Parkinson’s Disease: Unanswered Questions
Over the last two decades there have been spectacular advances in understanding and treating Parkinson’s disease, but there remain major areas of uncertainty and ignorance. The nigrostriatal pathway has features resembling the peripheral sympathetic system, rather than conventional central projections of sensory and motor nuclei. Like sympathetic activity, nigrostriatal function is diffuse, tonic, and more accessible to analysis by measuring biochemical rather than electrical changes. These findings are difficult to interpret in the context of the established importance of the basal ganglia in programming movement. The role of the depletion of dopamine in Parkinsonism is also unclear; we do not even know whether the impact of the deficit is more significant in the basal ganglia, or the substantia nigra. Confusion over the actions of dopamine underlies the obscurity of the mechanisms by which levodopa produces both wanted and unwanted effects. Finally, the nature of Parkinson’s disease is still an enigma: we have not identified its cause, and we do not know what influences its progress.
In attempting to elucidate the role of dopamine in brain function, Parkinson’s disease can be regarded as an experimental model wrought by nature. The introduction of levodopa as treatment, a development in which Prof. Birkmayer played such a pioneering role, has been the most important therapeutic advance in neurology over the last 20 years. But to avoid complacency, it is salutary to consider the extent of our ignorance of related neuropharmacology. This exercise leads to such an extensive list of unanswered problems that one may question whether the dimensions of a scientific advance can be measured by the number of new questions that it generates.
While the causal relationship between the dopamine deficit and the clinieal syndrome is beyond doubt, the detailed analysis of the relationship is diffieult, and no simple answers have been fortheoming. Under these eircumstanees it is timely to review our understanding and ignoranee of the role of dopamine in the extrapyramidal nervous system and the etiology, pathology and prognosis of Parkinson’s disease.
KeywordsSubstantia Nigra Dopaminergic Neuron Caudate Nucleus Motor Nucleus Sympathetic Innervation
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