Prevalence of vestibular and balance disorders in children and adolescents according to age: A multi-center study.

OBJECTIVES: Children differ from adults in the expression of dizziness symptoms and the causes of dizziness. In several studies, benign paroxysmal vertigo of childhood (BPVC) and vestibular migraine (VM) were seen exclusively in children with vertigo, but the age threshold used to define 'children' varies, and there are few reported studies about adolescents with dizziness. In this study, we investigated the prevalence of vestibular and balance disorders according to age category in a multi-center study (otolaryngology departments of 11 hospitals) of children and adolescents. METHODS: Children and adolescents aged under 18 who visited the otolaryngology departments of 11 hospitals for dizziness were included. We classified the patients into three categories: preschool (up to and including 6-year-olds), school age (7- to 12-year-olds), and adolescents (13- to 18-year-olds). These patients were reviewed retrospectively based on their clinical charts. RESULTS: In the preschool age group, BPVC was most common, followed by VM. In the school-age group, BPVC and VMs were most common, followed by psychogenic vertigo and benign paroxysmal positional vertigo (BPPV). In adolescents, VM was the most common, and Ménière's disease, cardiogenic vertigo, and BPVC, which are seen primarily in adults, were also seen in some adolescents. CONCLUSION: In children and adolescents with dizziness, VM and BPVC were the most common diseases, and prevalence of disease by age showed differing distributions. These findings will help in diagnosing and managing children and adolescents with vertigo.

Isolated horizontal positional nystagmus from a posterior fossa lesion.

Isolated vertigo with horizontal positional nystagmus as an impending sign of a central lesion has rarely been reported. Here we present neuro-otologic findings of patients with these clinical signs. Lesion overlays from 6 patients with ageotropic positional nystagmus revealed that the nodulus and vermis are common areas of injury. In contrast, 2 patients with geotropic positional nystagmus had cerebellar peduncle and lateral medullary lesions. These clinical findings suggest that vertigo with horizontal positional nystagmus, even in the absence of other initial neurological signs, may indicate a posterior fossa lesion, including that in the nodulus, vermis, and deep cerebellar structures.

Canal conversion between anterior and posterior semicircular canal in benign paroxysmal positional vertigo.

OBJECTIVE: To investigate the characteristics of canal conversion between the anterior and posterior semicircular canals in benign paroxysmal positional vertigo (BPPV). STUDY DESIGN: Retrospective chart review. SETTING: Secondary referral center. PATIENTS: A total of 709 patients who were treated with the Epley maneuver for BPPV of the anterior or posterior semicircular canal. INTERVENTIONS: Vestibular examinations with videonystagmography and the canalith repositioning procedure (CRP) to treat BPPV. RESULTS: Canal conversion between the anterior and posterior semicircular canals was observed in 18 (2.9%) patients who underwent CRP. In 13 (2.3%) of 564 patients initially diagnosed with posterior canal BPPV (PC-BPPV), switch to anterior canal BPPV (AC-BPPV) was observed at a follow-up visit. In 5 (12.1%) of 41 patients who presented with AC-BPPV, canal switch to PC-BPPV occurred more frequently (p = 0.005). The average number of CRPs before nystagmus resolution was 3.6 in conversion cases versus 1.6 in the nonconversion group (p < 0.001). CONCLUSION: Canal conversion between the anterior and posterior semicircular canals can occur during treatment. The possibility of canal conversions should be considered for appropriate management of BPPV of the vertical semicircular canals.

Syndromic Hearing Loss in Association with PTPN11-Related Disorder: The Experience of Cochlear Implantation in a Child with LEOPARD Syndrome.

