Intracerebral transplantation of fetal ventral mesencephalon for patients with advanced Parkinson's disease. Methodology and 6-month to 1-year follow-up in 3 patients

In order to launch a new transplantation program for Parkinson's disease (PD), we evaluated the safety and efficacy of fetal ventral mesencephalic grafts in 3 patients with advanced PD. Inclusion criteria and clinical evaluation followed strictly the Core Assessment Program for Intracerebral Transplantation. The transplantation procedure was based on the technique previously described by the groups in Lund (Sweden) and Créteil (France). The putamen contralateral to the site of predominant symptoms was unilaterally grafted in all patients. Magnetic resonance (MR)-based stereotactic guidance with multiplanar correlation was used to define 3 implantation trajectories in the precommissural, commissural, and postcommissural putamen. Fetal ventral mesencephalon was prepared from 6- to 8-week-old human embryos obtained from same-day abortions. Under general anesthesia, 8 deposits of 3 microliters of the fetal tissue were placed 1 mm apart along each implantation trajectory using a customized microsyringe and needle attached to the stereotactic frame. The patients recovered uneventfully from the neurosurgical procedure. Early postoperative MR clearly showed the implantation trajectories reaching the putamen in all patients. The follow-up period was of 12, 9 and 6 months, for each of the 3 patients, respectively. Clinical changes appeared between 3 and 6 months after transplantation and consisted of an increase in the 'on' periods and in quantitative bilateral improvement in the motor timed tests. There was an improvement of the Unified Parkinson's Disease Rating Scale score and an improvement of rigidity. Tremor was unchanged, and there was a slight and transient increase in dyskinesias. Neuropsychological follow-up revealed slight frontal alterations in 2 patients. Positron emission tomography demonstrated an increase of 18F-fluorodopa uptake in the grafted site. Adverse events include a reversible Cushing syndrome secondary to immunosuppression in 1 patient and a transient episode of confusion in another. The results of this study, designed as a prerequisite for a wider transplantation program, are in accordance with those previously reported by others and show that, using standardized neurosurgical techniques and methods of evaluation, transplantation is a reproducible and safe therapeutic approach which provides clinical benefits to patients with advanced PD.