| 1. |
- Kefalopoulou, Zinovia, et al.
(författare)
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Long-term clinical outcome of fetal cell transplantation for Parkinson disease : two case reports
- 2014
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Ingår i: JAMA Neurology. - : American Medical Association (AMA). - 2168-6157 .- 2168-6149. ; 71:1, s. 7-83
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE: Recent advances in stem cell technologies have rekindled an interest in the use of cell replacement strategies for patients with Parkinson disease. This study reports the very long-term clinical outcomes of fetal cell transplantation in 2 patients with Parkinson disease. Such long-term follow-up data can usefully inform on the potential efficacy of this approach, as well as the design of trials for its further evaluation.OBSERVATIONS: Two patients received intrastriatal grafts of human fetal ventral mesencephalic tissue, rich in dopaminergic neuroblasts, as restorative treatment for their Parkinson disease. To evaluate the very long-term efficacy of the grafts, clinical assessments were performed 18 and 15 years posttransplantation. Motor improvements gained gradually over the first postoperative years were sustained up to 18 years posttransplantation, while both patients have discontinued, and remained free of any, pharmacological dopaminergic therapy.CONCLUSIONS AND RELEVANCE: The results from these 2 cases indicate that dopaminergic cell transplantation can offer very long-term symptomatic relief in patients with Parkinson disease and provide proof-of-concept support for future clinical trials using fetal or stem cell therapies.
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| 2. |
- Li, Weihua, et al.
(författare)
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11C-PE2I and 18F-Dopa PET for assessing progression rate in Parkinson's : A longitudinal study
- 2018
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Ingår i: Movement Disorders. - : Wiley. - 0885-3185. ; 33:1, s. 117-127
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Tidskriftsartikel (refereegranskat)abstract
- 18F-dopa PET measuring aromatic l-amino acid decarboxylase activity is regarded as the gold standard for evaluating dopaminergic function in Parkinson's disease. Radioligands for dopamine transporters are also used in clinical trials and for confirming PD diagnosis. Currently, it is not clear which imaging marker is more reliable for assessing clinical severity and rate of progression. The objective of this study was to directly compare 18F-dopa with the highly selective dopamine transporter radioligand 11C-PE2I for the assessment of motor severity and rate of progression in PD. Thirty-three mild-moderate PD patients underwent 18F-dopa and 11C-PE2I PET at baseline. Twenty-three were followed up for 18.8 ± 3.4 months. Standard multiple regression at baseline indicated that 11C-PE2I BPND predicted UPDRS-III and bradykinesia-rigidity scores (P < 0.05), whereas 18F-dopa Ki did not make significant unique explanatory contributions. Voxel-wise analysis showed negative correlations between 11C-PE2I BPND and motor severity across the whole striatum bilaterally. 18F-Dopa Ki clusters were restricted to the most affected putamen and caudate. Longitudinally, negative correlations were found between striatal (increment)11C-PE2I BPND, (increment)UPDRS-III, and (increment)bradykinesia-rigidity, whereas no significant associations were found for (increment)18F-dopa Ki. One cluster in the most affected putamen was identified in the longitudinal voxel-wise analysis showing a negative relationship between (increment)11C-PE2I BPND and (increment)bradykinesia-rigidity. Striatal 11C-PE2I appears to show greater sensitivity for detecting differences in motor severity than 18F-dopa. Furthermore, dopamine transporter decline is closely associated with motor progression over time, whereas no such relationship was found with aromatic l-amino acid decarboxylase. 11C-PE2I may be more effective for evaluating the efficacy of neuroprotective treatments in PD.
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| 3. |
- Loane, Clare, et al.