Hearing loss (HL) is one of the most frequent clinical manifestations of patients who suffer with multi-systemic genetic disorders. HL in association with other physical stigmata is referred to as a syndromic form of HL. LEOPARD syndrome (LS) is one of the disorders with syndromic HL and it is caused by a mutation in the PTPN11 or RAF1 gene. In general, 5 year old children who undergo cochlear implantation usually show a marked change in behavior regarding sound detection within the first 6 months of implant use, but word identification may not be exhibited for at least another 6-12 months of implant use. We herein report on a 5-year-old girl with LS. Her clinical manifestations including bilateral sensorineural HL, which indicated the diagnosis of LS. We confirmed the diagnosis by identifying a disease-causing mutation in the PTPN11 gene, which was a heterozygous missense mutation Ala461Thr (c.1381G>A). She underwent cochlear implantation (CI) without complications and she is currently on regular follow-up at postoperative 1 year. This is the first reported case of CI in a patient with LS in the medical literature.

A Novel Frameshift Mutation of the USH2A Gene in a Korean Patient with Usher Syndrome Type II.

Usher syndrome type II (USH2) is the most common form of Usher syndrome, characterized by moderate to severe hearing impairment and progressive visual loss due to retinitis pigmentosa. It has been shown that mutations in the USH2A gene are responsible for USH2. The authors herein describe a 34-year-old Korean woman with the typical clinical manifestation of USH2; she had bilateral hearing disturbance and progressive visual deterioration, without vestibular dysfunction. Molecular genetic study of the USH2A gene revealed a novel frameshift mutation (c.2310delA; Glu771LysfsX17). She was heterozygous for this mutation, and no other mutation was found in USH2A, suggesting the possibility of an intronic or large genomic rearrangement mutation. To the best of our knowledge, this is the first report of a genetically confirmed case of USH2 in Korea. More investigations are needed to delineate genotype-phenotype correlations and ethnicity-specific genetic background of Usher syndrome.

Auditory characteristics and therapeutic effects of enzyme replacement in mouse model of the mucopolysaccharidosis (MPS) II.

Mucopolysaccharidosis (MPS) II is an X-linked metabolic disorder caused by dysfunction of iduronate-2-sulfatase (I2S). This abnormality causes the progressive accumulation of incompletely degraded glycosaminoglycans (GAGs) in the lysosomes. The auditory characteristics of MPS II in mouse models have not been reported. In this study, we evaluated the auditory characteristics of the MPS II in IDS knock-out (IDS-KO) mice. In addition, the effect of enzyme replacement therapy (ERT) on hearing was studied. The IDS-KO mice had normal histology of the cochlea and retained good hearing at 7 weeks of age. However, at 17 weeks of age, the hearing thresholds of the IDS-KO mice were elevated and exudates were found in the middle ear. The hearing thresholds of the enzyme-treated IDS-KO (IDS-ERT) mice were similar to the wild-type (WT) mice at 17 weeks. Moreover, the microstructure of the inner ear was similar to the IDS-KO by transmission electron microscopy. The histology findings indicated that the microstructure of the inner ear was similar in comparisons between IDS-KO and IDS-ERT mice, even after 10 weeks of treatment. However, the hearing deficits in the MPS II mouse model can be prevented if ERT is started before the onset of hearing impairment.

Open-type congenital cholesteatoma: differential diagnosis for conductive hearing loss with a normal tympanic membrane.

CONCLUSION: In patients with progressive conductive hearing loss and a normal tympanic membrane (TM), and with soft tissue density in the middle ear cavity (MEC) on temporal bone computed tomography (TBCT) scan, open-type congenital cholesteatoma (OCC) should be highly suspected and a proper surgical plan that includes mastoid exploration and second-stage operation is required. OBJECTIVE: The clinical presentation of OCC is very similar to congenital ossicular anomaly (COA) presenting with a conductive hearing loss with intact TM. Therefore, it is challenging to make a correct preoperative diagnosis in patients with OCC. We evaluated the clinical characteristics of OCC compared with those of COA to find diagnostic clues useful in diagnosis of OCC. METHODS: The medical records of 12 patients with surgically proven OCC and 14 patients with surgically proven COA were reviewed for demographic data, otologic history, preoperative TBCT findings, intraoperative findings, and pre- and postoperative audiologic data. RESULTS: There was no difference between OCC and COA based on demographic data, preoperative hearing, and ossicular status on TBCT. However, the presence of progressive hearing loss, soft tissue density in the MEC on TBCT scan, and the need for mastoid surgery and second-stage operation were significantly more frequent in OCC patients.

