Novel Variant in CEP250 Causes Protein Mislocalization and Leads to Nonsyndromic Autosomal Recessive Type of Progressive Hearing Loss.

Genetic hearing loss is the most common hereditary sensorial disorder. Though more than 120 genes associated with deafness have been identified, unveiled causative genes and variants of diverse types of hearing loss remain. Herein, we identified a novel nonsense homozygous variant in CEP250 (c.3511C>T; p.Gln1171Ter) among the family members with progressive moderate sensorineural hearing loss in nonsyndromic autosomal recessive type but without retinal degeneration. CEP250 encodes C-Nap1 protein belonging to the CEP protein family, comprising 30 proteins that play roles in centrosome aggregation and cell cycle progression. The nonsense variant in CEP250 led to the early truncating protein of C-Nap1, which hindered centrosome localization; heterologous expression of CEP250 (c.3511C>T) in NIH3T3 cells within cilia expression condition revealed that the truncating C-Nap1 (p.Gln1171Ter) was not localized at the centrosome but was dispersed in the cytosol. In the murine adult cochlea, Cep250 was expressed in the inner and outer hair cells. Knockout mice of Cep250 showed significant hair cell degeneration and progressive hearing loss in auditory brainstem response. In conclusion, a nonsense variant in CEP250 results in a deficit of centrosome localization and hair cell degeneration in the cochlea, which is associated with the progression of hearing loss in humans and mice.

Recurrence Rate and Risk Factors of Recurrence in Benign Paroxysmal Positional Vertigo: a Single-Center Long-Term Prospective Study With a Large Cohort.

OBJECTIVE: This study aimed to assess the long-term recurrence rate and correlations between recurrence and potential risk factors in patients with benign paroxysmal positional vertigo (BPPV). DESIGN: A total of 548 consecutive patients who demonstrated typical posterior or horizontal BPPV between January 2010 and December 2012 were included in this prospective study. All patients were contacted by phone every 6 months for 5 years and were asked to revisit the clinic when they experienced positional vertigo to be reexamined for recurrence. Recurrence of BPPV was defined as having positional vertigo and nystagmus confirmed following a symptom-free period of at least 7 days after complete resolution. We assessed the 5-year recurrence rate of BPPV, and the time point of recurrence in all patients as well as the risk factors of BPPV recurrence, including the clinical characteristics, therapeutic results of BPPV, and various comorbidities. RESULTS: Among the 548 patients, 121 (22.1 %) had at least one recurrence. Of these, 78 patients (54.5%) had only one recurrence within 5 years, while 43 (45.5%) patients experienced two or more recurrences. A recurrence occurred within 1 year in 82 patients (67.8%). The Cox proportional hazard ratio analysis found that head trauma (p = 0.015), Meniere's disease (p = 0.016), the number of canalith repositioning procedures performed (p = 0.037), and the number of previous vertigo attacks (p = 0.038) were significant risk factors of BPPV recurrence as opposed to hypertension or hyperlipidemia. CONCLUSIONS: The recurrence rate of BPPV was 22.1% at 5 years after the initial treatment. About 70% of recurred patients had a recurrence within 1 year. Head trauma, ipsilateral Meniere's disease, the number of canalith repositioning procedures performed, and the number of previous vertigo attacks were significant risk factors of BPPV recurrence.

Clinical Implications of Horizontal Beating Nystagmus Induced by Dix-Hallpike Test in the Diagnosis of Horizontal Canal Benign Paroxysmal Positional Vertigo.

OBJECTIVES: The purpose of this study was to identify the diverse patterns of nystagmus during the Dix-Hallpike test (DHT) and analyze their clinical significance in horizontal canal benign paroxysmal positional vertigo (HC-BPPV). STUDY DESIGN: Retrospective medical records review. PATIENTS: Two hundred ninety-five patients diagnosed with HC-BPPV. METHODS: Various nystagmus patterns identified during the DHT in patients with HC-BPPV were analyzed. The correlation between the affected side of HC-BPPV and the direction of the horizontal beating nystagmus (HBN) during the DHT was also analyzed. RESULTS: The nystagmus pattern during the DHT in 128 patients with geotropic HC-BPPV demonstrated, direction-changing positional nystagmus on both sides in 48 (37.5%) patients, HBN toward one side in 25 (19.6%) patients, and no nystagmus in 55 (42.9%) patients. In 144 patients with apogeotropic HC-BPPV, 54 (37.5%) patients presented with direction-changing positional nystagmus on both sides, 27 (18.8%) patients presented with HBN toward one side, and 63 (43.7%) patients did not show nystagmus during the DHT. The direction of HBN provoked by the DHT was significantly correlated with the affected side in each subtype of HC-BPPV (geotropic type, p = 0.049; apogeotropic type, p = 0.040; respectively). CONCLUSION: More than half of the patients with HC-BPPV (56.6%) showed HBN during the DHT. When HBN was present during the DHT, it may provide a clue for determining the subtype and affected side in diagnosis of HC-BPPV before performing the supine roll test.

