Abstract
IntroductionNeuropathological data and nuclear medicine imaging show extensive serotonergic impairment in Parkinson's disease (PD) and atypical parkinsonian syndromes (APS). The study aims at performing a case-controlled region-of-interest (ROI)-based analysis of 123I–N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl) nortropane (123I-FP-CIT) images to measure extrastriatal regional deficits in PD and APS, and assess their added diagnostic value in discriminating degenerative parkinsonisms from other conditions. MethodsWe included 157 patients with early degenerative parkinsonism (mean age 72.6 years, 44% female, mean disease duration at scan 1.6 years), i.e. PD (n = 59), multiple system atrophy parkinsonian variant (MSA-P, n = 17), progressive supranuclear palsy (PSP, n = 28), corticobasal syndrome (CBS, n = 19), dementia with Lewy bodies (DLB, n = 34) as well as 58 similarly-aged control participants. 123I-FP-CIT SPECT images were processed with statistical parametric mapping 12 (SPM12)-based PETPVE12 software and subjected to partial volume effect correction for ROI-based group comparisons. ResultsRelative to controls, all forms of degenerative parkinsonism showed decreased 123I-FP-CIT uptake in caudate nucleus, putamen but also pallidum and insula. In addition, a significant uptake reduction was observed in thalamus for MSA-P and PSP, in midbrain for PD and PSP, and in the amygdala for PSP (ANCOVA controlling for age, sex and antidepressant medication, all Bonferroni-corrected p < 0.007). Receiver-operating characteristics area-under-the-curve showed that adding extrastriatal evaluation led to higher accuracies in separating degenerative conditions from control participants (96.1% vs 94.9% with striatal ROIs only, p = 0.045). ConclusionThis study provides evidence of a major extrastriatal 123I-FP-CIT impairment, and therefore of an altered serotonergic transmission in PD and APS, confirming previous neuropathological and SERT imaging findings.
Highlights
Neuropathological data and nuclear medicine imaging show extensive serotonergic impairment in Parkinson's disease (PD) and atypical parkinsonian syndromes (APS)
CTL participants were diagnosed with parkinsonism or tremor not associated with dopaminergic degeneration, and with a normal visual and semiquantitative DaT assessment. 123I-FP-CIT single photon emission computed tomography (SPECT) was performed as a clinical diagnostic imaging assessment for suspected degenerative parkinsonism or distinction between dementia with Lewy bodies (DLB) and Alzheimer's disease
There was no significant difference among groups regarding age (p = 0.67, KW) – except when including DLB whose disease onset is usually later compared to degenerative parkinsonisms
Summary
Neuropathological data and nuclear medicine imaging show extensive serotonergic impairment in Parkinson's disease (PD) and atypical parkinsonian syndromes (APS). The study aims at performing a casecontrolled region-of-interest (ROI)-based analysis of 123I–N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl) nortropane (123I-FP-CIT) images to measure extrastriatal regional deficits in PD and APS, and assess their added diagnostic value in discriminating degenerative parkinsonisms from other conditions. Conclusion: This study provides evidence of a major extrastriatal 123I-FP-CIT impairment, and of an altered serotonergic transmission in PD and APS, confirming previous neuropathological and SERT imaging findings. Evidence from post-mortem and in vivo 11C- 3-amino-4(2-dimethylaminomethyl-phenylsulfanyl)benzonitrile (11C-DASB) positron emission tomography (PET) imaging has demonstrated serotonergic cell loss in degenerative forms of parkinsonism, especially in Parkinson's disease (PD) and progressive supranuclear palsy (PSP) [5].
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