title: Metabolic Covariant Network in Relation to Nigrostriatal Degeneration in Carbon Monoxide Intoxication-Related Parkinsonism.
abstract: Presence of parkinsonian features after carbon monoxide (CO) intoxication is well known and the severity was found to relate to the pre-synaptic dopaminergic deficits. There is no systemic study to analyse the functional network involved in CO-related Parkinsonism. Forty-five CO-related parkinsonism patients and 25 aged-matched controls completed the 3D T1-weighted imaging and (18)F-fluoro-2-deoxyglucose positron emission tomography (FDG-PET). Voxel-based morphometry (VBM) was performed to assess the structural and functional brain differences between the patients and controls. Spatial covariant networks responsible for distinguishing patients and controls were constructed using independent component analysis. For validation, the pre-synaptic dopaminergic functional network was established by regression model using striatal TRODAT-1 SPECT as the independent variable. The clinical significance of both networks was determined by correlation with the Unified Parkinson's Disease Rating Scale (UPDRS). Compared with controls, the spatial covariant signals of FDG-PET were significantly lower in the medial and lateral frontal, caudate nucleus, dorsomedial prefrontal areas, and temporal-parietal regions while the spatial intensities correlated significantly with UPDRS total scores. The functional network that correlated with striatum pre-synaptic dopaminergic uptakes included the midbrain, thalamus, caudate, lateral frontal cortex, ventral striatum, ventral, or dorsal anterior cingulate cortex. Both networks overlapped considerably and the topographies reflected structural damage pattern. Our study provides evidence that glucose metabolism in CO-parkinsonism patients pertains to an organized covariant pattern in the cortical regions that is spatially coherent with the cortical map of pre-synaptic dopamine deficits. As the fronto-temporal, striatum, and temporal-parietal areas were involved, the unique metabolic covariant network suggests a different pathophysiology in CO-related parkinsonism.
authors.affiliation: Department of Neurology, Cognition and Aging Center, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine Kaohsiung, Taiwan.
authors.forename: Chiung-Chih
authors.initials: CC
authors.lastname: Chang
authors.affiliation: Section of Dementia and Cognitive Impairment, Department of Neurology, Chang Gung Memorial HospitalLinkou, Taiwan; Graduate Institute of Humanities in Medicine, Taipei Medical UniversityTaipei, Taiwan.
authors.forename: Jung-Lung
authors.initials: JL
authors.lastname: Hsu
authors.affiliation: Department of Neurology, Cognition and Aging Center, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine Kaohsiung, Taiwan.
authors.forename: Wen-Neng
authors.initials: WN
authors.lastname: Chang
authors.affiliation: Department of Nuclear Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine Kaohsiung, Taiwan.
authors.forename: Shu-Hua
authors.initials: SH
authors.lastname: Huang
authors.affiliation: Department of Neurology, Cognition and Aging Center, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine Kaohsiung, Taiwan.
authors.forename: Chi-Wei
authors.initials: CW
authors.lastname: Huang
authors.affiliation: Department of Neurology, Cognition and Aging Center, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine Kaohsiung, Taiwan.
authors.forename: Ya-Ting
authors.initials: YT
authors.lastname: Chang
authors.affiliation: Department of Neurology, Cognition and Aging Center, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine Kaohsiung, Taiwan.
authors.forename: Nai-Ching
authors.initials: NC
authors.lastname: Chen
authors.affiliation: Department of Radiology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine Kaohsiung, Taiwan.
authors.forename: Chun-Chung
authors.initials: CC
authors.lastname: Lui
authors.affiliation: Department of Radiology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine Kaohsiung, Taiwan.
authors.forename: Chen-Chang
authors.initials: CC
authors.lastname: Lee
authors.affiliation: Department of Radiology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine Kaohsiung, Taiwan.
authors.forename: Shih-Wei
authors.initials: SW
authors.lastname: Hsu
keywords: carbon monoxide intoxication; metabolic covariant network; nigra-striatal degeneration; parkinsonian symptoms; pre-synaptic dopamine deficit