Dopamine Cell Implantation in Parkinson's Disease: Long-Term Clinical and 18F-FDOPA PET Outcomes
Open Access
- 15 December 2009
- journal article
- research article
- Published by Society of Nuclear Medicine in Journal of Nuclear Medicine
- Vol. 51 (1), 7-15
- https://doi.org/10.2967/jnumed.109.066811
Abstract
We have previously reported the results of a 1-y double-blind, placebo-controlled study of embryonic dopamine cell implantation for Parkinson's disease. At the end of the blinded phase, we found a significant increase in putamen uptake on 18F-fluorodopa (18F-FDOPA) PET reflecting the viability of the grafts. Nonetheless, clinical improvement was significant only in younger (age ≤ 60 y) transplant recipients, as indicated by a reduction in Unified Parkinson's Disease Rating Scale (UPDRS) motor scores. Methods: We now report long-term clinical and PET outcomes from 33 of the original trial participants who were followed for 2 y after transplantation and 15 of these subjects who were followed for 2 additional years. Longitudinal changes in UPDRS motor ratings and caudate and putamen 18F-FDOPA uptake were assessed with repeated-measures ANOVA. Relationships between these changes over time were evaluated by the analysis of within-subject correlations. Results: We found that UPDRS motor ratings declined over time after transplantation (P < 0.001). Clinical improvement at 1 y was relatively better for the younger transplant recipients and for men, but these age and sex differences were not evident at longer-term follow-up. Significant increases in putamen 18F-FDOPA uptake were evident at all posttransplantation time points (P < 0.001) and were not influenced by either age or sex. Posttransplantation changes in putamen PET signal and clinical outcome were significantly intercorrelated (P < 0.02) over the course of the study. Image analysis at the voxel level revealed significant bilateral increases in 18F-FDOPA uptake at 1 y (P < 0.001) in the posterior putamen engraftment sites. PET signal in this region increased further at 2 and 4 y after engraftment. Concurrently, this analysis disclosed progressive declines in radiotracer uptake in the nonengrafted caudate and ventrorostral putamen. Clinical improvement after transplantation correlated with the retention of PET signal in this region at the preoperative baseline. Conclusion: These results suggest that clinical benefit and graft viability are sustained up to 4 y after transplantation. Moreover, the dependence of clinical (but not imaging) outcomes on subject age and sex at 1 y may not persist over the long term. Last, the imaging changes reliably correlate with clinical outcome over the entire posttransplantation time course.This publication has 21 references indexed in Scilit:
- Changes in network activity with the progression of Parkinson's diseaseBrain, 2007
- Factors affecting the clinical outcome after neural transplantation in Parkinson's diseaseBrain, 2005
- Cell type analysis of functional fetal dopamine cell suspension transplants in the striatum and substantia nigra of patients with Parkinson's diseaseBrain, 2005
- A double‐blind controlled trial of bilateral fetal nigral transplantation in Parkinson's diseaseAnnals of Neurology, 2003
- Dyskinesia after fetal cell transplantation for parkinsonism: A PET studyAnnals of Neurology, 2002
- Short‐ and long‐term survival and function of unilateral intrastriatal dopaminergic grafts in Parkinson's diseaseAnnals of Neurology, 1997
- Regional changes in [18F]dopa metabolism in the striatum in Parkinson's diseaseBrain, 1996
- Clinical correlates of {18F}fluorodopa uptake in five grafted Parkinsonian patientsAnnals of Neurology, 1995
- Neuropathological Evidence of Graft Survival and Striatal Reinnervation after the Transplantation of Fetal Mesencephalic Tissue in a Patient with Parkinson's DiseaseThe New England Journal of Medicine, 1995
- Survival of Implanted Fetal Dopamine Cells and Neurologic Improvement 12 to 46 Months after Transplantation for Parkinson's DiseaseThe New England Journal of Medicine, 1992