| BackgroundInternational studies show that dizziness and vertigo are a significant burden on the general population,with 20-30% experiencing symptoms over a lifetime.Benign paroxysmal positional vertigo(BPPV)is the most common peripheral vestibular disease.Among the vertigo patients,eventually 17~42% patients are diagnosed with BPPV,which is the main cause of vertigo.BPPV is characterized by transient vertigo and specific nystagmus induced by the movement of patient’s head relative to gravity.The course of BPPV is self-limited,and the recurrence rate has been reported arranged from 13.7 % to 48% in one year following up and 13.3% to 65% within two years following up.BPPV had indeed a reduction on the number of falls before or after the canalith repositioning procedure(CRP).Falls make up the 6th cause of death in people with more than 65 years of age.It is estimated that 30% of the people above this age range fall at least once a year and that the falls are responsible for 70% of the accidental death in people with 75 years of age or more.An European cross-sectional study of BPPV shows it can occur in all ages,with a lifetime prevalence of 2.4%.The medical costs for diagnosis of BPPV have been estimated at US(?) 2 billion in the USA.According to data from South Korea in 2020,the number of hospital visits due to dizziness and vertigo will correspond to an increase of 52% in the future fifty years.At present,the per capita cost of BPPV diagnosis and treatment in China has been up to RMB(?)4,165.Moreover,with the aging of the population,the incidence of BPPV and the healthcare burden due to BPPV is likely to increase.Thus,BPPV does not appear to be a "mild" disease.The demographic studies in China reports the proportion of older people60-years old and more(12%)is expected to grow to approximately 34% by 2050.The chronic diseases,such as cardiovascular diseases,cancer and diabetes,have been the risks threatening Chinese health.Overall,more than 11.1% of the studied population simultaneously have more than one chronic disease,and multimorbidity is becoming the normal state.In other words,high risk of multimorbidity is also present in BPPV-prone populations.However,most guidelines are planned and implemented using a single disease approach in which diseases are treated in isolation.The treatment of BPPV mainly adopts the CRP,which is based on the mechanical principle in the acute stage,while ignoring the chronic damage during the alternation of remission and recurrence until the disabling stage.Therefore,if the association between the common comorbidities and BPPV can be evaluated,then the timely BPPV screening and positive treatment of related comorbidities will help effectively to prevent the occurrence and development of BPPV,reduce BPPV related dysfunctions and improve the qualities of life.So far,there has been no similar research work in the literature.This study plans to combine domestic and foreign literatures and clinical work summaries to select 17 comorbidities common in BPPV patients,for one-way analysis of variance with BPPV,and then include factors with significant differences in the multivariate analysis to extract data for further discussion.Though cupulolithiasis theory and canalolithiasis theory among the various theories on the pathogenesis of BPPV,have become the world widely accepted theories,the two mechanical theories cannot illustrate sufficiently the entire clinical appearances of BPPV in the anatomical respect,as while as the underlying molecular biological mechanisms.In recent years,the etiology of BPPV has gradually focused on the role of osteoporosis and vitamin D deficiency related to abnormal calcium metabolism in BPPV,and the progress is also accompanied by great controversy.There have had some scattered reports at the genetic level,but BPPV is more of an idiopathic disease,and the underlying physiological mechanism of inflammation and oxidative stress also arouse interest.Given the above research background,this study is intended to be progressed on three parts.Part one,the clinical characteristics of BPPV is to be analyzed to evaluate their influence on BPPV patient’s function.The correlation between 17 comorbid diseases,including ischemic stroke,cervical spondylosis,osteoporosis and