Overview

About amyotrophic lateral sclerosis (ALS)

Last reviewed 1 November 2026. General information only — it does not describe any individual's condition.

Names and terminology

• Amyotrophic lateral sclerosis (ALS) is the standard medical name.
• Motor neuron disease (MND) is the usual term in the UK, Ireland and Australia. It is an umbrella term that also includes rarer conditions such as primary lateral sclerosis and progressive muscular atrophy, so it is not always identical to ALS.
• Lou Gehrig's disease is a common name in the United States; Charcot's disease is a historical name.
• C9orf72 FTD/ALS (catalogued as FTDALS1, OMIM #105550) refers to frontotemporal dementia and/or ALS caused by a repeat expansion in the C9orf72 gene.
• Flail arm syndrome (also called brachial amyotrophic diplegia or the Vulpian-Bernhardt form) is a pattern of ALS, not a separate disease.

What happens in ALS

ALS damages motor neurons: the upper motor neurons that run from the brain to the spinal cord, and the lower motor neurons that run from the spinal cord to the muscles. As these cells stop working, muscles weaken and waste. Depending on which nerves are affected, this can involve the arms, legs, speech, swallowing and breathing. Some people also experience changes in thinking or behaviour, and a minority develop frontotemporal dementia (FTD).

How fast ALS progresses varies a great deal between people. Survival figures in research papers are averages for groups and cannot predict what will happen to any one person.

Genetics and C9orf72

Most people with ALS have no known family history ("sporadic" ALS). In a smaller group the disease runs in families, and a single gene change can be identified.

The most common known genetic cause is a repeat expansion in the C9orf72 gene: a short DNA sequence (GGGGCC) repeated hundreds or thousands of times instead of a few. In a large 2012 study of people of European ancestry it was found in about 7% of people with sporadic ALS and about 39% of those with familial ALS, and it was much rarer in Asian populations [1]. The same expansion can cause ALS, FTD, or both, even within one family.

• Inheritance. It is passed on in an autosomal dominant way: each child of a carrier has a 50% chance of inheriting it.
• Penetrance. Inheriting the expansion does not mean someone will certainly become ill, or when. The chance of developing symptoms rises with age and is incomplete [2, 3].
• Repeat size. Laboratories use different cut-offs to call a result normal, intermediate or expanded, and the expansion can vary in length between tissues. Families should ask their genetics service which thresholds the laboratory used.
• Testing. Evidence-based guidelines published in 2023 recommend offering genetic testing to all people with ALS, with genetic counselling. Relatives who are well may choose predictive testing as adults, after counselling [4].

There is no approved treatment aimed specifically at C9orf72. Two antisense drugs designed for it, BIIB078 [5] and WVE-004, were discontinued after early trials did not show clinical benefit. Laboratory research continues on how the expansion causes harm [6].

Patterns of ALS, including flail arm

Doctors describe ALS by where it starts (for example limb onset or bulbar onset, affecting speech and swallowing) and by which motor neurons are mainly involved. In the flail arm pattern, weakness and wasting affect mainly both arms, especially the shoulders and upper arms, while the legs and speech are relatively spared for a period.

In specialist clinic cohorts, people with the flail arm pattern lived longer on average than people with classic ALS [7]. A 2026 population study suggests that this advantage reflects predominant lower-motor-neuron involvement rather than arm onset as such [8]. These are averages, and the pattern can change as the disease progresses.

How ALS is diagnosed

There is no single test for ALS. Neurologists combine the history and examination with tests that look for evidence of motor neuron damage and rule out conditions that can look similar.

• Criteria. The Gold Coast criteria (2020) require progressive motor decline with upper and lower motor neuron signs in at least one body region, or lower motor neuron signs in two, after other causes are excluded [9]. A 2026 pooled analysis of 3,007 people found they identify about 96% of people with ALS, with less certain specificity [10].
• Electromyography (EMG) and nerve conduction studies detect nerve damage in muscles that may not yet be weak, and help exclude other nerve disorders.
• Neurofilament light chain, a protein released by damaged nerve cells, is usually raised in blood and spinal fluid in ALS. It supports a diagnosis but also rises in other neurological diseases [11].
• Imaging and blood tests help rule out other causes, such as problems in the neck or immune-mediated nerve conditions.

Approved treatments

No treatment cures ALS or reverses it. Approval and availability differ by country; ask your specialist team what applies where you live.

• Riluzole was the first approved ALS medicine. Its pivotal trial showed a modest survival benefit [12], and the 2024 European guideline recommends it [13].
• Edaravone is approved in the United States and some other countries. It is not authorised in the European Union, and the European guideline does not recommend it outside clinical trials [13].
• Tofersen is an antisense drug for people with ALS caused by changes in the SOD1 gene only. In its phase 3 trial it lowered neurofilament levels but did not meet its main clinical endpoint at 28 weeks [14]; it was approved in the US on the basis of the biomarker effect.

