Neurotoxicity of carbon monoxide targets caudate-mediated dopaminergic system

Abstract

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<0.01). Our results validated the initial hypothesis in that neurobehavioral deficits and parkinsonian symptoms were highly related. This association was independent of demographic factors and initial carboxyhemoglobin level. Within the presynaptic dopaminergic circuit, the clinical role of the caudate in mediating the clinical symptoms in CO intoxication may outweigh the putamen.

Keywords: Carbon monoxide intoxication; Caudate; Parkinsonian symptoms; Pre-synaptic dopamine deficit.