BPPV will be evaluated.Part two,the effect of osteoporosis and vitamin D deficiency on the onset of BPPV is to be investigated by systematic review and Meta-analysis.Part three,detecting the oxidative stress markers and inflammatory factors in the serum of BPPV patients,especially the non-enzyme oxidative stress markers,expands a new idea on the pathogenesis of BPPV.Part I Analysis of clinical features and risk factors of patients with BPPVObjectiveTo assess the impact of BPPV on patients’ functions by collecting all clinical data of BPPV patients admitted to our hospital and analyzing the clinical characteristics.To evaluate the association between 17 comorbid diseases,such as ischemic stroke,cervical spondylosis and osteoporosis and benign paroxysmal vertigo(BPPV).Subjects and Methods1.A total of 60 BPPV patients were enrolled in the study.Among them,patients with posterior semicircular canals were treated with Epley maneuver,patients with horizontal semicircular canals were treated with Barbecue maneuver,and patients with anterior semicircular canals were treated with reversal Epley maneuver.The clinical data of the patients were analyzed one by one,including family history,general conditions,symptoms,signs,laboratory,etc.The etiology,clinical manifestations,recurrence,and treatment effects of BPPV was summarized.2.The patient’s gender,age,cervical spondylosis,hypertension,diabetes mellitus,hyperuricemia,hyperlipidemia,ischemic stroke,vestibular neuronitis,Meniere’s disease,chronic suppurative otitis media,head trauma,history of dental surgery,cervical spondylosis,osteoporosis,sudden sensorineural hearing loss,history of coronary atherosclerotic heart disease and other data were subjected to one way ANOVA using chi-square test.3.The statistically significant indicators of the one-way ANOVA were enrolled in the Logistics multivariate regression analysis to explore the risk factors related to BPPV.Results1.Of the 60 patients,44 cases were primary BPPV,accounting for 73.33%,and 16 cases were secondary BPPV,accounting for 26.67%.The proportion of primary BPPV was significantly higher than that of secondary BPPV(p<0.01).2.The gender composition(male,female),affected ear(unilateral)and involvement of semicircular canals(posterior semicircular canal,horizontal semicircular canal,mixed type)of patients with primary BPPV and secondary BPPV were significantly different(p<0.05).There were no significant differences in age composition between the two groups(p>0.05).3.The DHI scores of primary BPPV patients before and after treatment were(41.55±6.26)and(19.66±4.95)respectively.The DHI scores of secondary BPPV patients before and after treatment were(40.71±5.38)and(24.56±4.32),respectively.There was no difference in DHI score between the primary and secondary BPPV patients before treatment(p>0.05),but after treatment the DHI score of primary BPPV patients was lower than that of secondary BPPV patients(p<0.05).4.After reduction treatment,22(50.00%)of primary BPPV patients had dizziness or nystagmus disappeared,17(38.64%)showed varying degrees of relief,and the effective rate of treatment was 88.64%.Among patients with secondary BPPV,6(37.50%)cases had dizziness or nystagmus disappeared,3(18.75%)cases showed varying degrees of relief,and the treatment effective rate was 56.25%.The effective rate of treatment in primary BPPV was higher than that of the secondary BPPV(p<0.05).5.During the follow-up period after treatment,12(27.27%)cases of primary BPPV recurred,and 8(50%)cases of secondary BPPV recurred.The recurrence rate of patients with secondary BPPV was significantly higher than that of patients with primary BPPV(p<0.01).6.One-way ANOVA analysis showed that gender(p<0.01),age(p<0.01),cervical spondylosis(p<0.01),osteoporosis(p<0.01),hypertension(p<0.01),diabetes mellitus(p<0.01),hyperuricemia(p<0.01),hyperlipidemia(p<0.05),ischemic stroke(p<0.01),vestibular neuronitis(p<0.05),Meniere’s disease(p<0.01),sudden sensorineural hearing loss(p<0.05)and head trauma(p<0.05)were correlated with BPPV.7.The statistically significant indicators in the one-way ANOVA analysis were included in the Logistic regression analysis.The results found that comorbidities including cervical spondylosis,head trauma,hypertension,diabetes