Diagnosis guide for clinicians

Amyotrophic lateral sclerosis (ALS): when to suspect it and what to test

Not a doctor or health care professional? This page is for clinicians.Go to the patient version

Amyotrophic lateral sclerosis is a progressive loss of motor neurons in the motor cortex, brainstem and spinal cord; the European Academy of Neurology guideline puts median survival at 3 years after onset.Source 2024 European guideline

It presents as a progressive, purely motor disorder; an Oxford review says florid fasciculations, bilateral tongue wasting, the split hand, head drop and emotionality carry high positive predictive value in that setting.

Source Turner and Talbot 2013 Oxford review

A 2020 review of 21 studies put the typical time from first symptom to diagnosis at 10 to 16 months, with misdiagnoses that often led to unnecessary procedures and surgeries.

Source Richards 2020 review

10 to 16 monthsTypical time from first symptom to diagnosis in a 2020 review of 21 studiesRichards 2020 review

52%Patients given at least 1 other diagnosis first in a Boston cohort of 304; each saw an average of 3 physiciansPaganoni 2014 Boston cohort

34 of 260Patients in a Lahey Clinic series who had surgery, in the 5 years before diagnosis, for symptoms later attributed to early ALSSrinivasan 2006 Lahey Clinic series

G12.21ICD-10-CM code, amyotrophic lateral sclerosisNLM ICD-10-CM lookup

Orphanet recordORPHA:803 ↗

Inheritance

Autosomal dominant, Autosomal recessive, Multigenic/multifactorial, X-linked dominant

Age of onset

Adult

Prevalence

1 to 9 per 100,000 annual incidence, United States
1 to 9 per 100,000 annual incidence, Europe
1 to 9 per 100,000 point prevalence, Europe

Also called

ALS, Charcot disease, Lou Gehrig disease

Live from Orphanet (INSERM) via Orphadata, licensed CC BY 4.0, data version 2026-06-23.

Print the one-page checklist →

Patterns to test Red flags Often mistaken for What to test Family screening ICD-10 codes Once confirmed For the patient

Patterns that should prompt a test for Amyotrophic lateral sclerosis (ALS)

Each sign below is common on its own, which is why Amyotrophic lateral sclerosis (ALS) is missed. Published studies describe these combinations as the picture to act on. Rows are ordered from the highest published figure to the lowest, within each kind of measure.

Where testing finds it

Share of each screened or biopsied group found to have Amyotrophic lateral sclerosis (ALS), from the cited studies. A bar spans the lowest to the highest published figure.

1
Clinical suspicion of ALS+Progressive motor impairment
3007 people with suspected ALS in 5 international studies pooled in a 2026 individual participant meta-analysis
ALS was the final diagnosis in 2443 of 3007 (81.2%, our division of the reported counts); the other 564 had a non-ALS neuromuscular diagnosis (Shrestha 2026). These were diagnostic accuracy studies in specialist centers, so the share reflects who was enrolled and is not a yield for unselected patients.Shrestha 2026 meta-analysis
81.2%

How often diagnosed patients show it

Share of patients already diagnosed who had the finding, in the group named on each row. Groups differ by age and type, so read each row with its group.

1
Progressive motor impairment after normal function+Upper and lower motor neuron signs in 1 body region, or lower motor neuron signs in 2
People with a final diagnosis of ALS in a Sydney cohort of 506, a Beijing cohort of 1185 and a 2026 meta-analysis of 3007
The Gold Coast criteria were met by 92% (Hannaford 2021), 96.6% (Shen 2021) and a pooled 96% (Shrestha 2026); pooled specificity was 0.68 with very low certainty.Shrestha 2026 meta-analysis
92% to 96.6%
2
Dysarthria, dysphonia or dysphagia that keeps progressing+A first referral to otolaryngology or a stroke clinic+Emotionality
49 patients with bulbar-onset ALS at an Oxford tertiary clinic
Half had been referred to otolaryngology or a stroke clinic before diagnosis, and emotionality was reported in 45% (Turner 2010).Turner 2010 Oxford bulbar series
45% to 50%
3
Weakness, slurred speech or swallowing difficulty+An earlier non-ALS diagnosis for the same symptoms
People later diagnosed with ALS in a Boston cohort of 304, a German series of 100 and a 6-country chart review of 795
Another diagnosis came first in 52% (Paganoni 2014), 44% (Kraemer 2010) and 35.0% (Goyal 2024, with UCB Pharma authors); neuropathy and spine disease were the most common in Boston.Paganoni 2014 Boston cohort
35% to 52%
4
Limb weakness without sensory symptoms+Surgery in the past 5 years for presumed radiculopathy, myelopathy, mononeuropathy or arthropathy
260 consecutive patients with ALS at Lahey Clinic, 1996 to 2004, and 100 consecutive patients in Essen, Germany
Surgery for symptoms later attributed to early ALS was recorded in 34 of 260 (13.1%, our division of the reported counts) in the 5 years before diagnosis, out of 55 (21%) who had any surgery (Srinivasan 2006); 12% had such surgery in the German series (Kraemer 2010).Srinivasan 2006 Lahey Clinic series
12% to 13.1%
5
ALS in a person of European ancestry+A family history of ALS or frontotemporal dementia, or none
People with ALS in European-ancestry populations, as summarized in a 2023 US consensus guideline funded by the ALS Association
The C9orf72 repeat expansion accounts for 1 in 10 cases whether or not there is a family history (Roggenbuck 2023).2023 US genetic testing guideline
10%
6
A working diagnosis of ALS+Atypical symptoms, a specific test result or failure to progress
437 referrals to the Irish ALS Register, 1993 to 1997
A mimic was the final diagnosis in 32 of 437 (7.3%), most often multifocal motor neuropathy (7) and Kennedy disease (4) (Traynor 2000).Traynor 2000 Irish mimic study
7.3%
7
Weakness or foot drop with spondylosis on imaging+No improvement after spinal decompression
1131 patients with typical sporadic ALS in a Houston motor neuron disease database
Spinal decompression after symptom onset was recorded in 4.2%; 86% of the 55 operations yielded no improvement (Yoshor 2005).Yoshor 2005 Houston study
4.2%
8
Dyspnea on exertion or orthopnea as the first symptom+Dropped head, widespread fasciculations or early weight loss
Patients with ALS at tertiary clinics in London, Ontario and Marseille
Respiratory onset accounted for 2.7% (Shoesmith 2007) and less than 3% (Gautier 2010) of ALS; only 14% of the Ontario patients presented acutely.Shoesmith 2007 Ontario series
2.7% to 3%

