Increased putamen hypercapnic vasoreactivity in levodopa-induced dyskinesia

In a rodent model of Parkinson's disease (PD), levodopa-induced involuntary movements have been linked to striatal angiogenesis - a process that is difficult to document in living human subjects. Angiogenesis can be accompanied by localized increases in cerebral blood flow (CBF) responses to hy...

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Bibliographic Details
Published in:JCI insight 2017-10, Vol.2 (20)
Main Authors: Jourdain, Vincent A, Schindlbeck, Katharina A, Tang, Chris C, Niethammer, Martin, Choi, Yoon Young, Markowitz, Daniel, Nazem, Amir, Nardi, Dominic, Carras, Nicholas, Feigin, Andrew, Ma, Yilong, Peng, Shichun, Dhawan, Vijay, Eidelberg, David
Format: Article
Language:English
Subjects:
Aged
Antiparkinson Agents - pharmacology
Cerebrovascular Circulation
Dyskinesia, Drug-Induced - metabolism
Dyskinesias - diagnostic imaging
Dyskinesias - etiology
Dyskinesias - metabolism
Female
Humans
Hypercapnia - metabolism
Levodopa - pharmacology
Levodopa - therapeutic use
Male
Middle Aged
Neuroimaging
Parkinson Disease - drug therapy
Putamen - metabolism
Sensorimotor Cortex - drug effects
Sensorimotor Cortex - pathology
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Summary:In a rodent model of Parkinson's disease (PD), levodopa-induced involuntary movements have been linked to striatal angiogenesis - a process that is difficult to document in living human subjects. Angiogenesis can be accompanied by localized increases in cerebral blood flow (CBF) responses to hypercapnia. We therefore explored the possibility that, in the absence of levodopa, local hypercapnic CBF responses are abnormally increased in PD patients with levodopa-induced dyskinesias (LID) but not in their nondyskinetic (NLID) counterparts. We used H215O PET to scan 24 unmedicated PD subjects (12 LID and 12 NLID) and 12 matched healthy subjects in the rest state under normocapnic and hypercapnic conditions. Hypercapnic CBF responses were compared to corresponding levodopa responses from the same subjects. Group differences in hypercapnic vasoreactivity were significant only in the posterior putamen, with greater CBF responses in LID subjects compared with the other subjects. Hypercapnic and levodopa-mediated CBF responses measured in this region exhibited distinct associations with disease severity: the former correlated with off-state motor disability ratings but not symptom duration, whereas the latter correlated with symptom duration but not motor disability. These are the first in vivo human findings linking LID to microvascular changes in the basal ganglia.
ISSN:2379-3708
2379-3708
DOI:10.1172/jci.insight.96411