Dyskinesias in Parkinson's disease: views from positron emission tomography studies

Niccolini, Flavia; Loane, Clare; Politis, Marios

doi:10.1111/ene.12362

Cited by 12 publications

(8 citation statements)

References 150 publications

(223 reference statements)

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“…Radiological studies in LID patients have revealed that LID is acutely triggered by large, transient increases in striatal dopamine release following Levodopa administration (6). Patients who do not have motor complications show stable levels of synaptic dopamine concentration after Levodopa administration (7–9). In comparison, at 4 h post Levodopa administration PD patients with motor complications have significant synaptic dopamine level reduction in the putamen, whereas in the stable group synaptic dopamine level remains constant (8, 9).…”

Section: Introductionmentioning

confidence: 99%

“…Patients who do not have motor complications show stable levels of synaptic dopamine concentration after Levodopa administration (7–9). In comparison, at 4 h post Levodopa administration PD patients with motor complications have significant synaptic dopamine level reduction in the putamen, whereas in the stable group synaptic dopamine level remains constant (8, 9). These findings suggest that rapid swing and turnover of Levodopa levels at striatal synapses may contribute to the development of Levodopa—induced motor complications (9).…”

Section: Introductionmentioning

confidence: 99%

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Blood Flow and Glucose Metabolism Dissociation in the Putamen Is Predictive of Levodopa Induced Dyskinesia in Parkinson's Disease Patients

et al. 2019

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Background: The forefront treatment of Parkinson's disease (PD) is Levodopa. When patients are treated with Levodopa cerebral blood flow is increased while cerebral metabolic rate is decreased in key subcortical regions including the putamen. This phenomenon is especially pronounced in patients with Levodopa-induced dyskinesia (LID).Method: To study the effect of clinically-determined anti-parkinsonian medications, 10 PD patients (5 with LID and 5 without LID) have been scanned with FDG-PET (a probe for glucose metabolism) and perfusion MRI (a probe for cerebral blood flow) both when they are ON and OFF medications. Patients additionally underwent resting state fMRI to detect changes in dopamine-mediated cortico-striatal connectivity. The degree of blood flow-glucose metabolism dissociation was quantified by comparing the FDG-PET and perfusion MRI data.Results: A significant interaction effect (imaging modality × medication; blood flow-glucose metabolism dissociation) has been found in the putamen (p = 0.023). Post-hoc analysis revealed that anti-parkinsonian medication consistently normalized the pathologically hyper-metabolic state of the putamen while mixed effects were observed in cerebral blood flow changes. This dissociation was especially predominant in patients with LID compared to those without. Unlike the prior study, this differentiation was not observed when cortico-striatal functional connectivity was assessed.Conclusion: We confirmed striatal neurovascular dissociation between FDG-PET and perfusion MRI in response to clinically determined anti-parkinsonian medication. We further proposed a novel analytical method to quantify the degree of dissociation in the putamen using only the ON condition scans, Putamen-to-thalamus Hyper-perfusion/hypo-metabolism Index (PHI), which may have the potential to be used as a biomarker for LID (correctly classifying 8 out 10 patients). For wider use of PHI, a larger validation study is warranted.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Blood Flow and Glucose Metabolism Dissociation in the Putamen Is Predictive of Levodopa Induced Dyskinesia in Parkinson's Disease Patients

et al. 2019

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“…The role of endogenous and exogenous 5‐HT innervation from the host or within the graft has been the focus of a lot of speculation in relation to both LID and graft‐induced dyskinesia. A detailed discussion is beyond the scope of this review and is discussed elsewhere (see Niccolini, Loane, & Politis, ; Shin, Garcia, Winkler, Bjorklund, & Carta, ), but in brief, there is a high degree of endogenous striatal serotonergic innervation which is enhanced following foetal cell transplantation. While there is strong evidence that L‐DOPA management through the endogenous striatal innervation contributes to dysregulation of L‐DOPA handling and thus LID (Carta & Björklund, ), the picture in relation to graft‐induced dyskinesia is less convincing.…”

Section: The Role Of L‐dopa In Graft‐induced Dyskinesiamentioning

confidence: 99%

L‐DOPA for Parkinson's disease—a bittersweet pill

Lane

2018

Eur J of Neuroscience

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3,4-dihydroxy-L-phenylalanine (L-DOPA) is the gold standard treatment for Parkinson's disease. It has earned that title through its highly effective treatment of some of the motor symptoms in the early stages of the disease but it is a far from perfect drug. The inevitable long-term treatment that comes with this chronic neurodegenerative condition raises the risk significantly of the development of motor fluctuations including disabling L-DOPA-induced dyskinesia. Being unsurpassed as a therapy means that understanding the mechanisms of dyskinesia priming and induction is vital to the search for therapies to treat these side effects and allow optimal use of L-DOPA. However, L-DOPA use may also have consequences (positive or negative) for the development of other interventions, such as cell transplantation, which are designed to treat or repair the ailing brain. This review looks at the issues around the use of L-DOPA with a focus on its potential impact on advanced reparative interventions.

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“…Recent studies suggest that GID development could be related to the composition of the grafted tissue [ 38 , 39 , 57 ]. It should be taken into consideration that DA cells are only about 5–10% of the cells within freshly dissociated VM tissue [ 58 , 59 ] and that the way in which VM tissue is stored or cultured prior to transplantation might alter the graft composition in favour of non-DA cells, such as reactive astrocytes [ 60 ].…”

Section: Graft Composition: the Serotonin Hypothesismentioning

confidence: 99%

Foetal Cell Transplantation for Parkinson’s Disease: Focus on Graft-Induced Dyskinesia

Tronci

Fidalgo

Carta

2015

Parkinson's Disease

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Transplantation of dopamine- (DA-) rich foetal ventral mesencephalic cells emerged as a promising therapy for Parkinson's disease (PD), as it allowed significant improvement of motor symptoms in several PD patients in open-label studies. However, double-blind clinical trials have been largely disappointing. The general agreement in the field is that the lack of standardization of tissue collection and preparation, together with the absence of postsurgical immunosuppression, played a key role in the failure of these studies. Moreover, a further complication that emerged in previous studies is the appearance of the so-called graft-induced dyskinesia (GID), in a subset of grafted patients, which resembles dyskinesia induced by L-DOPA but in the absence of medication. Preclinical evidence pointed to the serotonin neurons as possible players in the appearance of GID. In agreement, clinical investigations have shown that grafted tissue may contain a large number of serotonin neurons, in the order of half of the DA cells; moreover, the serotonin 5-HT1A receptor agonist buspirone has been found to produce significant dampening of GID in grafted patients. In this paper, we will review the recent preclinical and clinical studies focusing on cell transplantation for PD and on the mechanisms underlying GID.

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Dyskinesias in Parkinson's disease: views from positron emission tomography studies

Cited by 12 publications

References 150 publications

Blood Flow and Glucose Metabolism Dissociation in the Putamen Is Predictive of Levodopa Induced Dyskinesia in Parkinson's Disease Patients

Blood Flow and Glucose Metabolism Dissociation in the Putamen Is Predictive of Levodopa Induced Dyskinesia in Parkinson's Disease Patients

L‐DOPA for Parkinson's disease—a bittersweet pill

Foetal Cell Transplantation for Parkinson’s Disease: Focus on Graft-Induced Dyskinesia

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