The final cascade of amyotrophic lateral sclerosis (ALS) coincides with the onset of clinical neurological deficits and involves multifactorial interactive mechanisms. These terminal events include excitotoxicity, free radical accumulation and possibly immunological disturbances. They are probably predated by months or years by thus far unidentified triggers. Selective vulnerability of the corticomotneuronal system in ALS is likely due to degradation of several gene products essential to transmitter, receptor and nerve growth factor maintenance specific to this functional system. Therapeutic strategies involve neuroprotection, symptomatic and combination neuronal therapy targeted to the final cascade of ALS.
(Internal Medicine 34: 824-832, 1995)