Cochlear Implantation And Related Basic And Clinical Studies In The Children With Profound Sensorineural Hearing Loss And Inner Ear Malformation

Part I Image assessments in the patients with normal or abnormal inner ear and profound sensorineural hearing lossObjectiveTo discuss the value of high resolution computer tomography (HRCT) and magnetic resonance imaging (MRI) in children with abnormal inner ear and profound sensorineural hearing loss.Materials and MethodsHRCT and MRI were performed in386cochlear implantation (CI) applicants with congenital sensorineural hearing loss. The results were analyzed in order to select suitable cases and ears for cochlear implantation. For the cases with enlarged vestibular aqueduct and the control group, the largest diameter of the midpoint of vestibular aqueduct (VA) and the external aperture were measured on CT scan image, respectively. Meanwhile, the largest diameter of the midpoint and the external aperture of the bony part of endolymphatic sac (ES) were measured on MRI image. The normal children group, the normal cochlear position group and the cochlear position malformation group measured3parameters respectively:①the angle of the basal turn of the cochlea relative to the sagittal plane (∠α);②the angle of line from the vertical portion of facial nerve to round window niche relative to the sagittal plane (∠β);③the vertical distance from the vertical portion of facial nerve to the posterior wall of external auditory canal at the level of round window (Distance A). The data obtained from CT and MRI were statistically analyzed by correlation test and t test.ResultsForty-five cases had inner ear anomalies, the remaining341cases had no any anomalies. In total of45cases,30cases with enlarged vestibular aqueduct showed by CT and MRI. Three cases were found to be with cochlear rotation,∠β of3cases of the cochlear position malformation group all exceed the upper limit of reference range. We found that∠α>∠β in the normal children group and the normal cochlear position group, by contrast,∠α<∠β in the cochlear position malformation group.Four patients were found to be with Mondini dysplasia, two with incomplete partition I, one with stenosis of internal auditory canal, one with vestibules malformations and defect of internal auditory canal bottom, three with cochlear ossification.ConclusionAccurate diagnosis of enlarged vestibular aqueduct syndrome, cochlear ossification and cochlear nerve dysplasia could be detected with MRI.∠α and∠β can be used to assess the cochlear position and help to open cochlear correctly in cochlear implantation. HRCT and MRI were complementary and helpful in surgical treatment planning and prognosis predicting. MRI was important in the evaluation of auditory nerve. Preoperative detailed radiological evaluations are essential factors for the successful operation. Part II Molecular epidemiology in the patients with abnormal or normal inner ear and profound sensorineural hearing lossObjectiveTo explore the molecular epidemiology and effective genetic diagnostic method for the Chinese patients with nonsyndromic sensorineural hearing loss (NSHL), we reported our result of genetic examination based on DNA Microarray combining with DNA sequencing in the cochlear implantation (CI) applicants from China. A comparison of genotype between the cases with abnormal inner ear and the cases with normal inner ear was made to find the genetic cause of inner ear malformation.Methods278CI applicants with profound NSHL from our department, including42casess with malformation of inner ear, underwent genetic examination in our research. Genomic DNA from100health individuals was used as control group. The molecular pathogenesis of NSHL was analyzed with the DNA microarray which is able to perform mutation detection of9hot-spot mutations in4prevalent deaf-causing genes, including GJB2(35delG,176dell6bp,235delC and299delAT), GJB3(538C>T), SLC26A4(IVS7-2A>G,2168A>G) and mtDNA12SrRNA (1494C>T and1555A>G). Subsequently the results were confirmed with PCR and DNA sequencing. We stopped the examining process if homozygous or composite heterotic mutations were detected through DNA microarray, otherwise we examined the other exons until another mutation was found or examined all the rest exons.Results20.50%(57/278) of CI applicants were detected to have mutations in GJB2gene with DNA microarray. When DNA microarray combining with direct sequencing was applied,35.25%(98/278) cases were detected to have GJB2mutations. The difference between the two methods was statistically significant. Only11.90%(5/42) patients with inner ear malformation were detected to have GJB2mutations. The incidence of GJB2mutations in the278patients with NSHL is28.24%. The incidence of GJB2mutations of the NSHL patients with normal inner ears is28.24%, and it is5.95%in the cases with abnormal inner ears. The difference of the incidence in the NSHL patients between the group of abnormal inner ears and the control group was not statistically significant. A total of5polymorphism and10mutations of GJB2were detected in our research. The235delC is the most prevalent mutation detected, followed by109G>A and299delAT.9patients were found to carry mtDNA A1555G mutation and one found to carry1494C>T among278CI applicant.26cases were found to have SLC26A4mutation among278CI applicants with DNA microarray. Among30patients with large vestibular aqueduct,28cases were found to have mutations in SLC26A4gene with PCR and direct sequencing. A total of16SLC26A4mutations were identified in the study, including4novel mutations (G368X, IVS8-1G>T,IVS13+9C>T and Q696X). IVS7-2A>G was the most common mutation in Chinese, H723R and T410M were also common.Conclusions DNA microarray can be used to generally screen hot spot mutation of common genes in CI applicants with profound hearing loss. DNA microarray combining with direct sequencing analysis allows us to get accurate outcome in the genetic examination on a large scale. The incidence of GJB2mutations of the NSHL patients with normal inner ears is28.24%. The GJB2mutation is not the main cause of malformation of inner ear. IVS7-2A>G is the most prevalent SLC26A4mutation in Chinese patients with EVAS, followed by H723R and T410M. The4novel mutations found in our research could further our understanding of the cause for EVAS and improve diagnostics method for EVAS. Part III Cochlear implantation in the patients with abnormal inner ear and profound sensorineural hearing lossObjectiveTo evaluate the outcome and complications encountered in the patients with anomalous inner ear who underwent cochlear implantation.MethodRetrospective analyses included45patients with anomalous inner ear and profound sensorineural hearing loss who applied for cochlear implant at the Second Xiangya Hospital of Central South University from2006to2011. Fifty NSHL patients with normal inner ear were used as controls. To explore effective methods for the diagnosis and treatment of inner ear malformation, we summarize the radiological and otological evaluation, treatment and outcome of cochlear implantation in the cases.Results The most common inner ear malformation we found were enlarged vestibular aqueduct (EVA), incomplete partition Ⅱ (Mondini dysplasia), and cochlear ossification. Thirty-six patients with abnormal inner ear underwent cochlear implantation, of this number,30patients presented EVA,2patients with incomplete partition Ⅱ,3with cochlear rotation and1with cochlear ossification. The electrodes were fully inserted into the scale tympani of the cochlea in35cases except for1case with cochlear rotation. Perilymphatic/cerebrospinal fluid fluctuation occurred in30cases with EVA during the implantation. Leakage of cerebral spinal fluid (Gusher) occurred in2patients with Mondini dysplasia. They were controlled by inserting the electrode array and sealing the vestibule and cochlea with temporal fascia or muscle. None of the recipients developed severe complications after implantation. We achieved an electrical stimulation of the neural elements in35cases who received implantation successfully.Conclusions No differences were found between patients with normal cochleas and those with minor malformations such as enlarged vestibular aqueduct and incomplete partition. Comprehensive pre-operative radiographic and audiological evaluation and intraoperative exactly performing are essential factors of the successful operation.