Vestibular Function Change in a Vasopressin-Induced Hydrops Model

Kim, Minbum,Kim, Kyu-Sung by Otology Neurotology, Inc. Image copyright © 2017 Otology & neurotology Vol.38 No.10

HYPOTHESIS:: A vasopressin-induced endoymphatic hydrops model can represent an acute vertiginous attack in Menière’s disease (MD). BACKGROUND:: Previous animal models are not appropriate to evaluate the efficacy of new treatments for hydrops because they cannot represent an acute attack of MD. Recently, a new dynamic model was introduced for acute hydrops exacerbation using the vasopressin type 2 receptor agonist, desmopressin (1-deamino-8-D-Arginine vasopressin, VP); however, resulting changes in vestibular function have not been investigated. METHODS:: A total of 37 guinea pigs were used. Two to 4 weeks after surgical ablation of endolymphatic sacs in 33 guinea pigs, acute exacerbation of hydrops was induced by a single VP injection in 18 animals (group A). Next, two VP injections at 1 hour interval were administered to investigate the effect of multiple VP doses on vestibular function in the other 15 animals (group B). In the remaining four animals, VP was injected without surgery for the control group (control). Bidirectional sinusoidal harmonic acceleration (SHA) tests of vestibular function were performed. “Type I response” was defined as when the maximum slow-phase velocity (SPV) during left rotation (toward the operated ear) was lower than that during right rotation (toward the normal ear). In contrast, “Type II response” was defined as when maximum SPV at the left rotation was higher than that at the right rotation. Vestibular symmetry scores were analyzed at baseline and after each of two VP injections given 1 hour apart. RESULTS:: Vestibular symmetry scores increased at 1 hour after VP injection in all 18 animals in group A (p < 0.001). Two hours after VP injection, symmetry score decreased to the initial score. Two different types of vestibular response were observed after VP. However, the symmetry scores between type I and II responses were not significantly different (p = 0.173). In all 15 animals of Group B, vestibular asymmetry was sustained over 3 hours when two VP injections were given 1 hour apart. In three of Group B, the type of vestibular response changed from type II response to type I response after the 2nd VP injection; however, no animal demonstrated a shift from type I to type II response. CONCLUSION:: VP can transiently induce an acute exacerbation of hydrops and asymmetric vestibular dysfunction in guinea pigs. This model could help in studying new treatments for acute hydrops and in explaining the mechanism of bidirectional nystagmus in MD.

Targeted Exome Sequencing of Deafness Genes After Failure of Auditory Phenotype-Driven Candidate Gene Screening

Kim, Bong Jik,Kim, Ah Reum,Park, Gibeom,Park, Woong Yang,Chang, Sun O,Oh, Seung-Ha,Choi, Byung Yoon by Otology Neurotology, Inc. Image copyright © 2015 Otology & neurotology Vol.36 No.6

OBJECTIVE: To demonstrate the efficacy and advantages of targeted exome sequencing (TES) of known deafness genes in cases with failed or misleading auditory phenotype-driven candidate gene screening. STUDY DESIGN: Prospective cohort survey. SETTING: Otolaryngology department of a tertiary referral hospital. PATIENTS: Six hearing-impaired probands with seemingly non-syndromic features from six deaf families were enrolled in this study after failure of genetic diagnosis using auditory phenotype-driven candidate gene screening. INTERVENTION: TES of known deafness genes was performed in the six probands, and a final causative variant was pursued using subsequent filtering steps. MAIN OUTCOME MEASURE: Potential causative variants determined using TES were confirmed by previously introduced filtering steps. RESULTS: We detected causative variants in three (50%) of six families, and these variants were in the COCH, PAX3, and GJB2 genes. Additionally, we also recapitulated the recent finding from other report arguing for the non-pathogenic potential of MYO1A variant. CONCLUSIONS: TES of a deafness panel provides a comprehensive genetic screening tool that can be implemented without being misled by the audiogram configuration information and can complement incomplete clinical physical examinations. In addition, the secondary incidental finding obtained by TES contributes useful information regarding the deafness field.

