Amyotrophic lateral sclerosis: a clinical review

Topic: Amyloid, tau and blood-test diagnosis

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder affecting primarily the motor system, but in which extra-motor manifestations are increasingly recognized. The loss of upper and lower motor neurons in the motor cortex, the brain stem nuclei and the anterior horn of the spinal cord gives rise to progressive muscle weakness and wasting. ALS often has a focal onset but subsequently spreads to different body regions, where failure of respiratory muscles typically limits survival to 2-5 years after disease onset. In up to 50% of cases, there are extra-motor manifestations such as changes in behaviour, executive dysfunction and language problems. In 10%-15% of patients, these problems are severe enough to meet the clinical criteria of frontotemporal dementia (FTD). In 10% of ALS patients, the family history suggests an autosomal dominant inheritance pattern. The remaining 90% have no affected family members and are classified as sporadic ALS. The causes of ALS appear to be heterogeneous and are only partially understood. To date, more than 20 genes have been associated with ALS. The most common genetic cause is a hexanucleotide repeat expansion in the C9orf72 gene, responsible for 30%-50% of familial ALS and 7% of sporadic ALS. These expansions are also a frequent cause of frontotemporal dementia, emphasizing the molecular overlap between ALS and FTD. To this day there is no cure or effective treatment for ALS and the cornerstone of treatment remains multidisciplinary care, including nutritional and respiratory support and symptom management. In this review, different aspects of ALS are discussed, including epidemiology, aetiology, pathogenesis, clinical features, differential diagnosis, investigations, treatment and future prospects.

@article{masrori2020-32526057,
  author  = {Masrori, P. and Van Damme, P.},
  title   = {{Amyotrophic lateral sclerosis: a clinical review}},
  journal = {European journal of neurology},
  year    = {2020},
  doi     = {10.1111/ene.14393},
  pmid    = {32526057},
  url     = {https://doi.org/10.1111/ene.14393}
}

Key findings

• To date, more than 20 genes have been associated with ALS.

Why it matters

This clinical review of amyotrophic lateral sclerosis (ALS) notes that some ALS patients also have frontotemporal dementia, but it focuses on ALS. It does not provide information on treating, curing, or preventing Alzheimer's disease.

New to this subject? Start with our plain-English guide: Getting a diagnosis →

Study details

• Evidence strengthLow

Read the original

• DOI: 10.1111/ene.14393
• PubMed: 32526057
• Original source →
• Free full text: European Journal of Neurology →

Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).

Studies this one cites

Referenced by this study and also in the alzhub library, so you can read them here. Showing 12 of 16.

• TDP-43 Mutations in Familial and Sporadic Amyotrophic Lateral Sclerosis Science · 2008-02-28 · usefulness score 64/100 · Disease mechanisms
• Genome-wide association study identifies 19p13.3 (UNC13A) and 9p21.2 as susceptibility loci for sporadic amyotrophic lateral sclerosis Nature genetics · 2009-09-06 · usefulness score 64/100 · How common it is
• A hexanucleotide repeat expansion in C9ORF72 is the cause of chromosome 9p21-linked ALS-FTD Neuron · 2011-09-21 · usefulness score 63/100 · Lewy body dementia
• Prognosis for patients with amyotrophic lateral sclerosis: development and validation of a personalised prediction model The Lancet. Neurology · 2018-03-26 · usefulness score 63/100 · Getting a diagnosis
• Frontotemporal lobar degeneration: a consensus on clinical diagnostic criteria Neurology · 1998-12-01 · usefulness score 62/100 · Lewy body dementia
• Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis Science (New York, N.Y.) · 2006-10-01 · usefulness score 62/100 · Lewy body dementia
• Mutations in UBQLN2 cause dominant X-linked juvenile and adult-onset ALS and ALS/dementia Nature · 2011-08-21 · usefulness score 62/100 · Lewy body dementia
• Expanded GGGGCC hexanucleotide repeat in noncoding region of C9ORF72 causes chromosome 9p-linked FTD and ALS Neuron · 2011-09-21 · usefulness score 62/100 · Lewy body dementia
• Exome sequencing reveals VCP mutations as a cause of familial ALS Neuron · 2010-12-01 · usefulness score 61/100 · How common it is
• Amyotrophic lateral sclerosis Lancet (London, England) · 2017-05-25 · usefulness score 59/100 · Lewy body dementia
• TDP-43 and FUS in amyotrophic lateral sclerosis and frontotemporal dementia The Lancet. Neurology · 2010-10-01 · usefulness score 57/100 · Lewy body dementia
• Clinical diagnosis and management of amyotrophic lateral sclerosis Nature reviews. Neurology · 2011-10-11 · usefulness score 55/100 · Getting a diagnosis

Later studies that cite this one

6 studies in the alzhub library list this one in their references.

