Asymmetry of substantia nigra neuronal loss in Parkinson's disease and its relevance to the mechanism of levodopa related motor fluctuations.

A pathological study of 21 patients with Parkinson's disease of asymmetrical onset revealed significant asymmetry of degeneration of the substantia nigra with greater neuronal loss contralateral to the initially affected body side. It has previously been suggested that decline in duration of effectiveness of levodopa doses in Parkinsonian patients with motor oscillations is caused by loss of nigro-striatal dopaminergic terminals with consequent reduction in striatal dopamine storage capacity. If this is true, duration of levodopa motor response should be shorter on the more severely affected body side in patients with asymmetrical disease, as loss of contralateral striatal dopamine storage capacity should be greater. Serial motor evaluations in 20 patients with asymmetrical Parkinson's disease failed to reveal any such asymmetry of duration of motor response to levodopa. It is suggested that striatal dopamine storage is not an important determinant of duration of clinical response to levodopa doses.