Amyotrophic lateral sclerosis
Progressive motor neuron disease: upper and lower motor neuron signs, diagnostic criteria, riluzole, edaravone, respiratory and nutritional care, genetics.
- Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease of the voluntary motor system: both the upper motor neurons and the lower motor neurons are lost. [5]
- Weakness begins in a single body region, then spreads. Sensation is spared. [5]
- The diagnosis is clinical: it rests on finding upper and lower motor neuron signs in a progressive motor syndrome and excluding diseases that mimic it. Diagnostic criteria (Gold Coast, El Escorial) support, but do not replace, this judgment. [6]
- One approved disease-modifying drug, riluzole, has a modest benefit. Edaravone is approved in some regions but is not recommended routinely by the EAN guideline. Tofersen is offered as first-line treatment in SOD1-related ALS. [4] [5] [7]
- The foundations of care are multidisciplinary: riluzole, PEG or equivalent feeding when swallowing falters, non-invasive ventilation when breathing falters, symptom control, rehabilitation and advance care planning. [1] [2] [4]
By the end of this page you should be able to:
- Define ALS and explain the upper motor neuron and lower motor neuron distinction. [5]
- Recognise the common clinical patterns and elicit the key examination signs. [5]
- Outline diagnostic criteria and choose appropriate investigations. [6]
- Apply management principles, including riluzole, edaravone and respiratory and nutritional support. [4]
- Compare ALS with its principal mimics. [5]
- Discuss prognosis, genetics and family implications. [5]
DefinitionAmyotrophic lateral sclerosis
A progressive motor neuron disease in which upper motor neurons (the cortical cells and fibres of the corticospinal and corticobulbar tracts) and lower motor neurons (the anterior horn cells of the spinal cord and the motor nuclei of the cranial nerves) both degenerate. Voluntary muscle control is lost, but sensation is spared and cognitive change is not universal. [5]
ALS is not one uniform disease. Slightly differing motor and cognitive pictures are recognised:
- Classic ALS shows combined upper and lower motor neuron loss in one or more regions. [5]
- Bulbar ALS begins with dysarthria, dysphagia and dysphonia and has a median survival of about 2 years from onset. [5] [4]
- Progressive muscular atrophy has isolated lower motor neuron signs and may develop upper motor neuron signs during follow-up in up to 30% of patients. [5]
- Primary lateral sclerosis has isolated upper motor neuron signs and a median survival of more than 20 years; up to 3-5% of motor neuron disease is of this type. [5]
- Upper motor neuron predominant and flail arm or leg variants often spread more slowly than classic disease. [5]
- ALS with frontotemporal dementia affects about 10-15% of patients, and milder behavioural or cognitive change affects a further 35-40%. [5] [4]
The term motor neuron disease spectrum (or ALS and related motor neuron diseases) captures this range. [5]
ALS is uncommon but not rare. In Europe the incidence is estimated at 1.75-3 new cases per 100,000 people each year and the prevalence at 10-12 per 100,000. [5] In the age group at highest risk (45 to 75 years) the incidence is 4-8 per 100,000 each year. [5]
- Age. Symptoms usually begin between 58 and 63 years in sporadic ALS and 40-60 years in familial ALS. [5]
- Sex. Men have a higher risk than women; the estimated lifetime risk is about 1 in 350 in men and 1 in 400 in women. [5]
- Survival. Median survival is about 3 years from symptom onset, and deaths are mostly from respiratory failure. In bulbar disease the median survival is about 2 years. [5]
- Cognitive disease. About 10-15% meet criteria for frontotemporal dementia and 35-40% have milder behavioural or cognitive change. [5]
About 10% of ALS has an autosomal dominant familial pattern and 90% occurs without a family history (sporadic ALS). [5] More than 20 genes have been associated. The five commonest are expansions in C9orf72 and mutations in SOD1, TARDBP, FUS and TBK1, together explaining about 15% of all patients. [5] C9orf72 expansions account for 30-50% of familial and 7% of sporadic disease. [5] The common neuropathological signature is cytoplasmic TDP-43 aggregation, found in more than 95% of cases. [5] [4]
No modifiable risk factor is established beyond increasing age, male sex and a family history. [5] Regional differences in incidence are well documented and exposures are being studied, but no exposure is yet confirmed as causal in a way that supports firm advice. [5]
ALS is a heterogeneous syndrome at the molecular level. Implicated pathways include failure of proteostasis, excitotoxicity, neuroinflammation, mitochondrial dysfunction and oxidative stress, cytoskeletal disturbance and axonal transport defects, and disturbed RNA metabolism and DNA repair. [5] The clustering of ALS genes into pathways of protein quality control, RNA metabolism and axonal transport helps explain why very different mutations produce a similar clinical picture. [5]