mellitus,hyperlipidemia,ischemic stroke and sudden sensorineural hearing loss were significantly correlated with BPPV(p<0.05).Conclusions1.BPPV impairs the daily life function of patients,the response rate of CRP treatment for secondary BPPV is less good as primary,and the recurrence rate of secondary BPPV is higher in the 1-year follow-up period.DHI is not only a tool to evaluate BPPV dysfunction,but also has a value as a predictor of BPPV recurrence.BPPV is not a "benign,non-affecting" disease.2.Comorbids including cervical spondylosis,head trauma,hypertension,diabetes,hyperlipidemia,ischemic stroke and sudden sensorineural hearing loss are significantly correlated with BPPV and maybe the risks of BPPV.Timely intervention BPPV screening and related pathogenic risk factors treatment can originally prevent the onset of BPPV or reduce the recurrence of BPPV.Part II Effects of Vitamin D Deficiency and Osteoporosis in BPPV:A Systematic Review and Meta-analysisObjectiveThis study is proposed to methodically review the available evidence for meta-analysis to clarify:(1)whether vitamin D deficiency or osteoporosis is related to the occurrence of BPPV;(2)whether vitamin D deficiency or osteoporosis is related to the recurrence of BPPV;(3)whether vitamin D supplementation can prevent the onset of BPPV or reduce the recurrence rate of BPPV;(4)whether there are differences in the outcomes for different races.Materials and Methods1.Searches were performed in Pub Med,Embase and Cochrane Library.The keywords were: “vitamin D”,“25(OH)vitamin D”,“25-hydroxylvitamin D”,“25-hydroxyvitamin D” or “25(OH)D”;“osteoporosis” or “osteopenia”;“Bone Density” or “BMD”;“benign paroxysmal positional vertigo”,“BPPV” or “BPV”.Articles were screened according to the inclusion and exclusion criteria.2.Data extracted from the included literatures included basic characteristics of demographic and BPPV information,primary and secondary outcomes.The primary outcomes were the number of observed/experimental and control groups,the number of relapsed and non-relapsed groups,vitamin D deficiency and osteoporosis in the observed/experimental and control groups.The quality of the articles was also evaluated,the RCT articles were assessed by the Cochrane intervention system evaluation guidelines,and the quality evaluation of case-control studies and cohort studies was assessed by the Newcastle-Ottawa Scale(NOS)score.3.Data synthesis and analysis: Continuous variables were reported as weighted mean difference(WMD)and dichotomous variables were reported as odds ratios(ORs).Fixed-effect model or random-effect model was adopted.Subgroup analysis and sensitivity analysis were conducted according different races(East Asian yellow and non-East Asian yellow).The Meta-analysis was performed for data synthesis by the Review Manager software.Results1.Totally 338 studies were identified during the initial electronic search.27 studies,including 1 RCT,18 case-control studies and 8 cohort studies,were finally remained in this meta-analysis according to the inclusion and exclusion criteria.Both case-control studies and cohort studies were interpreted as medium and high quality.2.Main Meta-analysis: Vitamin D supplementation was effective in reducing the recurrence rate of BPPV(OR=0.17,95% CI= [0.05,0.55],p=0.003).Compared with normal people,BPPV patients have reduced serum 25(OH)D levels(MD=-2.23 [-4.40,-0.406]),higher rate of 25(OH)D insufficiency/deficiency(OR=2.0 [1.15,3.48]),reduced bone density and higher prevalence of osteoporosis(OR=2.37 [1.59,3.55]).Low levels of Serum 25(OH)D were showed in both relapsed and non-relapse groups,but there was no statistical difference between two groups(MD=-2.28 [-5.38,0.82],p=0.15);bone density OR=-0.25 [-0.68,0.17])as well as the incidence of osteoporosis(OR=1.69 [0.91,3.14])was with no statistical difference between the two groups.After sensitivity analysis,excluding the study of Stefano et al,the prevalence of osteoporosis was higher in the relapsed group.3.Subgroup analysis: In the non-yellow population subgroup,patients accepted the vitamin D supplementation showed lower recurrence rate of BPPV than those who did not accepted vitamin D supplementation(OR=0.08 [0.02,0.42]).The serum 25(OH)D level was low in East Asian BPPV patients(MD=-3.42 [-4.44,-2.40]),and with no statistical difference in non-East Asian yellow(MD=-0.33 [-5.68,5.03]).The occurrence of reduced serum 25(OH)D was lower in East Asian yellow patients than in normal subjects(MD=2.36 [1.74,3.19]),while there was no statistical difference in non-yellow population contrast to normal subjects.The bone density was low in East Asian yellow BPPV subgroup(MD=-0.92 [-1.30,-0.55]),and with no statistical difference in non-yellow subgroup;the prevalence of osteoporosis which was lower in East Asian yellow BPPV patients than normal subjects(OR=2.29 [1.82,2.89]),showed no statistical difference in in non-yellow subgroup.Both the subgroups failed to derive a statistical difference in serum 25(OH)D levels in patients with BPPV recurrence and non-recurrence(MD=0.77 [-3.90,2.36] and MD=-5.21 [-12.74,2.33]).The incidence of osteoporosis was higher in the East Asian yellow BPPV relapse group than in the non-relapse group(OR=2.84 [1.78,4.52]),with no statistical difference in non-yellow population subgroup.Conclusions1.Serum 25(OH)D insufficiency/deficient and osteoporosis are related to the incidence of BPPV,especially in East Asian yellow population.2.Lower serum 25(OH)D content is not clearly associated with BPPV recurrence,but exogenous vitamin D supplementation reduce the recurrence rate of BPPV.3.Supplementing vitamin D timely and improving osteoporosis can prevent the occurrence of BPPV to a certain extent.Part III Studies on the Levels of Oxidative Stress and Inflammation Related Factors in BPPV PatientsObjectiveThe changes of oxidative stress and inflammation levels before and after treatment of BPPV patients were tested to explore:(1)the role of enzyme and non-enzyme antioxidant system in the pathogenesis of BPPV;(2)the characters of the role of enzyme and non-enzymatic antioxidants in BPPV;(3)the value of TDH parameters(SS/SH,SS/TT,SH/TT)as new indicators evaluating BPPV oxidative stress;(4)the role of inflammation in the course of BPPV.Materials and Methods1.31 BPPV patients and 30 healthy people who met the entry criteria as control group were included to collect general information,clinical history and diagnosis and treatment information.2.All patients received 2 ml of venous blood on an empty stomach.Take the samples 1,500 g centrifuging for 10 min,isolate the serum and store them at-80℃ until further analysis.In addition to the necessary observations of this study,the serum biochemistry associated with kidney,thyroid and liver function,and levels of blood lipid and electrolyte(Na,K,Cl,and Ca)were tested,to rule out systemic diseases that could affect this study,such as renal insufficiency,liver disease,thyroid disease and hyperlipidemia.3.Serum SH,TT and SS levels in these samples were analyzed by Erel and Neselioglu methods,and the SS/SH,SS/TT and SH/TT ratios were calculated.4.AOC kit colorimetric method to test T-AOC,Hydroxylamine method to check SOD,Thiobarbituric acid(TBA)method to test MDA,modified Eckerson method to determine the activity,Double-antibody sandwich ELISA for determination of serum IL-1β,IL-6,and TNF-α levels.5.NCSS 2007 software(NCSS,Caseville,Utah)was used to analyze the data.Mean,standard deviation,median,minimum,maximum,frequency and percentage values are used as descriptive statistics.The independent sample t-test was used for the comparison between the data groups in accordance with the normal distribution,and the paired sample t-test was used for the intra-group analysis of the normal distribution data,and the Pearson chi-square test was used for the qualitative data test.The p value <0.05 was statistically significant.Results1.The SH levels of patients in the BPPV group before and after treatment were(305.22±59.70)and(375.95±38.95),respectively.SH levels of patients before and after treatment were significantly lower than those in the control group(p<0.001),but there was no difference in SH levels before and after treatment(p>0.05).The TT levels of patients in the BPPV group were(347.03±66.03)and(352.88±47.90)before and after treatment,respectively.The TT of patients before and after treatment was significantly lower than the control group(p<0.001),but there was no difference in TT levels in patients before and after treatment(p>0.05).The SS levels of