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Although the usual course is relentlessly progressive with death in half the cases within three years from onset, it can sometimes be protracted. Degeneration and loss of large motor neurons in the cerebral cortex, brainstem, and cervical and lumbar spinal cord are characteristic. Marked reduction in the number of large myelinated fibers is notable in the cervical and lumbar ventral roots. Peripheral nerves show reduced numbers of large myelinated fibers, acute axonal degeneration at all levels, and distal axonal atrophy. Motor end\u2010plates reveal small or absent nerve terminals. Subclinical non\u2013motor system involvement includes neuronal loss in Clarke's nucleus and dorsal root ganglia, degeneration of non\u2010motor tracts in the spinal cord, loss of receptors in the dorsal horns of the spinal cord, and myelinated fiber loss with segmental demyelination in sensory and mixed nerves. The serious implications of the diagnosis of ALS make it mandatory to exclude similar potentially treatable disorders. Management should be multidisciplinary, and discussions with the patient and family members should be frank and frequent. Discussions about ventilatory support should take place early in the disease so that death from respiratory failure can be prevented, when that is desired, and conversely to obviate the discontent and anger that accompany involuntary life on a ventilator.<\/jats:p>","DOI":"10.1002\/ana.410180302","type":"journal-article","created":{"date-parts":[[2005,1,1]],"date-time":"2005-01-01T08:09:12Z","timestamp":1104566952000},"page":"271-280","source":"Crossref","is-referenced-by-count":303,"title":["Amyotrophic lateral sclerosis: Part 1. 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