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Amyotrophic lateral sclerosis

Last updated: August 10, 2021

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Amyotrophic lateral sclerosis (ALS), formerly known as Lou Gehrig disease, is a neurodegenerative disease with upper and lower motor neuron dysfunction. The disease most commonly manifests between fifty and seventy years of age, often beginning with asymmetric weakness in the hands or feet. However, initial presentation is highly variable and some patients present with atypical/non-specific symptoms such as subtle vocal changes. As the disease progresses, most patients eventually develop one or both of the life-threatening symptoms: respiratory impairment and dysphagia. Riluzole and edaravone are currently the only drugs approved for the treatment of ALS. Multidisciplinary care is extremely important and includes nursing care, physiotherapy, and eventually assisted ventilation and enteral feeding. Most patients will die within 3–5 years, although approx. 30% have a chance of living longer.

  • Prevalence: 5/100,000 population in the US [1]
  • Incidence: 2–3 cases/100,000 population per year worldwide [2]
  • Sex: >
  • Mean age of onset is 65 years.
  • Familial history of ALS in 5–10% of cases ; 90–95% are sporadic

References:[2][3]

Epidemiological data refers to the US, unless otherwise specified.

The Definitive cause of ALS is still unknown. Studies have suggested an interaction between genetic predisposition and environmental factors.

Genetics

Mutations of the following genes have been found in approx. 70% of familial clusters and some sporadic cases. [4]

  • SOD1 [5]
    • Codes for superoxide dismutase
    • Mutations are associated with either a very aggressive or very slow disease progression
    • Account for 15–20% of familial ALS cases
  • TARDBP
    • Сodes for the TDP-43 protein involved in DNA repair
    • In ALS, abnormally ubiquitylated TDP-43 forms inclusions within motor neurons.
    • Accounts for ∼ 5% of familial ALS cases
  • C9orf72
    • Most common mutated gene in familial ALS (account for 30–40% of familial ALS cases)
    • Associated with a combination of ALS and frontotemporal dementia
  • FUS
    • Mutations are associated with a young-onset rapidly-progressing ALS. [1]
    • Accounts for ∼ 5% of familial ALS cases

Environmental risk factors [6]

  • Exposure to the following substances:
    • β-N-methylamino-L-alanine [7]
    • Pesticides (e.g., cis-chlordane, pentachlorobenzene) [8]
    • Lead
  • Head trauma
  • Individuals serving in US military [6][9]
  • Smoking

References:[10][11]

General disease characteristics

Early symptoms

Late symptoms

References:[11][12]

The differential diagnoses listed here are not exhaustive.

Rilouzole rilly helps treating Lou Gehrig disease

References:[14][15]

  • Most patients die within 3–5 years
  • 5-year-survival: 30%
  • 10-year-survival: 10–20%
  • Early bulbar and/or respiratory symptoms are associated with a worse prognosis

References:[1][16]

  1. Oskarsson B, Gendron TF, Staff NP. Amyotrophic Lateral Sclerosis: An Update for 2018. Mayo Clinic Proceedings. 2018; 93 (11): p.1617-1628. doi: 10.1016/j.mayocp.2018.04.007 . | Open in Read by QxMD
  2. Van Es MA, Hardiman O, Chio A, et al. Amyotrophic lateral sclerosis. The Lancet. 2017; 390 (10107): p.2084-2098. doi: 10.1016/s0140-6736(17)31287-4 . | Open in Read by QxMD
  3. Boylan K. Familial amyotrophic lateral sclerosis. Neurol Clin. 2015; 33 (4): p.807-830. doi: 10.1016/j.ncl.2015.07.001 . | Open in Read by QxMD
  4. Hardiman O, Al-Chalabi A, Chio A, et al. Amyotrophic lateral sclerosis. Nature Reviews Disease Primers. 2017; 3 (1). doi: 10.1038/nrdp.2017.71 . | Open in Read by QxMD
  5. Andersen PM, Al-Chalabi A. Clinical genetics of amyotrophic lateral sclerosis: what do we really know?. Nature Reviews Neurology. 2011; 7 (11): p.603-615. doi: 10.1038/nrneurol.2011.150 . | Open in Read by QxMD
  6. Oskarsson B, Horton DK, Mitsumoto H. Potential Environmental Factors in Amyotrophic Lateral Sclerosis. Neurol Clin. 2015; 33 (4): p.877-888. doi: 10.1016/j.ncl.2015.07.009 . | Open in Read by QxMD
  7. Cox PA, Sacks OW. Cycad neurotoxins, consumption of flying foxes, and ALS-PDC disease in Guam. Neurology. 2002; 58 (6): p.956-959. doi: 10.1212/wnl.58.6.956 . | Open in Read by QxMD
  8. Wang M-D, Little J, Gomes J, Cashman NR, Krewski D. Identification of risk factors associated with onset and progression of amyotrophic lateral sclerosis using systematic review and meta-analysis. Neurotoxicology. 2017; 61 : p.101-130. doi: 10.1016/j.neuro.2016.06.015 . | Open in Read by QxMD
  9. Beard JD, Kamel F. Military Service, Deployments, and Exposures in Relation to Amyotrophic Lateral Sclerosis Etiology and Survival. Epidemiol Rev. 2014; 37 (1): p.55-70. doi: 10.1093/epirev/mxu001 . | Open in Read by QxMD
  10. Beckman JS, Estévez AG, Crow JP, Barbeito L. Superoxide dismutase and the death of motoneurons in ALS. Trends Neurosci. 2001; 24 (11 Suppl): p.S15-20.
  11. Brown RH, Al-Chalabi A. Amyotrophic Lateral Sclerosis. N Engl J Med. 2017; 377 (2): p.162-172. doi: 10.1056/nejmra1603471 . | Open in Read by QxMD
  12. Hulisz D. Amyotrophic lateral sclerosis: disease state overview.. Am J Manag Care. 2018; 24 (15 Suppl): p.S320-S326.
  13. Daube JR. Electrodiagnostic studies in amyotrophic lateral sclerosis and other motor neuron disorders. Muscle Nerve. 2000; 23 (10): p.1488-1502.
  14. Miller RG, Mitchell JD, Moore DH. Riluzole for amyotrophic lateral sclerosis (ALS)/motor neuron disease (MND). Cochrane Database Syst Rev. 2012; 14 (3): p.CD001447. doi: 10.1002/14651858.CD001447.pub3 . | Open in Read by QxMD
  15. Körner S, Sienawski M, Kollewe K et al. Speech therapy and communication device: impact on quality of life and mood in patients with amyotrophic lateral sclerosis. Amyotroph Lateral Scler Frontotemporal Degener. 2013; 14 (1): p.20-25. doi: 10.3109/17482968.2012.69238 . | Open in Read by QxMD
  16. Chiò A, Logroscino G, Hardiman O, et al. Prognostic factors in ALS: A critical review. Amyotrophic Lateral Sclerosis. 2009; 10 (5-6): p.310-323. doi: 10.3109/17482960802566824 . | Open in Read by QxMD