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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Neurol. | doi: 10.3389/fneur.2019.01217

Blood flow and glucose metabolism dissociation in the putamen is predictive of levodopa induced dyskinesia in Parkinson’s disease patients

Maram Aljuaid1, 2,  Samuel T. Booth1, 2, 3, Douglas E. Hobson4, Andrew Borys4, Kelly Williams4, Audrey Katako1, 2, Lawrence Ryner5,  Andrew L. Goertzen5 and  Ji Hyun Ko1, 2*
  • 1Department of Human Anatomy and Cell Science, Max Rady College of Medicine ,University of Manitoba, Canada
  • 2Kleysen Institute for Advanced Medicine, University of Manitoba, Canada
  • 3University of Manitoba, Canada
  • 4Section of Neurology, University of Manitoba, Canada
  • 5Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Canada

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 phenomena is especially pronounced in patients with Levodopa-induced dyskinesia (LID).
Method: To study the effect of clinically-determined anti-parkinsonian medications, ten 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.
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 the ones 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 a 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.

Keywords: cerebral blood flow (CBF), glucose metabolism, magnetic resonance imaging, neurovascular coupling, Parkinson's disease, Positron emission 
tomography, Levodopa induced dyskinesia

Received: 01 Aug 2019; Accepted: 01 Nov 2019.

Copyright: © 2019 Aljuaid, Booth, Hobson, Borys, Williams, Katako, Ryner, Goertzen and Ko. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Ji Hyun Ko, Department of Human Anatomy and Cell Science, Max Rady College of Medicine ,University of Manitoba, Winnipag, R3E 0J9, Manitoba, Canada, ji.ko@umanitoba.ca