title: Extent of pre-operative L-DOPA-induced dyskinesia predicts the severity of graft-induced dyskinesia after fetal dopamine cell transplantation.
abstract: Graft-induced dyskinesia has emerged as a problematic side effect after transplantation of fetal dopamine cells into the striatum of patients with Parkinson's disease. These adverse effects of dystonic and choreatiform hyperkinesias that persisted even after withdrawal of L-DOPA medication are not yet fully understood, which poses a main obstacle for the re-initiation of neural transplantation in Parkinson's disease. The severity of pre-operative L-DOPA-induced dyskinesia has been proposed as one of several parameters influencing the development of graft-induced dyskinesia. We have therefore characterized graft-induced dyskinesia in the rat model of Parkinson's disease in animals with either mild or severe pre-operative L-DOPA-induced dyskinesia. We show that animals with intrastriatal grafts of fetal dopamine cells and severe pre-operative L-DOPA-induced dyskinesia will reduce their L-DOPA-induced dyskinesia scores by more than 75% but at the same time develop graft-induced dyskinesia of intermediate to strong severity. In contrast, animals with dopamine grafts of similar size but only mild pre-operative L-DOPA-induced dyskinesia also developed graft-induced dyskinesia but this was very mild and of intermediate severity only in a single animal. Severity of pre-operative L-DOPA-induced dyskinesia was correlated with the severity of graft-induced dyskinesia. Our data suggest that patients with no or only mild L-DOPA-induced dyskinesia may carry a lower risk for the development of graft-induced dyskinesia and therefore are better candidates to receive intracerebral grafts of fetal dopamine cells as compared to patients with more pronounced L-DOPA-induced dyskinesia.
authors.affiliation: Department of Neurology, University Hospital Freiburg, Breisacher Str. 64, 79106 Freiburg, Germany.
authors.forename: Joanna
authors.initials: J
authors.lastname: García
authors.forename: Thomas
authors.initials: T
authors.lastname: Carlsson
authors.forename: Máté
authors.initials: M
authors.lastname: Döbrössy
authors.forename: Guido
authors.initials: G
authors.lastname: Nikkhah
authors.forename: Christian
authors.initials: C
authors.lastname: Winkler
mesh_terms: D000662:Amphetamines / Q000633:toxicity; D000818:Animals; D001058:Apomorphine / Q000633:toxicity; D003342:Corpus Striatum / Q000187:drug effects / Q000503:physiopathology; D004195:Disease Models, Animal; D015259:Dopamine Agents / Q000633:toxicity; D018491:Dopamine Agonists / Q000633:toxicity; D059290:Dopaminergic Neurons / Q000637:transplantation*; D004409:Dyskinesia, Drug-Induced / Q000175:diagnosis / Q000503:physiopathology / Q000628:therapy; D020820:Dyskinesias / Q000175:diagnosis / Q000209:etiology / Q000503:physiopathology; D005260:Female; D016332:Fetal Tissue Transplantation / Q000009:adverse effects*; D007980:Levodopa / Q000633:toxicity*; D016627:Oxidopamine / Q000633:toxicity; D011183:Postoperative Complications / Q000175:diagnosis / Q000209:etiology / Q000503:physiopathology; D011237:Predictive Value of Tests; D051381:Rats; D017207:Rats, Sprague-Dawley; D012720:Severity of Illness Index; D013378:Substantia Nigra / Q000187:drug effects / Q000503:physiopathology / Q000601:surgery; D013565:Sympatholytics / Q000633:toxicity
chemical_list: D000662:Amphetamines; D015259:Dopamine Agents; D018491:Dopamine Agonists; D013565:Sympatholytics; D007980:Levodopa; D016627:Oxidopamine; D001058:Apomorphine