N-acetylcysteine and N-nitroarginine methyl ester attenuate Carboplatin-induced ototoxicity in dissociated spiral ganglion neuron cultures.

OBJECTIVES: Carboplatin, a platinum-containing anti-cancer drug used to treat a variety of cancers, induces ototoxicity. Since, reactive oxygen species (ROS) and nitric oxide (NO) seem to be responsible for this toxicity, the antioxidant, N-acetyl-L-cysteine (L-NAC), and NO synthetase inhibitor, N-nitro-L-arginine methyl ester (L-NAME) were predicted to have protective effects against carboplatin ototoxicity. The aim of this study was to test for the protective effects of L-NAC and L-NAME on cochlear hair cells and spiral ganglion neurons (SGNs). METHODS: Cochlear organotypic cultures and dissociated spiral ganglion neuron cultures, from mice postnatal day 5 cultures were used in this study. The cultures were treated with carboplatin alone or in combination with L-NAC or L-NAME, and carboplatin-induced damage was monitored. RESULTS: Treatment with carboplatin induced a significant loss of outer hair cells, while inner hair cells were preserved in the cochlear organotypic cultures. Addition of L-NAC or L-NAME reduced the amount of carboplatin-induced hair cell damage; the differences did not reach statistical significance. However, carboplatin significantly decreased the number of surviving SGNs in dissociated cultures. The toxic effects were significantly reduced by addition of L-NAC or L-NAME. In addition, carboplatin induced the loss of neurites from the SGN somata, and this was not blocked with L-NAC or L-NAME. CONCLUSION: The results of this study suggest that ROS and NO are involved in carboplatin-induced damage to hair cells and SGNs, and administration of L-NAC/L-NAME can be used to attenuate the toxicity.

A new measurement tool for speech development based on Ling's stages of speech acquisition in pediatric cochlear implant recipients.

OBJECTIVES: With the rapid increase of pediatric cochlear implantation (CI), there exists a need for a standardized assessment tool regarding speech and communication skills in children with CI. However, the current testing tools are not appropriate for the longitudinal evaluation of young children after CI. The aims of this study were to describe a progressive testing tool developed for the evaluation of speech acquisition and production in young children who have undergone CI and to examine its validity. METHODS: Sixty children younger than six years of age with CI participated in this study. A Korean version of Ling's stages (K-Ling) was developed based on the Ling speech teaching model to longitudinally assess phonologic and phonetic developments in young children after CI. The K-Ling, the Categories of Auditory Performance (CAP), and the Sequenced Language Scale for Infants (SELSI) were performed in the children with CI preoperatively and three, six, and 12 months postoperatively. Correlations among these three testing tools were analyzed. RESULTS: Auditory, language, and speech skills assessed using the CAP, SELSI, and K-Ling improved continuously for 12 months in young children following CI. Strong correlations were obtained among K-Ling's level, CAP scores, and the equivalent age of SELSI; correlation indices ranged from 0.540 to 0.800. CONCLUSIONS: The K-Ling was a valid evaluation tool regarding speech development in young children who are using CI and who are in the early stages of speech development. Longitudinal assessments of phonetic and phonologic developments may be attainable in young children using the K-Ling.

Sequence Variations and Haplotypes of the GJB2 Gene Revealed by Resequencing of 192 Chromosomes from the General Population in Korea.

