OsteopAmyotrophic Lateral Sclerosisorosis

Definition

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder characterized by the degeneration of upper and lower motor neurons, leading to muscle weakness, atrophy, spasticity, and eventual respiratory failure.

Epidemiology

• Incidence: 1–2 per 100,000 per year worldwide.
• Prevalence: approximately 5–7 per 100,000 population.
• Peak onset between 55–75 years; men slightly more affected than women.
• Most cases are sporadic (~90–95%), with 5–10% being familial.
• No clear ethnic predilection, though some genetic mutations are population-specific.

Etiology

• Mostly idiopathic; multifactorial with genetic and environmental factors.
• Familial ALS: mutations in SOD1, C9orf72, TARDBP, FUS genes.
• Risk factors: smoking, environmental toxins, repetitive trauma, military service (observed associations).
• Pathogenesis involves oxidative stress, excitotoxicity, mitochondrial dysfunction, protein aggregation, and neuroinflammation.

Pathophysiology

• Degeneration of upper motor neurons in the motor cortex causes spasticity and hyperreflexia.
• Degeneration of lower motor neurons in brainstem and spinal cord leads to muscle weakness, atrophy, and fasciculations.
• Progressive loss of motor neurons impairs voluntary movement and ultimately respiratory muscles.
• Glutamate excitotoxicity and oxidative stress contribute to neuronal apoptosis.
• Respiratory failure is the main cause of death.