LONG-TERM OUTCOME OF UNILATERALLY TRANSPLANTED PARKINSONIAN-PATIENTS .1. CLINICAL APPROACH

Five patients with Parkinson's disease, unilaterally transplanted with foetal mesencephalic cells into putamen (n = 1) or putamen and caudat e (n = 4), were followed throughout a period of 15-36 months after sur gery, according to the recommendations of the core assessment programm e for intracerebral transplantations (CAPIT). All these patients exhib ited an increase in fluorodopa uptake in the grafted putamen, which wa s most significant in the first and last patient of the series. Long-t erm bilateral improvement of skilled hand movements was observed start ing between the third and sixth month after grafting, and confirmed by the statistical analysis of CAPIT timed tests. A fluid to moderate ef fect on the amount of 'off' time and 'on-off' fluctuations was observe d whereas, apart from one case, no clear effect on gait, walking and s peech was found. One patient included in the study, already suffering slight cognitive impairment, clearly exhibited progression of a dement ia process after surgery. Daily living activities were clearly improve d in only one of the other four patients. At the end of the study peri od all patients needed L-dopa therapy at a similar or higher dose than before grafting, but, in most of them, other dopaminergic drugs were reduced or stopped. All patients exhibited bilateral dyskinesias befor e grafting that were greatly decreased in intensity a few months after surgery. Delayed asymmetrical dyskinesias, occurring on the side disp laying the better motor improvement, i.e. contralateral to the graft, were observed in three patients. These results suggest that neural tra nsplants may influence two central mechanisms involved in motor functi on and the onset of dyskinesias. These effects are likely to occur thr ough complex interactions with the post-synaptic dopaminergic receptor s. The occurrence of dyskinesias might simply reflect increased presyn aptic storage and release of dopamine. Alternatively it might, in part , represent some other long-term deleterious effect of the graft. Sinc e PET-scan data indicate that the reinnervation obtained is sub-optima l, it will be of interest to obtain a larger and denser reinnervation of the host striatum and to try, thereafter to reduce the dose of L-do pa.