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 caudate (n = 4), were followed throughout a period of 15-36 months after surgery, according to the recommendations of the core assessment programme for intracerebral transplantations (CAPIT). All these patients exhibited an increase in fluorodopa uptake in the grafted putamen, which was most significant in the first and last patient of the series. Long-term bilateral improvement of skilled hand movements was observed starting between the third and sixth month after grafting, and confirmed by the statistical analysis of CAPIT timed tests. A fluid to moderate effect on the amount of 'off' time and 'on-off' fluctuations was observed whereas, apart from one case, no clear effect on gait, walking and speech was found. One patient included in the study, already suffering slight cognitive impairment, clearly exhibited progression of a dementia process after surgery. Daily living activities were clearly improved in only one of the other four patients. At the end of the study period 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 before grafting that were greatly decreased in intensity a few months after surgery. Delayed asymmetrical dyskinesias, occurring on the side displaying the better motor improvement, i.e. contralateral to the graft, were observed in three patients. These results suggest that neural transplants may influence two central mechanisms involved in motor function and the onset of dyskinesias. These effects are likely to occur through complex interactions with the post-synaptic dopaminergic receptors. The occurrence of dyskinesias might simply reflect increased presynaptic storage and release of dopamine. Alternatively it might, in part, represent some other long-term deleterious effect of the graft. Since PET-scan data indicate that the reinnervation obtained is sub-optimal, 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-dopa.