Dataset Information

Metabolic network expression in parkinsonism: Clinical and dopaminergic correlations.

ABSTRACT: Little is known of the precise relationship between the expression of disease-related metabolic patterns and nigrostriatal dopaminergic dysfunction in parkinsonism. We studied 51 subjects with Parkinson's disease (PD) (18 non-demented, 24 demented, and 9 dementia with Lewy bodies) and 127 with atypical parkinsonian syndromes (47 multiple system atrophy (MSA), 38 progressive supranuclear palsy (PSP), and 42 corticobasal syndrome (CBS)) with ¹⁸F-fluorodeoxyglucose PET to quantify the expression of previously validated disease-related patterns for PD, MSA, PSP, and CBS and ¹⁸F-fluoropropyl-?-CIT PET to quantify caudate and putamen dopamine transporter (DAT) binding. The patients in each group exhibited significant elevations in the expression of the corresponding disease-related pattern ( p?

SUBMITTER: Ko JH

PROVIDER: S-EPMC5381458 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature

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Metabolic network expression in parkinsonism: Clinical and dopaminergic correlations.

Ko Ji Hyun JH Lee Chong Sik CS Eidelberg David D

Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism 20160721 2

Little is known of the precise relationship between the expression of disease-related metabolic patterns and nigrostriatal dopaminergic dysfunction in parkinsonism. We studied 51 subjects with Parkinson's disease (PD) (18 non-demented, 24 demented, and 9 dementia with Lewy bodies) and 127 with atypical parkinsonian syndromes (47 multiple system atrophy (MSA), 38 progressive supranuclear palsy (PSP), and 42 corticobasal syndrome (CBS)) with <sup>18</sup>F-fluorodeoxyglucose PET to quantify the ex ...[more]

PMID: 26980757

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Project description: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.

Project description:Multiple-system atrophy (MSA), progressive supranuclear palsy (PSP), and corticobasal syndrome (CBS) have signs and symptoms overlapping those of Parkinson disease (PD), complicating their clinical diagnosis. Although presynaptic dopaminergic brain imaging with PET and SPECT is clinically widely used for patients with suspected PD, the benefit of functional imaging in atypical parkinsonism syndromes remains unclear. We compared striatal presynaptic dopaminergic function in MSA parkinsonism variant (MSA-P), MSA cerebellar variant (MSA-C), PSP, CBS, and PD using combined quantitative data from all published studies. Methods: The PubMed database was searched from inception to August 2018 for the terms "dopamine" OR "dopaminergic" AND "PET" OR "SPECT" OR "SPET" and keywords related to PD, MSA, PSP, and CBS. In total, 1,711 publications were identified. PET or SPECT studies comparing patients with atypical parkinsonism to another diagnostic group (PD, MSA, PSP, or CBS) were included. Tracers for dopamine transporter (DAT), aromatic amino acid decarboxylase (AADC), or vesicular monoamine type 2 were investigated. Tracer binding data were extracted from the original articles. Heterogeneity of the data was examined using I 2 statistics, and a random-effects model was used to summarize data. Hedges g was used as an estimator of effect size in group comparisons. Results are reported according to PRISMA guidelines. Results: Thirty-five studies (29 DAT, 6 AADC, no vesicular monoamine type 2 studies) with 356 MSA-P patients, 204 PSP patients, 79 CBS patients, and 62 MSA-C patients were included in the metaanalysis. Caudate nucleus and putamen DAT function was clearly lower in PSP than in PD (caudate: 34.1% difference, g = -1.08, 95% confidence interval [CI] = -1.52 to -0.64; putamen: 18.2%, g = -0.86, 95% CI = -1.50 to -0.21) and MSA-P (striatum: 31.4%, g = -0.70, 95% CI = -1.21 to -0.19) and was clearly lower in MSA-P than in MSA-C (striatum: 46.0%, g = 1.46, 95% CI = 0.23 to 2.68). Although not significant because of limited data, aromatic l-AADC results paralleled the DAT findings. Conclusion: Striatal presynaptic DAT function is clearly lower in PSP patients than in PD and MSA-P patients and is clearly lower in MSA-P patients than in MSA-C patients.

Dataset Information

Metabolic network expression in parkinsonism: Clinical and dopaminergic correlations.

Publications

Metabolic network expression in parkinsonism: Clinical and dopaminergic correlations.

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