The visible result is combined upper and lower motor neuron degeneration. Anterior horn cells and cranial motor nuclei die, so muscles lose their lower motor innervation and waste; at the same time loss of cortical and corticospinal input removes inhibitory control, so reflexes remain brisk despite weakness. [5]
Clinical pearlCore contrast
Lower motor neuron loss gives weakness, wasting, fasciculation and reduced tone. Upper motor neuron loss gives spasticity, hyperreflexia and slowed or spastic movement. In classic ALS both are present, and it is precisely this combination that separates ALS from its mimics. [5]
Weakness usually begins focally. Common stories include "my hand no longer grips", "I limp on one leg", "I trip more often", or "my speech sounds thick". Bulbar onset occurs in 25-30% and presents with slurred speech, difficulty swallowing, a weak or breathy voice, or drooling. [5] As the disease progresses most patients develop both speech and swallowing difficulty, even when it did not start that way. [5]
Pain is not a defining feature, but cramps, stiffness, fasciculations and fatigue are common. Patients may also notice breathlessness on exertion, disturbed sleep or morning headache, because breathing weakens. [1] [5] About half of patients have some extra-motor behavioural or cognitive change; a minority present with frontotemporal dementia. [5] [4]
On examination ALS shows a combination of:
- Lower motor neuron signs: weakness, wasting, fasciculations and reduced tone. [5]
- Upper motor neuron signs: hyperreflexia (or preserved reflexes in a wasted muscle), spastic tone (especially flexors of the upper limbs and extensors of the lower limbs), slowness of movements such as tongue movement, and extensor plantar responses. [5]
In bulbar ALS the tongue may be wasted and fasciculating with flaccid dysarthria and dysphagia; pseudobulbar palsy, in contrast, shows a stiff, expressionless face, spastic dysarthria without tongue wasting, and an exaggerated jaw jerk. [5] Eye movements and sensation are spared; sphincter control is usually preserved until late.
A short vignette captures the pattern: a middle-aged man notices tripping and a weaker right grip over six months. He has cramps in the calves, fasciculation of the thigh, and on examination wasted intrinsic hand muscles with brisk reflexes and small but definite jaw weakness, intact sensation and brisk jaw jerk.
ALS mimics are estimated to account for about 7-8% of suspected cases, so this step matters. [5]
| Condition | Clue that separates it from ALS |
|---|---|
| Primary lateral sclerosis | Upper motor neuron signs only; no wasting or fasciculation; no denervation on electromyography for 4 years from onset; median survival over 20 years. [5] |
| Progressive muscular atrophy | Lower motor neuron signs only at presentation; up to 30% develop upper motor neuron signs later. [5] |
| Multifocal motor neuropathy with conduction block | Focal, asymmetric lower motor neuron weakness without wasting early; conduction block on nerve conduction studies; responds to immunoglobulin. [5] |
| Chronic inflammatory demyelinating polyneuropathy | Sensory involvement, demyelinating features; treatable. [5] |
| Hereditary spastic paraplegia | Slowly progressive symmetric spastic paraparesis; family history. [5] |
| Cervical radiculomyelopathy / spondylosis | Neck pain and sensory symptoms; cervical cord signal change on MRI. [5] |
| Inclusion body myositis | Slow, painless asymmetric weakness, often finger flexors and quadriceps; diagnostic muscle biopsy. [5] |
| Kennedy disease (bulbospinal muscular atrophy) | Bulbar, facial and proximal weakness with tremor in men; androgen metabolism. [5] |
| Myasthenia gravis / MuSK myasthenia | Fluctuating fatigable weakness; MuSK disease may give tongue wasting and be mistaken for bulbar ALS. [5] |
| Spinal muscular atrophy | Childhood or young adult onset, pronounced proximal weakness. [5] |
| Monomelic amyotrophy (Hirayama disease) | Focal, self-limited hand atrophy in young men; not progressive beyond one limb. [5] |
The diagnosis rests on history, examination, electrodiagnostic testing and neuroimaging. [5] Electromyography is the most useful confirmatory test for lower motor neuron involvement, showing fibrillation potentials, positive sharp waves and fasciculation potentials in relaxed muscles with chronic neurogenic change on contraction. [5] Nerve conduction studies exclude neuropathy and conduction block. MRI of the brain and spinal cord excludes structural lesions. [5] FDG-PET, if available, may show a hypometabolic pattern in the perirolandic and frontotemporal regions. [5] Creatine kinase is often mildly raised; serum chloride and bicarbonate may reflect chronic hypoventilation.
