Serotonin Transporter Distribution in the Brainstem of Multiple-System Atrophy–Parkinsonian Type: Insights from Pathology and ¹²³ I-FP-CIT SPECT Findings

Studies have demonstrated loss of serotonergic neurons in the brainstems of patients with multiple-system atrophy (MSA). This study aimed to semiquantitatively investigate the status of serotonin transporter (SERT) distribution in the brainstem of individuals with MSA-parkinsonian type (MSA-P) via ¹²³I-2β-carbomethoxy-3β-(4-iodophenyl)nortropane (¹²³I-FP-CIT) SPECT and compare it with pathologic findings in some cases. <b>Methods:</b> We administered ¹²³I-FP-CIT intravenously to 19 patients with MSA-P and 17 healthy controls (HCs) and performed SPECT and MRI scans. Specific binding ratio (SBR) images were generated, and summed voxel-based SBRs for the midbrain, pons, and entire brainstem were quantified. The Mann-Whitney <i>U</i> test was used to compare the MSA-P and HC groups, and receiver operating characteristic curves were used to analyze the midbrain-to-pons ratio of the summed voxel-based SBR. Further, we assessed postmortem SERT immunohistochemistry pathology in the brainstems of representative MSA-P cases and HCs to compare the distribution and density of SERT with SPECT findings. <b>Results:</b> ¹²³I-FP-CIT SPECT results revealed a significant summed voxel-based SBR decrease in the midbrain and an increase in the pons in the MSA-P group, although the brainstem summed voxel-based SBRs did not differ significantly (<i>P</i> < 0.05). The use of the midbrain-to-pons ratio for differentiation generated an area under the curve of 0.93. SERT immunostaining pathology, consistent with the ¹²³I-FP-CIT SPECT findings, demonstrated a significant decrease in SERT expression in the substantia nigra and a significant increase in the pontine raphe nucleus in patients with MSA-P. <b>Conclusion:</b> Our results indicate differences in SERT distribution in the brainstems of patients with MSA-P and HCs.