patients in the BPPV group before and after treatment were(20.91±9.77)and(22.14±7.96),respectively.There was no difference in SS levels between patients before treatment,patients after treatment and the control group(p>0.05).2.The SS/SH ratios of patients in the BPPV group before and after treatment were(10.23±4.81)and(10.67±4.45),respectively.The SS/SH ratios before and after treatment were significantly higher than those in the control group(p<0.001),but there was no difference between the SS/SH ratios before and after treatment(p>0.05).The SS/TT ratios of patients in the BPPV group before and after treatment were(8.23±3.42)and(8.59±2.91),respectively.The SS/TT ratios before and after treatment were significantly higher than those of the control group(p<0.001),but there was no difference between the SS/SH ratios before and after treatment(p>0.05).The SH/TT ratios of patients in the BPPV group before and after treatment were(83.54±6.84)and(82.83±5.83),respectively.The SH/TT ratios before and after treatment were significantly lower than those of the control group(p<0.001),but there was no difference in the SH/TT ratios before and after treatment(p>0.05).3.The T-AOC of patients in the BPPV group before and after treatment were(28.33±5.67)U/ml and(36.25±5.78)U/ml,respectively.The total antioxidant capacity of patients before treatment was significantly lower than that of the normal control group(p<0.01),and after treatment,it was higher than before treatment(p<0.05),but still lower than the normal level(p<0.05).4.The SOD of patients in the BPPV group before and after treatment were(274.10±15.29)U/ml and(436.14±20.13)U/ml,respectively.The SOD of the patients before treatment was significantly lower than that of the normal control group(p<0.01).The SOD level of patients after treatment was higher than that before treatment(p<0.05),but had no difference with the control group(p>0.05).5.The MDA of patients in the BPPV group before and after treatment were(574.10±25.29)nmol/ml and(436.14±20.13)nmol/ml,respectively.The MDA of the patients before treatment was significantly higher than that of the control group(p<0.01).The MDA of patients after treatment,was lower than that before treatment(p<0.05),but had no difference from the control group(p>0.05).6.The PON1 of patients in the BPPV group before and after treatment were(103.77±11.46)U/ml and(121.78±9.67)U/ml,respectively.The PON1 of patients before treatment was significantly lower than that of the normal control group(p<0.01).The PON1 of patients after treatment was higher than that before treatment(p<0.05),but had no difference from the control group(p>0.05).7.Before treatment,TNF-α,IL-1β and IL-6 in the BPPV group were(241.11±13.16)pg/ml,(92.00±7.65)pg/ml and(436±27.62)pg/ml,respectively.After treatment,TNF-α,IL-1β and IL-6 were(21.80±3.57)pg/ml,(18.38±3.12)pg/ml and(132±13.75)pg/ml,respectively.TNF-α in the BPPV group before treatment was significantly higher than that of the control group(p<0.01).The TNF-α of patients after treatment was lower than both patients before treatment and the control group(p<0.01).The IL-1β and IL-6 in the BPPV group before treatment were significantly higher than those of the control group(p<0.01).IL-1β and IL-6 of patients after treatment were significantly lower than that before treatment(p<0.01),but had no difference from the control group(p>0.05).Conclusions1.The participation of non-enzymatic antioxidants in oxidative stress plays a role in the development of BPPV and does not respond significantly to the physical process of canalith repositioning procedure for BPPV.The TDH parameters SS/SH,SS/TT,and SH/TT can be used as new indicators to assess the oxidative stress in BPPV patients.2.Compared to non-enzymatic antioxidants,enzymatic antioxidants are more rapid and sensitive to the changes during the course of BPPV.Through the oxidative stress status of BPPV,MDA is mainly regulated by enzymatic antioxidants rather than non-enzymatic antioxidants.3.The changes before and after the treatment of primary TNF-α,IL-1,and IL-6 levels indicate that inflammation is involved in the onset of the acute phase of BPPV patients,and the canalith repositioning procedure can relieve the inflammatory status of BPPV patients. |
PDF Full Text Request