Genetic testing of C9orf72, SOD1, TARDBP, FUS and TBK1 is routinely offered where there is a family history and increasingly offered to sporadic cases. [5] It should only be undertaken when genetic counselling is available. [5] Biomarkers such as neurofilament in cerebrospinal fluid support the diagnosis. [5]
A teaching Table of the more objective thresholds follows.
| Test | Role | Cut-off or interval that matters |
|---|---|---|
| Nerve conduction studies and needle EMG | Confirm lower motor neuron dysfunction; exclude neuropathy. [5] | Denervation in clinically affected and non-affected regions. [5] |
| MRI brain and spine | Exclude lesions. [5] | Normal in ALS. [5] |
| Pulse oximetry (rest, room air) | Detect respiratory impairment. [1] | Less than or equal to 92% with lung disease, less than or equal to 94% without lung disease triggers arterial or capillary blood gas analysis. [1] |
| Arterial carbon dioxide (PaCO2) | Detect hypoventilation. [1] | Greater than 6 kPa: urgent respiratory ventilation referral. [1] |
| Forced or vital capacity | Respiratory monitoring. [1] [2] | Practice parameter: risk of PEG placement rises when FVC falls below 50% of predicted. [2] |
| Respiratory function panel (NICE) | Decide referral for non-invasive ventilation. [1] | FVC or VC less than 50% predicted; or SNIP or MIP less than 40 cmH2O; or FVC or VC less than 80% with symptoms; or SNIP or MIP less than 65 (men) or 55 (women) with symptoms; or fall in SNIP or MIP of more than 10 cmH2O over 3 months. [1] |
| Genetic testing | Identify familial cause and guide counselling. [5] | Offered with family history; increasingly to sporadic cases. [5] |
| Genetic counselling | Discuss implications. [5] | Required before testing. [5] |
The diagnosis is clinical. Criteria exist for research and consistency, and clinicians should avoid letting an unduly strict set delay treatment.
Three requirements: [6]
- Progressive motor impairment documented by history or repeated assessment, following a period of normal motor function. [6]
- Upper and lower motor neuron dysfunction in at least one body region (both in the same region if only one region is involved), or lower motor neuron dysfunction in at least two regions. [6]
- Exclusion of other processes by appropriate investigation. [6]
Body regions are bulbar, cervical, thoracic and lumbosacral. Upper motor neuron dysfunction requires one of: hyperreflexia, pathological reflexes, spasticity, or slowed voluntary movement not due to lower motor neuron weakness or parkinsonism. Lower motor neuron dysfunction requires weakness with wasting, or electromyographic evidence of chronic neurogenic change plus ongoing denervation. [6]
The original El Escorial set defined four levels of diagnostic certainty (definite, probable, possible, suspected ALS); the revised (Airlie House) version added probable ALS with laboratory support. [6] A diagnosis of definite ALS by these criteria required upper and lower motor neuron involvement in three regions; probable in at least two regions with upper motor neuron loss above and lower below; possible in one region, or two with only upper below; suspected when only lower motor neuron signs were found. [6]
The Gold Coast criteria have higher sensitivity and more readily include lower motor neuron predominant phenotypes, but their specificity is less precise and more heterogeneous across settings. [6] In practice the criteria support a diagnosis already suspected clinically; they should not obstruct early multidisciplinary care. [5]
ALS management is best delivered by a specialist clinic-based multidisciplinary team, including a neurologist, specialist nurse, dietitian, physiotherapist, occupational therapist, respiratory physiologist, speech and language therapist and palliative care input. [3] [1] Such clinics improve delivery and may prolong survival and quality of life. [3] The team reviews people every 2-3 months, though this is adapted to need. [1]
Riluzole. Riluzole is the drug with the best evidence: it has antiglutamatergic effects and is recommended in the EAN, NICE and AAN guidance. [4] [1] [2] The recommended dose is 50 mg twice daily, offered lifelong from diagnosis. [4] [2] Evidence from randomised trials shows a modest effect, prolonging survival by about 2-3 months. [2] If adverse effects occur, reduce the dose and re-evaluate, and stop the drug if they persist. [4] Common adverse effects include nausea, diarrhoea, fatigue, dizziness and liver problems. [5] AAN advice is to offer riluzole to slow disease progression. [2]
Edaravone. Edaravone is a free radical scavenger. The licensed intravenous regimen is 60 mg infused over 60 minutes, daily for 14 days then 14 days off in the first cycle, and daily for 10 of 14 days with 14 days off thereafter. [7] A transfer to oral suspension (105 mg) uses the same cycle. [7] An intravenous edaravone trial of 60 mg per day for 2 weeks per month showed a smaller decline in the ALSFRS-R in selected patients over 6 months. [5] Sources differ on its place: the EAN panel currently does not recommend intravenous or oral edaravone outside a clinical trial, as an interim recommendation pending European phase III results, whereas product labelling and some national practice support its use in selected patients. [4] [5] [7] Follow local availability and guidelines, and involve the patient in the decision.
