Dyskinesias and dopamine cell replacement in Parkinson's disease: a clinical perspective

Abstract

Both increased and decreased dyskinesias have been reported from open label clinical trials of transplantation of human embryonic dopamine rich tissue in Parkinson's disease patients. In the first double-blind clinical transplantation trial, 15% of the grafted patients developed severe postoperative dyskinesias in the “off” phase. Since then, postoperative off-medication dyskinesias have been reported from two additional series of grafted patients. However, such dyskinesias are probably not a novel phenomenon. These dyskinesias have shown a different temporal development postoperatively compared to the antiparkinsonian graft effects, and no significant relationship with the magnitude of graft-derived dopaminergic reinnervation or symptomatic relief. However, positron emission tomography studies have indicated that an unbalanced putaminal dopaminergic function may contribute to this postoperative complication. While there is little doubt that intrastriatal grafts can induce dyskinesias, these appear to differ from common drug-induced dyskinesias. The term graft-induced dyskinesias (GID) is therefore suggested to more clearly identify this complication. While GID bear some phenomenological resemblance to biphasic drug induced dyskinesias, the mechanism(s) behind this complication remains obscure. Available data are scarce but allow for hypotheses to be generated that could (and should) be addressed in experimental animals.