Simultaneous intrastriatal and intranigral fetal dopaminergic grafts in patients with Parkinson disease: a pilot study

Report of three cases

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✓ The main neural transplantation strategy in Parkinson disease (PD) has been focused on reinnervating the striatum. The clinical results reported in patients who receive transplants have been limited and do not justify the use of neural transplantation as a routine therapeutic procedure for PD. Identifying the optimal target for transplantation may be one of the critical factors for optimizing clinical outcomes. Evidence from preclinical studies indicates that simultaneous intrastriatal and intranigral grafts (double grafts) may produce a more complete functional recovery. The authors report the clinical and positron emission tomography (PET) scanning results in three patients enrolled in a safety and feasibility pilot study who received double grafts and who have been followed for up to 13 months posttransplantation.

Patients included in the study had idiopathic PD. All patients underwent detailed assessments before and after surgery, in accordance with the Core Assessment Program for Intracerebral Transplantation. The patients received implants of fetal mesencephalic cell suspensions in the putamen and substantia nigra (SN) bilaterally. There were no intraoperative or perioperative complications. Follow-up PET scans demonstrated an increase in the mean fluorodopa uptake constant values in the putamen and SN 12 months postsurgery. Improvements were also noted in the total Unified Parkinson′s Disease Rating Scale, Hoehn and Yahr, Schwab and England, and pronation/supination scores after transplantation. The authors demonstrate the feasibility of reinnervating the SN and striatum by using a double transplant strategy in humans.

Article Information

Address reprint requests to: Ivar Mendez, M.D., Division of Neurosurgery, QEII Health Sciences Centre, New Halifax Infirmary, 1796 Summer Street, Room #3806, Halifax, Nova Scotia, Canada B3H 3A7. email: mendez@is.dal.ca.

© AANS, except where prohibited by US copyright law.

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Figures

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    Diagram illustrating the double transplant strategy. Four graft deposits are implanted into the putamen and one is implanted into the SN.

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    Axial T2-weighted MR images obtained 24 hours postoperatively in a patient with PD who received simultaneous intrastriatal and intranigral fetal VM grafts. A: Axial MR image depicting four tracts of graft deposits into the right putamen (arrow). B: Axial MR image depicting a graft deposit into the right SN (arrow).

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    Graphs showing the mean performance scores before and after surgery in the on and off state for total UPDRS, Hoehn and Yahr, and Schwab and England scores, and the timed motor task of pronation/supination for the right (R) and left hand (L). Error bars are marked with 95% confidence intervals. Overlapping error bars postoperatively indicate nonsignificant differences between the on and off states. n = number of patients; postop1, −2, and −3 = last three postoperative scores; preop1 and −2 = first and second preoperative scores.

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    Preoperative and postoperative fluorodopa PET scans obtained in a patient with PD (Case 3) who received simultaneous intrastriatal and intranigral fetal VM grafts. These images consist of parametric maps of fluorodopa Ki transformed into stereotactic space and overlaid on the patient's MR image (also in stereotactic space). The parametric maps were smoothed using an 8-mm gaussian filter. The axial, coronal, and sagittal sections demonstrate an increase in Ki in the midbrain and putamen bilaterally, likely resulting from surviving grafted dopamine neurons.

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