Also described, without a comparable figure

Carpal or cubital tunnel symptoms with weakness and atrophy in several nerve territories + No sensory symptoms, or no improvement after decompression: No patient frequency is given; 11% of surveyed hand surgeons had performed nerve decompression on a patient later diagnosed with ALS (Thomson 2023).Thomson 2023 hand surgery review
Florid fasciculations with bilateral tongue wasting + Split hand, head drop or emotionality + A progressive pure motor disorder: The review says these signs carry high positive predictive value and gives no frequency (Turner and Talbot 2013).Turner and Talbot 2013 Oxford review

These figures describe published study groups. They are not the chance that any one patient has Amyotrophic lateral sclerosis (ALS), and bars whose ranges overlap are not in a settled order.

Red flags for Amyotrophic lateral sclerosis (ALS)

What the cited sources describe, grouped by life stage and organ. Each line links to its source.

Any setting: the pattern that separates ALS from common problems

Progressive motor impairment after a period of normal motor function is the first requirement of the Gold Coast criteria.UK MND Clinical Studies Group on the Gold Coast criteria
Signs that an Oxford review says carry high positive predictive value in a progressive pure motor disorder: florid fasciculations, bilateral tongue wasting, the split hand, head drop, emotionality, and cognitive or behavioural impairment.Turner and Talbot 2013 Oxford review
Progressive weakness of neck extension has a very limited differential diagnosis with motor neuron disease high on the list, and the same review says it should not be attributed to cervical spondylosis.Turner and Talbot 2013 Oxford review
A hand surgery review lists weakness without sensory symptoms, weakness and atrophy in multiple nerve distributions, and symptoms that become bilateral and global.Thomson 2023 hand surgery review
Up to 50% of people with ALS have behavioural or cognitive problems from frontal and temporal involvement, and about 10% meet criteria for frontotemporal dementia at diagnosis, according to the European guideline.2024 European guideline
Older age, sporadic disease and limb onset were each associated with a longer time to diagnosis in a Boston cohort.Paganoni 2014 Boston cohort

Limb onset: what orthopedics, hand surgery and spine surgery see

Initial symptoms may mimic radiculopathy, myelopathy, mononeuropathy or arthropathy, according to a Lahey Clinic series.Srinivasan 2006 Lahey Clinic series
In that series of 260 consecutive patients, 55 (21%) had surgery in the 5 years before diagnosis, and 34 of the 55 (61%) were operated on for symptoms later attributed to early ALS.Srinivasan 2006 Lahey Clinic series
In a Houston database, 47 of 1131 patients with sporadic ALS (4.2%) had decompressive spinal surgery after symptom onset; 86% of the 55 operations yielded no improvement.Yoshor 2005 Houston study
Foot drop prompted spinal surgery in 11 of those patients, and in 10 it was later attributed solely to ALS.Yoshor 2005 Houston study
In a survey of the American Society for Surgery of the Hand, 11% of members had performed nerve decompression on a patient later diagnosed with ALS.Thomson 2023 hand surgery review
The same hand surgery review lists failure to improve after nerve decompression surgery as a red flag.Thomson 2023 hand surgery review
Symptoms such as emotionality and abnormal signs above the neck help avoid overinterpreting neck pathology, according to an Oxford review.Turner and Talbot 2013 Oxford review

Bulbar onset: what ENT, speech and swallowing services and stroke clinics see

Dysphonia, dysarthria and dysphagia are often the presenting symptoms in bulbar-onset patients, according to a University of Michigan report on otolaryngology in ALS care.Rubin 2012 otolaryngology report
In an Oxford series of 49 bulbar-onset patients, half had been referred to otolaryngology or a stroke clinic before diagnosis.Turner 2010 Oxford bulbar series
Emotionality was reported in 45% of that series, and the mean age at symptom onset was 68 years.Turner 2010 Oxford bulbar series
A case report describes a 61-year-old man sent to otolaryngology for 6 months of progressive dysphagia and dysphonia, in whom dysarthric, hypernasal speech raised the question of neuromuscular disease.Costa 2021 case report
A subset of bulbar-onset patients, typically elderly women, develop rapidly progressive anarthria with limb function preserved for many months.Turner and Talbot 2013 Oxford review
Tongue fasciculations with speech or swallowing difficulty appear on a hand surgery review's list of red flags.Thomson 2023 hand surgery review

Respiratory onset: what pulmonology, sleep and emergency physicians see

Respiratory symptoms were the first symptom in 2.7% of patients at an Ontario ALS clinic.Shoesmith 2007 Ontario series
Only 14% of those 21 patients presented acutely and needed emergency intubation.Shoesmith 2007 Ontario series
A Marseille series defines respiratory onset as dyspnea on exertion, dyspnea at rest or orthopnea as the first symptom of muscle weakness.Gautier 2010 Marseille series
Common features in that series were male sex, dropped head or camptocormia, widespread fasciculations, fairly preserved limb mobility and significant early weight loss.Gautier 2010 Marseille series
Its authors ask that general practitioners and chest physicians be reminded that neuromuscular respiratory insufficiency may be due to this form of ALS.Gautier 2010 Marseille series
An Oxford review notes that undiagnosed motor neuron disease is still admitted acutely in respiratory failure with superimposed pneumonia.Turner and Talbot 2013 Oxford review

Family history

The C9orf72 repeat expansion can present as frontotemporal dementia alone, ALS alone or both, and the presentation can differ within a family, according to GeneReviews.GeneReviews: C9orf72
A US consensus guideline says the C9orf72 expansion accounts for 1 in 10 ALS cases in European-ancestry populations, with or without a family history of ALS or frontotemporal dementia.2023 US genetic testing guideline
Juvenile-onset disease (before age 25) is very rare and typically comes with a family history; onset before 45 accounts for approximately 10% of patients, according to an Oxford review.Turner and Talbot 2013 Oxford review

Amyotrophic lateral sclerosis (ALS) is often mistaken for

Diagnoses patients commonly carry first, and why the sources say they are confused.

