Amyotrophic lateral sclerosis (ALS) (Lou Gehrig’s Disease)
Chronic degenerative incapacitating disorder characterised by the relentless progressive weakness and wasting of muscle until death from respiratory failure. Prevalence of 1.5-2.5/100 000. M>F. Usually begin in 6th-7th decade (median survival is 3-5 yrs). Most common motor neuron disease.
(Lou Gehrig played first base for New York Yankees, 1923-1939; played 2130 consecutive games; usually batted after Babe Ruth – died of ALS in 1941)
Pathogenesis unclear – due to deterioration of upper and lower motor neurones; may be an alteration in glutamate neurotransmitter system
Up to 10% have family history (autosomal dominant pattern); up to 20% have abnormality on chromosome 21 that codes for superoxide dismutase – enzyme that converts free radical ions; toxins have been suggested; increasing evidence is that it is autoimmune (antibodies found against voltage-fated calcium channels).
Initially complain of muscular weakness, usually asymmetrically affecting one limb – also fasciculations and atrophy (lower motor neuron signs) – 20-40% the lower limb (usually the foot dorsiflexors) spreads proximally and to other limb. Cramps may precede weakness. Develop spasticity, hyporeflexia (lower motor neurons), hyperreflexia (upper motor neurons), and atrophy. No significant sensory loss (up to 25% may develop decreased vibratory sensation).
Fasciculations occur early, but decrease later. Babinski’s sign.
EMG shows widespread denervation in presence of normal nerve conduction velocity
Muscle biopsy shows neurogenic atrophy
Serum CPK may be elevated (other tests normal)
Differential diagnosis – mononeuropathy, spinal cord compression, cervical spondylosis, hyperparathyroidism, metachromatic leukodystrophy, hexosaminidase A deficiency
Supportive (emotional, psychological and family) and symptomatic. Riluzole (sodium channel blocker that inhibit release of glutamate) may prolong survival by 2-3 months
Physiotherapy (exercises); speech therapy (for dysarthria); dietitian; occupational therapy (adaptive equipment, wheelchair and aids)
Gastrotomy tube if ability to chew and swallow affected or when high risk for aspiration occurs.
Baclofen or quinine for muscle cramps. May need antidepressants and sleep medications.