Tofersen. In patients with progressive ALS due to pathogenic mutations in SOD1, tofersen should be offered as first-line treatment; it is given intrathecally and its availability varies by country; the balance of benefits and harms must be discussed, especially in slowly progressive disease. [4]
Other agents. The evidence is insufficient for lithium carbonate. [2] Creatine 5-10 g daily and high-dose vitamin E should not be given. [2] Masitinib and cell-based therapies remain trial-only. [4]
- Exercise in a suitable resistance or passive programme maintains range of movement, reduces stiffness and contracture risk and supports function. [4]
- Cramps may respond to sodium channel blockers such as quinine sulfate 100-200 mg daily, gabapentin or carbamazepine, with baclofen if spasticity coexists; start quinine at low dose and monitor the cardiac effects. [4]
- Spasticity is treated with baclofen, tizanidine and muscle stretching. [5]
- Sialorrhoea is treated with anticholinergic drugs (amitriptyline, glycopyrrolate, oxybutynin) and botulinum toxin injection into salivary glands; refractory cases may benefit from botulinum toxin B or salivary gland radiation. [3] [5]
- Pseudobulbar affect may respond to dextromethorphan with quinidine where licensed. [3]
- Emotional lability may be treated with selective serotonin reuptake inhibitors, amitriptyline, benzodiazepines or dextromethorphan with quinidine. [5]
- Communication should be assessed early by speech and language therapy; augmentative and alternative communication, including eye-gaze systems, can preserve participation. [1]
- Multidisciplinary clinics are recommended. [3]
Cognitive impairment should be screened for, because many patients have mild impairment and some have frontotemporal dementia that affects consent and management. [3]
Nutrition is assessed from diagnosis, including weight, intake, hydration, swallowing and oral health. [1] Dietary change helps; a gastrostomy tube is an option when intake is insufficient or swallowing is hazardous. [5] Enteral nutrition via PEG stabilises body weight and probably prolongs survival. [2]
The NICE and EAN guidance agree that gastrostomy should be discussed early and revisited regularly, taking account of swallowing ability, weight loss, respiratory function, effort of feeding, choking risk and the patient's wishes. [1] [4] Early placement is safer; late gastrostomy carries risk of low body mass, respiratory complications, dehydration and higher procedural risk. [1] [4] If respiratory insufficiency is present, introduce non-invasive ventilation first and perform the gastrostomy with the patient established on it. [4] The patient should be referred without unnecessary delay. [1]
PEG placement risk rises when forced vital capacity falls below 50% predicted, although no single threshold is firmly supported. [2]
Respiratory failure is the usual cause of death, so this part of management deserves as much attention as the neurological part.
- Cough augmentation. Unassisted breath stacking or manual assisted cough is first-line for ineffective cough; assisted breath stacking or a mechanical cough assist device is used when bulbar dysfunction limits effect; suction may be added. [4]
- NIV. NIV should be offered to all patients with symptoms, signs or tests indicating respiratory insufficiency, and every effort should be made to enable NIV regardless of bulbar function. [4] NIV prolongs survival, may slow the decline of forced vital capacity and improve quality of life. [2] [4] Early initiation may improve compliance. [2]
- Thresholds for referral and testing are those of the NICE panel: baseline FVC or VC, SNIP and MIP, oximetry, blood gases and symptom review every 2-3 months; referral for NIV when criteria in Table 2 are met. [1]
- Diaphragmatic pacing is not recommended for ALS. [4]
- Invasive ventilation should be discussed as part of advance care planning, not as an emergency. [4]
- For breathlessness, opioids and benzodiazepines can be used when NIV is not tolerated or no longer helps. [1] [4]
Approach to suspected ALS
- Adult with progressive weaknessFocal onset, then spread; often distal before proximal
- Characterise the weakness and signsBoth upper and lower motor neuron signs; sensation usually spared
- Question: Are upper and lower motor neuron signs present in a region, or lower motor neuron signs in two regions?
