a neurodegenerative disease with upper and lower motor neuron dysfunction.

Epidemiology

Etiology

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

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

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

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

Electromyography
- Denervation: fibrillations, positive sharp waves, and large amplitudes
- Fasciculations

Myasthenia gravis
- Weakness improves with acetylcholinesterase inhibitors
- No UMN or LMN signs

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