Simultaneous intrastriatal and intranigral fetal dopaminergic grafts in patients with Parkinson disease: a pilot study
Report of three cases
Ivar Mendez
Ivar Mendez
Departments of Surgery (Neurosurgery), Medicine (Neurology), Anaesthesia and Gynaecology, Dalhousie University and Queen Elizabeth II Health Sciences Centre, Halifax; Neural Transplantation Laboratory, Department of Anatomy and Neurobiology, Dalhousie University, Halifax; McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada; and Departments of Community Health and Epidemiology, and Pharmacology, Dalhousie University, Halifax, Nova Scotia, Canada
Alain Dagher
Departments of Surgery (Neurosurgery), Medicine (Neurology), Anaesthesia and Gynaecology, Dalhousie University and Queen Elizabeth II Health Sciences Centre, Halifax; Neural Transplantation Laboratory, Department of Anatomy and Neurobiology, Dalhousie University, Halifax; McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada; and Departments of Community Health and Epidemiology, and Pharmacology, Dalhousie University, Halifax, Nova Scotia, Canada
Murray Hong
Departments of Surgery (Neurosurgery), Medicine (Neurology), Anaesthesia and Gynaecology, Dalhousie University and Queen Elizabeth II Health Sciences Centre, Halifax; Neural Transplantation Laboratory, Department of Anatomy and Neurobiology, Dalhousie University, Halifax; McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada; and Departments of Community Health and Epidemiology, and Pharmacology, Dalhousie University, Halifax, Nova Scotia, Canada
Paula Gaudet
Departments of Surgery (Neurosurgery), Medicine (Neurology), Anaesthesia and Gynaecology, Dalhousie University and Queen Elizabeth II Health Sciences Centre, Halifax; Neural Transplantation Laboratory, Department of Anatomy and Neurobiology, Dalhousie University, Halifax; McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada; and Departments of Community Health and Epidemiology, and Pharmacology, Dalhousie University, Halifax, Nova Scotia, Canada
Swarna Weerasinghe
Departments of Surgery (Neurosurgery), Medicine (Neurology), Anaesthesia and Gynaecology, Dalhousie University and Queen Elizabeth II Health Sciences Centre, Halifax; Neural Transplantation Laboratory, Department of Anatomy and Neurobiology, Dalhousie University, Halifax; McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada; and Departments of Community Health and Epidemiology, and Pharmacology, Dalhousie University, Halifax, Nova Scotia, Canada
Vivian McAlister
Departments of Surgery (Neurosurgery), Medicine (Neurology), Anaesthesia and Gynaecology, Dalhousie University and Queen Elizabeth II Health Sciences Centre, Halifax; Neural Transplantation Laboratory, Department of Anatomy and Neurobiology, Dalhousie University, Halifax; McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada; and Departments of Community Health and Epidemiology, and Pharmacology, Dalhousie University, Halifax, Nova Scotia, Canada
David King
Departments of Surgery (Neurosurgery), Medicine (Neurology), Anaesthesia and Gynaecology, Dalhousie University and Queen Elizabeth II Health Sciences Centre, Halifax; Neural Transplantation Laboratory, Department of Anatomy and Neurobiology, Dalhousie University, Halifax; McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada; and Departments of Community Health and Epidemiology, and Pharmacology, Dalhousie University, Halifax, Nova Scotia, Canada
Jacques Desrosiers
Departments of Surgery (Neurosurgery), Medicine (Neurology), Anaesthesia and Gynaecology, Dalhousie University and Queen Elizabeth II Health Sciences Centre, Halifax; Neural Transplantation Laboratory, Department of Anatomy and Neurobiology, Dalhousie University, Halifax; McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada; and Departments of Community Health and Epidemiology, and Pharmacology, Dalhousie University, Halifax, Nova Scotia, Canada
Sultan Darvesh
Departments of Surgery (Neurosurgery), Medicine (Neurology), Anaesthesia and Gynaecology, Dalhousie University and Queen Elizabeth II Health Sciences Centre, Halifax; Neural Transplantation Laboratory, Department of Anatomy and Neurobiology, Dalhousie University, Halifax; McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada; and Departments of Community Health and Epidemiology, and Pharmacology, Dalhousie University, Halifax, Nova Scotia, Canada
棕褐色ya Acorn
Departments of Surgery (Neurosurgery), Medicine (Neurology), Anaesthesia and Gynaecology, Dalhousie University and Queen Elizabeth II Health Sciences Centre, Halifax; Neural Transplantation Laboratory, Department of Anatomy and Neurobiology, Dalhousie University, Halifax; McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada; and Departments of Community Health and Epidemiology, and Pharmacology, Dalhousie University, Halifax, Nova Scotia, Canada
Harold Robertson
Departments of Surgery (Neurosurgery), Medicine (Neurology), Anaesthesia and Gynaecology, Dalhousie University and Queen Elizabeth II Health Sciences Centre, Halifax; Neural Transplantation Laboratory, Department of Anatomy and Neurobiology, Dalhousie University, Halifax; McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada; and Departments of Community Health and Epidemiology, and Pharmacology, Dalhousie University, Halifax, Nova Scotia, Canada
✓ 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.
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