Therapeutic efficacy of super-high-dose steroid therapy in patients with profound sudden sensorineural hearing loss: a comparison with conventional steroid therapy.

BACKGROUND: In patients with sudden sensorineural hearing loss (SSNHL), steroid therapy is an optional treatment method, but there is controversy about its dose. OBJECTIVE: We aimed to compare the efficacy of super-high-dose steroid therapy with that of conventional steroid therapy in patients with profound SSNHL (pSSNHL). MATERIAL AND METHODS: Fifty-two patients diagnosed with pSSNHL between March 2010 and May 2017 were divided into the following groups based on their steroid regimen: a conventional steroid regimen (prednisolone at 1.0 mg/kg/day for 10 days) was applied in Group 1, and a super-high-dose steroid regimen (prednisolone at 1.5 mg/kg/day for 14 days) was applied in Group 2. The treatment outcomes were compared between the groups at 2 and 4 weeks after the initial treatment by use of Siegel's criteria. RESULTS: Of the 52 patients, 31 were classified into Group 1 and 21 into Group 2. When comparing the proportion of patients in complete or partial recovery by Siegel's criteria, the recovery rate was significantly higher in Group 2 than in Group 1 (19% vs 0%, p = .022 at 2 weeks; 35.7% vs 7.4%, p = 0.035 at 4 weeks). CONCLUSIONS AND SIGNIFICANCE: Patients with pSSNHL treated using the super-high-dose steroid regimen demonstrated better recovery rates to serviceable hearing than did those treated using the conventional steroid regimen without significant complications.

Double-blind randomized controlled trial on efficacy of cupulolith repositioning maneuver for treatment of apogeotropic horizontal canal benign paroxysmal positional vertigo.

Backgrounds: Although various therapeutic maneuvers have been proposed, it is still unclear which maneuver is better to treat apogeotropic horizontal canal benign paroxysmal positional vertigo (HC-BPPV).Objectives: This study aimed to assess the therapeutic efficacy of the cupulolith repositioning maneuver (CuRM) in apogeotropic HC-BPPV in comparison with the therapeutic head-shaking maneuver and modified Lempert maneuver.Materials and Method: This is double-blind randomized prospective study. Forty-nine consecutive patients diagnosed with apogeotropic HC-BPPV were allocated randomly to CuRM (n = 18), therapeutic head-shaking (n = 16), or modified Lempert maneuver (n = 15). The presence of nystagmus and vertigo on positional testing were evaluated at 30 min, on 1 day, and 1 week after treatment.Results: There were no significant differences in any clinical characteristics between the three groups at randomization. After a single trial of therapeutic maneuvers on the initial visit day, the CuRM (38.9%) and therapeutic head shaking maneuver (12.5%) did not show differences compared to modified Lempert maneuver (33.3%). The therapeutic effects on the 2nd day and at 1 week after treatment also did not differ between the three groups.Conclusions: Although the CuRM is theoretically considered to be a better therapeutic method, the therapeutic efficacy of CuRM was not statistically different compared to the other two maneuvers.

Genetic Inheritance of Late-Onset, Down-Sloping Hearing Loss and Its Implications for Auditory Rehabilitation.

