Study On Predictors Of Efficacy Of Endolymphatic Sac Decompression In Meniere’s Disease And Genes Related To Meniere’s Disease

Objective1.To find the predictors of efficacy of endolymphatic sac decompression(ESD)in Meniere’s disease(MD),establish and verify the prediction model that vertigo cannot be completely controlled after ESD in patients with MD.2.To study the effect of vascular risk factors on the efficacy of ESD in patients with MD.3.To identify pathogenic genes for a family with delayed hearing loss and Menierlike symptomsMethods1.Based on the retrospective cohort data of 56 patients with unilateral MD who underwent ESD surgery,univariate analysis and multivariate analysis were performed to preliminarily explore the relationship between potential predictors and postoperative vertigo control.The stepwise regression method was used to select the optimal modeling variables,and the logistic regression model was es Tab lished with the outcome that postoperative vertigo was not completely controlled.The bootstrap method was used for internal validation.2.A retrospective cohort study was conducted on 52 patients with MD who underwent unilateral ESD.According to the risk classification of 10-year atherosclerotic cardiovascular diseases(ASCVD)before surgery,the vascular risk factors of patients were evaluated in general,and postoperative vertigo control grade and dysfunction score was compared between those who were classified as below low risk(low-risk group)and those who were classified as above medium risk(high-risk group).3.Whole exome sequencing(WES)was carried out for the proband,a patient,and a normal person in the family.The possible pathogenic mutations obtained from WES were verified in the family through Sanger sequencing.The pathogenicity analysis was carried out for the mutations satisfying the co-separation of genephenotype to identify whether the mutation was the genetic cause of this family.Results1.Univariate analysis found that the potential predictors,such as sex,age,duration of follow-up,course of the disease,duration of the attack,frequency of attack,pure tone average(PTA)of the patient’s speech frequency,audiogram type,glycerin test,Meniere disease classification,and 10-year ASCVD risk classification,were not statistically related to whether vertigo was completely controlled.Multivariate regression analysis showed that the PTA of the patient’s speech frequency and glycerin test had no statistical significance on whether to achieve complete control of vertigo(P>0.05),but the type of audiogram had statistical significance on whether to achieve complete control of vertigo(P=0.02).Through the stepwise regression method,the optimal modeling variables were found to be the type of audiogram and PTA of the patient’s speech frequency.The prediction model based on these two variables has good discrimination[area under ROC curve,AUC 0.72(95% CI 0.57-0.86)],and acceptable calibration(Brier score 0.21).2.The proportion of patients with surgical vertigo control grade above grade B in the low-risk group was 79.41%,and that in the high-risk group was 72.22%,the difference was not statistically significant(P=0.81).The score of dysfunction in both groups was significantly lower than that before the operation(P<0.01).The median decrease in dysfunction score in both groups was 2(1,2)points,and the difference was not statistically significant(P=0.73).3.It was found that the c.1271A>G mutation of the COCH gene was the possible genetic cause of the family.According to the ACMG guidelines,the mutation was a possible pathogenic mutation(PP1＿Strong+PM2+PP3+PP4).This article reported for the first time that the mutation was associated with hearing loss.Conclusion1.The prediction model based on the type of audiogram and PTA of the patient’s speech frequency can basically predict the occurrence of postoperative vertigo that cannot be completely controlled before surgery,and provide a reference for the selection of surgery for patients.2.Vascular risk factors have little effect on the efficacy of ESD in MD patients.Patients with one or more vascular risk factors can still obtain good vertigo control and dysfunction improvement through ESD.3.The mutation c.1271A>G of the COCH gene is the possible genetic cause of the family.This discovery enriched the genetic mutation spectrum of the COCH gene.