| 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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Apomorphine in the treatment of Parkinson's disease
- 2001
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Ingår i: Journal of Neuroscience Nursing. - 0888-0395. ; 33:1, s. 21-38
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Tidskriftsartikel (refereegranskat)abstract
- Apomorphine is a potent, nonselective, direct-acting dopamine-receptor agonist. Given subcutaneously, it has a rapid onset of antiparkinsonian action qualitatively comparable to that of levodopa. Despite its long history, it was not until peripheral dopaminergic side effects could be controlled by oral domperidone that the clinical usefulness of apomorphine in Parkinson's disease began to be investigated thoroughly in the mid-1980s. Although several routes have been tried, subcutaneous administration, either as intermittent injections or continuous infusion, is so far the best and most applied in the treatment of advanced, fluctuating Parkinson's disease. Clinical trials have shown stable efficacy with markedly reduced time spent in "off" phases as well as, for infusion therapy, reduced levodopa requirements. In the most successful cases, motor fluctuations disappear and the need for oral medication is eliminated. Adverse events are usually mild and dominated by cutaneous reactions. Neuropsychiatric side effects occur, but the influence of apomorphine on these remains controversial. Controlled long-term clinical trials are highly warranted to reveal the full potentials of this treatment. Careful patient selection and follow-up, where the specialized movement disorder nurse has a crucial role, are paramount for a successful long-term outcome. Apomorphine warrants a wider application in the treatment of advanced Parkinson's disease and should be tried before more invasive interventions are considered.
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| 3. |
- Hagell, Peter, et al.
(författare)
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Cell survival and clinical outcome following intrastriatal transplantation in Parkinson disease
- 2001
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Ingår i: Journal of Neuropathology and Experimental Neurology. - 0022-3069 .- 1554-6578. ; 60:8, s. 741-752
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Tidskriftsartikel (refereegranskat)abstract
- Intrastriatal transplantation of embryonic dopaminergic neurons is currently explored as a restorative cell therapy for Parkinson disease (PD). Clinical results have varied, probably due to differences in transplantation methodology and patient selection. In this review, we assess clinical trials and autopsy findings in grafted PD patients and suggest that a minimum number of surviving dopaminergic neurons is required for a favorable outcome. Restoration of [18F]-fluorodopa uptake in the putamen to about 50% of the normal mean seems necessary for moderate to marked clinical benefit to occur. Some studies indicate that this may require mesencephalic tissue from 3-5 human embryos implanted into each hemisphere. The volume, density and pattern of fiber outgrowth and reinnervation, as well as functional integration and dopamine release. are postulated as additional important factors for an optimal clinical outcome. For neural transplantation to become a feasible therapeutic alternative in PD, graft survival must be increased and the need for multiple donors of human embryonic tissue substantially decreased or alternate sources of donor tissue developed. Donor cells derived from alternative sources should demonstrate features comparable to those associated with successful implantation of human embryonic tissue before clinical trials are considered.
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| 4. |
- Hagell, Peter, et al.
(författare)
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Health-related quality of life following bilateral intrastriatal transplantation in Parkinson's disease
- 2000
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Ingår i: Movement Disorders. - 0885-3185. ; 15:2, s. 224-229
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Tidskriftsartikel (refereegranskat)abstract
- Intrastriatal transplantation of embryonic dopaminergic tissue is a new, experimental approach for the treatment of Parkinson's disease (PD). Clinical trials have shown longterm graft survival and therapeutically valuable improvements with decreased L-dopa dose and time spent in the "off"-phase, and reduced rigidity and hypokinesia. We have measured health-related quality of life (HRQoL) using the Nottingham Health Profile (NHP) in five patients subjected to bilateral transplantation in the caudate and putamen to explore the influence of intrastriatal grafts on HRQoL and the value of such measures in trials of restorative therapies. The results demonstrate improved HRQoL following transplantation, with individual patients showing striking improvements within different dimensions of the NHP as well as the NHP distress index (NHPD). The most pronounced improvements after grafting were observed for physical mobility along with emotional reactions and energy. These results indicate that intrastriatal transplantation of embryonic dopaminergic tissue can give rise to improvements within most areas of HRQoL, and that HRQoL measurements provide important information additional to that obtained by traditional, symptom-oriented assessment protocols. However, the optimal approach to HRQoL measurement in PD remains to be determined.
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| 5. |
- Hagell, Peter, et al.
(författare)
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Health status measurement in Parkinson's disease : validity of the PDQ-39 and Nottingham Health Profile
- 2003
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Ingår i: Movement Disorders. - : John Wiley & Sons Inc.. - 0885-3185 .- 1531-8257. ; 18:7, s. 773-783
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Tidskriftsartikel (refereegranskat)abstract
- We assessed the feasibility and psychometric properties of two commonly used health status questionnaires in Parkinson's disease (PD): the generic Nottingham Health Profile (NHP) and the disease-specific 39-item Parkinson's disease Questionnaire (PDQ-39), from a cross-sectional postal survey of PD patients (N = 81), using traditional and Rasch measurement methodologies. Overall response rate was 88%. Both questionnaires were found feasible, although the NHP performed less well. The PDQ-39 had fewer floor effects and was better able to separate respondents into distinct groups than the NHP, whereas the latter exhibited less ambiguous dimensionality and better targeting of respondents with non-extreme scores. Reliability and validity indices were similar, and potential differential item functioning by age and gender groups was found for both questionnaires. PDQ-39 response alternatives indicated ambiguity. With few exceptions, questionnaire scales were unable to meet recommended standards fully. While preliminary, this study illustrates the need for thorough evaluation of outcome measures and has implications beyond the questionnaires used here. Although promising, both questionnaires warrant further developmental work and stronger support of measurement validity before they could be considered fully suitable for valid use in PD, in particular in earlier stages of the disease.
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| 6. |
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| 7. |
- Hagell, Peter, et al.
(författare)
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International use of health status questionnaires in Parkinson's disease: translation is not enough.
- 2003
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Ingår i: Parkinsonism & Related Disorders. - 1873-5126. ; 10:2, s. 89-92
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Tidskriftsartikel (refereegranskat)abstract
- The present study assessed the linguistic and content validity of the Swedish version of the 39-item Parkinson's disease questionnaire (PDQ-39). The frame question, response alternatives and two of the 39 items yielded substantial linguistic and stylistic problems. Such shortcomings would be expected to influence responses to, and the quality of, the whole questionnaire. Data support content validity of the PDQ-39 as a functional health status questionnaire, although some shortcomings were identified. This preliminary study illustrates the need for documented linguistic validity before new language adaptations of patient-reported outcome measures can be considered suitable for use in clinical trials, research, and practice.
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| 8. |
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| 9. |
- 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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