OBJECTIVES: Late-onset, down-sloping sensorineural hearing loss has many genetic and nongenetic etiologies, but the proportion of this commonly encountered type of hearing loss attributable to genetic causes is not well known. In this study, the authors performed genetic analysis using next-generation sequencing techniques in patients showing late-onset, down-sloping sensorineural hearing loss with preserved low-frequency hearing, and investigated the clinical implications of the variants identified. DESIGN: From a cohort of patients with hearing loss at a tertiary referral hospital, 18 unrelated probands with down-sloping sensorineural hearing loss of late onset were included in this study. Down-sloping hearing loss was defined as a mean low-frequency threshold at 250 Hz and 500 Hz less than or equal to 40 dB HL and a mean high-frequency threshold at 1, 2, and 4 kHz greater than 40 dB HL. The authors performed whole-exome sequencing and segregation analysis to identify the genetic causes and evaluated the outcomes of auditory rehabilitation in the patients. RESULTS: There were nine simplex and nine multiplex families included, in which the causative variants were found in six of 18 probands, demonstrating a detection rate of 33.3%. Various types of variants, including five novel and three known variants, were detected in the MYH14, MYH9, USH2A, COL11A2, and TMPRSS3 genes. The outcome of cochlear and middle ear implants in patients identified with pathogenic variants was satisfactory. There was no statistically significant difference between pathogenic variant-positive and pathogenic variant-negative groups in terms of onset age, family history of hearing loss, pure-tone threshold, or speech discrimination scores. CONCLUSIONS: The proportion of patients with late-onset, down-sloping hearing loss identified with potentially causative variants was unexpectedly high. Identification of the causative variants will offer insights on hearing loss progression and prognosis regarding various modes of auditory rehabilitation, as well as possible concomitant syndromic features.

Optimal reassessment time for treatment response in posterior canal benign paroxysmal positional vertigo.

OBJECTIVES/HYPOTHESIS: The present study aimed to evaluate the optimal reassessment time for treatment response in posterior canal benign paroxysmal positional vertigo (PC-BPPV) following the initial Epley maneuver. STUDY DESIGN: Prospective, single-blinded, randomized study. METHODS: One hundred eight patients with PC-BPPV agreed to participate. These patients received a single modified Epley maneuver (recommended by the 2008 American Academy of Otolaryngology-Head and Neck Surgery guidelines) daily until positional nystagmus disappeared during the Dix-Hallpike maneuver 24 hours after the treatment. Repeated Dix-Hallpike testing to reassess the treatment response was performed at 1 hour (post-1 hour), every 24 hours (post-24 hours) until the positional nystagmus resolved, 1 week (post-1 week), and 1 month (post-1 month) following the therapeutic maneuver. The difference in the resolution rates at post-1 hour and post-24 hours reassessment was analyzed, and the recurrence rates at post-1 week and post-1 month were evaluated. RESULTS: The resolution rate was 67.6% at post-1 hour, which increased to 79.6% at post-24 hours reassessment. There was a statistically significant difference in the results of the Dix-Hallpike test between post-1 hour and post-24 hours follow-up. After complete resolution, nine out of 108 patients (8.3%) demonstrated recurrence within 1 month. CONCLUSIONS: Reassessment after 24 hours following the initial Epley maneuver is more advantageous than a 1-hour follow-up in patients with PC-BPPV. This information may be helpful for clinicians in deciding the appropriate follow-up period after treatment for PC-BPPV. LEVEL OF EVIDENCE: 1b Laryngoscope, 130:496-499, 2020.

Outcomes and Predictive Factors of Electroacoustic Stimulation Rehabilitation in Children With Limited Low-Frequency Hearing.

OBJECTIVE: To evaluate the clinical feasibility and auditory benefits of hearing rehabilitation using electroacoustic stimulation (EAS) after cochlear implantation (CI) and to identify the predictive factors for successful EAS rehabilitation in children with limited low-frequency hearing. STUDY DESIGN: Retrospective case review. SETTING: Tertiary referral hospital. PATIENTS: Seventeen children (21 ears) under the age of 15 years with residual low-frequency hearing who underwent CI using hearing preservation techniques. INTERVENTION: Patients underwent CI using hearing preservation techniques, and the postoperative audiograms were obtained to evaluate the hearing preservation rate. EAS rehabilitation was applied in patients with successful low-frequency hearing preservation. OUTCOME MEASURES: Improvements in speech perception in both quiet and noise conditions were compared between the EAS mode and the CI-only mode. The predictive factors for successful EAS rehabilitation in children were analyzed. RESULTS: Functional low-frequency residual hearing less than or equal to 85 dB at 250 and 500 Hz was achieved postoperatively in six of 21 ears, and successful EAS rehabilitation was possible in nine of 21 ears. Better speech perception scores were observed in quiet conditions using the EAS mode compared with the CI-only mode, although the difference did not reach statistical significance. Significantly, better scores were observed in noise conditions with the EAS mode compared with the CI-only mode. Postoperative low-frequency pure-tone average was the only significant predictive factor of successful EAS rehabilitation. CONCLUSION: CI surgery using hearing preservation techniques with EAS rehabilitation should be performed in children, even in patients with limited residual hearing, to improve auditory outcomes.

