Investigation of the ototoxicity of gadoteridol (ProHance) and gadodiamide (Omniscan) in mice.

CONCLUSION: In the mouse, when a tympanic perforation is present, gadoteridol does not seem to cause ototoxicity. Gadodiamide may cause mild ototoxicity other than toxicity to the outer hair cells of the cochlea. OBJECTIVES: Endolymphatic hydrops have been visualized through intra-tympanic injection of gadolinium-based contrast agents (GBCAs) and three-dimensional fluid-attenuated inversion recovery (3-D FLAIR) magnetic resonance imaging. However, reports on the safety of GBCAs are limited. This study aimed to assess ototoxicity of gadoteridol and gadodiamide. METHOD: In a prospective, randomized, controlled trial, myringotomies in the left ear were performed in 20 male C57 BL/6 mice. After testing the baseline auditory brainstem response (ABR) (range = 8-32 kHz), the test solution (gadoteridol, gadodiamide, saline, or cisplatin) was injected into the left ear. ABR testing was repeated 14 days after test solution application. In morphological experiments, images of post-mortem surface preparations were assessed for cochlear hair cell status. RESULTS: At 14 days following gadoteridol application, there was no significant change in ABR thresholds at 8, 16, or 32 kHz. Gadodiamide application caused a significant change in the ABR threshold at 8 kHz. Apparent cochlear hair cell loss was not observed in the surface preparation after gadoteridol or gadodiamide application.

Interaural Difference of Wave V Predicting Postoperative Hearing in Gardner-Robertson Class II Acoustic Neuroma Patients.

Patients with acoustic neuroma classified in Gardner and Robertson (GR) Class II should be considered to have useful hearing, and patients classified in Class III should be considered to have not-useful hearing. Therefore, it is important for acoustic neuroma surgery to distinguish between postoperative GR Class II and Class III patients by brainstem auditory evoked potentials (BAEPs). We evaluate which BAEP parameter is the best for predicting postoperative GR Class II or III in 36 preoperative GR Class II patients with unilateral acoustic neuroma. Delay in wave V latency, reduction ratio in wave V amplitude, and interaural difference of wave V (IT5) are evaluated by a receiver-operating characteristic (ROC) curve in this study. IT5 is the best distinguishing parameter between postoperative Class II and Class III. IT5 below 1.12 millisecond (msec) should be a good marker to preserve postoperative useful hearing. Thus, comparing the latency of wave V on both sides is important, and surgeons would be able to make more informed decisions during surgery by checking IT5 on BAEPs.

Modified transnasal endoscopic medial maxillectomy with medial shift of preserved inferior turbinate and nasolacrimal duct.

Although transnasal endoscopic medial maxillectomy (TEMM) is effective for the treatment of inverted papilloma (IP) in maxillary sinus (MS), it involves resection of the inferior turbinate (IT). TEMM also involves resection of the nasolacrimal duct (ND) in many cases to gain better access. Therefore, we developed a novel procedure in which the preserved IT and ND are shifted medially for a complete resection of IP in the MS. Incision was made in the mucosa of the lateral wall along the anterior margin of the IT. After removal of the medial maxillary wall except the ND and the lateral nasal mucosa, the anterior lateral mucosa of the nose, including the IT and the ND, was shifted in the medial direction to allow wider access to the MS. The tumor was removed together with the attachment through the anterior side of the ND. This modified TEMM was performed in 10 patients with IP. The IT and ND were preserved in all patients. We have not observed epiphora after this surgery. The advantages of the novel approach presented herein include: 1) preservation of the IT, ND, and lateral nasal mucosa; 2) wide access to the MS by shifting the IT, ND, and lateral nasal mucosa in the medial direction; and 3) direct access to the MS through anterior space of the ND, resulting in easier operation with a straight endoscope and instruments. This approach is a safe and effective method to obtain wide and straight access to the MS and to resect IP in the MS.

Impaired quality of sleep in Ménière's disease patients.

