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Factors affecting the clinical outcome after neural transplantation in Parkinson's disease

Piccini, P; Pavese, N; Hagell, Peter LU ; Reimer, Jan LU ; Björklund, Anders LU ; Oertel, WH; Quinn, NP; Brooks, DJ and Lindvall, Olle LU (2005) In Brain 128(12). p.2977-2986
Abstract
Intrastriatal grafts of embryonic mesencephalic tissue can survive in the brains of patients with Parkinson's disease, but the degree of symptomatic relief is highly variable and some cases develop troublesome dyskinesias. Here we explored, using clinical assessment and F-18-dopa and C-11-raclopride PET, factors which may influence the functional outcome after transplantation. We observed increased F-18-dopa uptake in the grafted putamen, signifying continued survival of the transplanted dopaminergic neurons, in parallel with a progressive reduction of F-18-dopa uptake in non-grafted regions for the whole patient group. The patients with the best functional outcome after transplantation exhibited no dopaminergic denervation in areas... (More)
Intrastriatal grafts of embryonic mesencephalic tissue can survive in the brains of patients with Parkinson's disease, but the degree of symptomatic relief is highly variable and some cases develop troublesome dyskinesias. Here we explored, using clinical assessment and F-18-dopa and C-11-raclopride PET, factors which may influence the functional outcome after transplantation. We observed increased F-18-dopa uptake in the grafted putamen, signifying continued survival of the transplanted dopaminergic neurons, in parallel with a progressive reduction of F-18-dopa uptake in non-grafted regions for the whole patient group. The patients with the best functional outcome after transplantation exhibited no dopaminergic denervation in areas outside the grafted areas either preoperatively or at 1 or 2 years post-operatively. In contrast, patients with no or modest clinical benefit showed reduction of F-18-dopa in ventral striatum prior to or following transplantation, which may have limited graft-induced improvement. We obtained no evidence that dyskinesias were caused by abnormal dopamine (DA) release from the grafts. As has been observed for intrinsic dopaminergic neurons, there was a significant correlation between F-18-dopa uptake and methamphetamine-induced change of C-11-raclopride binding (as a measure of DA release) in the putamen containing the graft. Furthermore, we observed no correlation between C-11-raclopride binding in anterior, posterior or entire putamen under basal conditions or after methamphetamine, and dyskinesia severity scores in the contralateral side of the body. Withdrawal of immunosuppression at 29 months after transplantation caused no reduction of F-18-dopa uptake or worsening of UPDRS motor score, indicating continued survival and function of the graft. However, patients showed increased dyskinesia scores, which might have been caused either by growth of the graft or worsening of a low-grade inflammation around the graft. These findings indicate that poor outcome after transplantation is associated with progressive dopaminergic denervation in areas outside the grafts, a process which may have started already before surgery. Also, that the development of dyskinesias after transplantation is not associated with excessive DA release from the grafts. Finally, our data provide evidence that long-term immunosuppression can be withdrawn without interfering with graft survival or the motor recovery induced by transplantation. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
neural transplantation, Parkinson's disease, dyskinesias, dopamine, positron emission tomography
in
Brain
volume
128
issue
12
pages
2977 - 2986
publisher
Oxford University Press
external identifiers
  • pmid:16246865
  • wos:000233667500023
  • scopus:28544441892
ISSN
1460-2156
DOI
10.1093/brain/awh649
language
English
LU publication?
yes
id
5a069128-17bb-4dff-ab5a-341dce85a6f0 (old id 211892)
date added to LUP
2007-08-13 14:21:05
date last changed
2017-11-05 03:45:47
@article{5a069128-17bb-4dff-ab5a-341dce85a6f0,
  abstract     = {Intrastriatal grafts of embryonic mesencephalic tissue can survive in the brains of patients with Parkinson's disease, but the degree of symptomatic relief is highly variable and some cases develop troublesome dyskinesias. Here we explored, using clinical assessment and F-18-dopa and C-11-raclopride PET, factors which may influence the functional outcome after transplantation. We observed increased F-18-dopa uptake in the grafted putamen, signifying continued survival of the transplanted dopaminergic neurons, in parallel with a progressive reduction of F-18-dopa uptake in non-grafted regions for the whole patient group. The patients with the best functional outcome after transplantation exhibited no dopaminergic denervation in areas outside the grafted areas either preoperatively or at 1 or 2 years post-operatively. In contrast, patients with no or modest clinical benefit showed reduction of F-18-dopa in ventral striatum prior to or following transplantation, which may have limited graft-induced improvement. We obtained no evidence that dyskinesias were caused by abnormal dopamine (DA) release from the grafts. As has been observed for intrinsic dopaminergic neurons, there was a significant correlation between F-18-dopa uptake and methamphetamine-induced change of C-11-raclopride binding (as a measure of DA release) in the putamen containing the graft. Furthermore, we observed no correlation between C-11-raclopride binding in anterior, posterior or entire putamen under basal conditions or after methamphetamine, and dyskinesia severity scores in the contralateral side of the body. Withdrawal of immunosuppression at 29 months after transplantation caused no reduction of F-18-dopa uptake or worsening of UPDRS motor score, indicating continued survival and function of the graft. However, patients showed increased dyskinesia scores, which might have been caused either by growth of the graft or worsening of a low-grade inflammation around the graft. These findings indicate that poor outcome after transplantation is associated with progressive dopaminergic denervation in areas outside the grafts, a process which may have started already before surgery. Also, that the development of dyskinesias after transplantation is not associated with excessive DA release from the grafts. Finally, our data provide evidence that long-term immunosuppression can be withdrawn without interfering with graft survival or the motor recovery induced by transplantation.},
  author       = {Piccini, P and Pavese, N and Hagell, Peter and Reimer, Jan and Björklund, Anders and Oertel, WH and Quinn, NP and Brooks, DJ and Lindvall, Olle},
  issn         = {1460-2156},
  keyword      = {neural transplantation,Parkinson's disease,dyskinesias,dopamine,positron emission tomography},
  language     = {eng},
  number       = {12},
  pages        = {2977--2986},
  publisher    = {Oxford University Press},
  series       = {Brain},
  title        = {Factors affecting the clinical outcome after neural transplantation in Parkinson's disease},
  url          = {http://dx.doi.org/10.1093/brain/awh649},
  volume       = {128},
  year         = {2005},
}