Differential Diagnosis Of Multiple System Atrophy-Parkinsonism And Parkinson'S Disease Using Alpha-Synuclein And External Anal Sphincter Electromyography

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 alpha-syn which included total alpha-syn (alpha- syn(Total)), phosphorylated-ser129 alpha-syn (alpha-syn(PS129)) and oligomeric alpha-syn (alpha-syn(Olig)) 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 alpha-syn in EVs of saliva, EAS-EMG for MSA-P.Results:In EVs of saliva, the alpha-syn(Total)concentrations were lower in MSA-P than PD (P= 0.003). No significant difference was shown in alpha-syn(Olig)and alpha-syn(PS129). alpha-syn(Total)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 alpha-syn(Total)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 alpha-syn(Total)in salivary EVs and EAS-EMG could help efficiently distinguish MSA-P from PD.