Hisashi Tokano

Six1 controls patterning of the mouse otic vesicle

Six1 is a member of the Six family homeobox genes, which function as components of the Pax-Six-Eya-Dach gene network to control organ development. Six1 is expressed in otic vesicles, nasal epithelia, branchial arches/pouches, nephrogenic cords, somites and a limited set of ganglia. In this study, we established Six1-deficient mice and found that development of the inner ear, nose, thymus, kidney and skeletal muscle was severely affected. Six1-deficient embryos were devoid of inner ear structures, including cochlea and vestibule, while their endolymphatic sac was enlarged. The inner ear anomaly began at around E10.5 and Six1 was expressed in the ventral region of the otic vesicle in the wild-type embryos at this stage. In the otic vesicle of Six1-deficient embryos, expressions of Otx1, Otx2, Lfng and Fgf3, which were expressed ventrally in the wild-type otic vesicles, were abolished, while the expression domains of Dlx5, Hmx3, Dach1 and Dach2, which were expressed dorsally in the wild-type otic vesicles, expanded ventrally. Our results indicate that Six1 functions as a key regulator of otic vesicle patterning at early embryogenesis and controls the expression domains of downstream otic genes responsible for respective inner ear structures. In addition, cell proliferation was reduced and apoptotic cell death was enhanced in the ventral region of the otic vesicle, suggesting the involvement of Six1 in cell proliferation and survival. In spite of the similarity of otic phenotypes of Six1- and Shh-deficient mice, expressions of Six1 and Shh were mutually independent.

Vlgr1 is required for proper stereocilia maturation of cochlear hair cells.

Very large G‐protein coupled receptor (Vlgr1b) is the largest known G‐protein coupled receptor. Its function is unknown, although mice with deletion of Vlgr1 (Vlgr1b together with other splicing variants, Vlgr1c, Vlgr1d and Vlgr1e) are known to exhibit audiogenic seizure susceptibility and VLGR1 is reported to be the gene responsible for Usher type 2C syndrome. We demonstrated here that Vlgr1‐mutated mice suffered from a hearing defect because of inner ear dysfunction, as indicated by auditory brainstem response (ABR) and distortion product oto‐acoustic emissions (DPOAE). The expression of Vlgr1 was identified in the developing hair cells perinatally, and the translated products were seen to be localized in the base of stereocilia on hair cells using confocal microscopy. This Vlgr1 localization was limited to the base of stereocilia within approximately 200–400 nm from the apical surface of hair cells, as shown by immunoelectron microscopy. The Vlgr1‐mutated mice exhibited malformation of the stereocilia; the cochlear hair bundles were apparently normal at birth but then became disarranged at postnatal day 8. Furthermore, the stereocilia in the mutant mice became slanted and disarranged thereafter. These results indicate that loss of Vlgr1 resulted in abnormal development of stereocilia formation.

Comparison of acute low-tone sensorineural hearing loss versus meniere's disease by electrocochleography

To clarify the pathogenesis of acute low-tone sensorineural hearing loss (ALHL), we retrospectively compared the electrocochleographic findings from 20 patients with ALHL with those from 58 patients with Menieres disease (MD) classified into 4 groups (MD1 through MD4) according to their pure tone average. The mean summating potential-action potential ratio in the ALHL group was 0.35 ± 0.13, which was significantly higher than the control ratio but similar to the ratio seen in the MD1 group (pure tone average < 25 dB hearing level). The mean detection threshold of the cochlear microphonics in the ALHL group was 32.0 ± 9.4 dB normal hearing level, which was again similar to that seen in the MD1 group. Moreover, more than 50% of patients with ALHL had normal cochlear microphonics input-output curves. We therefore conclude that the pathogenesis of ALHL arises from an endolymphatic hydrops with little or no impairment of hair cells that resembles early-stage MD.

Postoperative Vestibular-evoked Myogenic Potentials in Cases with Vestibular Schwannomas

Although still the subject of discussion, vestibular-evoked myogenic potentials (VEMPs) have been considered to reflect the function of the saccular and, more recently, the cochlear tracts. To accurately determine the precise afferent pathway carrying VEMPs, we studied the outcomes of VEMPs and other examinations in patients with unilateral vestibular schwannomas. Eleven patients with unilateral vestibular schwannomas resected using a middle cranial fossa approach were included in the study. Patients underwent pure-tone threshold audiometry, caloric tests and analysis of auditory brainstem responses (ABRs) and VEMPs pre- and postoperatively. The results were compared with those obtained in patients with intact superior or inferior vestibular and cochlear nerves. Among the 11 patients studied, 4 retained their VEMPs postoperatively. Three of the 10 patients with inferior vestibular schwannomas exhibited normal VEMPs, preserved hearing levels (20 dB HL) and anatomically intact superior vestibular nerves. In all of these cases, ABRs more closely correlated with VEMPs than with caloric responses. In one of the cases with inferior vestibular schwannomas, VEMPs were preserved postoperatively and VEMP latencies were shortened, which indicates the preoperative presence of a conduction block in either the cochlear or superior vestibular nerve. VEMPs may be conducted in both the superior vestibular and cochlear nerves, as well as in the inferior vestibular nerve. Thus, evaluation of saccular nerve function should be performed carefully, especially in cases where hearing is preserved. It appears that cochlear conduction may proceed along two pathways, one direct and the other via the brainstem, but this remains to be verified.

Meningioma of the internal auditory canal with extension into the vestibule

Meningiomas account for approximately 18 to 19 per cent of all brain tumours. Although they can arise in numerous locations, meningiomas of the internal auditory canal (IAC) are rare. Most tumours that originate in the IAC are schwannomas of the VIIIth cranial nerve (acoustic neuromas). We report a case of a meningioma which appears to originate from the IAC and extends into the vestibule. The clinical findings and the radiographical features of meningiomas of the IAC are similar to those of acoustic neuromas. Pre-operative differentiation between acoustic neuromas and meningiomas of the IAC may be difficult.

Solitary infantile myofibromatosis in the lateral orbit floor showing spontaneous regression.

Infantile myofibromatosis is a rare benign tumour usually occurring early in infancy. We describe the case of a 10-year-old boy with solitary infantile myofibromatosis in the left lateral orbit floor which regressed spontaneously. Although our patient was older than previously reported cases and showed bony destruction confirmed by computed tomography (CT), this tumour was diagnosed as infantile myofibromatosis based on immunohistochemical findings. The tumour disappeared spontaneously six months after incisional biopsy, that also indicated this tumour was an infantile myofibromatosis.

Three-dimensional imaging of ENT diseases with helical computed tomography

We have employed helical computed tomography (CT) to evaluate ear, nose and throat diseases, and present herein seven typical cases: middle ear surgery, osteoma of the external ear canal, maxillary fracture, tripod fracture, submandibular gland calculus, epiglottic abscess and vocal fold palsy. Helical (CT) facilitates the assessment of these diseases and its high diagnostic value is described.

A Case of Descending Necrotizing Mediastinitis Penetrating to the Esophagus

Here, we present the case of a 78-year-old man with a deep neck infection that caused descending necrotizing mediastinitis that extended from the pharynx to the stomach and was accompanied by two large esophageal fistulas and multiple gastric ulcers. We believe that the series of lesions were the signs of a hidden carcinoma.