Contributor: Gordon K. Klintworth
Amyotrophic lateral sclerosis (Lous Gehrig disease, motor neuron disease)  is a common neurodegenerative disease with an annual incidence of 1-2 per 100,000 and a lifetime risk of 1 per 800. The disease is characterized by progressive paralysis and death usually withnin 2-5 years of diagnosis. Most cases (~90%) are sporadic, but ~10% are familial with an autosomal recessive, autosomal dominant, X-linked recessive modes of inheritance. At least 12 genetic loci have been identified and mutations in three genes (SOD1, ALSIN, SETX) are known to cause the disorder. The disease is characterized by a degeneration of the upper motor neurons in the brain stem and motor cortex and lower motor neurons in the spinal cord. Upper motor neuron loss leads to clonus and hyperreflexia. Lower motor neuron signs are muscle atrophy [atrophy - muscle], weakness, and fasciculations. Typically sensation and  cognition is not impaired. Four genetically distinct types of amyotrophic lateral sclerosis have been identified: amyotrophic lateral sclerosis type 1, amyotrophic lateral sclerosis type 2, amyotrophic lateral sclerosis type 3, amyotrophic lateral sclerosis type 4, amyotrophic lateral sclerosis type 5, amyotrophic lateral sclerosis type 6, amyotrophic lateral sclerosis type 7, amyotrophic lateral sclerosis type 8. Other disorders with amyotrophic lateral sclerosis are amyotrophic lateral sclerosis with polyglucosan bodies, amyotrophic lateral sclerosis with frontotemporal dementia, and amyotrophic lateral sclerosis/Parkinsonian-dementia complex. The differential diagnosis includes lead toxicity, multifocal motor neuropathy, postpoliomyelitis syndrome, hyperparathyroidism, hyperthyroidism, a paraneoplastic syndrome, and infections of the central nervous system.