• Molecular Mechanisms of Protein Aggregation in ALS-FTD: Focus on TDP-43 and Cellular Protective Responses Cells · 2025-05-08 · usefulness score 44/100 · Brain tissue and pathology
• Cognitive and Behavioral Manifestations in ALS: Beyond Motor System Involvement Diagnostics (Basel, Switzerland) · 2021-03-30 · usefulness score 44/100 · Digital health tools
• The role of autophagy in the pathogenesis and treatment of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) Autophagy Reports · 2025-03-20 · usefulness score 42/100 · Lewy body dementia
• ALS and Huntington Disease: Unraveling the Connections between TDP-43 and Huntingtin Journal of Neuroscience · 2026-03-11 · usefulness score 40/100 · Brain tissue and pathology
• Compositional Control of Aging Kinetics in TDP-43 Condensates PRX Life · 2025-10-07 · usefulness score 39/100 · Brain tissue and pathology
• TDP-43 Regulates Rab4 Levels to Support Synaptic Vesicle Recycling and Neuromuscular Connectivity in Drosophila and Human ALS Models International Journal of Molecular Sciences · 2025-11-14 · usefulness score 38/100 · Brain tissue and pathology

Related studies in Getting a diagnosis

• Characterization of frontotemporal dementia and/or amyotrophic lateral sclerosis associated with the GGGGCC repeat expansion in C9ORF72 Brain : a journal of neurology · 2012-03-01 · usefulness score 60/100
• The overlap of amyotrophic lateral sclerosis and frontotemporal dementia Neurology · 2002-10-01 · usefulness score 59/100
• The syndrome of cognitive impairment in amyotrophic lateral sclerosis: a population-based study Journal of neurology, neurosurgery, and psychiatry · 2011-08-11 · usefulness score 55/100
• Amyotrophic lateral sclerosis - frontotemporal spectrum disorder (ALS-FTSD): Revised diagnostic criteria Amyotrophic lateral sclerosis & frontotemporal degeneration · 2017-01-05 · usefulness score 54/100
• Are amyotrophic lateral sclerosis patients cognitively normal? Neurology · 2003-04-01 · usefulness score 54/100
• Intraneuronal aluminum accumulation in amyotrophic lateral sclerosis and Parkinsonism-dementia of Guam Science (New York, N.Y.) · 1982-09-01 · usefulness score 51/100

Also tagged “bodies”

1,017 studies in the library carry the topic tag “bodies”; these are this study's neighbours in a fixed, alphabetical-by-hash tour of them, not the closest in content. All 1,017 tagged studies.

• alpha-synuclein fibrillogenesis is nucleation-dependent. Implications for the pathogenesis of Parkinson's disease The Journal of biological chemistry · 1999-07-01 · usefulness score 45/100 · Lewy body dementia
• The frontotemporal dementia-motor neuron disease continuum Lancet (London, England) · 2016-03-14 · usefulness score 56/100 · Getting a diagnosis
• Phenotype associated with APP duplication in five families Brain : a journal of neurology · 2006-09-07 · usefulness score 57/100 · Brain tissue and pathology

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More on Getting a diagnosis

• A review that covers this ground The prevalence and incidence of dementia with Lewy bodies: a systematic review of population and clinical studies Psychological medicine · 2013-03-25 · usefulness score 65/100
• Newest in this subject The Contribution of Routinely Collected Clinical Data to Dementia Identification in Primary Care: A Cross-Sectional Study Research Square · 2026-10-28 · Preprint — not yet peer-reviewed · usefulness score 16/100
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See all studies in Getting a diagnosis →