Hisakuni Fukuoka

Achievement of hearing preservation in the presence of an electrode covering the residual hearing region

Abstract Conclusions: With full insertion with a long electrode, hearing preservation can be achieved even in the presence of a long electrode covering the residual hearing region. Objectives: Advances in developing new atraumatic concepts of electrode design as well as surgical technique have enabled hearing preservation after cochlear implantation surgery, and EAS (electric acoustic stimulation) accompanied with hearing preservation is a new trend for patients with residual hearing at the lower frequencies. However, full insertion with a long/medium electrode and hearing preservation is still a challenging field that calls for discussion. Method: In this study, round window insertion, an atraumatic electrode, and dexamethasone administration were used and atraumaticity (hearing preservation and conservation of vestibular function) was evaluated with full insertion of the electrode. Results: Postoperative evaluation after full insertion of the electrodes showed that hearing at low frequencies was well preserved in all five cases. Combined postoperative imaging with the referential tonotopic map confirmed achievement of full insertion and indicated the corresponding frequencies and the depth of the electrode. Achievement of atraumaticity of round window insertion in the present cases was confirmed from the viewpoint of the minimal drilling time as well as the preserved vestibular function.

Mutations in the WFS1 gene are a frequent cause of autosomal dominant nonsyndromic low-frequency hearing loss in Japanese

AbstractMutations in WFS1 are reported to be responsible for two conditions with distinct phenotypes; DFNA6/14/38 and autosomal recessive Wolfram syndrome. They differ in their associated symptoms and inheritance mode, and although their most common clinical symptom is hearing loss, it is of different types. While DNFA6/14/38 is characterized by low frequency sensorineural hearing loss (LFSNHL), in contrast, Wolfram syndrome is associated with various hearing severities ranging from normal to profound hearing loss that is dissimilar to LFSNHL (Pennings et al. 2002). To confirm whether within non-syndromic hearing loss patients WFS1 mutations are found restrictively in patients with LFSNHL and to summarize the mutation spectrum of WFS1 found in Japanese, we screened 206 Japanese autosomal dominant and 64 autosomal recessive (sporadic) non-syndromic hearing loss probands with various severities of hearing loss. We found three independent autosomal dominant families associated with two different WFS1 mutations, A716T and E864K, previously detected in families with European ancestry. Identification of the same mutations in independent families with different racial backgrounds suggests that both sites are likely to be mutational hot spots. All three families with WFS1 mutations in this study showed a similar phenotype, LFSNHL, as in previous reports. In this study, one-third (three out of nine) autosomal dominant LFSNHL families had mutations in the WFS1 gene, indicating that in non-syndromic hearing loss WFS1 is restrictively and commonly found within autosomal dominant LFSNHL families.

The responsible genes in Japanese deafness patients and clinical application using Invader assay

Discovery of deafness genes has progressed but clinical application lags because of the genetic heterogeneity. To establish clinical application strategy, we reviewed the frequency and spectrum of mutations found in Japanese hearing loss patients and compared them to those in populations of European ancestry. Screening revealed that in Japanese, mutations in GJB2, SLC26A4, and CDH23, and the mitochondrial 12S rRNA are the major causes of hearing loss. Also, mutations in KCNQ4, TECTA, COCH, WFS1, CRYM, COL9A3, and KIAA1199 were found in independent autosomal dominant families. Interestingly, spectrums of GJB2, SLC26A4, and CDH23 mutations in Japanese were quite different from those in Europeans. Simultaneous screening of multiple deafness mutations based on the mutation spectrum of a corresponding population using an Invader panel revealed that approximately 30% of subjects could be diagnosed. This assay will enable us to detect deafness mutations in an efficient and practical manner in the clinical platform. We conclude that specific racial populations may have unique deafness gene epidemiologies; therefore, ethnic background should be considered when genetic testing is performed. Simultaneous examination of multiple mutations based on a populations spectrum may be appropriate and effective for detecting deafness genes, facilitating precise clinical diagnosis, appropriate counseling, and proper management.

Comparison of the diagnostic value of 3 T MRI after intratympanic injection of GBCA, electrocochleography, and the glycerol test in patients with Meniere's disease

Abstract Conclusion. 3 T MRI after intratympanic injection of gadolinium-based contrast agent (GBCA) is more useful for the diagnosis of endolymphatic hydrops compared with the glycerol test and electrocochleography (ECoG). Objective: To investigate the relationship between 3 T MRI after intratympanic injection of GBCA, the glycerol test, and ECoG in patients with Menieres disease (MD). Methods: A total of 20 patients with MD were evaluated. Diluted gadodiamide (a gadolinium-based contrast agent) was administered to the bilateral tympanic cavity by injection through the tympanic membrane. After 24 h, the endolymphatic hydrops was evaluated by a 3.0 T MR scanner. To investigate cochlear hydrops, the glycerol test and ECoG were carried out in all patients. Results: A positive result was observed in 11 patients (55%) in the glycerol test and in 12 patients (60%) by ECoG. The incidence of positive findings when evaluating the same patients with both the glycerol test and ECoG increased to 75%. Nineteen of 20 (95%) patients showed positive results for 3 T MRI.

