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The adjective degenerative has no great appeal to the modern neurologist. For one thing, it has an unpleasant nonmedical connotation, referring as it does to a state of moral turpitude or deviant behavior. More important, it is not a satisfactory term medically, since it implies an inexplicable decline from a previous level of normalcy to a lower level of function an ambiguous conceptualization of disease that satis es neither theoretician nor scientist. It is becoming increasingly evident that many of the diseases included in this category depend on genetic factors, or at least they appear in more than one member of the same family, in which case they are more properly designated as heredodegenerative. Even more diseases, not differing in any fundamental way from the heredodegenerative ones, occur sporadically, i.e., as isolated instances in given families. For diseases of this type, Gowers in 1902 suggested the term abiotrophy, by which he meant a lack of vital endurance of the affected neurons, resulting in their premature death. This concept embodies an untested, unproven hypothesis that aging and degenerative changes of cells are based on the same process. Understandably, contemporary neuropathologists are reluctant to attribute to simple aging the diverse processes of cellular diseases that are constantly being revealed by ultrastructural and molecular genetic techniques. The reader may be perplexed by the inconsistent use of the terms atrophy and degeneration, both of which are applied to diseases of this category. Spatz argued that on purely histopathologic grounds they are different. Atrophy speci es a gradual wasting and loss of a system of neurons, leaving in their wake no degradative products and only a sparsely cellular, brous gliosis. Degeneration refers to a more rapid process of neuronal, myelin, or tissue breakdown, the degradative products of which evoke a more vigorous reaction of phagocytosis and cellular astrogliosis. The difference lies in both the speed and the type of breakdown. It is of some interest that many of the diseases characterized by degeneration, in Spatz s sense of the term, are now known to be of metabolic origin, while very few of the purely atrophic ones have been shown to have a metabolic basis. There are also, within recent memory, several examples of diseases that were formerly classed as degenerative but are now known to have a metabolic, toxic, or nutritional basis or to be caused by a slow virus or a nonviral transmissible agent. It seems reasonable to expect that with increasing knowledge, more and more diseases whose causes are now unknown will nd their way into these categories. As was pointed out in Chap. 29, on aging, more than half of the normal life cycle of the organism involves a slow deterioration of organ function. Such changes in the nervous system are manifest in every sensory and motor system and in all cerebral functions. The basis of these aging changes is theoretically at the neuronal level, but it is not fully understood. A fundamental problem is the distinction of these aging deteriorations from degenerative disease. When the latter appears in adult life, one must assume that the clinical presentation is modi ed to some extent by life-cycle phenomena the patient s function being a gestalt of both processes. 895 BRIEF HISTORY OF THE VL4%
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