First diagnosis	Why it is confused
Neuropathy	Neuropathy was the most common alternative diagnosis in a Boston cohort, at 28% of those recorded.Paganoni 2014 Boston cohort
Spine disease, including cervical or lumbar radiculopathy and spondylotic myelopathy	Spine disease made up 18% of alternative diagnoses in the Boston cohort.Paganoni 2014 Boston cohort
Spondylosis with nerve root or cord impingement on imaging	A Houston neurosurgery study says the high incidence of spondylosis at the mean age of ALS onset can make ALS hard to recognize as the cause of weakness.Yoshor 2005 Houston study
Cervical spondylotic myelopathy	The cervical spine brings upper and lower motor neurons close together, and incidental spondylosis is highly prevalent among people with motor neuron disease.Turner and Talbot 2013 Oxford review
Carpal tunnel or cubital tunnel syndrome	A hand surgery review says ALS can mimic compressive neuropathies, especially early in the course.Thomson 2023 hand surgery review
Stroke or transient ischemic attack	Vascular disease made up 11% of alternative diagnoses in the Boston cohort.Paganoni 2014 Boston cohort
A stroke clinic or otolaryngology problem in bulbar onset	Half of 49 bulbar-onset patients in Oxford had been referred to otolaryngology or stroke clinics before diagnosis.Turner 2010 Oxford bulbar series
An ear, nose and throat problem	ENT problems made up 7% of alternative diagnoses in the Boston cohort.Paganoni 2014 Boston cohort
Myasthenia gravis	Neuromuscular junction disorders made up 9% of alternative diagnoses in the Boston cohort.Paganoni 2014 Boston cohort
Parkinson's disease, hereditary spastic paraplegia or progressive supranuclear palsy	Other neurodegenerative diseases made up 11% of alternative diagnoses in the Boston cohort.Paganoni 2014 Boston cohort
Muscle disease	Muscle disease made up 6% of alternative diagnoses in the Boston cohort.Paganoni 2014 Boston cohort
Any first misdiagnosis	In a chart review of 795 patients in Europe and the US, with UCB Pharma employees among the authors, 35.0% had at least 1 initial misdiagnosis, and their mean time to diagnosis was 10.4 months against 6.9 months.Goyal 2024 chart review

Codes patients often carry before this diagnosis

For spotting the pattern in a problem list or registry. Descriptions are checked daily against NLM's ICD-10-CM service; this is not coding advice.

Carpal tunnel syndrome, unspecified, right, left or bilateral upper limbs G56.00, G56.01, G56.02, G56.03

A hand surgery review says ALS can mimic carpal and cubital tunnel syndromes early in its course.Thomson 2023 hand surgery review

Radiculopathy, cervical region M54.12

A Lahey Clinic series lists radiculopathy among the conditions early ALS may mimic.Srinivasan 2006 Lahey Clinic series

Other spondylosis with myelopathy, cervical region M47.12

Cervical decompression made up 56% of spinal operations done after ALS symptom onset in a Houston study.Yoshor 2005 Houston study

Foot drop, right, left or unspecified foot M21.371, M21.372, M21.379

Foot drop prompted spinal surgery in 11 patients in the Houston study, and in 10 it was later attributed solely to ALS.Yoshor 2005 Houston study

Polyneuropathy, unspecified G62.9

Neuropathy was the most common alternative diagnosis in a Boston cohort.Paganoni 2014 Boston cohort

Dysarthria and anarthria R47.1

Half of an Oxford bulbar-onset series had been sent to otolaryngology or a stroke clinic first.Turner 2010 Oxford bulbar series

Dysphagia, unspecified, or dysphonia R13.10, R49.0

Dysphonia, dysarthria and dysphagia are often the presenting symptoms in bulbar-onset patients.Rubin 2012 otolaryngology report

Cerebral infarction, unspecified, or transient cerebral ischemic attack, unspecified I63.9, G45.9

Vascular disease made up 11% of alternative diagnoses in the Boston cohort.Paganoni 2014 Boston cohort

Fasciculation R25.3

Fasciculations at first symptoms were an independent predictor of a shorter time to diagnosis in the Boston cohort.Paganoni 2014 Boston cohort

Dyspnea, unspecified, or orthopnea R06.00, R06.01

A Marseille series defines respiratory onset by dyspnea or orthopnea as the first symptom.Gautier 2010 Marseille series

Testing for Amyotrophic lateral sclerosis (ALS), step by step

The testing order the cited guidance describes, by who it applies to. It summarizes published guidance and is not a plan for any one patient.

Anyone with progressive weakness, wasting, slurred speech or swallowing difficulty and no sensory explanation

History and neurological examination
The UK MND Clinical Studies Group states that the diagnosis remains fundamentally clinical, with EMG as an adjunct to a history and examination-led process.UK MND Clinical Studies Group on the Gold Coast criteria

Anyone with suspected ALS

Gold Coast criteria
Three requirements: progressive motor impairment documented by history or repeated assessment and preceded by normal motor function; upper and lower motor neuron dysfunction in at least 1 body region (both in the same region if only 1 is involved), or lower motor neuron dysfunction in at least 2 body regions; and investigations excluding other disease processes.UK MND Clinical Studies Group on the Gold Coast criteria
Upper motor neuron signs, as the criteria define them
At least 1 of: increased deep tendon reflexes, including a reflex in a clinically weak and wasted muscle or spread to adjacent muscles; pathological reflexes such as the Hoffmann or Babinski sign, crossed adductor reflex or snout reflex; spasticity; or slowed, poorly coordinated voluntary movement not explained by lower motor neuron weakness or parkinsonian features.UK MND Clinical Studies Group on the Gold Coast criteria
Lower motor neuron signs and body regions
Either weakness with wasting on examination, or EMG showing both chronic neurogenic change and ongoing denervation. The body regions are bulbar, cervical, thoracic and lumbosacral; a region counts when 2 limb muscles with different root and nerve supply, 1 bulbar muscle or 1 thoracic muscle are abnormal.UK MND Clinical Studies Group on the Gold Coast criteria