(författare)
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Aberrant nigral diffusion in Parkinson's disease : A longitudinal diffusion tensor imaging study
- 2016
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Ingår i: Movement Disorders. - : Wiley. - 0885-3185. ; 31:7, s. 6-1020
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Measuring microstructure alterations with diffusion tensor imaging in PD is potentially a valuable tool to use as a biomarker for early diagnosis and to track disease progression. Previous studies have reported a specific decrease of nigral fractional anisotropy in PD. However, to date the effect of disease progression on nigral or striatal diffusion indices has not been fully explored.METHODS: We have conducted a cross-sectional and longitudinal diffusion tensor imaging study in 18 early stage, treated PD patients and 14 age-matched controls. PD patients were scanned on 2 occasions OFF medication, 19.3 months apart (standard deviation = 3.1 months). Longitudinal change of regional nigral and striatal measures of fractional anisotropy and mean diffusivity were calculated using a region-of-interest approach.RESULTS: Region-of-interest analysis demonstrated that at baseline, PD patients and controls did not differ in regard to diffusion indices in any region assessed. A significant difference of nigral fractional anisotropy and mean diffusivity between controls and PD patients at follow-up was detected and confirmed with longitudinal analysis within PD patients. Alterations in striatal regions were not detected in either group or over time.CONCLUSION: Our findings indicate that nigral diffusion measure may be a valuable measure of disease progression. In the future, larger longitudinal studies will confirm whether diffusion indices may serve as sensitive and clinically meaningful measures of disease progression in PD. © 2016 International Parkinson and Movement Disorder Society.
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| 4. |
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| 5. |
- Nørgaard, Martin, et al.
(författare)
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Cerebral serotonin transporter measurements with [11C]DASB : A review on acquisition and preprocessing across 21 PET centres
- 2019
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Ingår i: Journal of Cerebral Blood Flow and Metabolism. - 0271-678X .- 1559-7016. ; 39:2, s. 210-222
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Tidskriftsartikel (refereegranskat)abstract
- Positron Emission Tomography (PET) imaging has become a prominent tool to capture the spatiotemporal distribution of neurotransmitters and receptors in the brain. The outcome of a PET study can, however, potentially be obscured by suboptimal and/or inconsistent choices made in complex processing pipelines required to reach a quantitative estimate of radioligand binding. Variations in subject selection, experimental design, data acquisition, preprocessing, and statistical analysis may lead to different outcomes and neurobiological interpretations. We here review the approaches used in 105 original research articles published by 21 different PET centres, using the tracer [11C]DASB for quantification of cerebral serotonin transporter binding, as an exemplary case. We highlight and quantify the impact of the remarkable variety of ways in which researchers are currently conducting their studies, while implicitly expecting generalizable results across research groups. Our review provides evidence that the foundation for a given choice of a preprocessing pipeline seems to be an overlooked aspect in modern PET neuroscience. Furthermore, we believe that a thorough testing of pipeline performance is necessary to produce reproducible research outcomes, avoiding biased results and allowing for better understanding of human brain function.
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| 6. |
- Politis, Marios, et al.
(författare)
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Clinical application of stem cell therapy in Parkinson's disease
- 2012
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Ingår i: BMC Medicine. - : Springer Science and Business Media LLC. - 1741-7015. ; 10
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Forskningsöversikt (refereegranskat)abstract
- Cell replacement therapies in Parkinson's disease (PD) aim to provide long-lasting relief of patients' symptoms. Previous clinical trials using transplantation of human fetal ventral mesencephalic (hfVM) tissue in the striata of PD patients have provided proof-of-principle that such grafts can restore striatal dopaminergic (DA-ergic) function. The transplants survive, reinnervate the striatum, and generate adequate symptomatic relief in some patients for more than a decade following operation. However, the initial clinical trials lacked homogeneity of outcomes and were hindered by the development of troublesome graft-induced dyskinesias in a subgroup of patients. Although recent knowledge has provided insights for overcoming these obstacles, it is unlikely that transplantation of hfVM tissue will become routine treatment for PD owing to problems with tissue availability and standardization of the grafts. The main focus now is on producing DA-ergic neuroblasts for transplantation from stem cells (SCs). There is a range of emerging sources of SCs for generating a DA-ergic fate in vitro. However, the translation of these efforts in vivo currently lacks efficacy and sustainability. A successful, clinically competitive SC therapy in PD needs to produce longlasting symptomatic relief without side effects while counteracting PD progression.