Distribution and frequencies of CDH23 mutations in Japanese patients with non-syndromic hearing loss

Mutations in the CDH23 gene are known to be responsible for both Usher syndrome type ID (USH1D) and non‐syndromic hearing loss (DFNB12), and the molecular confirmation of the CDH23 gene has become important in the diagnosis of these conditions. The present study was performed to find whether the CDH23 mutations are also responsible for non‐syndromic hearing loss in patients in the Japanese population. A total of 51 sequence variants were found in 64 Japanese probands with non‐syndromic sensorineural hearing impairment from autosomal recessive families. Among them, at least four missense mutations in six patients from five families were confirmed to be responsible for deafness by segregation study. All mutations detected were missense mutations, corroborating the previous reports regarding DFNB12. The present data confirmed that CDH23 mutations are frequently found and significantly responsible in Japanese. Interestingly, the CDH23 mutation spectrum in Japanese is very different from that found in Caucasians. This Japanese spectrum may be representative of those in Eastern Asian populations and its elucidation is expected to facilitate the molecular diagnosis of DFNB12 and USH1D.

Semi-quantitative evaluation of endolymphatic hydrops by bilateral intratympanic gadolinium-based contrast agent (GBCA) administration with MRI for Meniere's disease

Conclusion: Bilateral intratympanic administration of a gadolinium-based contrast agent (GBCA) in MRI was successfully performed and proved to be beneficial in the semi-quantitative evaluation of endolymphatic hydrops. Such image-based diagnosis will lead to re-revaluation and reclassification of the diagnostic criteria for Menieres disease (MD). Objective: To visualize endolymphatic hydrops semi-quantitatively in patients with MD, by using bilateral intratympanic GBCA administration with MRI. Patients and methods: A total of 13 patients were evaluated, including 12 with MD and one with acute low-tone sensorineural hearing loss. Diluted gadodiamide (a kind of GBCA) was administered to the bilateral tympanic cavity by injection through the tympanic membrane. After 24 h, the endolymphatic hydrops was evaluated with a 3.0 T MR scanner. The areas enhanced by gadodiamide were measured semi-quantitatively. Results: Three-dimensional, fluid-attenuated inversion recovery (3D-FLAIR) MRI showed that the gadodiamide successfully penetrated the round window membrane, entering the perilymphatic space and delineating the gadodiamide-enhanced perilymphatic and gadodiamide-negative endolymphatic spaces of the inner ear. All the patients with MD showed a reduced gadodiamide-enhanced area representing the perilymphatic space, and the quantitative ratio was 0.15 to 0.85. Furthermore, endolymphatic hydrops was also demonstrated in the patient with atypical MD who had fluctuating low frequency sensorineural hearing loss without vertigo.

Endolymphatic hydrops and therapeutic effects are visualized in ‘atypical’ Meniere's disease

A 53-year-old male with fluctuating low frequency sensorineural hearing loss and tinnitus, but without vertigo, was evaluated by MRI obtained by intratympanic injection of a gadolinium-based contrast agent (GBCA) before and after the administration of isosorbide. The endolymphatic hydrops was semi-quantitatively evaluated by a 3.0-T MR scanner. For quantification, the affected side/contralateral side ratios were calculated. A gadodiamide (a kind of GBCA)-enhanced space surrounding the endolymph in the affected side with a 0.50 ratio (which may have represented endolymphatic hydrops) improved after isosorbide therapy to a 0.98 ratio. Thus, endolymphatic hydrops was demonstrated in a patient with ‘atypical’ Menieres disease (MD), suggesting that at least some atypical MD may share similar etiology with, and therefore be a continuum of, MD. Also, therapeutic effects could be visualized by using MRI. Therefore, MRI-based diagnosis of MD-related disease will be a powerful tool not only because of its precision but also its usefulness for therapeutic evaluation.

Effects of EAS cochlear implantation surgery on vestibular function

Abstract Conclusions: The patients who received electric acoustic stimulation (EAS) cochlear implantation had relatively good vestibular function compared with the patients who did not have residual hearing. The vestibular function was well preserved after atraumatic EAS surgery. The round window approach and soft electrode are preferred to decrease the risk of impairing vestibular function. Objectives: The aim of this study was to examine the characteristic features of vestibular functions before and after implantations in patients undergoing EAS. Methods: Vestibular functions in patients who underwent EAS implantation were examined by caloric testing and vestibular evoked myogenic potential (VEMP) in 11 patients before and in 13 patients after implantation. Results: Preoperative evaluation showed that of the 11 patients, most (73%) had good vestibular function. One of 11 patients (9%) had decreased response in postoperative VEMP but all of the patients had unchanged results in postoperative caloric testing.

Vestibular functions of hereditary hearing loss patients with GJB2 mutations.

Objectives: Mutations in the GJB2 gene have been of particular interest as it is the most common causative gene for congenital deafness in all populations. Detailed audiological features, including genotype-phenotype correlations, have been well documented. However, in spite of abundant gene as well as protein expression in the vestibular end organs, neither vestibular symptoms nor vestibular functions have yet been elucidated. In the present study, vestibular functions were evaluated in patients diagnosed with GJB2-related deafness. Subjects and Methods: Vestibular functions were evaluated by caloric test and cervical vestibular evoked myogenic potential (cVEMP) testing in 24 patients with biallelic GJB2 mutations. Results and Discussion: Twenty-one of 23 patients (91.3%) had normal caloric responses and significantly lower cVEMP amplitudes than the control subjects. In the patients who were able to undergo vestibular testing, the mostly normal reactions to caloric testing indicated that the lateral semicircular canal was intact. However, the majority of GJB2 patients showed low cVEMP reactions, indicating a saccular defect.