Extrastriatal ¹²³I-FP-CIT SPECT impairment in degenerative parkinsonisms

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 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.

We 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.

Relative 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).

This 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.