Many experimental drugs are in trials. Results from small or early studies, and company announcements, often do not hold up in larger trials. For example, a phase 2b trial of low-dose interleukin-2 did not meet its main goal, although a subgroup did better [15]. The research feed tracks these results as they are published.

Care and support

The 2024 European Academy of Neurology guideline [13] emphasises:

• Specialised multidisciplinary care — a coordinated team (neurology, nursing, physiotherapy, occupational and speech therapy, nutrition, respiratory and palliative care). A 2026 Austrian study linked a specialised clinic with longer survival [16].
• Breathing support. Non-invasive ventilation through a mask improved survival and quality of life in a randomised trial, particularly in people without severe swallowing problems [17].
• Nutrition. Weight loss is common; early discussion of feeding support, including a feeding tube (gastrostomy), is recommended. A high-calorie supplement did not improve survival overall in a randomised trial [18].
• Communication. Early speech assessment and access to communication aids, including voice banking and eye-gaze devices.
• Exercise. Evidence is limited; a Cochrane review found too few trials to draw firm conclusions [19]. A physiotherapist can advise on safe activity.
• Planning ahead. Advance care planning, discussed at a pace that suits the person and their family.

International support: the International Alliance of ALS/MND Associations lists national associations. In Europe, the European Reference Network for neuromuscular diseases (EURO-NMD) connects specialist centres.

What is still unknown

• Why motor neurons degenerate in most people with ALS, and why progression varies so much.
• Whether reliable biomarkers can speed up diagnosis and make trials shorter and more informative.
• Which treatments might slow C9orf72-related disease; none has yet succeeded in people.
• How to predict who among healthy carriers of a genetic change will become ill, and when.

References

1. Majounie E, et al. Frequency of the C9orf72 hexanucleotide repeat expansion in patients with ALS and FTD. Lancet Neurol 2012. doi:10.1016/S1474-4422(12)70043-1
2. Murphy NA, et al. Age-related penetrance of the C9orf72 repeat expansion. Sci Rep 2017. doi:10.1038/s41598-017-02364-1
3. Douglas AGL, et al. Personalised penetrance estimation for C9orf72-related ALS and FTD. BMJ Neurol Open 2024. doi:10.1136/bmjno-2024-000792
4. Roggenbuck J, et al. Evidence-based consensus guidelines for ALS genetic testing and counseling. Ann Clin Transl Neurol 2023. doi:10.1002/acn3.51895
5. van den Berg LH, et al. Safety, tolerability, and pharmacokinetics of antisense oligonucleotide BIIB078 in C9orf72-associated ALS. Lancet Neurol 2024. doi:10.1016/S1474-4422(24)00216-3
6. Jiang X, et al. Blocking RAN translation without altering repeat RNAs rescues C9ORF72-related ALS and FTD phenotypes. Science 2026. doi:10.1126/science.adv2600
7. Wijesekera LC, et al. Natural history and clinical features of the flail arm and flail leg ALS variants. Neurology 2009. doi:10.1212/01.wnl.0000345041.83406.a2
8. Calvo A, et al. What do ALS motor phenotypes measure? J Neurol 2026. doi:10.1007/s00415-026-14134-z
9. Shefner JM, et al. A proposal for new diagnostic criteria for ALS. Clin Neurophysiol 2020. doi:10.1016/j.clinph.2020.04.005
10. Shrestha N, et al. Gold Coast criteria for ALS diagnosis: individual participant data meta-analysis. J Neurol 2026. doi:10.1007/s00415-026-14046-y
11. Verde F, et al. CSF and blood neurofilament light chain levels in ALS and FTD: a meta-analysis. Eur J Neurol 2024. doi:10.1111/ene.16371
12. Bensimon G, et al. A controlled trial of riluzole in ALS. N Engl J Med 1994. doi:10.1056/NEJM199403033300901
13. Van Damme P, et al. EAN guideline on the management of ALS in collaboration with ERN EURO-NMD. Eur J Neurol 2024. doi:10.1111/ene.16264
14. Miller TM, et al. Trial of antisense oligonucleotide tofersen for SOD1 ALS. N Engl J Med 2022. doi:10.1056/NEJMoa2204705
15. Bensimon G, et al. Low-dose IL-2 as add-on therapy to riluzole (MIROCALS). Lancet 2025. doi:10.1016/S0140-6736(25)00262-4
16. Keritam O, et al. Implementation of specialised care improves survival in patients with ALS. Neurol Res Pract 2026. doi:10.1186/s42466-026-00528-x
17. Bourke SC, et al. Effects of non-invasive ventilation on survival and quality of life in ALS: a randomised controlled trial. Lancet Neurol 2006. doi:10.1016/S1474-4422(05)70326-4
18. Ludolph AC, et al. Effect of high-caloric nutrition on survival in ALS. Ann Neurol 2020. doi:10.1002/ana.25661
19. Dal Bello-Haas V, Florence JM. Therapeutic exercise for people with ALS or MND. Cochrane Database Syst Rev 2013. doi:10.1002/14651858.CD005229.pub3