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

Aljuaid, Maram; Booth, Samuel; Hobson, Douglas E.; Borys, Andrew; Williams, Kelly T.; Katako, Audrey; Ryner, Lawrence; Goertzen, Andrew L.; Ko, Ji Hyun

doi:10.3389/fneur.2019.01217

Cited by 15 publications

(13 citation statements)

References 49 publications

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“…Previous perfusion imaging studies in humans have shown an increase in striatal blood flow in LID patients in response to l‐ dopa treatment much more than non‐LID patients 11,32 and in rat models with toxin‐induced parkinsonism 12 . The increased blood flow was normalized when medication was withdrawn, which indicates that there is a change in the vasomotor response regulated by astrocytes and endothelial smooth muscle, rather than a static change in the microvascular architecture 11 .…”

Section: Discussionmentioning

confidence: 98%

The Vasomotor Response to Dopamine Is Altered in the Rat Model of l‐dopa‐Induced Dyskinesia

et al. 2020

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A BS TRACT: Background: Levodopa (L-dopa) is the frontline treatment for motor symptoms of Parkinson's disease. However, prolonged use of L-dopa results in a motor complication known as levodopa-induced dyskinesia (LID) in~50% of patients over 5 years. Objectives: We investigated neurovascular abnormalities in a rat model of LID by examining changes in angiogenesis and dopamine-dependent vessel diameter changes. Methods: Differences in striatal and nigral angiogenesis in a parkinsonian rat model (6-OHDA lesion) treated with 2 doses of L-dopa (saline, 2, and 10 mg/kg/day subcutaneous L-dopa treatment for 22 days) by 5-bromo-2'deoxyuridine (BrdU)-RECA1 co-immunofluorescence. Difference in the vasomotor response to dopamine was examined with 2-photon laser scanning microscopy and Dodt gradient imaging. Results: We found that the 10 mg/kg L-dopa dosing regimen induced LID in all animals (n = 5) and induced significant angiogenesis in the striatum and substantia nigra. In contrast, the 2 mg/kg treatment induced LID in 6 out of 12 rats and led to linearly increasing LID severity over the 22-day treatment period, making this a promising model for studying LID progression longitudinally. However, no significantly different level of angiogenesis was observed between LID versus non-LID animals. Dopamine-induced vasodilatory responses were exaggerated only in rats that show LID-like signs compared to the rest of groups. Additionally, in juvenile rats, we showed that DA-induced vasodilation is preceded by increased Ca 2+ release in the adjacent astrocytes. Conclusion: This finding supports that astrocytic dopamine signaling controls striatal blood flow bidirectionally, and the balance is altered in LID.

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Section: Discussionmentioning

confidence: 98%

The Vasomotor Response to Dopamine Is Altered in the Rat Model of l‐dopa‐Induced Dyskinesia

et al. 2020

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“…Alzheimer's disease-like CBF pattern analysis. The CBF maps were derived from pCASL data as previously described 35 using ASL Perfusion MRI data processing toolbox (https ://cfn.upenn .edu/~zewan g/ asltb x.php). The resulting CBF images were co-registered to the corresponding T1-weighted image, spatial normalized by wrapping to the MNI standard space, then smoothed using 8 mm Gaussian filter.…”

Section: Mri Data Acquisition All Subjects Underwent Mri Using a 3 Tmentioning

confidence: 99%

Elevated caudate connectivity in cognitively normal Parkinson’s disease patients

Wright

Alhindi

Millikin

et al. 2020

Sci Rep

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Mild cognitive impairment (MCI) is common in Parkinson’s disease patients. However, its underlying mechanism is not well understood, which has hindered new treatment discoveries specific to MCI. The aim of this study was to investigate functional connectivity changes of the caudate nucleus in cognitively impaired Parkinson’s patients. We recruited 18 Parkinson’s disease patients—10 PDNC [normal cognition Parkinson’s disease; Montreal Cognitive Assessment (MoCA) ≥ 26], 8 PDLC (low cognition Parkinson’s disease; MoCA < 26) —and 10 age-matched healthy controls. All subjects were scanned with resting-state functional magnetic resonance imaging (MRI) and perfusion MRI. We analyzed these data for graph theory metrics and Alzheimer’s disease-like pattern score, respectively. A strong positive correlation was found between the functional connectivity of the right caudate nucleus and MoCA scores in Parkinson’s patient groups, but not in healthy control subjects. Interestingly, PDNC’s functional connectivity of the right caudate was significantly higher than both PDLC and healthy controls, while PDLC and healthy controls were not significantly different from each other. We found that Alzheimer’s disease-like metabolic/perfusion pattern score correlated with MoCA scores in healthy controls, but not in Parkinson’s disease. Increased caudate connectivity may be related to a compensatory mechanism found in cognitively normal patients with Parkinson’s disease. Our findings support and complement the dual syndrome hypothesis.

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“…The presence of LID in PD patients is associated with higher PHI values. It is possible that this parameter can be used as a marker to assess the risk of developing LID in patients with PD [ 27 ].…”

Section: Resultsmentioning

confidence: 99%

Current Knowledge on the Background, Pathophysiology and Treatment of Levodopa-Induced Dyskinesia—Literature Review

Hutny

Hofman

Klimkowicz‐Mrowiec

et al. 2021

JCM

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Levodopa remains the primary drug for controlling motor symptoms in Parkinson’s disease through the whole course, but over time, complications develop in the form of dyskinesias, which gradually become more frequent and severe. These abnormal, involuntary, hyperkinetic movements are mainly characteristic of the ON phase and are triggered by excess exogenous levodopa. They may also occur during the OFF phase, or in both phases. Over the past 10 years, the issue of levodopa-induced dyskinesia has been the subject of research into both the substrate of this pathology and potential remedial strategies. The purpose of the present study was to review the results of recent research on the background and treatment of dyskinesia. To this end, databases were reviewed using a search strategy that included both relevant keywords related to the topic and appropriate filters to limit results to English language literature published since 2010. Based on the selected papers, the current state of knowledge on the morphological, functional, genetic and clinical features of levodopa-induced dyskinesia, as well as pharmacological, genetic treatment and other therapies such as deep brain stimulation, are described.

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

Cited by 15 publications

References 49 publications

The Vasomotor Response to Dopamine Is Altered in the Rat Model of l‐dopa‐Induced Dyskinesia

The Vasomotor Response to Dopamine Is Altered in the Rat Model of l‐dopa‐Induced Dyskinesia

Elevated caudate connectivity in cognitively normal Parkinson’s disease patients

Current Knowledge on the Background, Pathophysiology and Treatment of Levodopa-Induced Dyskinesia—Literature Review

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