Yes
- Apply Gold Coast or El Escorial criteria and exclude mimicsElectrodiagnostic studies, MRI brain and spine, blood tests
- Confirm diagnosis and tell the patient sensitivelyBegin multidisciplinary care
No
- Investigate like a mimicElectrophysiology, imaging, genetic and autoimmune tests
- Reassess as the picture evolvesALS may still emerge over months
- Start riluzole and assess eligibility for tofersen or edaravone50 mg riluzole twice daily; tofersen for SOD1 disease
- Measure respiratory function, nutritional status and swallowingBaseline tests trigger NIV and gastrostomy planning
- Optimise multidisciplinary, nutritional, respiratory and symptom careReview every 2-3 months
- Respiratory failure and respiratory infection from diaphragmatic and intercostal weakness; most deaths result from this. [5] [4]
- Aspiration pneumonia and dehydration from dysphagia. [1] [5]
- Malnutrition and low body mass from reduced intake. [1]
- Joint contractures, stiffness and pressure problems from immobility. [4]
- Pseudobulbar affect, depression and anxiety. [3] [5]
- Cognitive and behavioural change, including frontotemporal dementia. [5] [3]
- Deep venous thrombosis risk during immobility. [4]
Median survival is about 3 years from symptom onset, and bulbar disease has a median survival of about 2 years. [5] Prognostic markers of shorter survival include bulbar onset, weight loss, worse respiratory function, older age, lower ALSFRS or ALSFRS-R score and shorter symptom-to-diagnosis interval. [1] Some patients live much longer, particularly those with primary lateral sclerosis or the slower variants. [5]
There is no known primary prevention. Secondary prevention is not possible because no pre-symptomatic test or prophylactic treatment is established for ALS. [5]
What is possible is genetic counselling and testing for at-risk relatives of people with familial ALS, with clear discussion that testing before symptoms appear has unresolved consequences. [5] Genetic counselling is also essential for people found to carry a pathogenic variant, because several genes are shared between ALS and frontotemporal dementia. [5]
- Pregnancy. ALS during pregnancy is uncommon and management is for an experienced multidisciplinary team, including obstetric, neurological and respiratory specialists. The pregnancy itself must be managed around respiratory capacity and nutrition; advance planning for delivery and peripartum respiratory support is advisable. [1] [2]
- Children and young adults. Juvenile ALS is rare; early or familial onset should prompt investigation for genetic causes and for conditions that mimic it. [5]
- Older adults. Comorbidity, cognitive reserve and tolerance of interventions weigh more heavily. NIV and gastrostomy remain options, but decisions should be led by function, preferences and realistic expectations, and advance care planning should begin early. [1] [3]
- A transthoracic echocardiogram is not the key test here; the bedside is. Focus on focal, progressive motor weakness with both upper and lower motor neuron signs and spared sensation. [5]
- Basic screening scales and regular weight measurement, plus awareness of nocturnal sleep-disordered breathing, may be more realistic than full respiratory physiology. [2]
- Manual assisted cough, breath stacking, low-technology augmentative communication, careful swallowing advice and home-based multidisciplinary support produce practical benefit. [2] [4]
- Avoid interventions that cannot be supported locally and refer early for feeding and respiratory care where available. [1]
- Clinical neuroanatomy and spinal cord syndromes (motor neuron signs; upper versus lower motor neuron lesions)
- Frontotemporal dementia
- Respiratory failure and mechanical ventilation
- Feeding, gastrostomy and parenteral nutrition
- Genetics of neurodegenerative disease
- Palliative care and advance care planning
- ALS is a fatal, combined upper and lower motor neuron disease; sensation is spared. [5]
- It is clinical: upper and lower motor neuron signs in a progressive motor syndrome with mimics excluded. [5]
- Incidence in Europe is about 1.75-3 per 100,000 each year; median survival is about 3 years. [5]
- About 10% of cases are familial, most often autosomal dominant; the five commonest genes explain about 15% of all patients. [5]
- Gold Coast criteria are more sensitive; El Escorial criteria remain widely quoted. [6]
- Riluzole 50 mg twice daily is the standard pharmacological treatment with a modest survival benefit. [4] [2]
- Edaravone is given as 60 mg intravenously over 60 minutes in defined cycles; its routine use is not recommended by the EAN panel at present. [4] [7]
- Multidisciplinary, nutritional and ventilatory support underpin care; PEG stabilises weight and PEG timing matters. [2] [1]
- NIV should be offered for respiratory insufficiency and probably prolongs survival; diaphragmatic pacing is not used. [4] [1]
- Gastrostomy and early planning improve outcome; discussion should begin early. [1] [4]
- Prognosis depends on onset site, weight, respiration, age and functional score. [1]
- There is no primary prevention; genetic counselling is the main preventive tool. [5]
Answer each one in your head first, then open the answer.
