Clinical significance of the pallidoreticular pathway in patients with carbon monoxide intoxication.

Whereas globus pallidus lesions resulting from carbon monoxide intoxication have been extensively described in the literature, the clinical significance of pallidoreticular lesions has rarely been mentioned. This study incorporated information from functional and structural imaging to explore the correlations of pallidoreticular lesions with parkinsonian features and neurobehavioural performance. Twenty-five patients (11 males) with globus pallidus lesions after carbon monoxide intoxication and 25 age- and sex-matched controls were enrolled for detailed neurological examinations, cognitive testing, susceptibility weighted imaging, diffusion tensor imaging and 99mTc-TRODAT-1 single photon emission computed tomography. The post-processing analysis of the neuroimaging included voxel-based morphometry to assess the regional atrophy, tract-based spatial statistics related to white matter involvement, tractography to investigate the rostral and caudal projections from the midbrain level and specific uptake ratios of 99mTc-TRODAT-1 for presynaptic dopaminergic transporter activity. In susceptibility weighted imaging, low-intensity pallidoreticular lesions were detected from the minimal-intensity projections, which were visible in only 7.7% of the T(1)-weighted images and 15.4% of the T(2)-weighted images, whereas inhomogeneous intensities were detected in the globus pallidus. The patients were further divided into two subgroups based on the presence (n = 13) or absence (n = 12) of pallidoreticular lesions. The patients with pallidoreticular lesions showed increased parkinsonian features, poorer performances on the neuropsychiatric tests, lower 99mTc-TRODAT-1 availability in both the caudate and the putamen and greater atrophy of the thalamus, posterior corpus callosum, cerebral peduncle and white matter surrounding the globus pallidus compared to those without pallidoreticular lesions. The tractography results obtained with seed regions of interest in the substantia nigra showed rostral projections to the supplementary motor cortex and anterior cingulate cortex via the globus pallidus; the two pathways were distinct but ran in parallel, caudal to the level of the globus pallidus. In conclusion, the presence of pallidoreticular lesions after carbon monoxide intoxication indicates a poorer cognitive state, which is associated with extensive grey and white matter damage in addition to the damage to the nigra-striatal neuronal networks. The presence of parkinsonian features may be related to pallidal and presynaptic dopaminergic dysfunction. The sensitivity for detecting pallidoreticular lesions can be greatly improved by using susceptibility weighted imaging compared with conventional imaging.