Functional Study of Mucus Secretion of the Eustachian Tube in Guinea Pigs

Choi, Hyun Seung,Yang, Won Sun,Kim, Sang Cheol,Lee, Won Il,Lee, Hyun Jae,Choi, Jae Young Otology Neurotology, Inc. 2010 Otology & Neurotology Vol.31 No.5

OBJECTIVES:: Our aim was to verify neural regulation of submucous gland mucus secretions in the Eustachian tubes of guinea pigs. STUDY DESIGN:: Prospective animal study. METHODS:: Eustachian tubes harvested from 12 guinea pigs were used for this study. For real-time resolution of pure glandular secretion, we used a modified method of single-gland optical measurement. Secretory monitoring was undertaken after each preparation with phenylephrine, isoproterenol, forskolin, and substance P. To confirm the viability of each tissue, we examined glandular secretion after treatment with carbachol. Secretory effects of each agonist were evaluated by comparing with basal secretion using a Student's t test (p < 0.01). RESULTS:: The Ca-elevating agonists carbachol and substance P showed greater effects on submucous gland secretions of the Eustachian tube than the cyclic adenosine monophosphate (cAMP)-elevating agonists forskolin and isoproterenol. However, phenylephrine, although it belongs to the Ca-elevating agonist group, did not show any significant secretory effect. CONCLUSION:: The optical measurement method used in this study had the merit of real-time resolution of submucous glandular secretion. Submucous glandular secretion in the Eustachian tube was regulated by both Ca- and cAMP-elevating agonists, and Ca-elevating agonists seemed to be more potent than cAMP-elevating agonists except phenylephrine. Our results suggest that not only the autonomic nerve system but also the neuropeptides such as substance P are closely related to glandular secretion in the Eustachian tube, and &bgr;-adrenergic receptors seem to be more related to submucous glandular secretion of the Eustachian tube in guinea pig than α-adrenergic receptors.

Recovery of Vestibulogastrointestinal Symptoms During Vestibular Compensation After Unilateral Labyrinthectomy in Rats

Lee, Jae Hee,Ameer, Abduhl Nasir,Choi, Myoung Ae,Lee, Moon Young,Kim, Min Sun,Park, Byung Rim Otology Neurotology, Inc. 2010 Otology & Neurotology Vol.31 No.2

BACKGROUND:: The loss of unilateral vestibular function causes vestibulogastrointestinal symptoms that include nausea and vomiting. However, the temporal changes occurring on vestibular compensation are unclear. Thus, the temporal changes and the role of the cerebellum in the recovery of vestibulogastrointestinal symptoms after unilateral labyrinthectomy (UL) were investigated in this study. METHODS:: Vestibulogastrointestinal symptoms were evaluated for intestinal transit and geometric center, whereas vestibulo-ocular symptoms were represented by spontaneous nystagmus. Expression of the c-Fos protein was observed in the vestibular nuclei. These were measured at 30 minutes and at 2, 6, and 24 hours after UL in rats. RESULTS:: Intestinal transit was 66.3% ± 7.6% in the control animals but significantly decreased to 40.7% ± 7.8%, 46.3% ± 6.3%, and 48.6% ± 10.8% at 30 minutes (p < 0.01), 2 hours (p < 0.01), and 6 hours (p < 0.05) after UL, respectively. The intestinal transit showed a recovery to control levels 24 hours after UL. The geometric center was 5.6 ± 0.4 in control animals but significantly decreased to 2.1 ± 0.4, 2.9 ± 0.3, and 4.0 ± 0.3 at 30 minutes, 2 hours, and 6 hours after UL, respectively (p < 0.01). Recovery of the geometric center to control levels, 24 hours after UL, was reported. Uvulonodullectomy significantly decreased the intestinal transit and geometric center for 24 hours after surgery (p < 0.01). Moreover, UL in uvulonodullectomized animals significantly decreased the intestinal transit and geometric center for 24 hours after surgery (p < 0.01). Pretreatment of the UL animals with MK-801 significantly increased the geometric center 30 minutes after surgery (p < 0.01). Unilateral labyrinthectomy produced spontaneous nystagmus, 28.9 ± 1.5, 23.3 ± 1.4, 17.5 ± 1.5, and 9.2 ± 0.9 beats per 10 seconds at 30 minutes and at 2, 6, and 24 hours after UL, respectively. Expression of the c-Fos protein was significantly increased in the medial vestibular nuclei and inferior vestibular nuclei at 1, 2, and 6 hours after UL, and the expression was significantly decreased in animals that were pretreated with MK-801 (p < 0.01). CONCLUSION:: These results suggest that the recovery of vestibulogastrointestinal symptoms is faster than that of vestibulo-ocular symptoms and that the cerebellum and glutamate have an important role to play in the recovery of symptoms after UL.