OBJECTIVES: Hearing impairment (HI) is the most common sensory deficit in human. The Gap Junction Protein, Beta-2 (GJB2) gene encodes the protein connexin 26, and this gene accounts for up to half of the cases of autosomal recessive nonsyndromic HI. This study was conducted to obtain a set of sequence variations (SVs) of the GJB2 gene among Koreans from the general population for making molecular genetic diagnoses and performing genetic counseling. METHODS: We resequenced the GJB2 gene in 192 chromosomes from 96 adult individuals of Korean descent and who were without a history of hearing difficulty. The data of the SVs was obtained and the haplotypes were reconstructed from the data. RESULTS: Five SVs were observed, including a novel one (c.558G>A; p.T186T), with the allele frequencies ranging from 0.5% (1/192) to 41% (79/192). The linkage disequilibrium study and haplotype construction showed that some of the SVs are in tight linkage, resulting in a limited number of haplotypes. CONCLUSION: We observed SVs of the GJB2 gene with different allele frequencies, and a limited number of haplotypes were constructed. The data from this study can be used as reference data for GJB2-related hearing genetic studies, including studies on the founder effect and population genetics, and this data is particularly relevant to people of East Asian decent.

Hearing Outcomes According to the Types of Mastoidectomy: A Comparison between Canal Wall Up and Canal Wall Down Mastoidectomy.

OBJECTIVES: The aim of this study was to compare the hearing outcomes between canal wall up mastoidectmy (CWUM) and canal wall down mastoidectmy (CWDM). METHODS: One hundred seventy one chronic suppurative otitis media (CSOM) patients were enrolled in this retrospective study. The patients who underwent the second staged ossiculoplasty at least 6 months after mastoidectomy and who had an intact, well aerated tympanic cavity as well as intact mobile stapes at the time of operation were selected from the medical record. Based on the type of mastoid surgery, the patients were categorized into two groups: the CWUM (n=38) and CWDM groups (n=133). The hearing results of the CWUM and CWDM groups were compared using the pre- and post-operative air-bone gap (ABG) at 3 months after ossiculoplasty. RESULTS: The preoperative ABG in both groups (CWUM and CWDM) were 28.4±15.6 dB and 31.8±14.5 dB, respectively (P=0.18). Both groups didn't show any significant difference (10.9 dB vs. 13.5 dB, respectively) (P=0.21) for the postoperative ABG closure. The proportion of patients with an ABG less than 20 dB was 58.6% of the CWDM patients and 68.4% of the CWUM patients (P=0.25). CONCLUSION: The type of mastoid surgery (CWUM and CWDM) did not affect the hearing results of CSOM patients. When choosing the type of mastoidectomy procedure for CSOM surgery, the hearing outcomes are basically the same for both types of procedure.

Up-regulation of MUC5AC and MUC5B mucin genes in chronic rhinosinusitis.

BACKGROUND: Excess mucus production and hypersecretion characterize upper airway diseases. The primary mechanisms leading to mucus hypersecretion in chronic rhinosinus inflammation are not well understood. Mucus hypersecretion is commonly accompanied by goblet cell and submucosal gland cell hyperplasia. It is important to identify which mucin gene messenger RNAs (mRNAs) are expressed in the sinus mucosa. OBJECTIVES: To investigate the expression of MUC5AC and MUC5B mRNAs and localization of these proteins in human sinus mucosa and to compare the expression of MUC5AC and MUC5B mRNAs in normal and in chronic sinus mucosa. DESIGN: Twenty chronic maxillary sinusitis mucosa samples and 20 normal maxillary sinus mucosa samples were obtained; RNAs were extracted from sinus mucosa, and semiquantitative reverse transcription-polymerase chain reaction was performed for MUC5AC and MUC5B. Localization of these proteins was sought by using immunohistochemical analysis. RESULTS: The levels of MUC5AC and MUC5B mRNA in chronic rhinosinusitis were significantly increased compared with those in normal sinus mucosa (P =.02). In inflammed sinus mucosa, MUC5AC protein was expressed in the cytoplasm of the goblet cell in the surface epithelium, and MUC5B expression was restricted to mucous cells of the submucosal glands and to the epithelium of sinus mucosa. However, in the normal sinus mucosa, MUC5AC and MUC5B proteins were expressed at low levels in the sinus epithelium and submucosal glands, respectively. CONCLUSION: These results suggest that up-regulation of MUC5AC and MUC5B, which are major components of respiratory secretion in chronic rhinosinusitis, may play important roles in the pathogenesis of sinus hypersecretion in chronic rhinosinusitis.