Deterioration in Distortion Product Otoacoustic Emissions in Auditory Neuropathy Patients With Distinct Clinical and Genetic Backgrounds.

OBJECTIVES: Auditory neuropathy (AN) is a clinical disorder characterized by the absence of auditory brainstem response and presence of otoacoustic emissions. A gradual loss of otoacoustic emissions has been reported for some cases of AN. Such cases could be diagnosed as cochlear hearing loss and lead to misunderstanding of the pathology when patients first visit clinics after the loss of otoacoustic emissions. The purpose of this study was to investigate the time course of changes in distortion product otoacoustic emissions (DPOAEs) in association with patients' genetic and clinical backgrounds, including the use of hearing aids. DESIGN: DPOAE measurements from 31 patients with AN were assessed. Genetic analyses for GJB2, OTOF, and mitochondrial m.1555A> G and m.3243A> G mutations were conducted for all cases, and the analyses for CDH23 and OPA1 were conducted for the selected cases. Patients who were younger than 10 years of age at the time of AN diagnosis were designated as the pediatric AN group (22 cases), and those who were 18 years of age or older were designated as the adult AN group (9 cases). DPOAE was measured at least twice in all patients. The response rate for DPOAEs was defined and analyzed. RESULTS: The pediatric AN group comprised 10 patients with OTOF mutations, 1 with GJB2 mutations, 1 with OPA1 mutation, and 10 with indefinite causes. Twelve ears (27%) showed no change in DPOAE, 20 ears (46%) showed a decrease in DPOAE, and 12 ears (27%) lost DPOAE. Loss of DPOAE occurred in one ear (2%) at 0 years of age and four ears (9%) at 1 year of age. The time courses of DPOAEs in patients with OTOF mutations were divided into those with early loss and those with no change, indicating that the mechanism for deterioration of DPOAEs includes not only the OTOF mutations but also other common modifier factors. Most, but not all, AN patients who used hearing aids showed deterioration of DPOAEs after the start of using hearing aids. A few AN patients also showed deterioration of DPOAEs before using hearing aids. The adult AN group comprised 2 patients with OPA1 mutations, 2 with OTOF mutations, and 5 with indefinite causes. Four ears (22%) showed no change in DPOAE, 13 ears (72%) showed a decrease, and one ear (6%) showed a loss of DPOAE. Although the ratio of DPOAE decrease was higher in the adult AN group than in the pediatric AN group, the ratio of DPOAE loss was lower in the adult AN group. DPOAE was not lost in all four ears with OPA1 mutations and in all four ears with OTOF mutations in the adult group. CONCLUSIONS: DPOAE was decreased or lost in approximately 70% of pediatric and about 80% of adult AN patients. Eleven percent of pediatric AN patients lost DPOAEs by 1 year of age. Genetic factors were thought to have influenced the time course of DPOAEs in the pediatric AN group. In most adult AN patients, DPOAE was rarely lost regardless of the genetic cause.

Simultaneous Presentation of Definite Vestibular Migraine and Definite Ménière's Disease: Overlapping Syndrome of Two Diseases.

Objectives: To review the clinical records of patients that exhibited the clinical features of both vestibular migraine (VM) and Ménière's disease (MD) during each episodic vertigo attack and to discuss the possible pathophysiology of such combination of symptoms. Subjects: Ten patients that were selected according to criteria based on a combination of the diagnostic criteria for definite MD and VM (9 females and one male, age: 22-54 years) were enrolled. They were required to show features of both diseases in each vertigo attack. Methods: The patients' medical histories and pure-tone audiometry, cervical vestibular evoked myogenic potential (cVEMP), video head-impulse test (vHIT), and caloric test results were examined. cVEMP was recorded using 500 and 1,000 Hz short tone bursts (125dBSPL, air-conducted), 500 Hz-1,000 Hz cVEMP slope, an index of endolymphatic hydrops in the saccule was calculated using normalized amplitudes of p13-n23. For performing vHIT, each subject was seated 1.5 m in front of a target and asked to keep watching it as their head was passively rotated by the examiner. Their eye movements were evaluated using video-oculography while their head movements were recorded using inertial sensors. Results: The patients were predominantly female. On average, the onset of migrainous headaches occurred 9 years earlier than the onset of vertigo attacks. All of the patients but one had migraines with auras. Five of the 10 patients had a family history of vertigo attacks accompanied by both migrainous and auditory symptoms. The patients mainly displayed hearing loss at low frequencies. Nine patients exhibited 500-1,000 Hz cVEMP slope < -19.9, which was suggestive of endolymphatic hydrops. None of the patients who underwent vHIT showed abnormal canal function. One patient showed unilaterally decreased caloric responses. Conclusions: These patients presented with simultaneous MD and VM signs/symptoms might be referred to "VM/MD overlapping syndrome (VM/MD-OS)" as a new clinical syndrome.

Recovery of endocochlear potential after severe damage to lateral wall fibrocytes following acute cochlear energy failure.

Reduction of endocochlear potential (EP) is one of the main causes of sensorineural hearing loss. In this study, we investigated changes in the EP using a mouse model of acute cochlear energy failure, which comprised severe cochlear lateral wall damage induced by the local administration of 3-nitropropionic acid to the inner ear. We also analyzed the correlation between EP changes and histological findings in the cochlear lateral wall. We detected the recovery of the EP and hearing function at lower frequencies after severe damage of the cochlear lateral wall fibrocytes at the corresponding region. Remodeling of the cochlear lateral wall was associated with EP recovery, including the re-expression of ion transporters or gap junctions (i.e. Na/K/ATPase-ß1 and connexin 26). These results indicate a mechanism for late-phase hearing recovery after severe deafness, which is frequently observed in clinical settings.

[Clinical analysis of malignant submandibular tumor].

The 14 cases of malignant submandibular tumor whose treatment outcome we analyzed between 1989 and 2008 included 5 of adenoid cystic carcinoma, 3 of squamous cell carcinoma, 2 each of mucoepidermoid carcinoma, and carcinoma ex pleomorphic adenoma, and 1 each of carcinosarcoma and large-cell carcinoma. One subject was diagnosed with T1, 7 with T2, 4 with T3, and 2 with T4. Lymph node involvement occurred in 5, -1 with N1 and 4 with N2. None had distant metastasis on the first visit. Seven were treated by surgery alone, 3 by surgery followed by radiotherapy, 2 by surgery followed by radio-and chemotherapy, and 1 by optimized supportive care. The surgical resection area was decided by tumor extension. Neck dissection was done in 9. Overall 5-year survival for all cases based on the Kaplan-Meier method was 57%. All with carcinoma ex pleomorphic adenoma, carcinosarcoma, or large-cell carcinoma remain alive. For those with adenoid cystic carcinoma 5-year survival is 80%, with mucoepidermoid carcinoma 50%, with squamous cell carcinoma 0%, and with carcinosarcoma 0%, respectively. The 5-year survival for stage I subjects was 100%, for stage II 83%, for stage III 50%, and for stage IV 0%. Surgical resection and postoperative radiotherapy were done in cases of minimal extraglandular extension or microscopically positive margins, with satisfactory results. Treatment efficacy for high-grade and advanced stage, however, requires more improvement.