Functional and Molecular Expression of Epithelial Sodium Channels in Cultured Human Endolymphatic Sac Epithelial Cells

Kim, Sung Huhn,Park, Hun Yi,Choi, Hyun Seung,Chung, Hyun Pil,Choi, Jae Young Otology Neurotology, Inc. 2009 Otology & Neurotology Vol.30 No.4

HYPOTHESIS:: Epithelial sodium channels are expressed in cultured human endolymphatic sac (ES) epithelial (HESE) cells and epithelial sodium channel (ENaC) expression is suppressed by interleukin 1&bgr;. BACKGROUND:: The ES is part of the membranous labyrinth in the inner ear that plays an important role in maintaining homeostasis of the endolymphatic fluid system. However, the exact mechanism of fluid volume regulation is not yet known. METHODS:: The ES specimens were harvested during acoustic neuroma surgery (n = 13) using the translabyrinthine approach and were subcultured with high-epidermal growth factor (25 ng/mL) media. RESULTS:: The serially passaged HESE cells differentiated into a monolayer of confluent cells and some of the cultured cells had features of mitochondria-rich cells. Reverse transcription-polymerase chain reaction revealed that ENaC subunits are expressed in the cultured HESE cells. We also confirmed the presence of an ENaC-dependent short-circuit current in the cultured HESE cells. Interestingly, ENaC mRNA expression and ENaC-dependent current decreased after treatment with interleukin 1&bgr; (10 nmol/L for 24 h). CONCLUSION:: These findings suggest that ENaC plays an important role in fluid absorption in the human ES and that its function may be altered during inflammatory conditions.

Lessons From Follow-Up Examinations in Patients With Vestibular Neuritis: How to Interpret Findings From Vestibular Function Tests at a Compensated Stage

Park, HongJu,Shin, JungEun,Jeong, YongSoo,Kwak, HiBoong,Lee, YeoJin Otology Neurotology, Inc. 2009 Otology & Neurotology Vol.30 No.6

OBJECTIVES:: Most patients complaining of dizziness seek medical services in the interictal period, which is thought to be a compensated stage. Thus, we wanted to investigate the results of vestibular function tests (VFTs) at a compensated stage in patients with vestibular neuritis to determine the presence and the sides of vestibular hypofunction. STUDY DESIGN:: Retrospective case series review. METHODS:: We analyze the results of VFT including spontaneous nystagmus (SN), caloric, vibration-induced nystagmus (VIN), head-shaking nystagmus (HSN), and subjective visual vertical (SVV) tests in 38 patients (M/F = 23:15; age range, 15-85 yr) with vestibular neuritis observed at around 2 months after the onset of vertigo. RESULTS:: Thirty-seven (97%) of 39 patients showed pathologic results in at least 1 test. Pathologic results, based on caloric, SN, VIN, HSN, and SVV tests, were observed in 29 (76%), 20 (53%), 24 (63%), 33 (87%), and 15 patients (39%). Twenty-nine showed pathologic canal paresis (CP) on the affected side and 9 patients (24%) showed normal CP. There was no patient with pathologic CP on the intact side. In 29 patients with pathologic CP, pathologic results, based on SN, VIN, HSN, and SVV tests, were observed in 16 (55%), 20 (69%), 26 (90%), and 13 patients (45%). Three (10%) of 29 patients showed pathologic VIN or HSN, indicating that the intact side is pathologic. In 9 patients with normal CP, pathologic results, based on SN, VIN, HSN, and SVV tests, were observed in 4 (44%), 4, 7 (78%), and 2 patients (22%). Five (56%) of 9 patients showed pathologic results on the intact side at least in 1 test, and the pathologic sides by each test were not the same. CONCLUSION:: Our findings suggest that we can detect vestibular imbalance in patients with unilateral vestibular hypofunction through a set of VFTs even when CP is normal at a compensated stage. The CP side indicated by caloric test was the real affected side when CP was pathologic, even if the results of other tests were normal or rarely indicated that the intact side was pathologic. If CP was within reference range, other tests can show the previous presence of vestibular imbalance; however, they could not predict the side of the vestibular hypofunction. These data provide strong support for enrolling a set of VFT when evaluating a dizzy patient.

