Abstract
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.
Authors
Vincent A. Jourdain, Katharina A. Schindlbeck, Chris C. Tang, Martin Niethammer, Yoon Young Choi, Daniel Markowitz, Amir Nazem, Dominic Nardi, Nicholas Carras, Andrew Feigin, Yilong Ma, Shichun Peng, Vijay Dhawan, David Eidelberg
Figure 4
Hypercapnic CBF responses in the sensorimotor cortex.