Background

Where the criteria come from
The criteria were published in Clinical Neurophysiology in August 2020 as a proposal from an international group of authors.Gold Coast criteria proposal
How the criteria compare
In a 2026 individual participant meta-analysis of 3007 people from 5 studies, sensitivity was 0.96 for Gold Coast against 0.87 for both older sets; specificity was 0.68, 0.73 and 0.72, with very low certainty.Shrestha 2026 meta-analysis

Most people with suspected ALS

Needle EMG
The Awaji consensus affirmed the utility of needle EMG and nerve conduction studies. It treats chronic neurogenic change on EMG as equivalent to clinical information and, in suspected ALS, fasciculation potentials as equivalent to fibrillation potentials and positive sharp waves.Awaji consensus
What EMG adds, and its limits
The UK MND Clinical Studies Group says EMG remains valuable for showing clinically occult lower motor neuron involvement, but is far from 100% sensitive and highly operator dependent.UK MND Clinical Studies Group on the Gold Coast criteria

Suspected multifocal motor neuropathy or another inflammatory neuropathy, or prominent sensory features

Nerve conduction studies
An Oxford review says conduction block shown by an experienced neurophysiologist is diagnostic of multifocal motor neuropathy but is not always detectable.Turner and Talbot 2013 Oxford review

Progressive limb weakness with mixed signs and no signs above the neck

MRI of the cervical spine
This is the scenario in which the Oxford review gives cervical MRI its greatest value. It names lumbar MRI for a lower motor neuron syndrome affecting only the legs, and brain MRI for isolated dysphagia without prominent dysarthria or for hemiparesis.Turner and Talbot 2013 Oxford review

When a myopathy is suspected

Serum creatine kinase
The Oxford review treats a creatine kinase above 1000IU/L as a clue to a diagnosis other than motor neuron disease, such as inclusion body myositis.Turner and Talbot 2013 Oxford review

People whose main complaint is fasciculations

Thyroid function and electrolytes
Approximately 10% of thyrotoxic patients display florid fasciculations. The Oxford review says people under 40 with fasciculations, no weakness and normal thyroid function and electrolytes can be reassured without EMG.Turner and Talbot 2013 Oxford review

Slowly progressive myelopathy, especially with sensory impairment

Vitamin B12 and copper
The Oxford review calls B12 and copper deficiency well-recognised causes of slowly progressive myelopathy that typically come with sensory impairment.Turner and Talbot 2013 Oxford review

Atypical lower motor neuron presentations

Copper deficiency presenting as lower motor neuron disease
A St. Louis report describes 3 copper-deficient patients, 2 referred with presumed ALS, whose weakness stabilized or mildly improved with copper replacement.Weihl 2006 copper deficiency report

Suspected multifocal motor neuropathy

Anti-GM1 antibodies
The Oxford review calls anti-GM1 ganglioside antibodies a helpful adjunct that is only 50% sensitive. It says early intravenous immunoglobulin may limit axonal loss in that neuropathy.Turner and Talbot 2013 Oxford review

Men with gradually progressive lower motor neuron weakness, especially with gynecomastia

Androgen receptor CAG repeat test
GeneReviews says spinal and bulbar muscular atrophy (Kennedy disease) is established in a male by a hemizygous expansion of more than 35 CAG repeats in AR.GeneReviews: Kennedy disease

Slow progression or early, disproportionate weakness of the finger flexors

Muscle biopsy or quantitative EMG
A Columbia series found that 9 of 70 patients with biopsy-proven inclusion body myositis (13%) had first been diagnosed with motor neuron disease; routine EMG showed fibrillation potentials in all 9.Dabby 2001 Columbia series

Suspected inflammatory neuropathy, primary progressive multiple sclerosis or a paraneoplastic disorder

Cerebrospinal fluid
The Oxford review gives CSF its greatest value when white cell count or protein is significantly raised, or when oligoclonal bands are sought.Turner and Talbot 2013 Oxford review

Bulbar presentations in which myasthenia gravis is considered

Acetylcholine receptor antibodies
Antibody testing for myasthenia gravis was done in 22% of an Oxford bulbar-onset series, neurophysiology in 80% and brain imaging in 69%.Turner 2010 Oxford bulbar series

Everyone

No mandatory test list
The Oxford review states that motor neuron disease is a clinical diagnosis with no mandatory investigations, and that tests are those justified by the history and signs, EMG included.Turner and Talbot 2013 Oxford review

Background, and trial eligibility

Older criteria: revised El Escorial and Awaji
El Escorial defined definite, probable, possible and suspected ALS; the revision added a laboratory-supported probable category, and Awaji removed it while counting fasciculations with chronic neurogenic change. Up to 22% of patients die while still classed as possible ALS.Shrestha 2026 meta-analysis

All persons with ALS, with or without a family history

Genetic testing offer
A 2023 US consensus guideline funded by the ALS Association says all persons with ALS should be offered single-step testing: a C9orf72 assay plus sequencing of SOD1, FUS and TARDBP at a minimum. It notes that earlier European guidelines limited testing to familial ALS or the SOD1 D90A phenotype. The 2024 European guideline does not address gene testing but reports a growing consensus to offer rapid gene testing to all people with ALS.2023 US genetic testing guideline

All persons with ALS who are offered testing

Genetic counseling
The same guideline says genetic counseling and education should be provided to all persons with ALS, and that everyone tested should receive posttest counseling.2023 US genetic testing guideline

Adults with ALS

SOD1 result and tofersen
The Qalsody label covers adults with ALS who have a mutation in the SOD1 gene, under accelerated approval based on a reduction in plasma neurofilament light chain.Qalsody label

People with progressive ALS caused by pathogenic SOD1 mutations

SOD1 result in the European guideline
The European guideline says to offer tofersen as first-line treatment and to discuss that it may be associated with serious adverse events. It remarks that tofersen may not be available in all countries.2024 European guideline