Can Magnetic Resonance Imaging Provide Clues to the Inner Ear Functional Status of Enlarged Vestibular Aqueduct Subjects With PDS Mutation?

Oh, Seung-Ha,Choi, Byung Yoon,Son, Kyu Ri,Lee, Kang Jin,Chang, Sun O.,Kim, Chong-Sun Otology Neurotology, Inc. 2008 Otology & neurotology Vol.29 No.5

OBJECTIVES:: The goal of this study was to characterize the signal intensity (SI) pattern in the endolymphatic duct/sac from T2-weighted spin echo magnetic resonance (MR) images and T2*-weighted 3-dimensional (3-D) constructive interference in steady state (CISS) MR images that were obtained from a homogenous group of patients with an enlarged vestibular aqueduct (EVA) associated with SLC264 (PDS) mutations. STUDY DESIGN:: A retrospective study. SETTING:: Tertiary referral center. PATIENTS:: Eleven subjects (22 ears), with at least 1 SLC26A4 mutation and bilateral EVA confirmed by temporal bone computed tomography, were enrolled. INTERVENTION:: The MR images of 22 ears were reviewed retrospectively. MAIN OUTCOME MEASURES:: The SI of the endolymphatic sac (ES) from 2 sequences were compared and reviewed. The presence of anomalies of the vestibule were also evaluated. In addition, the caloric test results were also reviewed to characterize the vestibular function in a subset of our cohort (12 ears). RESULTS:: T2*-weighted 3-D CISS MR images revealed a more variable SI in the enlarged endolymphatic system than did the T2-weighted images. There was a hierarchy for the order of SI loss from the endolymphatic system on the T2*-weighted 3-D CISS MR images. There were 3 cases where the SI loss from the intraosseous ES, on the T2*-weighted 3-D CISS images, was associated with an abnormal caloric response. CONCLUSION:: The SI of the ES observed on T2*-weighted 3-D CISS images of EVA patients, with SLC26A4 mutations, showed a distinctive pattern, and the results from this study suggest a potential role for the MR imaging in providing physicians with better information about the functional status of the inner ear.

Jugular Foramen Schwannoma: Analysis on Its Origin and Location

Song, Mee Hyun,Lee, Hye Yeon,Jeon, Je Sool,Lee, Jong Dae,Lee, Ho-Ki,Lee, Won-Sang Otology Neurotology, Inc. 2008 Otology & neurotology Vol.29 No.3

OBJECTIVE:: To examine the microsurgical anatomy of the jugular foramen and correlate anatomical findings to clinical manifestations of jugular foramen schwannomas concerning tumor origin and location. STUDY DESIGN:: Anatomical analysis of jugular foramen was performed by dissection of 25 cadavers (50 sides). By retrospective review of 9 cases of jugular foramen schwannomas surgically treated, the origin and location of tumor were studied. SETTING:: Tertiary referral center. MAIN OUTCOME MEASURES:: The anatomical characteristics of jugular foramen, lower cranial nerves, and inferior petrosal sinus were correlated with the origin and growth pattern of jugular foramen schwannomas. RESULTS:: The superior and inferior ganglions of the glossopharyngeal nerve and the superior ganglion of the vagus nerve were located within the jugular foramen. The superior ganglions of the glossopharyngeal and vagus nerves were located superiorly, whereas the inferior ganglion of the glossopharyngeal nerve was found inferiorly in relation to the inferior petrosal sinus orifice. In our series of 9 cases of jugular foramen schwannoma, the most common nerve of origin was the vagus nerve, followed by the glossopharyngeal nerve. CONCLUSION:: The reason for the predilection of the jugular foramen schwannoma for the glossopharyngeal and vagus nerves may be associated with the presence of their ganglions within the jugular foramen. Also, the inferior petrosal sinus may act as a barrier to tumor growth, and the location of the ganglion of tumor origination within the jugular foramen in relation to the inferior petrosal sinus may be correlated to the predominant direction of tumor extension.