Progressive hearing loss in vitamin A-deficient mice which may be protected by the activation of cochlear melanocyte.

Vitamin A deficiency (VAD) produces various pathologic phenotypes in humans and animals. However, evidence regarding the effect of VAD on hearing function has been inconsistent. In this study, we evaluated the effect of VAD on hearing function in two mouse models of VAD. Hearing ability was evaluated on the basis of auditory brainstem response from 3 to 20 weeks after birth in C57BL/6 (pigmented) and imprinting control region (albino) mice. The two mice strains were divided into the VAD (purified vitamin A-free diet from 7 days after pregnancy) and control (normal diet) groups. Albino VAD mice exhibited hearing loss after 6 weeks and became deaf at 18 weeks. Histological findings revealed degenerative changes in outer hair cells and neuronal loss in the spiral ganglion in albino VAD mice. In contrast, pigmented VAD mice, except those with middle-ear infection, showed no significant hearing loss. Interestingly, pigmented VAD mice exhibited melanocyte activation in the stria vascularis and upregulation of tyrosinase. Recovery of hearing after noise exposure was poorer in pigmented VAD mice than in control mice. In conclusion, complete VAD might be related to age-related or noise-induced hearing loss in mice, protection against which might involve melanocyte activation.

Typical sensory organization test findings and clinical implication in acute vestibular neuritis.

OBJECTIVE: Sensory organization test (SOT) is used to evaluate postural instability. We wanted to characterize the SOT findings in patients with acute vestibular neuritis (VN). METHODS: Eighty-seven patients with VN were enrolled. The bithermal caloric and SOT were performed, and the results were compared with those from the dizziness handicap inventory (DHI). Abnormal SOT patterns were classified: severe, visual vestibular, vestibular, inconsistent, or normal patterns. The results were also analyzed by sensory analysis (somatosensory, visual, vestibular, and visual preference) and composite scores. RESULTS: Sixty-one patients (70%) showed abnormal findings for conditions 5 and/or 6 (vestibular pattern), and half (30 of 61, 49%) of them showed additional abnormal results in more than conditions 5 and 6. In pattern analysis, the vestibular pattern (abnormal in conditions 5 and 6) was the most common pattern (36%), and the visual vestibular pattern (abnormal in conditions 4, 5, and 6) was the second most common (24%). In sensory analysis, vestibular dysfunction was observed in 59 patients (68%), visual dysfunction in 37 (43%), visual preference in 17 (20%), and somatosensory dysfunction in 5 (6%). Composite scores of SOT showed a significant correlation with the DHI scores, though no correlation was observed between DHI and caloric results (p<0.05). CONCLUSION: VN can adversely influence on postural instability, with more severe patterns as well as classical vestibular patterns, indicating that abnormal vestibular inputs can influence postural stability in all SOT conditions and subjective symptom in patients with acute VN is more closely associated with the postural instability rather than canal dysfunction.

Natural history of horizontal canal benign paroxysmal positional vertigo is truly short.

The objective of the study is to characterize the natural course of positional vertigo and nystagmus in patients with horizontal canal benign paroxysmal positional vertigo (h-BPPV) and to analyze the difference in the natural course between the two variants of h-BPPV. We conducted a prospective study in 106 patients with geotropic type h-BPPV [h-BPPV (Geo)] (n = 43) and apogeotropic type h-BPPV [h-BPPV (Apo)] (n = 63) who agreed and signed the written informed consent of no treatment. All patients were asked to answer a detailed interview about the onset time of positional vertigo and to visit the hospital every 1-3 days. At every visit, they were interviewed about cessation time of positional vertigo and positional nystagmus was assessed. The mean period ± SD between the onset and remission of vertigo in the h-BPPV (Geo) was 6.7 ± 6.3 days, whereas that in the h-BPPV (Apo) was 3.7 ± 4.1 days. In addition, the mean period ± SD from the initial diagnosis to the disappearance of positional nystagmus in the h-BPPV (Geo) was 4.7 ± 3.9 days, whereas that in the h-BPPV (Apo) was 4.4 ± 5.0 days. Although the duration until natural remission of positional nystagmus did not differ between the two variants of h-BPPV, the remission of vertigo occurred faster in h-BPPV (Apo) than h-BPPV (Geo) (p < 0.05). The natural course of h-BPPV is much shorter than that indicated in previous reports. The positional vertigo disappeared faster in the h-BPPV (Apo) compared to the h-BPPV (Geo) unlike the positional nystagmus.

