Neurotoxicity of carbon monoxide targets caudate-mediated dopaminergic system

• Published in: Neurotoxicology (Park Forest South) 2018-03, Vol.65, p.272-279
• Main Authors: Sun, Tzu-Kuan, Chen, Yen-Yu, Huang, Shu-Hua, Hsu, Shih-Wei, Lee, Chen-Chang, Chang, Wen-Neng, Huang, Chi-Wei, Lui, Chun-Chung, Lien, Chia-Yi, Cheng, Ju-Ling, Chang, Chiung-Chih
• Format: Article
• Language: English
• Subjects: Adult; Basal ganglia; Brain diseases; Carbon monoxide; Carbon monoxide intoxication; Carbon Monoxide Poisoning - complications; Carbon Monoxide Poisoning - diagnostic imaging; Carbon Monoxide Poisoning - pathology; Carboxyhemoglobin; Carboxyhemoglobin - metabolism; Caudate; Caudate Nucleus - metabolism; Caudate Nucleus - pathology; Central nervous system diseases; Cognitive ability; Demographics; Dopamine - metabolism; Dopamine receptors; Dopaminergic Neurons - metabolism; Dopaminergic Neurons - pathology; Evaluation; Female; Humans; Hypokinesia; Intoxication; Male; Medical imaging; Movement disorders; Neostriatum; Neural networks; Neurodegenerative diseases; Neuroimaging; Neurology; Neurons; Neuropsychological Tests; Neurotoxicity; Organotechnetium Compounds - metabolism; Parkinson Disease, Secondary - chemically induced; Parkinson Disease, Secondary - complications; Parkinson Disease, Secondary - diagnostic imaging; Parkinson Disease, Secondary - pathology; Parkinson's disease; Parkinsonian symptoms; Patients; Posture; Pre-synaptic dopamine deficit; Predictive Value of Tests; Putamen; Regression analysis; Severity of Illness Index; Suicides & suicide attempts; Tomography, Emission-Computed, Single-Photon; Tremors; Tropanes - metabolism; Young Adult
• ISSN: 0161-813X; 1872-9711
• DOI: 10.1016/j.neuro.2017.11.007

•The implications of 99mTcTRODAT-1 for carbon monoxide intoxication parkinsonism is proposed.•The neurobehavioral deficits and parkinsonian symptoms were highly related.•Presynaptic caudate dopaminergic deficits mediate the clinical symptoms. The clinical features of parkinsonism in carbon monoxide (CO) intoxication have been associated with striatal-related neuronal networks. As parkinsonian and neuropsychiatric features are both related to presynaptic dopaminergic integrity, the aim of this study was to explore the clinical significance of 99mTcTRODAT-1 in grading neurobehavioral scores and parkinsonian severity in CO intoxication. We enrolled 64 patients with CO intoxication, including 29 with parkinsonism (parkinsonism[+] group) and 35 without (parkinsonism[−] group). All of the patients received 99mTcTRODAT-1 neuroimaging evaluations, comprehensive neurobehavioral tests and assessments of the severity of parkinsonism using Unified Parkinson's Disease Rating Scale (UPDRS)-part III motor score. Univariate and multivariate regression analyses were used to test the predictive factors and scores for a diagnosis of parkinsonism and its severity. The parkinsonism(+) group had significantly lower cognitive scores and higher neuropsychiatric total scores compared with the parkinsonism(−) group, both of which were independently related to the severity of parkinsonism. 99mTcTRODAT-1 regional caudate signals were correlated with tremors at rest, action or postural tremors of the hands, bradykinesia and hypokinesia, and visuospatial, verbal fluency, abstract thinking and digit backwards scores. Scores of the neurobehavioral tests and UPDRS items were highly correlated (p