Nigral degeneration in Parkinson's disease in relation to clinical features.

Neuronal loss in the substantia nigra (SN) in Parkinson's disease (PD) shows a topographical organisation where the lateral part of the SN is more affected. This is--due to projection of the lateral SN mainly to the putamen--reflected in more complete loss of dopamine content in the putamen than in the caudate nucleus. Of the parkinsonian symptoms rigidity and hypokinesia are associated with neuronal loss in the lateral substantia nigra and the resulting dopamine loss in the putamen. Neuronal mechanisms other than degeneration of the nigrostriatal system seem to be involved in the pathophysiology of tremor. Cognitive impairment and dementia in PD is related to dysfunction of the cortical cholinergic system, especially in the frontal cortex. The brain dopaminergic system, however, contributes as a subcortical component to cognitive impairment in PD. Clinical studies have shown that selegiline may slow down the progression of PD. We studied postmortem samples of patients treated with selegiline and levodopa and those with levodopa alone. The number of medial nigral neurons was significantly higher in the selegiline group. Treatment with selegiline might retard the death of nigral neurons, but further studies are needed to confirm the preliminary findings.