All people with ALS

Riluzole at diagnosis
The European guideline says to offer lifelong riluzole to all people with ALS at diagnosis.2024 European guideline

Where testing goes wrong

The UK MND Clinical Studies Group says the sensitivity shortfall of EMG is most often seen in upper motor neuron predominant ALS, particularly with bulbar onset, often with no tongue or limb EMG findings.UK MND Clinical Studies Group on the Gold Coast criteria
The same group says over-reliance on EMG as a diagnostic test in such cases leads to avoidable diagnostic delay.UK MND Clinical Studies Group on the Gold Coast criteria
A Houston neurosurgery study concludes that ALS must be considered in patients with weakness even when imaging shows spondylosis with nerve root or spinal cord impingement.Yoshor 2005 Houston study
In a German series of 100 patients, 12% had surgery for symptoms later attributed to ALS, and time to diagnosis differed significantly between operated and non-operated patients.Kraemer 2010 German series
Lower motor neuron signs alone do not exclude ALS; the Gold Coast criteria accept lower motor neuron dysfunction in 2 body regions without upper motor neuron signs.UK MND Clinical Studies Group on the Gold Coast criteria
Gold Coast specificity is uncertain: a 2026 meta-analysis pooled 0.68 with very low certainty, and its authors support use with mimic exclusion and longitudinal reassessment.Shrestha 2026 meta-analysis
A Beijing study of 1185 patients put Gold Coast sensitivity at 96.6%, against 85.1% and 85.3% for the older criteria, but its own Gold Coast specificity was 17.4% among 23 patients with other diagnoses; it cites an earlier specificity of 88.5% from a Sydney cohort.Shen 2021 Beijing cohort
The Sydney study of 506 patients found a smaller gap in sensitivity (92% against 90.3% and 88.6%), which its authors called comparable, with greater sensitivity and specificity for Gold Coast in atypical phenotypes.Hannaford 2021 Sydney cohort
The opposite error also occurs: in the Irish ALS Register, 32 of 437 referrals (7.3%) were rediagnosed with a mimic, most often multifocal motor neuropathy (7 cases) and Kennedy disease (4 cases).Traynor 2000 Irish mimic study
Diagnoses in that register were revised because of atypical symptoms, specific test results or failure to progress.Traynor 2000 Irish mimic study
Multifocal motor neuropathy typically shows weakness with very little wasting and no bulbar involvement, and reflexes can be brisk in up to 20% of cases.Turner and Talbot 2013 Oxford review
A Baxalta-funded review lists features that point to multifocal motor neuropathy: stepwise progression in single nerve territories, no bulbar or respiratory involvement, conduction block, no upper motor neuron signs, sparse fasciculations and GM1 antibodies.Lawson 2018 review (Baxalta-funded)
Inclusion body myositis can look neurogenic on routine EMG; 7 of 9 misdiagnosed patients in a Columbia series had fasciculation potentials and none had definite upper motor neuron signs.Dabby 2001 Columbia series
Kennedy disease is suggested by very slow symmetrical progression, absent or reduced reflexes, chin fasciculations and gynecomastia.Turner and Talbot 2013 Oxford review
Patients with bulbar symptoms may report diurnal variation, and a very few test falsely positive for acetylcholine receptor antibodies; eye signs point toward myasthenia gravis.Turner and Talbot 2013 Oxford review
Fasciculations alone are part of normal physiology; the Oxford review says people with motor neuron disease rarely present with them as the main complaint.Turner and Talbot 2013 Oxford review
Older category labels such as possible or probable ALS implied doubt where there was usually none, and patients frequently died without leaving those categories.UK MND Clinical Studies Group on the Gold Coast criteria
A negative gene panel does not exclude ALS; current testing fails to identify a genetic cause in a significant proportion of familial cases.2023 US genetic testing guideline
Many ALS variants are incompletely penetrant, and the US guideline lists variants of unknown significance among the harms of testing without pretest counseling.2023 US genetic testing guideline
An Oxford review warns against depolarising muscle relaxants in people with severe denervation, because they may precipitate dangerous hyperkalemia.Turner and Talbot 2013 Oxford review
Time to diagnosis has not shortened: at a Massachusetts center the median stayed at 12 months from 2007 to 2021, with means of 11.9 months for bulbar, 15.9 for limb and 19.7 for respiratory onset.Fang 2024 Massachusetts cohort
In Medicare claims for 78,520 people diagnosed from 2011 to 2021, the mean time from first neurologist visit to diagnosis was 9.6 months with ALS or neuromuscular specialists and 16.7 months with other neurologists.Dave 2025 ALS Association study

Where to test

NIH Genetic Testing Registry: amyotrophic lateral sclerosis: Lists the gene tests and panels that laboratories have submitted under the ALS concept. ALS itself is a clinical diagnosis, so these tests look for a genetic cause and do not confirm or exclude the disease. NIH does not independently verify submissions or endorse any laboratory.NIH GTR
ALS Identified Program (Invitae) (drugmaker-sponsored): Sponsored, no-charge 26-gene panel that includes C9orf72, SOD1, FUS and TARDBP, with post-test genetic counseling. Open to people 18 or older in the US and Puerto Rico with a diagnosis of ALS or a family history of ALS. The program page carries an About Biogen statement and says third parties and commercial organizations that support the program may receive de-identified patient data and ordering clinicians' contact details. Biogen makes Qalsody (tofersen).ALS Identified sponsored testing program

Family screening and referral

Who else in the family

A US consensus guideline says posttest counseling should cover risks for specific family members when a pathogenic or likely pathogenic variant is found, including the availability of presymptomatic testing.2023 US genetic testing guideline
Presymptomatic testing of adult relatives is described in that guideline as a personal choice that should be performed with appropriate genetic counseling.2023 US genetic testing guideline
Each child of a person with a C9orf72 expansion has a 50% chance of inheriting it; a parent who carries it may have no symptoms because penetrance is reduced and age dependent.GeneReviews: C9orf72
Penetrance studies estimate a high disease risk for some SOD1 and FUS variants and a much lower risk for others, including the C9orf72 expansion.2023 US genetic testing guideline
For people with no family history of ALS or frontotemporal dementia, the lifetime risk of ALS in first-degree relatives appears to be 1% to 3% in European populations.2023 US genetic testing guideline
Kennedy disease is X-linked: carrier females have a 50% chance of passing the expansion to each child, and affected males pass it to each daughter.GeneReviews: Kennedy disease

