Pathophysiology

Current theories for cell death include excitotoxins (glutamate), free radicals, heavy metals, viral agents, and autoimmune reactions against such tissues as spinal cord collagen.3 Programmed cell death due to apoptosis is also being studied as a possible etiology. The most likely cause of ALS is genetic superoxide dismutase dysfunction related to a variety of environmental insults. 4

Gross central nervous system (CNS) pathology includes frontal cortical atrophy, degeneration of the corticospinal and spinocerebellar tracts, a reduction in large cervical and lumbar motor neurons, and cranial nerve nuclei degeneration. Both motor and sensory peripheral nerves are noted to undergo axonal degeneration and segmental demyelination, including motor end plate and axon terminal involvement.

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