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| 7. |
- Politis, Marios, et al.
(författare)
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Graft-Induced Dyskinesias in Parkinson's Disease: High Striatal Serotonin/Dopamine Transporter Ratio
- 2011
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Ingår i: Movement Disorders. - : Wiley. - 0885-3185. ; 26:11, s. 1997-2003
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Tidskriftsartikel (refereegranskat)abstract
- Graft-induced dyskinesias are a serious complication after neural transplantation in Parkinson's disease. One patient with Parkinson's disease, treated with fetal grafts 14 years ago and deep brain stimulation 6 years ago, showed marked improvement of motor symptoms but continued to suffer from OFF-medication graft-induced dyskinesias. The patient received a series of clinical and imaging assessments. Positron emission tomography and single-photon emission computed tomography 14 years posttransplantation revealed an elevated serotonin/dopamine transporter ratio in the grafted striatum compatible with serotonergic hyperinnervation. Inhibition of serotonin neuron activity by systemic administration of a 5-HT1A agonist suppressed graft-induced dyskinesias. Our data provide further evidence that serotonergic neurons mediate graft-induced dyskinesias in Parkinson's disease. Achieving a normal striatal serotonin/dopamine transporter ratio following transplantation of fetal tissue or stem cells should be necessary to avoid the development of graft-induced dyskinesias. (C) 2011 Movement Disorder Society
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| 8. |
- Politis, Marios, et al.
(författare)
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Serotonergic Neurons Mediate Dyskinesia Side Effects in Parkinson's Patients with Neural Transplants
- 2010
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Ingår i: Science Translational Medicine. - : American Association for the Advancement of Science (AAAS). - 1946-6242 .- 1946-6234. ; 2:38
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Tidskriftsartikel (refereegranskat)abstract
- Troublesome involuntary movements in the absence of dopaminergic medication, so-called off-medication dyskinesias, are a serious adverse effect of fetal neural grafts that hinders the development of cell-based therapies for Parkinson's disease. The mechanisms underlying these dyskinesias are not well understood, and it is not known whether they are the same as in the dyskinesias induced by L-dopa treatment. Using in vivo brain imaging, we show excessive serotonergic innervation in the grafted striatum of two patients with Parkinson's disease, who had exhibited major motor recovery after transplantation with dopamine-rich fetal mesencephalic tissue but had later developed off-medication dyskinesias. The dyskinesias were markedly attenuated by systemic administration of a serotonin [5-hydroxytryptamine (5-HT)] receptor (5-HT1A) agonist, which dampens transmitter release from serotonergic neurons, indicating that the dyskinesias were caused by the serotonergic hyperinnervation. Our observations suggest strategies for avoiding and treating graft-induced dyskinesias that result from cell therapies for Parkinson's disease with fetal tissue or stem cells.
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| 9. |
- Politis, Marios, et al.