Who to refer to

The American Academy of Neurology practice parameter says multidisciplinary clinic referral should be considered to optimize care delivery and prolong survival (Level B) and may be considered to enhance quality of life (Level C).AAN 2009 practice parameter
The European guideline says to provide coordinated care through a clinic-based specialist ALS multidisciplinary team, with assessments usually every 3 to 6 months.2024 European guideline
In the Irish ALS Register, median survival was 7.5 months longer for the 82 patients who attended a multidisciplinary ALS clinic than for the 262 followed in general neurology clinics.Traynor 2003 Irish clinic study
A later study of 719 cases across Ireland and Northern Ireland found a survival benefit for multidisciplinary clinic attendance (hazard ratio 0.59, 95% CI 0.49 to 0.71).Rooney 2015 Ireland study
Not every study agrees: a registry study of 126 patients in Puglia, Italy found no difference in median survival (17.6 against 18 months).Zoccolella 2007 Puglia study
According to the ALS Association, most US ALS centers can see urgent referrals within 2 weeks, and it asks that referrals state "CLINICAL SUSPICION FOR ALS".ALS Association thinkALS page
In an ALS Association study, more than 75% of its certified centers reported wait times of 4 weeks or less for new ALS consultations.Dave 2025 ALS Association study
The UK MND Clinical Studies Group suggests the diagnosis be conveyed by a clinician who knows the proposed plan of care.UK MND Clinical Studies Group on the Gold Coast criteria
Orphanet lists the disease as ORPHA:803 and maps it to ICD-10 code G12.2.Orphanet cross-references

Find a specialist by state

From the CMS NPI Registry, a public directory of US clinicians by registered specialty. A listing is not an endorsement and says nothing about experience with Amyotrophic lateral sclerosis (ALS); patient organizations and academic centers can often name experienced clinicians.

ICD-10-CM codes for Amyotrophic lateral sclerosis (ALS)

For orders, referrals and prior authorization. Each code is checked daily against NLM's ICD-10-CM service.

G12.21Amyotrophic lateral sclerosisCurrent in NLM's ICD-10-CM listNLM ICD-10-CM lookup

Once the diagnosis is confirmed

Amyotrophic lateral sclerosis (ALS) drugs for prescribers3 prescribing guides, side by side: Qalsody, Radicava ORS, Rilutek.Open trials: 221Screen a de-identified patient against every recruiting Amyotrophic lateral sclerosis (ALS) study on ClinicalTrials.gov.Patient and family pageThe plain-language Amyotrophic lateral sclerosis (ALS) page, with trials, treatments and help paying.

For the patient: why your doctor ordered this test

Plain language a patient can read or take home.

Your doctor ordered these tests because some of your symptoms, such as weakness, muscle twitching, slurred speech or trouble swallowing, can have many causes. One of the causes doctors check for is ALS, a disease of the nerve cells that control muscles.

No single test shows ALS. Doctors look at how your symptoms have changed over time and examine your muscles and reflexes. A nerve and muscle test called an EMG, scans and blood tests help them look for other conditions that can look similar, and some of those conditions can be treated.

If ALS is diagnosed, your doctors or health care professionals may offer a gene test and genetic counseling, because one approved medicine is only for people with a change in a gene called SOD1. They may also refer you to a clinic where a team of ALS specialists works together.

Get emergency help right away if you have trouble breathing or cannot swallow.

Questions clinicians ask about Amyotrophic lateral sclerosis (ALS) testing

Which combinations of findings should prompt testing for amyotrophic lateral sclerosis (ALS)?

In published screening and biopsy studies, the highest yields came from clinical suspicion of ALS plus progressive motor impairment (81.2% of 3007 people with suspected ALS in 5 international studies pooled in a 2026 individual participant meta-analysis). Among patients already diagnosed, the most common combination began with progressive motor impairment after normal function, seen in 92% to 96.6% of people with a final diagnosis of ALS in a Sydney cohort of 506, a Beijing cohort of 1185 and a 2026 meta-analysis of 3007. These figures describe study groups, not any one patient's chance of having amyotrophic lateral sclerosis (ALS).

How long does it take to diagnose ALS?

A 2020 review of 21 studies put the typical time from first symptom to diagnosis at 10 to 16 months. In a Boston cohort of 304 patients the median was 11.5 months, 52% received at least 1 other diagnosis first and each saw an average of 3 physicians. A Massachusetts study of 448 patients found the median of 12 months unchanged from 2007 to 2021.

What are the Gold Coast criteria for ALS?

The Gold Coast criteria have 3 requirements: progressive motor impairment preceded by normal motor function; upper and lower motor neuron dysfunction in at least 1 body region, or lower motor neuron dysfunction in at least 2; and investigations excluding other disease processes. A 2026 meta-analysis of 3007 people put sensitivity at 0.96, against 0.87 for the revised El Escorial and Awaji criteria, with specificity of 0.68 rated very low certainty.

How often do people with ALS have unnecessary surgery before diagnosis?

Published series report 4.2% to 13% for surgery prompted by symptoms later attributed to ALS (13% is our division of 34 by 260). In a Lahey Clinic series, 55 of 260 patients (21%) had surgery in the 5 years before diagnosis, 34 of them for symptoms later attributed to ALS. A German series found 12%, and a Houston database found 4.2% had spinal decompression after symptom onset, with no improvement after 86% of operations.

Which ALS mimics are treatable, and how are they excluded?

In the Irish ALS Register, 7.3% of 437 referrals were rediagnosed, most often with multifocal motor neuropathy, in which an Oxford review says early intravenous immunoglobulin may limit axonal loss, and which is sought with nerve conduction studies for conduction block and anti-GM1 antibodies. Other mimics in the sources cited here include cervical spine disease (MRI), copper and B12 deficiency, thyrotoxicosis as a cause of fasciculations (thyroid function), inclusion body myositis (creatine kinase, muscle biopsy) and Kennedy disease (AR gene test).

