| 1. |
- Angot, Elodie, et al.
(författare)
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Dissecting the potential molecular mechanisms underlying alpha-synuclein cell-to-cell transfer in Parkinson's disease.
- 2009
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Ingår i: Parkinsonism & Related Disorders. - 1873-5126. ; 15 Suppl 3, s. 143-147
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Tidskriftsartikel (refereegranskat)abstract
- Alpha-synuclein (alpha-syn) aggregation is central to neuropathological changes in Parkinson's disease. The aggregates spread within the central nervous system according to a very predictable pattern. A prion-like transmission of alpha-syn aggregates has been recently proposed to explain this propagation pattern. First, we review the growing evidence for such a mechanism. This process is likely to occur in three consecutive steps: (i) exit of alpha-syn template from the donor cell, (ii) entry to the recipient cell and (iii) initiation of the nucleation. In a second part, we discuss the possible underlying mechanisms for each of these steps, based on our current knowledge about how cells handle alpha-syn but also other proteins involved in neurodegenerative diseases with a prion-like propagation. Finally, we discuss which molecular species of alpha-syn (monomer, oligomer, fibril) could be the seeding-competent species and whether this seeding process could be a common mechanism in neurodegenerative diseases.
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| 2. |
- Blomstedt, Patric, et al.
(författare)
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Acute severe depression induced by intraoperative stimulation of the Substatia Nigra : a case-report
- 2008
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Ingår i: Parkinsonism & Related Disorders. - : Elsevier. - 1353-8020 .- 1873-5126. ; 14:3, s. 253-256
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- We present a 62 years old man with Parkinson's disease (PD) who underwent bilateral stimulation in the subthalamic nucleus (STN). During the intraoperative evaluation, stimulation through the lowest contact in the right STN area, induced an acute depressive state, during which the patient was crying and expressing that he did not want to live. The patient returned to his normal state of mood within seconds after the cessation of stimulation. Repeated blinded stimulations resulted in the same response. Immediate postoperative magnetic resonance imaging (MRI) revealed that the lowest contact of the right electrode was located in the substantia nigra.
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| 3. |
- Blomstedt, Patric, et al.
(författare)
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Pallidotomy versus pallidal stimulation
- 2006
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Ingår i: Parkinsonism & Related Disorders. - : Elsevier BV. - 1353-8020 .- 1873-5126. ; 12:5, s. 296-301
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Tidskriftsartikel (refereegranskat)abstract
- Both posteroventral pallidotomy and pallidal deep brain stimulation (DBS) have a documented effect on Parkinsonian symptoms. DBS is more costly and more laborious than pallidotomy. The aim of this study was to analyse the respective long-term effect of each surgical procedure on contralateral symptoms in the same patients. Five consecutive patients, two women and three men, who at first surgery had a mean age of 64 years and a mean duration of disease of 18 years, received a pallidotomy contralateral to the more symptomatic side of the body. At a mean of 14 months later, the same patients received a pallidal DBS on the side contralateral to the pallidotomy. All patients had on–off phenomena and dyskinesias. There were three left-sided and two right-sided pallidotomies, and, subsequently, two left-sided and three right-sided pallidal DBS. The latest evaluation was performed 37 months (range 22–60) after the pallidotomy and 22 months (range 12–33) after the pallidal DBS. Mean UPDRS motor score pre-operatively was 49 and at last follow-up 33 (32.7% improvement, p<0.05). Appendicular items 20–26 contralateral to pallidotomy remained improved more significantly than contralateral to DBS. Dyskinesia scores were also improved more markedly contralateral to the pallidotomy. Two patients exhibited moderate dysarthria and one patient severe dysphonia following DBS. Symptoms contralateral to the chronologically older pallidotomy, especially dyskinesias, rigidity and tremor, were still more improved than symptoms contralateral to the more recent pallidal DBS, despite numerous post-operative patient visits to optimise stimulation parameters.
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| 4. |
- Cenci Nilsson, Angela
(författare)
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L-DOPA-induced dyskinesia: cellular mechanisms and approaches to treatment.
