| 1. |
- Hagell, Peter, et al.
(författare)
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Clinical rating of dyskinesias in Parkinson's disease: use and reliability of a new rating scale
- 1999
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Ingår i: Movement Disorders. - 0885-3185. ; 14:3, s. 448-455
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Tidskriftsartikel (refereegranskat)abstract
- Drug-induced dyskinesias (DID) manifested as hyperkinetic and/or dystonic movements or postures are common problems in Parkinson's disease (PD). Novel therapeutic interventions may offer possibilities to counteract these common adverse effects of an otherwise necessary treatment. To be able to evaluate the effects of such interventions on DID, reliable and relevant clinical assessment tools are needed. We tested the inter- and intrarater reliability of a new clinical dyskinesia rating scale consisting of separate ratings of different body parts, including lateralization and separate ratings of dystonia and hyperkinesias. Interrater reliability was tested both with and without a defined scoring code and clarification of the dystonia section. The nondefined version was also tested for intrarater reliability. Thirteen raters independently reviewed 23 videotape sequences showing PD patients performing standardized motor tests. Inter- and intrarater agreement was significant in all evaluations, and no differences were detected when comparing ratings performed with the defined and nondefined version of the scale. The rationale for, and the role and use of, the present scale are addressed.
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| 2. |
- Hagell, Peter, et al.
(författare)
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Sequential bilateral transplantation in Parkinson's disease: effects of the second graft
- 1999
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Ingår i: Brain. - : Oxford University Press (OUP). - 1460-2156. ; 122:6, s. 1121-1132
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 3. |
- Piccini, P, et al.
(författare)
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Dopamine release from nigral transplants visualized in vivo in a Parkinson's patient
- 1999
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Ingår i: Nature Neuroscience. - : Springer Science and Business Media LLC. - 1546-1726 .- 1097-6256. ; 2:12, s. 1137-1140
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Tidskriftsartikel (refereegranskat)abstract
- Synaptic dopamine release from embryonic nigral transplants has been monitored in the striatum of a patient with Parkinson's disease using [11C]-raclopride positron emission tomography to measure dopamine D2 receptor occupancy by the endogenous transmitter. In this patient, who had received a transplant in the right putamen 10 years earlier, grafts had restored both basal and drug-induced dopamine release to normal levels. This was associated with sustained, marked clinical benefit and normalized levels of dopamine storage in the grafted putamen. Despite an ongoing disease process, grafted neurons can thus continue for a decade to store and release dopamine and give rise to substantial symptomatic relief.
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| 4. |
- Schierle, Gabriele, et al.
(författare)
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Caspase inhibition reduces apoptosis and increases survival of nigral transplants
- 1999
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Ingår i: Nature Medicine. - : Springer Science and Business Media LLC. - 1546-170X .- 1078-8956. ; 5:1, s. 97-100
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Tidskriftsartikel (refereegranskat)abstract
- Transplantation of embryonic nigral tissue ameliorates functional deficiencies in Parkinson disease. The main practical constraints of neural grafting are the shortage of human donor tissue and the poor survival of dopaminergic neurons grafted into patients, which is estimated at 5-10% (refs. 3,4). The required amount of human tissue could be considerably reduced if the neuronal survival was augmented. Studies in rats indicate that most implanted embryonic neurons die within 1 week of transplantation, and that most of this cell death is apoptotic. Modified peptides, such as acetyl-tyrosinyl-valyl-alanyl-aspartyl-chloro-methylketone (Ac-YVAD-cmk), that specifically inhibit proteases of the caspase family effectively block apoptosis in a plethora of experimental paradigms, such as growth factor withdrawal, excitotoxicity, axotomy, cerebral ischemia and brain trauma. Here we examined the effects of caspase inhibition by Ac-YVAD-cmk on cell death immediately after donor tissue preparation and on long-term graft survival. Treatment of the embryonic nigral cell suspension with Ac-YVAD-cmk mitigated DNA fragmentation and reduced apoptosis in transplants. It also increased survival of dopaminergic neurons grafted to hemiparkinsonian rats, and thereby substantially improved functional recovery.
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| 5. |
- Wenning, Gregor K, et al.
(författare)
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Short- and long-term survival and function of unilateral intrastriatal dopaminergic grafts in Parkinson's disease
- 1997
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Ingår i: Annals of Neurology. - : Wiley. - 1531-8249 .- 0364-5134. ; 42:1, s. 95-107
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Tidskriftsartikel (refereegranskat)abstract
- Six patients with Parkinson's disease were followed for 10 to 72 months after human embryonic mesencephalic tissue from four to seven donors was grafted unilaterally into the putamen (4 patients) or putamen plus caudate (2 patients). After 8 to 12 months, positron emission tomography showed a 68% increase of 6-L-[18F]-fluorodopa uptake in the grafted putamen, no change in the grafted caudate, and minor decreases in nongrafted striatal regions. There was therapeutically valuable improvement in 4 patients, but only modest changes in the other 2, both of whom developed atypical features. Patient 4 was without L-dopa from 32 months and had normal fluorodopa uptake in the grafted putamen at 72 months. Overall, the L-dopa dose was reduced by a mean of 10 and 20%, "off" time was reduced by 34 and 44%, and the "off" phase Unified Parkinson's Disease Rating Scale motor score by 18 and 26%, and the duration of the response to a single L-dopa dose increased by 45 and 58% during the first and second years after surgery, respectively. Rigidity and hypokinesia improved bilaterally, but mainly contralateral to the implant. No consistent changes in dyskinesias were observed. We conclude that transplantation of embryonic mesencephalic tissue leads to highly reproducible survival of dopaminergic neurons, inducing clinically valuable improvements in most recipients.
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