The Effect Of Serum 25(OH)-D On The Related Examinations And Clinical Manifestations Of BPPV And Endolymphatic Hydrops

Chapter 1 The role of different degrees of serum 25(OH)-D deficiency in idiopathic BPPV formation,treatment effect,and prognosisBackground:Vertigo is the most common cause of disability,and BPPV is the most common type of peripheral vertigo.Although the diagnostic criteria of BPPV are clear and the treatment methods are standardized,the high recurrence rate and the incidence of residual dizziness(RD)up to 50%after reduction are difficult problems for clinicians at present.It has been confirmed that a low VD level is one of the recurrence factors,and abnormal Caloric test(C-Test)and VD deficiency in RD patients are also considered as risk factors for RD.VD regulates the activity of calcium channels in the inner ear,and plays a key regulatory role in the formation and metabolism of calcium carbonate in the otolithic component.The rate of VEMP abnormalities in VD deficiency increased compared with those in normal healthy people,and the abnormal rate of ophthalmic myogenic evoked potential(OVEMP)in BPPV was as high as 66.7%,while the cervical myogenic evoked potential(CVEMP)abnormalities suggested a poor prognosis of BPPV.However,it is still controversial whether VD is directly related to the occurrence of BPPV,and the relationship between the degree of VD deficiency and the severity of otolith function and RD is not yet clear.There is still no clear indicator to predict the recurrence rate in patients with idiopathic BPPV.Establishing the relationship between VD and otolith and vestibular function is of great significance to guide the clinical treatment effect and prognosis.Objective:To explore the correlation of otolith function(CVEMP,OVEMP,C-Test)and 25(OH)-D.Regression models were established to predict residual vertigo and recurrence with three different grades of independent variables 25(OH)-D which can provide decision-making guidance for clinical practice.Further comparison of otolith function in patients before and after VD supplementation to clarify the mechanism of recurrence rate from the perspective of the otolith function.Methods:This paper uses a cross-sectional study method.All the selected patients were confirmed patients with idiopathic BPPV in the vertigo outpatient department of Shandong Provincial Hospital from March 2017 to February 2020,including 90 cases of initial onset and 48 cases of recurrence.The included data of the patients included general characteristics(sex,age,affected side,involved semicircular canal,number of CRPs,DHI self-score after reduction,duration of vertigo at visit[T]),functional data(latency of each wave of binaural CVEMP,OVEMP,amplitude,wave interval,binaural asymmetry ratio[AR],C-Test binaural slow phase velocity[SPV],one side of the semicircular canal paresis[CP]),laboratory tests:morning fasting serum 25(OH)-D.To study the effect of 25(OH)-D on the occurrence of BPPV:compare the mean values of serum 25(OH)-D in the control group,the initial group(T<1 month)and the relapse group(T≥1 month and reset).According to less than 10ng/ml,10～20ng/ml,and>20 ng/ml,25(OH)-D was divided into three groups:severely deficient,insufficient and normal.Compare the proportion of three groups in general characteristics to clarify the effect of 25(OH)-D on the therapeutic effect.The functional data of all patients were divided into three groups according to bilateral normality,unilateral abnormality,and bilateral abnormality,and the average value of 25(OH)-D in each group was compared to clarify its influence on otolith and vestibular function.When analyzing the influencing factors of RD,they were divided into no RD group(DHI≤30)and RD group(DHI>30).During the treatment,patients with abnormal 25(OH)-D were randomly selected to supplement VD as the experimental group,and the patients without supplementation were selected as the control group.The differences in otolith and vestibular function were compared between the two groups at the initial visit and three months later.Results:1.Abnormal serum 25(OH)-D affects BPPV relapse period and therapeutic effectCompared with the control group and the primary group,the mean value of 25(OH)-D in the recurrence group was the lowest,The difference is statistically significant(P<0.000).The proportion of 25(OH)-D abnormalities in women,number of CRPs>3 times,patients with RD was significantly higher than in men,patients with CRPs≤3 times and no RD.Correlation coefficient between sex,number of CRPs,RD and serum 25(OH)-D grade were 0.28,-0.22,-0.38 respectively.25(OH)-D was affected by gender,the lower the level was,the greater the number of CRPs>3 and the greater the possibility of RD.2.Serum 25(OH)-D affects otolith and vestibular functionThe difference in mean 25(OH)-D between bilateral abnormal group and normal group of C-Test