Abstract
Little is known about the relationship between regional cerebral blood flow (rCBF) change and clinical improvement in patients with Parkinson's disease (PD). Single-photon emission computed tomography (SPECT) measurement of cerebral blood flow allows evaluation of temporal changes in brain function, and using SPECT, we aimed to identify motor improvement-related rCBF changes in response to the administration of antiparkinsonian drugs. Thirty PD patients (16 without dementia; 14 with dementia) were scanned with technetium-99m labeled ethyl cysteinate dimer SPECT and were rated with the Movement Disorder Society-Unified Parkinson's Disease Rating Scale part III, both before and after a single administration of antiparkinsonian drugs. The SPECT data were processed using Statistical Parametric Mapping 2, the easy Z-score Imaging System, and voxel-based Stereotactic Extraction Estimation. The rCBF responses in the deep brain structures after administration of antiparkinsonian drugs tended to be larger than those in cortical areas. Among these deep brain structures, the rCBF increases in the substantia nigra (SN), lateral geniculate (LG) body, and medial geniculate (MG) body correlated with drug efficacy (p < 0.05, respectively). A subgroup analysis revealed that the motor improvement-related rCBF change in the MG was statistically significant, irrespective of cognitive function, but the significant changes in the LG and SN were not found in subjects with dementia. In conclusion, our SPECT study clearly exhibited drug-driven rCBF changes in PD patients, and we newly identified motor improvement-related rCBF changes in the LG and MG. These results suggest that rCBF changes in these regions could be considered as candidates for clinical indicators for objective evaluation of disease progression. Furthermore, functional studies focusing on the LG and MG, especially in relation to therapies using audio-visual stimuli, may bring some new clues to explain the pathophysiology of PD.
Highlights
Parkinson’s disease (PD) is a chronic progressive neurological disease manifesting with motor symptoms of resting tremor, rigidity, bradykinesia, and postural instability, as well as nonmotor symptoms such as constipation, orthostatic hypotension, and hallucination [1]
Antiparkinsonian drugs significantly increased regional cerebral blood flow (CBF) (rCBF) in the putamen (Put), external segment of the globus pallidus (GPe), internal segment of the globus pallidus (GPi), and the substantia nigra (SN) in the basal ganglia; the lateral geniculate (LG) body, medial geniculate (MG) body, pulvinar (Pul), ventral anterior nucleus (VA), and ventral posterior nucleus (VP) in the thalamus; and the insula (Ins), primary visual cortex (PVC), red nucleus (RN), and somatosensory association cortex (SSAC)
Within the frontal cortex, there was a slight increase in rCBF in the dorsolateral prefrontal cortex (DLPFC) but decreased rCBF in the anterior cingulate cortex (ACC), inferior frontal gyrus (IFG), and orbitofrontal cortex (OFC)
Summary
Parkinson’s disease (PD) is a chronic progressive neurological disease manifesting with motor symptoms of resting tremor, rigidity, bradykinesia, and postural instability, as well as nonmotor symptoms such as constipation, orthostatic hypotension, and hallucination [1]. Little is known about the relationship between improvement in clinical features and the CBF changes occurring immediately after a single administration of antiparkinsonian drugs to PD patients under long-term antiparkinsonian treatment. We used conventional SPECT methods to show that antiparkinsonian drugs significantly increased regional CBF (rCBF) in the lenticular nucleus of PD patients, while decreasing it in the frontal cortex [13]. In this previous study, the SPECT acquisitions were made on separate days, and it was not possible to directly observe the temporal CBF changes occurring immediately after a single administration of antiparkinsonian drugs
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