Neuronal cell loss as preprogrammed pathways of cascade type might implicate such systems as oxidative stress in a setting of embryonic fate determination. Such programmed selectivity in neuronal susceptibility in diseases ranging from amyotrophic lateral sclerosis to Parkinson’s disease and Alzheimer type dementia might integrally recategorize neurodegenerative states that evolve in terms of embryonic attributes of cell types and subtypes. Even multiple sclerosis as an apparent dichotomy of direct myelin damage and of an evolving pattern of oligodendrocyte loss might implicate systems such as cell lysis in terms of predetermined embryonic attributes of the oligodendrocyte that responds to injury. It is in terms of neuronal and glial participation of cell fate determination and response that one may account for a dual occurrence of familial and sporadic variants of disease entities that progress both as patterns of disease manifestation and as system progression of lesions in neurodegeneration or demyelination.