and CVEMP was statistically significant,with P values of 0.013 and 0.017,respectively.There were statistically significant differences between the normal and abnormal groups of OVEMP,with P values of 0.000 and 0.015,respectively.The 25(OH)-D content of patients was divided into three grades:severe deficiency,insufficient,and normal.There was a linear relationship between the 25(OH)-D grade classification and otolith and vestibular function.The Pearson correlation results showed that the R values were 0.226,0.327,0.3,and P<0.05.The results of C-Test,CVEMP and OVEMP were combined into binary variables:abnormal group(unilateral abnormality,bilateral abnormality)and normal group.Different grades of 25(OH)-D had predictive significance for otolith and vestibular function.The three regression models can correctly classify 70%,60.9%and 71.7%of BPPV patients with otolith and vestibular function respectively.Predicting the normal rate of C-Test,CVEMP and OVEMP in patients with idiopathic BPPV,patients with severe 25(OH)-D deficiency(<10ng/ml)were 0.329 times,0.059 times,and 0.058 times higher than those with normal 25(OH)-D.Only the normal rate of OVEMP in patients with 25(OH)-D deficiency(10-20ng/ml)was 0.246 times that of normal patients.3.Serum 25(OH)-D affects RD through CVEMP and is linearly correlated with DHI.In otolith and vestibular function test,only CVEMP test was correlated with RD group,P=0.005;25(OH)-D value and DHI had a weak positive correlation,with a correlation coefficient of 0.17.The multiple linear regression model of the dependent variable DHI score was statistically significant.25.3%of the variance in DHI scores could be explained by changes in 25(OH)-D,CVEMP(adjusted R2=0.219)4.Serum 25(OH)-D affects relapse rate through OVEMPThe difference in OVEMP between the primary group and the recurrence group was statistically significant,P=0.01;the recurrence regression model was statistically significant(χ2=24.856,P=0.002).The model could correctly classify 72.5%of the subjects.Among the independent variables included in the model,only 25(OH)-D was statistically significant.Severe 25(OH)-D deficiency(<10ng/ml)increased the risk of recurrence by 11.589 times compared with normal patients,and 25(OH)-D insufficient(10-20 ng/ml)increased the recurrence risk by 4.011 times compared with normal patients;ROC area under curve(AUC)was 0.745,and 25(OH)-D had meaningful prediction of recurrence rate.5.Changes in otolith function after 3 months of vitamin D supplementationCompared with the control group,the incubation period of OVEMP N10 wave in the experimental group was shortened after three months,and the amplitude of P10N16 wave in some patients was significantly increased.VD supplementation can accelerate the recovery of otolith function.Conclusion:Serum 25(OH)-D deficiency(<10ng/ml)directly affects otolith,vestibular function and recurrence rate;25(OH)-D value and DHI score have a linear correlation,25(OH)-D level and CVEMP prediction of DHI scores to assess RD.Although supplementation of 25(OH)-D can shorten the latency of OVEMP N10 wave,it cannot be explained that it is entirely the effect of 25(OH)-D,it may be its own regulation and vestibular compensatory effect.Chapter 2 Preliminary study on the correlation between serum 25(OH)-D and endolymphatic hydrops by using inner ear MR gadolinium imaging techniqueBackground:Although membranous hydrops is the most common pathological phenomenon in otology,their cause remains a mystery.Hydrops mainly occurs in Meniere’s disease(MD),with fluctuating hearing loss and recurrent vertigo as the main clinical manifestations.It can appear in different stages of disease.In clinical work,we encounter membranous labyrinth with only cochlear or vestibular symptoms.In patients with hydrops,MRI analysis shows that 44%-75%of patients with unilateral MD have endolymphatic hydrops(EH)in the contralateral ear.Most scholars believe that the main mechanism of endolymphatic hydrops is the autoimmune reaction of the inner ear.Clinical studies have found that when patients lack Vitamin D(VD),under the same treatment plan,the hearing level of Sudden sensorineural hearing loss(SSNHL)patients in the VD supplementation group and the vertigo symptoms of MD patients can be significantly improved.This suggests that the immune function of VD also plays an important role in inner ear diseases.Therefore,clarifying the correlation between VD and hydrops has the most important clinical significance for explaining clinical doubts and intervening in the formation and progression of hydrops.With the development of intravenous gadolinium endolymph delayed imaging magnetic resonance(IV-Gd MRI)technology,EH is further refined into cochlear,vestibular,and semicircular canal hydrops,and further divided into different grades and scores.The research is more targeted and persuasive.Objectives:By detecting