a neurodegenerative disease with upper and lower motor neuron dysfunction.
Epidemiology
- Mean age of onset is 65 years.
Etiology
Pathophysiology
- Classically affects the entire motor neuron system at two or more levels (both upper and lower motor neuron degeneration).
- Upper motor neurons in the precentral gyrus and, frequently, prefrontal cortex
- Lower motor neurons in the anterior horn of the spinal cord and brainstem
- Pathology
- UMN: degeneration & atrophy of lateral corticospinal tracts, precentral gyrus
- LMN: degeneration of anterior horn (thin anterior roots) & cranial nerve motor nuclei
- Muscle: denervation atrophy (angular fibers with crowded nuclei)
Clinical features
General disease characteristics
- Both upper motor neuron (UMN) and lower motor neuron (LMN) signs are present (see Upper motor neuron (UMN) injury vs. lower motor neuron (LMN) injury)
- Constant disease progression: it usually starts in one arm and/or leg then progresses to the contralateral side
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, dysphagia, and tongue atrophy (20% of cases at disease onset)
- Pseudobulbar palsy with pseudobulbar affect may develop.
- Fasciculations, cramps, and muscle stiffness
- Weight loss
- Split hand sign: a wasting pattern in which the muscles of the thenar eminence atrophy due to degeneration of the lateral portion of the anterior horn of the spinal cord
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.
- Life-threatening symptoms
- Respiratory failure due to paralysis of respiratory muscles
- Dysphagia due to bulbar weakness or pseudobulbar palsy
Diagnosis
- Electromyography
- Denervation: fibrillations, positive sharp waves, and large amplitudes
- Fasciculations
Differential Diagnosis
- Myasthenia gravis
- Weakness improves with acetylcholinesterase inhibitors
- No UMN or LMN signs
Treatment
- Riluzole
- A sodium-channel blocker that inhibits glutamate release in the CNS and decreases glutamate excitotoxicity
- Prolongs survival and slows functional decline in patients with ALS (on average, for 3 months)
- Edaravone
- A free radical scavenger
- Has been shown to slow functional decline in some patients with ALS