| 1. |
- Brundin, Patrik, et al.
(författare)
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Bilateral caudate and putamen grafts of embryonic mesencephalic tissue treated with lazaroids in Parkinson's disease
- 2000
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Ingår i: Brain. - 1460-2156. ; 123, s. 1380-1390
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Tidskriftsartikel (refereegranskat)abstract
- Five parkinsonian patients were transplanted bilaterally into the putamen and caudate nucleus with human embryonic mesencephalic tissue from between seven and nine donors. To increase graft survival, the lipid peroxidation inhibitor tirilazad mesylate was administered to the tissue before implantation and intravenously to the patients for 3 days thereafter. During the second postoperative year, the mean daily L-dopa dose was reduced by 54% and the UPDRS (Unified Parkinson's Disease Rating Scale) motor score in 'off' phase was reduced by a mean of 40%. At 10-23 months after grafting, PET showed a mean 61% increase of 6-L-[(18)F]fluorodopa uptake in the putamen, and 24% increase in the caudate nucleus, compared with preoperative values. No obvious differences in the pattern of motor recovery were observed between these and other previously studied cases with putamen grafts alone. The amount of mesencephalic tissue implanted in each putamen and caudate nucleus was 42 and 50% lower, respectively, compared with previously transplanted patients from our centre. Despite this reduction in grafted tissue, the magnitudes of symptomatic relief and graft survival were very similar. These findings suggest that tirilazad mesylate may improve survival of grafted dopamine neurons in patients, which is in agreement with observations in experimental animals.
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| 2. |
- Hagell, Peter, et al.
(författare)
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Dyskinesias following neural transplantation in Parkinson's disease.
- 2002
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Ingår i: Nature Neuroscience. - : Springer Science and Business Media LLC. - 1546-1726 .- 1097-6256. ; 5:7, s. 627-628
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Tidskriftsartikel (refereegranskat)abstract
- Severe dyskinesias during the 'off' phases (periods of increased Parkinson's disease (PD) disability) have been observed following intrastriatal transplantation of human embryonic mesencephalic tissue. Here we retrospectively analyzed 14 patients who were followed for up to 11 years after grafting, and found that dyskinesias (abnormal involuntary movements and postures) increased during postoperative off phases, but were generally of mild to moderate severity. Dyskinesia severity was not related to the magnitude of graft-derived dopaminergic re-innervation, as judged by (18)F-labeled 6-L-fluorodopa (FD) positron emission tomography (PET), indicating that off-phase dyskinesias probably did not result from excessive growth of grafted dopaminergic neurons.
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| 3. |
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| 4. |
- Kahlon, Babar, et al.
(författare)
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Comparison between the lumbar infusion and CSF tap tests to predict outcome after shunt surgery in suspected normal pressure hydrocephalus.
- 2002
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Ingår i: Journal of Neurology, Neurosurgery and Psychiatry. - : BMJ. - 1468-330X .- 0022-3050. ; 73:6, s. 721-726
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To compare the lumbar infusion test and the cerebrospinal fluid (CSF) tap test for predicting the outcome of shunt surgery in patients with suspected normal pressure hydrocephalus. METHODS: 68 patients with suspected normal pressure hydrocephalus were studied. The absence of preceding history indicated idiopathic disease in 75% of these. All patients were assessed twice with walking and psychometric tests before lumbar infusion test and tap test assessments. The lumbar infusion test was done using a constant infusion rate (0.80 ml/min) and regarded as positive if the steady state CSF plateau pressure reached levels of > 22 mm Hg (resistance to outflow > 14 mm Hg/ml/min). The tap test was regarded as positive if two or more of four different test items improved after CSF removal. As the variability in baseline test results was large, the better of two evaluations was used in comparisons with the results after CSF removal, as well as to evaluate the outcome after shunt surgery. Only patients with a positive lumbar infusion test or a positive tap test had surgery. RESULTS: The results of the CSF tap test and the lumbar infusion test agreed in only 45% of the patients. Of the total cohort, 47 (69%) had positive test results and were operated on; 45 (96%) of these reported subjective improvement, and postoperative assessments verified the improvements in 38 (81%). Improvements were highly significant in walking, memory, and reaction time tests (p < 0.001). Most of the patients improved by surgery (84%) were selected by a positive lumbar infusion test, and only 42% by a positive tap test. Positive predictive values were 80% for lumbar infusion test and 94% for tap test. The false negative predictions in the operated group were much higher (58%) with the tap test than with the lumbar infusion test (16%). CONCLUSIONS: Both the lumbar infusion test and the tap test can predict a positive outcome of shunt operations in unselected patients with suspected normal pressure hydrocephalus. The two tests are complementary and should be used together for optimal patient selection.
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| 5. |
- Piccini, P, et al.
(författare)
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Delayed recovery of movement-related cortical function in Parkinson's disease after striatal dopaminergic grafts
- 2000
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Ingår i: Annals of Neurology. - 1531-8249. ; 48:5, s. 689-695
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Tidskriftsartikel (refereegranskat)abstract
- Intrastriatal transplantation of dopaminergic neurones aims to repair the selective loss of nigrostriatal projections and the consequent dysfunction of striatocortical circuitries in Parkinson's disease (PD). Here, we have studied the effects of bilateral human embryonic dopaminergic grafts on the movement-related activation of frontal cortical areas in 4 PD patients using H2 15O positron emission tomography and a joystick movement task. At 6.5 months after transplantation, mean striatal dopamine storage capacity as measured by 18F-dopa positron emission tomography was already significantly elevated in these patients. This was associated with a modest clinical improvement on the Unified Parkinson's Disease Rating Scale, whereas the impaired cortical activation was unchanged. At 18 months after surgery, there was further significant clinical improvement in the absence of any additional increase in striatal 18F-dopa uptake. Rostral supplementary motor and dorsal prefrontal cortical activation during performance of joystick movements had significantly improved, however. Our data suggest that the function of the graft goes beyond that of a simple dopamine delivery system and that functional integration of the grafted neurones within the host brain is necessary to produce substantial clinical recovery in PD.
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