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Brain, Vol. 122, No. 6, 1121-1132, June 1999
© 1999 Oxford University Press

Sequential bilateral transplantation in Parkinson's disease

Effects of the second graft

.

P. Hagell1, A. Schrag5, P. Piccini7, M. Jahanshahi6, R. Brown6, S. Rehncrona2, H. Widner1,4, P. Brundin4, J. C. Rothwell6, P. Odin1, G. K. Wenning5, P. Morrish7, B. Gustavii3, A. Björklund4, D. J. Brooks7, C. D. Marsden5,6,1, N. P. Quinn5 and O. Lindvall11

1 Division of Neurology and 2 Division of Neurosurgery, Department of Clinical Neuroscience and 3 Department of Obstetrics and Gynaecology, University Hospital and 4 Division of Neurobiology, Department of Physiology and Neuroscience, University of Lund, Lund, Sweden and 5 University Department of Clinical Neurology and 6 MRC Human Movement and Balance Unit, Institute of Neurology, National Hospital for Neurology and Neurosurgery and 7 MRC Cyclotron Unit, Hammersmith Hospital, London, UK

Correspondence to: Olle Lindvall, Section of Restorative Neurology, Division of Neurology, Department of Clinical Neuroscience, University Hospital, S-221 85 Lund, Sweden

Five parkinsonian patients who had received implants of human embryonic mesencephalic tissue unilaterally in the striatum 10–56 months earlier were grafted with tissue from four to eight donors into the putamen (four patients) or the putamen plus the caudate nucleus (one patient) on the other side, and were followed for 18–24 months. After 12–18 months, PET showed a mean 85% increase in 6-L-[18F]fluorodopa uptake in the putamen with the second graft, whereas there was no significant further change in the previously transplanted putamen. Two patients exhibited marked additional improvements after their second graft: `on–off' fluctuations virtually disappeared, movement speed increased, and L-dopa could be withdrawn in one patient and reduced by 70% in the other. The improvement in one patient was moderate. Two patients with atypical features, who responded poorly to the first graft, worsened following the second transplantation. These findings indicate that sequential transplantation in patients does not compromise the survival and function of either the first or the second graft. Moreover, putamen grafts that restore fluorodopa uptake to normal levels can give improvements of major therapeutic value.

neural grafting; Parkinson's disease; dopamine; striatum; positron emission tomography

MPTP = 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine; UPDRS = Unified Parkinson's Disease Rating Scale

1 {dagger} Deceased


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