Dataset Information

PET Molecular Imaging Research of Levodopa-Induced Dyskinesias in Parkinson's Disease.

ABSTRACT: To review the current status of positron emission tomography (PET) molecular imaging research of levodopa-induced dyskinesias (LIDs) in Parkinson's disease (PD).Recent PET studies have provided robust evidence that LIDs in PD are associated with elevated and fluctuating striatal dopamine synaptic levels, which is a consequence of the imbalance between dopaminergic and serotonergic terminals, with the latter playing a key role in mishandling presynaptic dopamine release. Long-term exposure to levodopa is no longer believed to solely induce LIDs, as studies have highlighted that PD patients who go on to develop LIDs exhibit elevated putaminal dopamine release before the initiation of levodopa treatment, suggesting the involvement of other mechanisms, including altered neuronal firing and abnormal levels of phosphodiesterase 10A. Dopaminergic, serotonergic, glutamatergic, adenosinergic and opioid systems and phosphodiesterase 10A levels have been shown to be implicated in the development of LIDs in PD. However, no system may be considered sufficient on its own for the development of LIDs, and the mechanisms underlying LIDs in PD may have a multisystem origin. In line with this notion, future studies should use multimodal PET molecular imaging in the same individuals to shed further light on the different mechanisms underlying the development of LIDs in PD.

SUBMITTER: Pagano G

PROVIDER: S-EPMC5626800 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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PET Molecular Imaging Research of Levodopa-Induced Dyskinesias in Parkinson's Disease.

Pagano Gennaro G Yousaf Tayyabah T Politis Marios M

Current neurology and neuroscience reports 20171003 11

<h4>Purpose of review</h4>To review the current status of positron emission tomography (PET) molecular imaging research of levodopa-induced dyskinesias (LIDs) in Parkinson's disease (PD).<h4>Recent findings</h4>Recent PET studies have provided robust evidence that LIDs in PD are associated with elevated and fluctuating striatal dopamine synaptic levels, which is a consequence of the imbalance between dopaminergic and serotonergic terminals, with the latter playing a key role in mishandling presy ...[more]

PMID: 28975571

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Project description:Background: Adaptive Deep Brain Stimulation (aDBS) is now considered as a new feasible and effective paradigm to deliver DBS to patients with Parkinson's disease (PD) in such a way that not only stimulation is personalized and finely tuned to the instantaneous patient's state, but also motor improvement is obtained with a lower amount of energy transferred to the tissue. Amplitude-controlled aDBS was shown to significantly decrease the amplitude-driven total electrical energy delivered to the tissue (aTEED), an objective measure of the amount of energy transferred by DBS amplitude to the patient's brain. However, there is no direct evidence of a relationship between aTEED and the occurrence of DBS-related adverse events in humans. Objective: In this work, we investigated the correlation of aTEED with the occurrence of levodopa-induced dyskinesias pooling all the data available from our previous experiments using aDBS and cDBS. Methods: We retrospectively analyzed data coming from 19 patients with PD undergoing surgery for STN-DBS electrode positioning and participating to experiments involving cDBS and aDBS delivery. Patients were all studied some days after the surgery (acute setting). The aTEED and dyskinesia assessments (Rush Dyskinesia Rating Scale, RDRS) considered in the Med ON-Stim ON condition. Results: We confirmed both that aTEED values and RDRS were significantly lower in the aDBS than in cDBS sessions (aTEED mean value, cDBS: 0.0278 ± 0.0011 j, vs. aDBS: 0.0071 ± 0.0003 j, p < 0.0001 Wilcoxon's rank sum; normalized RDRS mean score, cDBS: 0.66 ± 0.017 vs. aDBS: 0.45 ± 0.01, p = 0.025, Wilcoxon's rank sum test). In addition, we found a direct significant correlation between aTEED and RDRS (ρ = 0.44, p = 0.0032, Spearman's correlation). Conclusions: Our results provide a first piece of evidence that aTEED is correlated to the amount of levodopa-induced dyskinesias in patients with PD undergoing STN-DBS, thus supporting the role of aDBS as feasible and safe alternative to cDBS.

Dataset Information

PET Molecular Imaging Research of Levodopa-Induced Dyskinesias in Parkinson's Disease.

Publications

PET Molecular Imaging Research of Levodopa-Induced Dyskinesias in Parkinson's Disease.

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