Amyotrophic lateral sclerosis would constitute a system complex of heightened neuronal susceptibility that is dependent on skeletal myofiber participation towards further progression of such neuronal injury. Indeed, a simple concept of neurofilament disorganization and abnormal protein trafficking might implicate systems of direct and indirect consequence in inducing both myofiber denervation atrophy on a selective axonal basis of involvement and also a possible pathway of susceptibility towards further intraneuronal disorganization. Indeed, in terms of neuropathologic lesions such as neurofilament skeins and axonal spheroids in a complex setting of aggregation and inclusion bodies in the perikaryon, one might perhaps strictly recognize skeletal myofiber atrophy as a central target of pathology of motoneuron injury in a context however of further induced injury to such motoneurons as resulting from active myofiber atrophy. In simple terms, individual skeletal myofibers that atrophy on an individual axonal basis of injury would constitute a main mechanism for further self-propagation of progressive injury to the supplying axon. Indeed, amyotrophic lateral sclerosis would appear a disease process with active overcompensatory neuronal attempts at recovery further contributing to the disease activity.