(författare)
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Serotonin Neuron Loss and Nonmotor Symptoms Continue in Parkinson's Patients Treated with Dopamine Grafts
- 2012
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Ingår i: Science Translational Medicine. - : American Association for the Advancement of Science (AAAS). - 1946-6242 .- 1946-6234. ; 4:128
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Tidskriftsartikel (refereegranskat)abstract
- Cell therapy studies in patients with Parkinson's disease (PD) have been confined to intrastriatal transplantation of dopamine-rich fetal mesencephalic tissue in efforts to improve motor performance. Although some PD patients receiving the dopamine-rich grafts showed improvements in motor symptoms due to replacement of dopaminergic neurons, they still suffered from nonmotor symptoms including depression, fatigue, visual hallucinations, and sleep problems. Using functional imaging and clinical evaluation of motor and nonmotor symptoms in three PD patients transplanted with intrastriatal fetal grafts 13 to 16 years previously, we assessed whether reestablishment of dopaminergic neuronal networks is sufficient to improve a broad range of symptoms. At 13 to 16 years after transplantation, dopaminergic innervation was restored to normal levels in basal ganglia and preserved in a number of extrabasal ganglia areas. These changes were associated with long-lasting relief of motor symptoms. Then, we assessed the integrity of their serotonergic and norepinephrine neuronal systems using [C-11]DASB {[C-11]3-amino-4-(2-dimethylaminomethylphenylthio) benzonitrile} positron emission tomography (PET) and F-18-dopa PET, respectively. F-18-Dopa uptake in the locus coeruleus was within the normal range. In contrast, [C-11] DASB uptake in the raphe nuclei and regions receiving serotonergic projections was markedly reduced. These results indicate ongoing degeneration of serotonergic raphe nuclei and their projections to regions involved in the regulation of sleep, arousal, feeding, satiety, mood, and emotion. Our findings indicate that future cell-based therapies using fetal tissue or stem cells in PD patients may require additional grafts of serotonergic neurons to relieve nonmotor symptoms by restoring serotonergic neurotransmission in specific cerebral targets.
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| 10. |
- Politis, Marios, et al.
(författare)
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Sexual health among the oldest old : a population-based study among people aged 85 years and older in Stockholm, Sweden
- 2024
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Ingår i: Sexual Medicine. - 2050-1161. ; 12:2
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Tidskriftsartikel (refereegranskat)abstract
- Background Sexual health is an important contributor to the well-being and life satisfaction of people aged >= 85 years, known as the oldest old. However, little is known about sexual health in this population.Aim To examine aspects of sexual health among the oldest old and explore its associations with sociodemographic, health-related, and lifestyle factors.Methods We conducted a population-based cross-sectional study including 183 individuals aged >= 85 years who were residents in Stockholm County, Sweden. Responders (response rate, 63%) were interviewed on a range of health, sociodemographic, and lifestyle parameters, including aspects of sexual health. Participants' responses to the sexual health items were reported as proportions with 95% CIs. Associations were examined with multivariable logistic regression.Outcomes We examined sexual activity, sexual satisfaction, problems related to sexual health, and inquiries on sexual health by a health care provider.Results Twelve percent of participants (95% CI, 8%-17.6%) were sexually active, and 63.9% (95% CI, 56.5%-70.9%) were satisfied with their sexual lives during the past year. A third (35%; 95% CI, 28.4%-42.2%) reported at least a problem related to sexual health. Only 2.2% (95% CI, 0.6%-5.5%) were asked about sexual health by a health care provider, while 8.2% (95% CI, 4.7%-13.2%) identified a need for such an assessment. Yet, 85.2% (95% CI, 79.3%-90.0%) indicated no need for their sexual health to be evaluated by a health care provider. Being partnered was positively associated with sexual activity (adjusted odds ratio, 9.13; 95% CI, 2.53-32.90), whereas having strong social support was positively associated with being satisfied with one's sexual life (adjusted odds ratio, 2.96; 95% CI, 1.53-5.74).Clinical Implications Health care providers should be proactive in assessing the sexual health of the oldest individuals.Strengths and Limitations A representative sample of an underresearched population was used in this study. However, the generalizability of our findings may be restricted due to the small sample. To maintain statistical power from a relatively small sample, we might have lost explanatory power. Given the observational cross-sectional nature of the data, we cannot draw causal inferences based on the observed associations.Conclusions A 10th of participants were sexually active, and the majority were satisfied with their sexual lives. Although many participants reported problems related to sexual health, few expressed the need to discuss sexual health with health care providers. Future studies should explore potential barriers to addressing sexual health and unmet health care needs among the oldest old.
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