Identification of a novel nonsynonymous mutation of EYA1 disrupting splice site in a Korean patient with BOR syndrome.

The EYA1 gene is known as the causative gene of BOR (Branchio-oto-renal) syndrome which is a genetic disorder associated with branchial cleft cysts of fistulae, hearing loss, ear malformation, and renal anomalies. Although approximately 40% of patients with BOR syndrome have mutations in the EYA1 gene and over 130 disease-causing mutations in EYA1 have been reported in various populations, only a few mutations have been reported in Korean families. In this study, genetic analysis of the EYA1 gene was performed in a Korean patient diagnosed with BOR syndrome and his parents. A de novo novel missense mutation, c.418G>A, located at the end of exon 6, changed glycine to serine at amino acid position 140 (p.G140S) and was suspected to affect normal splicing. Our in vitro splicing assay demonstrated that this mutation causes exon 6 skipping leading to frameshift and truncation of the protein to result in the loss of eyaHR. To the best of our knowledge, this is the first report revealing that a missense mutation in the exon disturbs normal splicing as a result of a substitution of the last nucleotide of an exon in EYA1.

Persistent spontaneous nystagmus following a canalith repositioning procedure in horizontal semicircular canal benign paroxysmal positional vertigo.

IMPORTANCE: Nystagmus can occur spontaneously from multiple causes. Direction-changing positional nystagmus on the supine roll test is a characteristic clinical feature in horizontal semicircular canal benign paroxysmal positional vertigo. One of several mechanisms of spontaneous nystagmus is plugging of the otoconia, which has been described as a canalith jam. OBSERVATIONS: We evaluated a 52-year-old woman with a history of geotropic variant of horizontal semicircular canal benign paroxysmal positional vertigo on the right side who had been treated with a modified Lempert maneuver 3 months earlier. The patient had persistent spontaneous nystagmus, despite a positional change after the canalith repositioning procedure. A bithermal caloric test result demonstrated unilateral canal paresis on the right side. The following day, the patient's symptoms and nystagmus had subsided. On a repeated bithermal caloric test, a normal response was demonstrated on both sides. CONCLUSIONS AND RELEVANCE: To our knowledge, this is the first report of a case that shows on video persistent nystagmus findings consistent with a canalith jam. We discuss a possible mechanism underlying this phenomenon.

Intrafamilial phenotypic variability in families with biallelic SLC26A4 mutations.

OBJECTIVES/HYPOTHESIS: Enlarged vestibular aqueduct (EVA) and hearing loss are known to be caused by SLC26A4 mutations, but large phenotypic variability exists among patients with biallelic SLC26A4 mutations. Intrafamilial phenotypic variability was analyzed in multiplex EVA families carrying biallelic SLC26A4 mutations to identify the contribution of SLC26A4 mutations and other genetic or environmental factors influencing the clinical manifestations. STUDY DESIGN: Retrospective case series. METHODS: Eleven multiplex Korean families with EVA and hearing loss that carry biallelic mutations of the SLC26A4 gene were included. Genetic analysis for SLC26A4 and other genes including FOXI1, FOXI1-DBD, and KCNJ10 was performed. The auditory and other phenotypes were compared among siblings with the same SLC26A4 mutations. RESULTS: The difference in the auditory phenotypes was identified between siblings in approximately half of the EVA families. Families with SLC26A4 mutations other than H723R homozygous mutations demonstrated more phenotypic variability, especially in those carrying IVS7-2A>G splice site mutation. Cochlear malformation was a consistent finding among siblings with the same SLC26A4 mutations. No mutation was identified in the FOXI1, FOXI1-DBD, and KCNJ10 genes in the tested families. CONCLUSIONS: The possibility of variability concerning auditory phenotype should be considered even within family members carrying the same SLC26A4 mutations when providing genetic counseling to multiplex EVA families. Mutations in the currently known genes associated with EVA other than SLC26A4 were not found to be responsible for the intrafamilial phenotypic variability. Modifier genes or environmental factors other than the currently known genes seem to play a role in the phenotypic expressions of EVA patients.

