairline. Definite ALS was diagnosed based on neurological abnormalities and electromyography results.[ncbi.nlm.nih.gov]
  • We examined a 66-year-old Japanese woman manifesting gait disturbance and spastic dysarthria for 6years with positive family history.[ncbi.nlm.nih.gov]
  • Neurological examination disclosed spastic dysarthria, atrophic tongue with fasciculations, brisk jaw and limb tendon reflexes, and bilateral Hoffman sign. Electrophysiological assessment confirmed ALS.[ncbi.nlm.nih.gov]
Ataxia
  • Blood from ND patients with PD, ALS and Ataxia with movement dysfunctions were obtained to analyse mRNA and protein expressions of the above mentioned factors in lymphocytes.[ncbi.nlm.nih.gov]
  • We herein describe the case of a woman with amyotrophic lateral sclerosis (ALS) showing errors in her choice of Japanese kana characters in her mobile text messages and agraphia of the kana in her handwriting in spite of the absence of weakness, ataxia[ncbi.nlm.nih.gov]
  • A 75-year-old female patient presented with cerebellar ataxia, bulbar palsy and cognitive impairment. In the later course of disease signs for affection of the second motor neuron evolved and she was diagnosed with ALS.[ncbi.nlm.nih.gov]
  • 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]
  • KEYWORDS: ATXN2; Amyotrophic lateral sclerosis; CAG repeat expansion; Spinocerebellar ataxia type 2[ncbi.nlm.nih.gov]
Slurred Speech
  • speech, stumbling, and muscle twitching for 3 years.[ncbi.nlm.nih.gov]
  • The earliest symptoms of Lou Gehrig's Disease may include: Tripping and falling Hand weakness or clumsiness Weakness in your leg, feet or ankles Slurred speech or trouble swallowing Difficulty walking or doing your normal daily activities Difficulty holding[disabled-world.com]
  • 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]
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]
  • […] lateral sclerosis (ALS), also known as Charcot's disease and Lou Gehrig's disease, is a disease of unknown cause characterized by slowly progressive degeneration of upper motor neurons (UMNs) and lower motor neurons (LMNs). [1] The UMN findings include hyperreflexia[emedicine.com]
  • Symptoms of upper motor neuron involvement include spasticity and exaggerated reflexes ( hyperreflexia ) including an overactive gag reflex.[web.archive.org]
  • Clinical manifestations include progressive weakness, atrophy, fasciculation, hyperreflexia, dysarthria, dysphagia, and eventual paralysis of respiratory function.[icd10data.com]
Foot Drop
  • This usually begins on one side of the body and can cause loss of hand dexterity, shoulder function, a foot-drop or walking difficulty. In about 25% of cases the onset in “Bulbar” with difficulty articulating and swallowing.[alsbc.ca]
  • The patient may develop foot drop resulting in a fall or sprain. Fasciculations may present early on in the disease, particularly in the tongue.[emedicine.com]
  • Clinical examination revealed right foot drop, distal amyotrophy of the right lower limb, and fasciculations in the 4 limbs. Deep tendon reflexes were brisk with a left extensor plantar response.[dx.doi.org]
  • Common early symptoms are: a weakened grip, which can cause difficulty picking up or holding objects weakness at the shoulder that makes lifting the arm difficult a "foot drop" caused by weak ankle muscles dragging of the leg slurred speech ( dysarthria[web.archive.org]
  • Common early symptoms include: a weakened grip, which can cause difficulty picking up or holding objects weakness at the shoulder that makes lifting the arm difficult a "foot drop" caused by weak ankle muscles dragging of the leg slurred speech ( dysarthria[web.archive.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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Last updated: 2018-06-21 19:36