Neuroleptic-induced Parkinsonism: Clinicopathological study

Abstract

Background: Drug-induced parkinsonism is a well-known complication of several different drugs--the most common being neuroleptic-induced parkinsonism. However, very few autopsies have been reported in such cases.

Methods: Patients assessed at Movement Disorders Clinic Saskatchewan are offered brain autopsy. Detailed clinical records are kept.

Results: Brains were obtained from 7 drug-induced parkinsonism patients with parkinsonian symptom onset coinciding with use of drugs known to produce parkinsonism. Six were on antipsychotics and 1 was on metoclopramide. Three cases were treated with levodopa for parkinsonism. In two cases, parkinsonian features reversed after stopping the offending agent. Both had autopsy evidence of preclinical PD. In 4 of the remaining 5, dopamine-blocking drugs were continued until death. In 4 of those 5, brain histology revealed no cause for the parkinsonism, but 1 had mild SN neuronal loss without Lewy bodies.

Conclusion: This study shows that reversal of parkinsonism after discontinuing offending drugs does not indicate absence of underlying pathology. Neuroleptics can unmask preclinical PD in patients with insufficient SN damage for the disease to manifest clinically. Though the mechanism of sustained parkinsonian features after discontinuing neuroleptics remains to be established, it is unlikely that dopamine receptor block leads to retrograde SN neuronal degeneration. Furthermore, L-dopa does not appear to be toxic to SN.

Keywords: drug induced; neuroleptic-induced; parkinsonism; pathology; substantia nigra.