Overview
Definition
A rapidly progressive, fatal neurodegenerative disease that selectively destroys both upper and lower motor neurons.
Epidemiology
Most common motor neuron disease. Average age of onset is 55-75. Survival is typically 3-5 years from symptom onset.
Etiology & Risk Factors
- Mostly sporadic (90%).
- Familial cases (10%) linked to mutations in SOD1, C9orf72, or TDP-43.
Clinical Symptoms
- Asymmetric limb weakness (often starting with hand clumsiness or foot drop)
- Upper Motor Neuron (UMN) signs: Spasticity, hyperreflexia, Babinski sign
- Lower Motor Neuron (LMN) signs: Muscle atrophy, fasciculations (twitching), weakness
- Bulbar involvement: Dysarthria, dysphagia, pseudobulbar affect (inappropriate laughing/crying)
- Sensation and eye movements are typically SPARED.
Clinical Approach
Diagnosis
- Clinical diagnosis based on the presence of UMN and LMN signs in multiple body regions
- EMG: Evidence of active and chronic denervation (fibrillation potentials, fasciculations) across multiple spinal segments
- Must rule out structural lesions (cervical myelopathy) via MRI
Management
- No cure exists.
- Riluzole (Glutamate antagonist): Prolongs survival by a few months
- Edaravone (free radical scavenger): May slow clinical decline in early disease
- Non-invasive ventilation (BiPAP) significantly improves quality of life and survival
- PEG tube placement for severe dysphagia
Complications
- Respiratory failure (invariably the cause of death)
- Malnutrition (due to severe dysphagia)