• Clinical science

Amyotrophic lateral sclerosis

Abstract

Amyotrophic lateral sclerosis (ALS), also 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 is the only drug that has proven effective in the treatment of ALS and is indicated for all patients. 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

  • Incidence: 2–3 cases/100,000 population per year
  • Sex: >
  • Mean age of onset is 65 years
  • Can be sporadic (90%) or familial (10%)

References:[1][2]

Epidemiological data refers to the US, unless otherwise specified.

Etiology

  • Unknown

Pathophysiology

Classically affects the entire motor neuron system at two or more levels (both upper and lower motor neuron degeneration); . Subtypes of the disease exist that only affect certain parts of the motor system (e.g., UMN only, LMN only, prefrontal cortex only, bulbar muscles only).Can be caused by mutations of superoxide dismutase 1, though the mutation is found only in a minority of patients

References:[1]

Clinical features

General disease characteristics

UMN LMN
Muscle tone
  • ↓ flaccid
Tendon reflexes
Findings
  • Constant disease progression: it usually starts in one arm and/or leg then progresses to the contralateral side and eventually, after months or years, affects the respiratory system.

Early symptoms

  • Symptoms are highly variable and potentially non-specific (e.g., subtle vocal changes or difficulties grasping objects)
  • Asymmetric limb weakness, often beginning with weakness in the hands and feet
  • Bulbar symptoms such as dysarthria and dysphagia (20% of cases at disease onset)
  • Fasciculations, cramps, and muscle stiffness

Late symptoms

  • Cognitive impairment (approx. 15% of ALS patients meet the criteria for frontotemporal dementia)
  • Autonomic symptoms (e.g., constipation) and sensory loss are possible but rare
  • Life-threatening symptoms
    • Respiratory failure due to paralysis of respiratory muscles
    • Dysphagia due to bulbar weakness

References:[1]

Diagnostics

  • Physical examination (including testing reflexes, Babinski's sign, etc.)
  • Electromyography
    • Denervation: indicated, e.g., by fibrillations, positive sharp waves, and large amplitudes
    • Fasciculations
  • Nerve conduction studies: usually normal
  • MRI and laboratory tests to exclude other potential diagnoses (see “Differential diagnosis” above)
  • Increased creatine kinase

References:[3][1]

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
  • Multidisciplinary and symptomatic therapy

References:[4][5]

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:[1][6]

  • 1. Armon C. Amyotrophic Lateral Sclerosis. In: Lorenzo N. Amyotrophic Lateral Sclerosis. New York, NY: WebMD. http://emedicine.medscape.com/article/1170097. Updated March 23, 2016. Accessed March 1, 2017.
  • 2. Boylan K. Familial amyotrophic lateral sclerosis. Neurol Clin. 2015; 33(4): pp. 807–830. doi: 10.1016/j.ncl.2015.07.001.
  • 3. Daube JR. Electrodiagnostic studies in amyotrophic lateral sclerosis and other motor neuron disorders. Muscle Nerve. 2000; 23(10): pp. 1488–1502. pmid: 11003783.
  • 4. 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.
  • 5. 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.
  • 6. 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.
  • 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.
last updated 10/27/2018
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