- 2007
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Ingår i: Parkinsonism & Related Disorders. - 1873-5126. ; 13 Suppl 3, s. 263-267
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Tidskriftsartikel (refereegranskat)abstract
- L-DOPA-induced dyskinesia (LID) is a common complication of the treatment of Parkinson's disease, and its precise mechanisms have long remained unknown. Rodent models of LID provide a tool to dissect the impact of specific factors on the development and expression of dyskinetic movements. This short review will summarize recent findings from rodent studies that have consolidated and considerably expanded our mechanistic understanding of LID. Based on the experimental findings, the review will propose a chart of possible treatment options acting on different pathophysiological levels.
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| 5. |
- Cenci Nilsson, Angela, et al.
(författare)
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Plastic effects of L-DOPA treatment in the basal ganglia and their relevance to the development of dyskinesia.
- 2009
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Ingår i: Parkinsonism & Related Disorders. - 1873-5126. ; 15 Suppl 3, s. 59-63
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Tidskriftsartikel (refereegranskat)abstract
- The development of L-DOPA-induced dyskinesia (LID) is attributed to plastic responses triggered by dopamine (DA) receptor stimulation in the parkinsonian brain. This article reviews studies that have uncovered different levels of maladaptive plasticity in animal models of LID. Rats developing dyskinesia on chronic L-DOPA treatment show abnormal patterns of signaling pathway activation and synaptic plasticity in striatal neurons. In addition, these animals show a gene expression profile indicative of structural cellular plasticity, including pronounced upregulation of genes involved in extracellular matrix remodeling, neurite extension, synaptic vesicle trafficking, and endothelial and cellular proliferation. Structural changes of neurons and microvessels within the basal ganglia are currently being unraveled by detailed morphological analyses. The structural and functional adaptations induced by L-DOPA in the brain can be viewed as an attempt to meet increased metabolic demands and to boost cellular defense mechanisms. These homeostatic responses, however, also predispose to the appearance of dyskinesia and other complications during the course of the treatment.
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| 6. |
- Cenci Nilsson, Angela, et al.
(författare)
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Rodent models of treatment-induced motor complications in Parkinson's disease
- 2009
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Ingår i: Parkinsonism and Related Disorders. - 1873-5126. ; 15 Suppl 4, s. 7-13
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Tidskriftsartikel (refereegranskat)abstract
- Treatment-induced motor complications represent a major clinical problem in Parkinson's disease (PD). Pharmacological dopamine (DA) replacement with l-dopa causes motor fluctuations and abnormal involuntary movements (dyskinesia) in the vast majority of the patients. Intrastriatal grafts of embryonic dopaminergic neurons can cause dyskinesia too, as shown by clinical trials of neural transplantation in PD. Animals models of these complications can be produced in rats and mice in which the nigrostriatal DA pathway has been severely damaged. Rodent models allow investigators to explore mechanistic hypotheses at the cellular and molecular level. Moreover, the rat model of L-dopa-induced abnormal involuntary movements shows both face validity and predictive validity relative to the corresponding disorder in primates, and provides a cost effective tool to evaluate novel antidyskinetic interventions. This article reviews the strategies that have been used to reproduce different motor complications of PD treatment in rodents, and comments on their range of applicability.
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| 7. |
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| 8. |
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| 9. |
- Hjelmgren, Jonas, et al.
(författare)
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Estimating the value of novel interventions for Parkinson's disease: An early decision-making model with application to dopamine cell replacement.
- 2006
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Ingår i: Parkinsonism & Related Disorders. - : Elsevier BV. - 1873-5126 .- 1353-8020. ; 12:7, s. 443-452
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Tidskriftsartikel (refereegranskat)abstract
- A long-term cost-effectiveness model for early decision-making and estimation of outcomes of novel therapeutic procedures for Parkinson's disease (PD) was developed based on the Hoehn and Yahr (HY) stages of PD. Results provided support for model validity. Model application to a future dopamine cell replacement therapy indicated long-term cost offsets and gains in quality-adjusted life years (QALYs) in early onset PD (HY III-IV), as compared to standard drug therapy. The maximum price premium (i.e., profit or compensation for developmental costs) for the intervention to remain cost-effective was estimated to EURO12000-64000 according to cost-per-QALY thresholds of EURO38000-70000 and depending on whether all or only medical direct costs are considered. The study illustrates the value of early health economic modeling and the described model shows promise as a means to estimate outcomes and aid decision-making regarding novel interventions for PD. (c) 2006 Elsevier Ltd. All rights reserved.
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| 10. |
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