- Clinical science
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.
- Incidence: 2–3 cases/100,000 population per year
- Sex: ♂ > ♀
- Mean age of onset is 65 years
- Can be sporadic (90%) or familial (10%)
Epidemiological data refers to the US, unless otherwise specified.
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.
- Upper motor neurons in the precentral gyrus; and, frequently, prefrontal cortex
- Lower motor neurons; in the anterior horn of the spinal cord and brainstem
General disease characteristics
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- 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.
- 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
- Cognitive impairment (approx. 15% of ALS patients meet the criteria for
- Autonomic symptoms (e.g., constipation) and sensory loss are possible but rare
- Respiratory failure due to paralysis of respiratory muscles
- Dysphagia due to bulbar weakness
- Physical examination (including testing reflexes, Babinski's sign, etc.)
- Denervation: indicated, e.g., by fibrillations, positive sharp waves, and large amplitudes
- Nerve conduction studies: usually normal
- MRI and laboratory tests to exclude other potential diagnoses (see “Differential diagnosis” above)
- Increased creatine kinase
- Slowly progressing asymmetrical weakness, esp. in the muscles of the distal extremities
- Muscle atrophy is rare
- EMG can reveal conduction blocks
- Highly elevated anti-GM1-ganglioside antibody titers
The differential diagnoses listed here are not exhaustive.
- Multidisciplinary and symptomatic therapy
- 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