Auditory and Speech Performance in Deaf Children With Deaf Parents After Cochlear Implant

Park, Ga Young,Moon, Il Joon,Kim, Eun Yeon,Chung, Eun-wook,Cho, Yang-Sun,Chung, Won-Ho,Hong, Sung Hwa Otology Neurotology, Inc. 2013 Otology & neurotology Vol.34 No.2

OBJECTIVE: To evaluate the auditory and speech outcome in deaf children with deaf parents (CDP) after cochlear implantation (CI), emphasizing both the presence of additional caregiver and patients’ main communication mode. STUDY DESIGN: Retrospective case review. SETTING: Cochlear implant center at a tertiary referral hospital. PATIENTS: Fourteen CDP and 14 age- and sex-matched deaf children with normal-hearing parents (CNH). MAIN OUTCOME MEASURE(S): The Korean version of Ling’s stage (K-Ling) and Category of Auditory Perception (CAP) were administered to the children to assess the speech production and auditory perception abilities, preoperatively and 3, 6, 12, and 24 months after CI. To elucidate the effects of the additional caregiver and main communication mode of the implanted child, the patients were divided into the following groups: with additional caregiver(s) who have normal hearing (n = 11) versus without additional caregiver (n = 3); sign language plus oral communication (S+O) group (n = 9) versus oral communication only (O) group (n = 5). RESULTS: CAP scores and K-Ling stages improved remarkably in both CDP and CNH, and no significant differences were found between the 2 groups. Within the CDP group, CAP scores and K-Ling stages improved significantly in CDP with an additional caregiver than those without. Auditory perception and speech production performances in the S+O group were similar to those in the O group. CONCLUSION: CDP can develop similarly to CNH in auditory perception and speech production, if an additional caregiver with normal hearing provides sufficient support and speech input. In addition, using sign language in addition to oral language might not be harmful, and these children can be a communication bridge between their deaf parents and society.

Subjective Visual Vertical During Eccentric Rotation in Patients With Benign Paroxysmal Positional Vertigo

Hong, Seok Min,Park, Moon Suh,Cha, Chang Il,Park, Chan Hum,Lee, Jun Ho Otology Neurotology, Inc. 2008 Otology & Neurotology Vol.29 No.8

OBJECTIVE:: There have been only a few reports of subjective visual vertical (SVV) in patients with benign paroxysmal positional vertigo (BPPV), and each showed slightly different results. SVV measurement during eccentric rotation that stimulated only 1 labyrinth was known to show a considerable improvement in comparison with conventional SVV as a clinical measure of otolith function. But there has not been a report regarding SVV during eccentric rotation in patients with BPPV. We therefore measured SVV during eccentric rotation and investigated the function of utricles in patients with BPPV. STUDY DESIGN:: Retrospective study. SETTING:: Tertiary referral center. PATIENTS:: Twenty-three patients with BPPV. INTERVENTION:: Diagnostic procedure. MAIN OUTCOME MEASURES:: SVV was measured in 23 patients with BPPV and 20 normal subjects. We compared the SVV values before and during eccentric rotation toward the right and left in both patients with BPPV and the control group. RESULTS:: Between BPPV patients and the control group, no difference in the SVV value was observed in pre-eccentric rotation, but significant differences of SVV values were found during eccentric rotation. CONCLUSION:: We identified utricular dysfunction in patients with BPPV during eccentric rotation and suggested that eccentric rotation might be a good method to measure utricular dysfunction.