Table_1_Differential Diagnosis of Multiple System Atrophy-Parkinsonism and Parkinson's Disease Using α-Synuclein and External Anal Sphincter Electromyography.docx

Background and aim: Discriminating multiple system atrophy-parkinsonism (MSA-P) from Parkinson's disease (PD) is challenging. We aimed to provide a new method to make an identification between MSA-P and PD by combining biofluid marker with electrophysiology marker.
Methods: The XYCQ EV Enrichment KIT was applied to extract extracellular vesicles (EVs) from saliva. The levels of α-syn which included total α-syn (α- synTotal), phosphorylated-ser129 α-syn (α-synPS129) and oligomeric α-syn (α-synOlig) in EVs of saliva were tested by new developed Electrochemiluminescence (ECL) assays. We collected multi-motor unit potential (MUP) of all participants who conducted external anal sphincter electromyography (EAS-EMG). The duration, phase, amplitude and satellite potential of EAS-EMG were analyzed. The Receiver operator characteristic (ROC) curve was adopted to analyze the diagnostic utility of α-syn in EVs of saliva, EAS-EMG for MSA-P.
Results: In EVs of saliva, the α-synTotal concentrations were lower in MSA-P than PD (P = 0.003). No significant difference was shown in α-synOlig and α-synPS129. α-synTotal 4.46 pg/ng distinguished MSA-P from PD with area under the curve (AUC) 0.804. Compared with PD, the duration, phase and satellite potential of EAS-EMG in MSA-P were increased (P = 0.002, 0.008, 0.001). There was no significant difference in amplitude. ROC curve showed that the duration (AUC: 0.780), phase (AUC: 0.751), and satellite potential (AUC: 0.809) had both diagnostic value for MSA-P. The combination of α-synTotal in salivary EVs and EAS-EMG (including duration, phase and satellite potential) could efficiently make a differentiation between MSA-P and PD with sensitivity of 100% and specificity of 86%. The AUC value was 0.901.
Conclusion: The study suggested the combination of α-synTotal in salivary EVs and EAS-EMG could help efficiently distinguish MSA-P from PD.