Benign paroxysmal positional vertigo with simultaneous involvement of multiple semicircular canals.

BACKGROUND AND OBJECTIVES: Benign paroxysmal positional vertigo (BPPV) generally involves a single semicircular canal (single canal BPPV) but it has been reported that more than one semicircular canal on either the same or the opposite side can be involved in 6.8-20% of the cases (multiple canal BPPV). In this study, the clinical characteristics of multiple canal BPPV were analyzed and compared to those of single canal BPPV. MATERIALS AND METHODS: Retrospective analysis was performed on 1054 consecutive patients diagnosed with BPPV. Multiple canal BPPV was diagnosed when the combination of typical nystagmus was provoked by the Dix-Hallpike and supine head roll tests. Canalith repositioning maneuver was performed sequentially starting with the semicircular canal causing more severe nystagmus or symptoms. Clinical characteristics and the treatment course were statistically compared between single canal BPPV and multiple canal BPPV. RESULTS: Among the 1054 patients, single canal BPPV was diagnosed in 1005 patients (95.4%) while multiple canal BPPV was diagnosed in 49 patients (4.6%). BPPV involving semicircular canals on the same side was more common (79.6%) than BPPV with bilateral involvement. The most common combination of the involved canals was ipsilateral posterior and horizontal semicircular canals (63.3%). Multiple canal BPPV was significantly more associated with underlying otologic diseases, especially labyrinthitis. Multiple canal BPPV required more treatment sessions and longer duration of treatment to achieve resolution of nystagmus and symptoms. CONCLUSIONS: As all cases of multiple canal BPPV were treated successfully although a longer duration of treatment and more treatment sessions were required compared to single canal BPPV, the results of our study could aid in making an accurate diagnosis and providing appropriate treatment of multiple canal BPPV.

A case of labyrinthine fistula by cholesteatoma mimicking lateral canal benign paroxysmal positional vertigo.

Acute peripheral vestibulopathy, of which the chief complaint is positional vertigo, comprises benign paroxysmal positional vertigo (BPPV), labyrinthitis, labyrinthine fistula, and cerebellopontine angle tumors. Since the typical presentation of labyrinthine fistulas may be sensorineural hearing loss, positional vertigo, or disequilibrium, it is often difficult to distinguish from BPPV or Meniere's disease. Herein we report a 61-year-old female patient with typical symptoms and signs attributable to geotropic type variant of the lateral semicircular canal BPPV on the left side, who eventually was confirmed as having a labyrinthine fistula from chronic otitis media with cholesteatoma on the left side. This is another case where, even in the presence of isolated vertigo showing typical findings of acute peripheral vestibulopathy, other otologic symptoms and signs must not be overlooked.

Mutational analysis of EYA1, SIX1 and SIX5 genes and strategies for management of hearing loss in patients with BOR/BO syndrome.

BACKGROUND: Branchio-oto-renal (BOR) or branchio-otic (BO) syndrome is one of the most common forms of autosomal dominant syndromic hearing loss. Mutations in EYA1, SIX1 and SIX5 genes have been associated with BOR syndrome. In this study, clinical and genetic analyses were performed in patients with BOR/BO syndrome focusing on auditory manifestations and rehabilitation. METHODS: The audiologic manifestations were reviewed in 10 patients with BOR/BO syndrome. The operative findings and hearing outcome were analyzed in patients who underwent middle ear surgeries. The modality and outcome of auditory rehabilitation were evaluated. Genetic analysis was performed for EYA1, SIX1, and SIX5 genes. RESULTS: All patients presented with mixed hearing loss. Five patients underwent middle ear surgeries without successful hearing gain. Cochlear implantation performed in two patients resulted in significant hearing improvement. Genetic analysis revealed four novel EYA1 mutations and a large deletion encompassing the EYA1 gene. CONCLUSIONS: Auditory rehabilitation in BOR/BO syndrome should be individually tailored keeping in mind the high failure rate after middle ear surgeries. Successful outcome can be expected with cochlear implantations in patients with BOR/BO syndrome who cannot benefit from hearing aids. The novel EYA1 mutations may add to the genotypic and phenotypic spectrum of BOR syndrome in the East Asian population.