Who with ALS should have genetic testing, and which genes?

All persons with ALS should be offered testing, according to a 2023 US consensus guideline of 35 statements funded by the ALS Association. It specifies a C9orf72 assay plus sequencing of SOD1, FUS and TARDBP at a minimum, with genetic counseling. The Qalsody (tofersen) label covers adults with ALS who have a SOD1 mutation. The guideline notes that earlier European guidance limited testing to familial ALS; the 2024 European guideline does not address gene testing but reports a growing consensus to offer rapid gene testing to all people with ALS.

Does referral to a multidisciplinary ALS clinic change outcomes?

Median survival was 7.5 months longer for multidisciplinary clinic patients in an Irish register study, and a later Irish study reported a hazard ratio of 0.59. An Italian registry study found no survival difference. The American Academy of Neurology rates referral to prolong survival as Level B, and the European guideline recommends clinic-based multidisciplinary team care.

What is the ICD-10 code for ALS?

The ICD-10-CM code is G12.21, amyotrophic lateral sclerosis. It was confirmed in the National Library of Medicine's ICD-10-CM lookup on November 12, 2026.

Sources

A proposal for new diagnostic criteria for ALS. Clinical Neurophysiology 2020;131(8):1975-1978 (Shefner JM, Al-Chalabi A, Baker MR et al; no competing interests declared), via PubMed record, which carries no abstract, 2020-04-19.
Diagnosing ALS: the Gold Coast criteria and the role of EMG. Practical Neurology 2022;22(3):176-178 (Turner MR; UK MND Clinical Studies Group; no specific funding and no competing interests declared), via PubMed Central, 2022-01-06.
Electrodiagnostic criteria for diagnosis of ALS. Clinical Neurophysiology 2008;119(3):497-503 (de Carvalho M, Dengler R, Eisen A et al), via PubMed abstract; funding and disclosures not seen, 2007-12-27.
Gold Coast criteria for ALS diagnosis: individual participant data meta-analysis. Journal of Neurology 2026;273(9):532 (Shrestha N, Munn Z, Calma A et al; no funding received for the manuscript; several authors are involved in the Australian MND guideline), via PubMed Central, 2026-08-19.
The Gold Coast criteria increases the diagnostic sensitivity for amyotrophic lateral sclerosis in a Chinese population. Translational Neurodegeneration 2021;10(1):28 (Shen D, Yang X, Wang Y et al, Peking Union Medical College Hospital; Chinese government research funding; no competing interests declared), via PubMed Central, 2021-08-09.
Diagnostic Utility of Gold Coast Criteria in Amyotrophic Lateral Sclerosis. Annals of Neurology 2021;89(5):979-986 (Hannaford A, Pavey N, van den Bos M et al), via PubMed abstract; funding and disclosures not seen, 2021-02-24.
Time to diagnosis and factors affecting diagnostic delay in amyotrophic lateral sclerosis. Journal of the Neurological Sciences 2020;417:117054 (Richards D, Morren JA, Pioro EP, Cleveland Clinic), via PubMed abstract; funding and disclosures not seen, 2020-07-24.
Diagnostic timelines and delays in diagnosing amyotrophic lateral sclerosis (ALS). Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration 2014;15(5-6):453-456 (Paganoni S, Macklin EA, Lee A et al, Massachusetts General Hospital; authors report NIH and foundation funding and some drugmaker consulting), via PubMed Central, 2014-07-01.
Contributions of neurologists to diagnostic timelines of ALS and thinkALS as an early referral instrument for clinicians. Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration 2025;26(3-4):215-224 (Dave KD, Oskarsson B, Yersak J et al; lead authors are ALS Association staff, and 1 author is also affiliated with Amylyx Pharmaceuticals), via PubMed abstract, 2024-12-10.
Misdiagnosis of amyotrophic lateral sclerosis in clinical practice in Europe and the USA: a patient chart review and physician survey. Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration 2024;25(1-2):16-25 (Goyal NA, Bonar K, Savic N et al; 3 authors are UCB Pharma employees and 2 work for Adelphi Real World; funding statement not seen), via PubMed abstract, 2024-01-23.
Clinical and genetic factors affecting diagnostic timeline of amyotrophic lateral sclerosis: a 15-year retrospective study. Neurological Research 2024;46(9):859-867 (Fang T, Pacut P, Bose A et al, University of Massachusetts Chan Medical Center), via PubMed abstract; funding and disclosures not seen, 2024-06-02.
Diagnostic problems and delay of diagnosis in amyotrophic lateral sclerosis. Clinical Neurology and Neurosurgery 2010;112(2):103-105 (Kraemer M, Buerger M, Berlit P), via PubMed abstract; funding and disclosures not seen, 2010-02.
Inappropriate surgeries resulting from misdiagnosis of early amyotrophic lateral sclerosis. Muscle and Nerve 2006;34(3):359-360 (Srinivasan J, Scala S, Jones HR, Saleh F, Russell JA), via PubMed abstract; funding and disclosures not seen, 2006-09.
Incidence and characteristics of spinal decompression surgery after the onset of symptoms of amyotrophic lateral sclerosis. Neurosurgery 2005;57(5):984-989 (Yoshor D, Klugh A 3rd, Appel SH, Haverkamp LJ), via PubMed abstract; funding and disclosures not seen, 2005-11.
Misdiagnosis in Amyotrophic Lateral Sclerosis. The Journal of Hand Surgery (American volume) 2023;48(8):822-826 (Thomson CG, Hutchinson PR, Stern PJ), via PubMed abstract; funding and disclosures not seen, 2023-05-16.
Mimics and chameleons in motor neurone disease. Practical Neurology 2013;13(3):153-164 (Turner MR, Talbot K, University of Oxford; funding from the Medical Research Council and the Motor Neurone Disease Association; no competing interests), via PubMed Central, 2013-04-24.
