Die Pathoklise [Parkinson's disease]

The history of the concept of selective vulnerability of the basal ganglia with particular respect to the substantia nigra is briefly reviewed. During the past century attention has gradually focussed down from gross lesions of the basal ganglia through cell morphometry and presently to the level of the intracellular neurobiology. Despite an abundance of reported morphological and neurochemical changes it remains unresolved whether these findings indicate primary aetiological factors or secondary consequences of nigral cell death. In this debate, while MPTP has proven to be a most amenable model for the study of secondary parkinsonism it has not resolved the dilemma; equally uncertain are the claims derived from the MPTP hypothesis of nigral vulnerability that selective MAO inhibition has a protective effect on the natural history of Parkinson's disease. Some of the evidence, past and present, will be reviewed in so far that it reflects upon the concept of pathoclisis and the selective vulnerability of nigral cells and recent evidence from clinical trials and from the study of human foetal nigral cells in tissue culture will be presented.