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. Methods: 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 U 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. Results: 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 (P < 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. Conclusion: Our results indicate differences in SERT distribution in the brainstems of patients with MSA-P and HCs.

Both Parkinson's disease (PD) and the Multiple system atrophy-parkinsonian type (MSA-P) belong to the category of α-synucleinopathies, characterized by overlapping clinical manifestations and a high risk of misdiagnosis. The aim of this study is to provide objective imaging biomarkers for differentiating PD from MSA-P. We enrolled 25 patients with PD, 15 patients with MSA-P, and 20 healthy controls (HC). Resting-state functional magnetic resonance imaging (rs-fMRI) was employed to analyze regional homogeneity (ReHo) differences between PD and MSA-P groups. The discriminative capacity of ReHo values in these differential brain regions for distinguishing PD from MSA-P was subsequently evaluated. Compared to MSA-P, PD showed decreased ReHo in cerebellar lobule IX, left fusiform gyrus, and right thalamus, but increased ReHo in the right cuneus. In PD, ReHo in cerebellar lobule IX, left fusiform gyrus negatively correlated with UPDRS-III scores (r=- 0.8548, P< 0.001), while right cuneus ReHo positively correlated (r=0.6526, P=0.0004). The ReHo values in cerebellar lobule IX, left fusiform gyrus showed optimal discriminative power between PD and MSA-P groups, achieving an area under the curve (AUC) of 0.8693 (P< 0.001). Our study enhances understanding of altered neural synchronization in specific brain regions under rs-fMRI in PD and MSA-P. We established the link between ReHo changes in localized areas and PD clinical manifestations. Notably, ReHo alterations in cerebellar lobules IX and fusiform gyrus serve as potential biomarkers for differentiating PD from MSA-P.

There is increasing evidence linking Parkinson's disease (PD) to lipids, such as the presence of lipids in the core of Lewy bodies in PD brains or high-molecular-weight adiponectin (APN) in phosphorylated α-synuclein-positive Lewy bodies. This study aimed to verify whether APN levels are associated with neurodegenerative diseases. The association between APN and body weight was also investigated. The following parameters were measured using venous blood sampling: HDL-C, LDL-C, glucose, and lipids, including APN. PD patients receiving dopaminergic treatments had significant higher APN than that of de-novo PD, progressive supranuclear palsy (PSP) or multiple system atrophy- parkinsonian type (MSA-P). Multivariate analysis using ANCOVA revealed a significant difference in APN levels between treated PD patients and de-novo PD patients (adjusted mean difference of -4.273 μg/ml, p = 0.037]), or PSP patients (adjusted mean difference of -4.756 μg/ml, p = 0.034]). BMIs were mildly higher in de-novo PD patients compared to treated PD patients (adjusted mean difference of 1.686, p = 0.074]). After adjustment, APN levels were positively correlated with HDL-cholesterol (HDL-C) in patients with PD (regression coefficient=0.479, P < 0.001), but not total cholesterol, or LDL-C. This correlation was not evident in patients with MSA-P, or PSP. APN likely plays a role in the composition of lipid rafts, particularly in patients with treated PD. The correlation between APN and HDL-C may be a marker that differentiates PD from MSA-P, or PSP.

A 64-year-old woman presented with a progressive movement disorder for 4 years, characterized by freezing of gait and left lower extremity discoordination. DaTScan performed 1 year after the presentation was abnormal and consistent with Parkinsonian syndrome. The patient went on to suffer from orthostatic symptomatology resulting in loss of consciousness. She also suffered from urinary incontinence and nocturia. The patient then underwent 18 F-FDG brain PET/MRI, which demonstrated markedly decreased tracer uptake in the bilateral putamina, with accompanying putaminal atrophy, marginal T2-hyperintensity (putaminal rim sign), and central T2* hypointensity. Collectively the imaging findings and clinical presentation are compatible with multiple system atrophy, parkinsonian type (MSA-P).

In multiple system atrophy with parkinsonian type (MSA-P), the dual-task cost and the underlying neurological mechanisms remain under-researched. We included 20 early-stage MSA-P patients and 10 matched healthy controls (HC). Using a video-based gait analysis machine, we explored gait characteristics under three conditions: single-task gait (STG), dual-task gait with backward counting (DTG-BC), and dual-task gait with spontaneous animal naming (DTG-SAN). Neuroimaging scans were collected to analyze the gray matter and white matter structures related to the dual-task cost in MSA-P. Our neuroimaging analysis focused on the infratentorial structures, as previous studies have indicated that these regions are closely related to dual-task cost. There were no differences in gait metrics between MSA-P and HC in STG. In the DTG-BC, patients with MSA-P exhibited a higher dual-task cost burden, as indicated by longer turning durations and shorter swing cycles compared to HC. MSA-P patients had decreased gray matter volume in the right culmen and increased radial diffusivity in the left declive compared to HC. Diffusion tensor imaging analysis showed that the higher dual-task cost of the right swing cycle in DTG-BC was related to the higher mean diffusivity of the left mesencephalic locomotor region (MLR). Additionally, a higher dual-task cost of turning duration in DTG-BC was related to increased axial diffusivity and radial diffusivity in the white matter of the bilateral culmen. Patients with MSA-P exhibited a higher dual-task burden compared to HC, and WM deficit in MLR and culmen were related to the disease's specific dual-task cost in MSA-P.