Amyotrophic lateral sclerosis mimic syndromes: a population-based study. Archives of Neurology 2000;57(1):109-113 (Traynor BJ, Codd MB, Corr B et al; Irish ALS Register), via PubMed abstract; funding and disclosures not seen, 2000-01.
Inclusion body myositis mimicking motor neuron disease. Archives of Neurology 2001;58(8):1253-1256 (Dabby R, Lange DJ, Trojaborg W et al), via PubMed abstract; funding and disclosures not seen, 2001-08.
Motor neuron disease associated with copper deficiency. Muscle and Nerve 2006;34(6):789-793 (Weihl CC, Lopate G, Washington University), via PubMed abstract; funding and disclosures not seen, 2006-12.
The Potential Misdiagnosis of Multifocal Motor Neuropathy as Amyotrophic Lateral Sclerosis-A Case Series. US Neurology 2018;14(2):102-107 (Lawson V, Robbins NM; funded in full by Baxalta, later acquired by Shire; 1 author reports advisory board work for immunoglobulin makers), via PubMed Central, 2018-11-12.
Spinal and Bulbar Muscular Atrophy. GeneReviews, University of Washington, Seattle (La Spada A; updated January 8, 2026), via PubMed abstract, 2026-01-08.
C9orf72 Frontotemporal Dementia and/or Amyotrophic Lateral Sclerosis. GeneReviews, University of Washington, Seattle (Gossye H, Engelborghs S, Van Broeckhoven C, van der Zee J; updated December 17, 2020), via PubMed abstract, 2020-12-17.
The diagnostic pathway and prognosis in bulbar-onset amyotrophic lateral sclerosis. Journal of the Neurological Sciences 2010;294(1-2):81-85 (Turner MR, Scaber J, Goodfellow JA et al), via PubMed abstract; funding and disclosures not seen, 2010-05-10.
A new member of the multidisciplinary ALS team: the otolaryngologist. Amyotrophic Lateral Sclerosis 2012;13(2):229-232 (Rubin AD, Griffin GR, Hogikyan ND, Feldman EL), via PubMed abstract; funding and disclosures not seen, 2012-02.
Otolaryngologist's role in the diagnosis of amyotrophic lateral sclerosis. BMJ Case Reports 2021;14(2):e234504 (Costa JB, Pereira D, Duarte D, Viana M), via PubMed abstract; funding and disclosures not seen, 2021-02-23.
Prognosis of amyotrophic lateral sclerosis with respiratory onset. Journal of Neurology, Neurosurgery and Psychiatry 2007;78(6):629-631 (Shoesmith CL, Findlater K, Rowe A, Strong MJ; no competing interests declared), via PubMed abstract, 2006-11-06.
ALS with respiratory onset: clinical features and effects of non-invasive ventilation on the prognosis. Amyotrophic Lateral Sclerosis 2010;11(4):379-382 (Gautier G, Verschueren A, Monnier A et al), via PubMed abstract; funding and disclosures not seen, 2010-08.
Evidence-based consensus guidelines for ALS genetic testing and counseling. Annals of Clinical and Translational Neurology 2023;10(11):2074-2091 (Roggenbuck J, Eubank BHF, Wright J, Harms MB, Kolb SJ; ALS Genetic Testing and Counseling Guidelines Expert Panel; funded by the ALS Association; 2 authors report consulting for Biogen, Ionis and others), via PubMed Central, 2023-09-10.
QALSODY (tofersen), intrathecal, prescribing information (openFDA label record, SPL version 4). Biogen Inc., via DailyMed and openFDA, 2026-10-23.
Sponsored genetic testing | ALS Identified™ Program | Invitae. Invitae (page copyright Labcorp); the program page carries an About Biogen statement, 2026-11-12.
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(6):e16264 (Van Damme P, Al-Chalabi A, Andersen PM et al; commissioned by the EAN; many authors report advisory or trial work for Biogen and other drugmakers), via PubMed Central, 2024-03-12.
Practice parameter update: the care of the patient with amyotrophic lateral sclerosis: multidisciplinary care, symptom management, and cognitive/behavioral impairment (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 2009;73(15):1227-1233 (Miller RG, Jackson CE, Kasarskis EJ et al; Quality Standards Subcommittee of the American Academy of Neurology), via PubMed abstract, 2009-10-13.
Effect of a multidisciplinary amyotrophic lateral sclerosis (ALS) clinic on ALS survival: a population based study, 1996-2000. Journal of Neurology, Neurosurgery and Psychiatry 2003;74(9):1258-1261 (Traynor BJ, Alexander M, Corr B, Frost E, Hardiman O), via PubMed abstract; funding and disclosures not seen, 2003-09.
A multidisciplinary clinic approach improves survival in ALS: a comparative study of ALS in Ireland and Northern Ireland. Journal of Neurology, Neurosurgery and Psychiatry 2015;86(5):496-501 (Rooney J, Byrne S, Heverin M et al), via PubMed abstract; funding and disclosures not seen, 2014-12-30.
ALS multidisciplinary clinic and survival. Results from a population-based study in Southern Italy. Journal of Neurology 2007;254(8):1107-1112 (Zoccolella S, Beghi E, Palagano G et al), via PubMed abstract; funding and disclosures not seen, 2007-04-13.
thinkALS™ for Faster Diagnosis. The ALS Association (patient foundation), 2026-11-12.
Amyotrophic lateral sclerosis, ORPHA:803, rare disease cross-referencing (Orphadata API). Orphanet, INSERM, via Orphadata, CC BY 4.0, 2026-06-23.
NIH Genetic Testing Registry tests for amyotrophic lateral sclerosis, concept C0002736 (59 tests listed in NCBI E-utilities on November 12, 2026). National Center for Biotechnology Information, NIH, 2026-11-12.
ICD-10-CM search results for "G12.21" (Clinical Table Search Service). National Library of Medicine, 2026-11-12.

A reference for licensed professionals, checked against its sources on November 12, 2026. It summarizes what the cited guidance says and does not tell anyone how to diagnose or treat a specific patient. Guidelines change; the current guideline and the treating clinician's judgment govern. Trial Friend is an independent information service, not a medical provider.