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

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

doi:10.3389/fneur.2019.01217

Maram Aljuaid, Kelly Williams + Show 7 more

Open Access

https://doi.org/10.3389/fneur.2019.01217

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Abstract

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.

Highlights

The forefront treatment of Parkinson’s disease (PD) is Levodopa
We investigate if clinically determined anti-parkinsonian medications dissociate the cerebral blood flow (CBF) and glucose metabolic activity using perfusion MRI and FDG-positron emission tomography (PET), respectively
We further propose an analytic method to quantify the degree of dissociation in the putamen which may have the potential to be used as a biomarker for Levodopa induced dyskinesia (LID)

Summary

Introduction

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). LID can be a very disabling and hard to treat side effect once it is established. It interferes with the patient’s quality of life and places a significant burden on the health care system. Amantadine is, to date, the only US Food and Drug Administration approved anti-dyskinetic medication that does not compromise antiparkinsonian medication’s benefit [1], but it typically loses its efficacy in an average of 8 months [3]

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