Can the affected semicircular canal be predicted by the initial provoking position in benign paroxysmal positional vertigo?

OBJECTIVES/HYPOTHESIS: The study evaluated the relationship between the position that initially provoked vertigo and the affected semicircular canal (SCC) in patients with benign paroxysmal positional vertigo (BPPV), and aimed to predict the side affected by BPPV through history taking regarding the provoking position. STUDY DESIGN: Prospective study at a tertiary hospital. METHODS: A total of 521 patients with BPPV involving the posterior or horizontal SCCs performed questionnaires at initial visit asking to choose the initial provoking position among the 10 positions corresponding to one of the three planes (roll, pitch, or yaw). After excluding 45 patients showing signs of simultaneous multiple canal or anterior canal involvement, the frequency of the provoking positions and the correlation between the side of the provoking position and the ear affected by BPPV were analyzed. RESULTS: There were 239 patients with posterior SCC BPPV (p-BPPV) and 237 patients with horizontal SCC BPPV (h-BPPV). The waking-up position was the most common provoking position in both types of BPPV. Statistically significant correlation was demonstrated between the side of the provoking position at the onset of vertigo and the affected side by BPPV (P < .01) in patients with p-BPPV as well as h-BPPV (geotropic type [Geo]), but not in patients with h-BPPV (apogeotropic type [Apo]). CONCLUSIONS: History taking regarding the side of provoking position at the onset of vertigo may help predict the side affected by BPPV in p-BPPV and h-BPPV (Geo). When h-BPPV (Apo) is suspected, further detailed examinations using additional localization methods should be performed.

Relationship between electrically evoked auditory brainstem response and auditory performance after cochlear implant in patients with auditory neuropathy spectrum disorder.

OBJECTIVE: To analyze the pattern of electrically evoked auditory brainstem response (EABR) in auditory neuropathy spectrum disorder (ANSD) patients and to compare their performances with controls. STUDY DESIGN: Retrospective analysis. SETTING: Tertiary referral center. PATIENTS: Eleven patients with ANSD and 9 control subjects with sensorineural hearing loss who did not have neural pathology. INTERVENTION: Diagnostic. MAIN OUTCOME MEASURES: Patients and control subjects each received a cochlear implant (CI) and underwent EABR. EABR threshold, wave V latency, and amplitude were measured as EABR parameters. The results of EABR were categorized as good response, variable response, or no response. Speech perception ability was assessed by the categories of auditory performance (CAP) score. RESULTS: All controls responded to EABR, whereas 6 of the 11 ANSD patients did not respond to EABR. The EABR threshold of the ANSD patients was measured almost within the value of disease controls. However, the Wave V latency displayed variable lengths, and the amplitude showed a wider distribution compared with the value of the disease control. The EABR response group among the ANSD patients showed relatively good performance after CI. In contrast, the nonresponse group demonstrated variable outcomes, although all of them still benefited from CI. CONCLUSION: The data suggested that all ANSD patients require CI and that EABR results can help establish realistic expectations about future performance. Even if electrical stimulation fails to generate sufficiently synchronized signal for eliciting EABR, CI provides at least partial, measurable auditory benefit in ANSD.

Genetic analysis of auditory neuropathy spectrum disorder in the Korean population.

Auditory neuropathy spectrum disorder (ANSD) is caused by dys-synchronous auditory neural response as a result of impairment of the functions of the auditory nerve or inner hair cells, or synapses between inner hair cells and the auditory nerve. To identify a causative gene causing ANSD in the Korean population, we conducted gene screening of the OTOF, DIAPH3, and PJVK genes in 19 unrelated Korean patients with ANSD. A novel nonsense mutation (p.Y1064X) and a known pathogenic mutation (p.R1939Q) of the OTOF gene were identified in a patient as compound heterozygote. Pedigree analysis for these mutations showed co-segregation of mutation genotype and the disease in the family, and it supported that the p.Y1064X might be a novel genetic cause of autosomal recessive ANSD. A novel missense variant p.K1017R (c.3050A>G) in the DIAPH3 gene was also identified in the heterozygous state. In contrast, no mutation was detected in the PJVK gene. These results indicate that no major causative gene has been reported to date in the Korean population and that pathogenic mutations in undiscovered candidate genes may have an effect on ANSD.