A middle-aged man develops a right hand grip weakness that spreads to the forearm over months. On examination there is wasting of the first dorsal interosseous, fasciculation of the arm and brisk reflexes at the elbow and knee. There is no sensory loss. What is the diagnosis and what two levels of the motor system are involved?
Show answerHide answer
Amyotrophic lateral sclerosis. Wasting, fasciculation and weakness are lower motor neuron findings; the brisk reflexes in a wasted limb are upper motor neuron findings. The combination, with spared sensation, is the classic picture. [5]
Which of the following statements about riluzole is correct: it is disease-modifying, given at 50 mg twice daily, given only for 6 months, or used only in bulbar-onset disease?
A 55-year-old woman has bulbar-onset disease with weight loss and forced vital capacity just above the referral threshold. What two planning decisions are most urgent and how do they interact?
Why has the Gold Coast set of criteria been preferred by many clinicians for diagnosis in recent years?
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It requires progressive motor impairment plus upper and lower motor neuron dysfunction in one region (or lower only in two regions), plus exclusion of alternatives, so it captures lower motor neuron predominant phenotypes earlier and is more sensitive than the El Escorial criteria. Its specificity is less precise and more variable. [6]
How does amyotrophic lateral sclerosis differ from multifocal motor neuropathy and inclusion body myositis?
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Multifocal motor neuropathy has focal lower motor neuron weakness with nerve conduction block and responds to immunoglobulin. Inclusion body myositis is a slow, asymmetric myopathy often affecting finger flexors and quadriceps and is diagnosed by muscle biopsy. Neither combines upper and lower motor neuron signs. [5]
A patient asks what will happen to their breathing and how it will be supported. What is the best answer to plan with them?
Show answerHide answer
Breathing weakens in most patients and is the usual cause of death. Plan regular respiratory monitoring, cough augmentation, introduction of non-invasive ventilation when criteria are met, and discussion of invasive ventilation as part of advance care planning rather than as an emergency. Diaphragmatic pacing is not used. [4] [1]
- National Institute for Health and Care Excellence (NICE). Motor neurone disease: assessment and management. NICE guideline NG42 (published 2016). Accessed .
- 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). Neurology 2009;73(15):1218-1226. doi:10.1212/WNL.0b013e3181bc0141 (AAN practice parameter, reaffirmed 2026). Accessed .
- Miller RG, Jackson CE, Kasarskis EJ, et al. Practice parameter update: the care of the patient with amyotrophic lateral sclerosis: multidisciplinary care, symptom management, and cognitive/behavioral impairment (an evidence-based review). Neurology 2009;73(15):1227-1233 (AAN practice parameter, reaffirmed 2026). Accessed .
- Van Damme P, Al-Chalabi A, Andersen PM, et al. European Academy of Neurology (EAN) guideline on the management of amyotrophic lateral sclerosis in collaboration with European Reference Network for Neuromuscular Diseases (ERN EURO-NMD). European Journal of Neurology 2024;31:e16264. doi:10.1111/ene.16264. Accessed .
- Masrori P, Van Damme P. Amyotrophic lateral sclerosis: a clinical review. European Journal of Neurology 2020;27(10):1918-1929. doi:10.1111/ene.14393. Accessed .
- Shrestha N, Munn Z, Calma A, et al. Gold Coast criteria for ALS diagnosis: individual participant data meta-analysis. Journal of Neurology 2026;273:532. doi:10.1007/s00415-026-14046-y. Accessed .
- DailyMed (US National Library of Medicine). Label: EDARAVONE injection, solution (RADICAVA). Prescribing information, accessed 2026-11-01. Accessed .
Educational content for medical students and doctors. It is not a substitute for clinical judgement or local guidelines.