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.