the level of 25(OH)-D in patients with EH,combined with IV-Gd MRI technology,in patients with unilateral EH,study the level of 25(OH)-D in the pure tone audiometry of the affected ear in different frequency bands,electrocochleography(ECochG),The influence of binaural Caloric test(C-Test),preliminary exploration of the effect of VD on EH,to intervene in the generation and development of hydrops,to provide a possibility to explain the clinical fluctuating hearing loss and periodic vertigo.Method:1.Case selectionUsing IV-Gd MRI delayed 3D-FLAIR imaging,patients who showed unilateral endolymphatic hydrops were screened for inclusion in the study.The selected patients were diagnosed the with delayed membranous labyrinth(DEH),diagnosed and with MD,SSNHL.2.Imaging examination and reconstruction methods,imaging grading of EHMRI examinations were performed with 3.0T Philips MR,32-channel head and neck coils,and all patients underwent enhanced MR examination of the internal auditory canal,with a 4-hour delay imaging.When evaluating hydro vestibular,three mutually perpendicular semicircular canals were used to establish coordinates,and the relationship between the saccule and the utricle was simultaneously displayed on the axial plane and the oblique sagittal plane.Referring to the consensus of domestic experts,the visual score combined with the saccule to utricle ratio inversion(SURI)in the classification of vestibular hydrolysis was used to classify vestibular and cochlear hydrops into 0,normal;1,mild hydrops;2,severe hydrops.The hydrops was scored according to the degree of visualization of the vestibule,cochlea,and three semicircular canals,and the total score was from 0(no visualization)to 18(complete visualization).3.ExaminationThe frequency of PTA examination,it is divided into low frequency,middle frequency high-frequencyency average hearing threshold.The main index included in the C-Test examination is binaural slow phase angular velocity(SPV),that is,the sum of the absolute value of the peak SPV of unilateral cold and heat stimulation,EcochG SP/AP ratio of affected ear.Result:Finally,50 cases of confirmed MD,29 cases of SSNHL,and 3 cases of DEH were included.There was no statistical difference in the mean of 25(OH)-D among the three groups.The difference in SPV between ears was statistically significant,P=0.016.There were correlations between ECochG SP/AP and hydrops score,cochlear and vestibular hydrops grades,P<0.000.Scatter plots of SP/AP and IF PTA show a linear correlation.1.Correlation study of related examinations and vestibular and cochlear hydropsThe level of vestibular hydrops was correlated with 25(OH)-D,SP/AP,and SPV in the affected ear,and the difference between groups was statistically significant(P=0.018,0.013,0.012);25(OH)-D was linear with SPV in the contralateral ear Positive correlation,correlation coefficient r=0.275,the severity of EH vertigo symptoms may be related to whether the contralateral vestibular-ocular reflex(VOR)is damaged.The level of cochlear hydrops was correlated with SP/AP,high-frequency PTA,and SPV of the affected ear,and the difference between the groups was statistically significant(P=0.005,0.023,0.001);25(OH)-D had a linear negative correlation with low-frequency PTA,the correlation coefficient r=-0.323,so the early low-frequency fluctuating hearing loss of EH hydrops was regulated by 25(OH)-D.2.Regression analysis for predicting vestibular and cochlear hydropsThe presence or absence of cochlear and vestibular hydrops was used as the dependent variable,and binary regression analysis was performed.Only the hydro-cochlear model was statistically significant.Among the 5 independent variables included,only 25(OH)-D and high-frequency PTA had predictive significance for cochlear hydrops,and the model could correctly classify 86.6%of the study subjects.For each 1-unit increase in high-frequency PTA,the risk of hydro-cochlear hydrops increased by 5.1%,and for each 1-unit decrease in 25(OH)-D,the risk of cochlear hydrops increased by 17.1%.The regression model of vestibular hydrops was not statistically significant.It suggested that the cochlear hydrops extended to the base of the cochlea and the vestibular area,the high-frequency PTA decreased and the VOR function was impaired.When the vestibular hydrops was severe,the vestibular response was weakened or even terminated due to bilateral VOR damage.Conclusion:In unilateral EH patients with hydrops classification,25(OH)-D was associated with contralateral SPV and affected VOR response.Although 25(OH)-D was lower in severe hydrops,it had no predictive effect on hydro-vestibular.In the grading of hydro-cochlear hydrops,25(OH)-D is related to low-frequency PTA and affects auditory nerve conduction.Highfrequency25(OH)-D have predictive significance for cochlear hydrolysis.Therefore,EH patients need to check serum 25(OH)-D levels.