• Clinical science

Amyotrophic lateral sclerosis

Summary

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.

Epidemiology

  • 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.
  • Can be sporadic (90%) or familial (10%).

References:[3][2]

Epidemiological data refers to the US, unless otherwise specified.

Etiology

The definitive cause of ALS is still unknown, studies have suggested an interaction between genetic predisposition and environmental factors. [4]

  • Genetics: Mutations of the following genes have been found in approx. 70% of familial clusters and some sporadic cases. [5]
    • SOD1: codes for superoxide dismutase; mutations are associated with either a very agressive or very slow disease progression [6]
    • TARDBP
    • C9orf72
    • FUS: Mutations are associated with a young-onset rapidly-progressing ALS. [1]
  • Environmental risk factors [7]
    • Exposure to the following substances:
      • β-N-methylamino-L-alanine [8]
      • Pesticides (e.g., cis-chlordane, pentachlorobenzene) [9]
      • Lead
    • Head trauma
    • Individuals serving in US military [7][10]
    • Smoking

Pathophysiology

References:[11][4]

Clinical features

General disease characteristics

Early symptoms

Late symptoms

  • Cognitive impairment (approx. 15% of ALS patients meet the criteria for frontotemporal dementia)
  • Autonomic symptoms (e.g., constipation, bladder dysfunction) may develop; the mechanism of development is unclear. [1]
  • Life-threatening symptoms
    • Respiratory failure due to paralysis of respiratory muscles
    • Dysphagia due to bulbar weakness

References:[12][4]

Diagnostics

References:[13][1][4]

Pathology

Macroscopic: atrophy of the entire motor system, e.g., narrowing of gray matter due to atrophy of ventral roots

Differential diagnoses

The differential diagnoses listed here are not exhaustive.

Treatment

  • Riluzole: a glutamate antagonist
    • Decreases glutamate excitotoxicity in neurons
    • Prolongs survival of ALS patients (on average, for 3 months) [1]
  • Edaravone (free radical scavenger): has been shown to slow functional decline in some patients with ALS
  • Multidisciplinary and symptomatic therapy

Rilouzole rilly helps treating Lou Gehrig disease

References:[14][15]

Prognosis

  • 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:[16][1]

  • 1. Oskarsson B, Gendron TF, Staff NP. Amyotrophic Lateral Sclerosis: An Update for 2018. Mayo Clinic Proceedings. 2018; 93(11): pp. 1617–1628. doi: 10.1016/j.mayocp.2018.04.007.
  • 2. Van Es MA, Hardiman O, Chio A, et al. Amyotrophic lateral sclerosis. The Lancet. 2017; 390(10107): pp. 2084–2098. doi: 10.1016/s0140-6736(17)31287-4.
  • 3. Boylan K. Familial amyotrophic lateral sclerosis. Neurol Clin. 2015; 33(4): pp. 807–830. doi: 10.1016/j.ncl.2015.07.001.
  • 4. Brown RH, Al-Chalabi A. Amyotrophic Lateral Sclerosis. N Engl J Med. 2017; 377(2): pp. 162–172. doi: 10.1056/nejmra1603471.
  • 5. 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.
  • 6. Andersen PM, Al-Chalabi A. Clinical genetics of amyotrophic lateral sclerosis: what do we really know?. Nature Reviews Neurology. 2011; 7(11): pp. 603–615. doi: 10.1038/nrneurol.2011.150.
  • 7. Oskarsson B, Horton DK, Mitsumoto H. Potential Environmental Factors in Amyotrophic Lateral Sclerosis. Neurol Clin. 2015; 33(4): pp. 877–888. doi: 10.1016/j.ncl.2015.07.009.
  • 8. Cox PA, Sacks OW. Cycad neurotoxins, consumption of flying foxes, and ALS-PDC disease in Guam. Neurology. 2002; 58(6): pp. 956–959. doi: 10.1212/wnl.58.6.956.
  • 9. 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: pp. 101–130. doi: 10.1016/j.neuro.2016.06.015.
  • 10. Beard JD, Kamel F. Military Service, Deployments, and Exposures in Relation to Amyotrophic Lateral Sclerosis Etiology and Survival. Epidemiol Rev. 2014; 37(1): pp. 55–70. doi: 10.1093/epirev/mxu001.
  • 11. Beckman JS, Estévez AG, Crow JP, Barbeito L. Superoxide dismutase and the death of motoneurons in ALS. Trends Neurosci. 2001; 24(11 Suppl): pp. S15–20. pmid: 11881740.
  • 12. Hulisz D. Amyotrophic lateral sclerosis: disease state overview. Am J Manag Care. 2018; 24(15 Suppl): pp. S320–S326. pmid: 30207670.
  • 13. Daube JR. Electrodiagnostic studies in amyotrophic lateral sclerosis and other motor neuron disorders. Muscle Nerve. 2000; 23(10): pp. 1488–1502. pmid: 11003783.
  • 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.
  • 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): pp. 20–25. doi: 10.3109/17482968.2012.69238.
  • 16. Chiò A, Logroscino G, Hardiman O, et al. Prognostic factors in ALS: A critical review. Amyotrophic Lateral Sclerosis. 2009; 10(5-6): pp. 310–323. doi: 10.3109/17482960802566824.
last updated 11/04/2020
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