Objective: We aimed to visualize a serotonin transporter (SERT) based on ¹²³I-FP-CIT SPECT, and assessing the binding distribution characteristics of the brainstems between patients with multiple system atrophy (MSA) and controls and elucidate the correlations between the specific binding ratios (SBRs) of SERT and clinical indices in MSA patients.

Background: Previous studies have shown that serotonin neuronal loss in the brainstem of MSA is associated with autonomic failure and sudden death. Our findings demonstrate that serotonin dysfunction assessed by CSF 5-HIAA levels may be associated with MSA severity. However, the association between SERT and the pathophysiology of MSA is unclear.

Method: We enrolled 17 controls and 28 patients diagnosed with MSA according to the MDS MSA criteria. Among these patients, 25 had clinically established MSA, 3 had clinically probable MSA, 16 had MSA-P and 12 had MSA-C. There were 13 females and 15 males with a mean age of 62.9±8.8 years and a mean disease duration of 28.4±16.7 months. The mean CSF 5-HIAA levels was 9.3±5.0 ng/mL. We performed ¹²³I-FP-CIT SPECT and 3D T1-weighted MRI to fix a reference lesion in the occipital lobe. The regions of interest were transferred to the SPECT images. The SBR distribution image was generated for the whole brainstem, midbrain and pons. We compared the total SBR of SERT at each site between MSA and controls and evaluated the correlation between SBR values and clinical scores in MSA. In addition, we also investigated the pathological examinations in other 10 MSA patients.

Results: The SERT-SBR was lower in the midbrain with MSA-P. Notably, the pons/midbrain ratio was significantly higher in both MSA-P and MSA-C patients (sensitivity 1.00; specificity 0.88; AUC 0.98) than in controls. Pathological studies also confirmed that SERT was increased in the pons and decreased in the midbrain. SBR did not correlate with CSF 5-HIAA levels, and there was no relationship in the principal component analysis. In MSA-P, SERT SBR in the midbrain and pons showed a negative correlation with UMSARS Part I and II.

Conclusion: An increased in SERT SBR in the pons and pons/midbrain ratios in MSA was observed, independent of clinical phenotype, disease duration, and CSF 5-HIAA levels. This feature was commonly detected in early and advanced stages.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/serotonin-transporter-dynamics-in-multiple-system-atrophy-insights-from-123i-fp-cit-spect-imaging/