OBJECTIVE: To evaluate the quality of sleep in Ménière's disease patients with the use of polysomnography. STUDY DESIGN: Prospective study using polysomnography administered in patients diagnosed as "Definite Meniere's disease cases" according to the guidelines of the American Academy of Otolaryngology-Head and Neck Surgery. METHODS: Thirty-five patients, 17 male and 18 female, aged 31 to 71 (58 average) years with active, unilateral, cochleovestibular Ménière's disease refractory to medical management underwent polysomnography. The results were compared with 35 healthy controls matched for age and sex. All participants underwent full-night polysomnography, and a sleep medicine physician interpreted the results. RESULTS: Total sleeping time in Ménière's disease was significantly higher than in controls. Stage 2 sleep was significantly longer and stage 3+4 shorter in Ménière's disease than controls, while there was no difference of stage 1 and REM. Arousal index was significantly higher in Ménière's disease than in controls. Five cases of severe OSAS were found in Ménière's disease and 4 cases in controls; 4 cases of PLMD were found in patients and 3 in controls. CONCLUSIONS: Our finding of decreased deep sleep and an elevated arousal index is a striking new finding in Ménière's disease. This poor quality of sleep in Ménière's disease patients has received little attention in the past, but may cause additional stress and lead to a negative spiral of symptoms.

The role of bone morphogenetic protein 4 in inner ear development and function.

Bone Morphogenetic Protein 4 (BMP4) is a member of the TGF-beta superfamily and is known to be important for the normal development of many tissues and organs, including the inner ear. Bmp4 homozygous null mice die as embryos, but Bmp4 heterozygous null (Bmp4(+/-)) mice are viable and some adults exhibit a circling phenotype, suggestive of an inner ear defect. To understand the role of BMP4 in inner ear development and function, we have begun to study C57BL/6 Bmp4(+/-) mice. Quantitative testing of the vestibulo-collic reflex, which helps maintain head stability, demonstrated that Bmp4(+/-) mice that exhibit circling behavior have a poor response in the yaw axis, consistent with semicircular canal dysfunction. Although the hair cells of the ampullae were grossly normal, the stereocilia were greatly reduced in number. Auditory brainstem responses showed that Bmp4(+/-) mice have elevated hearing thresholds and immunohistochemical staining demonstrated decreased numbers of neuronal processes in the organ of Corti. Thus Bmp4(+/-) mice have structural and functional deficits in the inner ear.

Vestibulo-collic reflex (VCR) in mice.

The vestibulo-collic reflex (VCR) attempts to stabilize head position in space during motion of the body. Similar to the better-studied vestibulo-ocular reflex, the VCR is subserved by relatively direct, as well as indirect pathways linking vestibular nerve activity to cervical motor neurons. We measured the VCR using an electromagnetic technique often employed to measure eye movements; we attached a loop of wire (head coil) to an animal's head using an adhesive; then the animal was gently restrained with its head free to move within an electromagnetic field, and was subjected to sinusoidal (0.5-3 Hz) or abrupt angular acceleration (peak velocity approximately 200 degrees/s). Head rotation opposite in direction to body rotation was assumed to be driven by the VCR. To confirm that the compensatory head movements were in fact vestibular in origin, we plugged the horizontal canal unilaterally and then retested the animals 2, 8 and 15 days after the lesion. Two days after surgery, the putative VCR was almost absent in response to abrupt or sinusoidal rotations. Recovery commenced by day 8 and was nearly complete by day 15. We conclude that the compensatory head movements are vestibular in origin produced by the VCR. Similar to other species, there are robust compensatory mechanisms that restore the VCR following peripheral lesions.

Direct inner ear infusion of dexamethasone attenuates noise-induced trauma in guinea pig.

The protective effect of dexamethasone (DEX) against noise-induced trauma, as reflected in hair cell destruction and elevation in auditory brainstem response (ABR) sensitivity, was assessed in guinea pigs. The animals were administered DEX (1, 10, 100, and 1000 ng/ml) or artificial perilymph (AP) via a mini-osmotic pump directly into scala tympani and, on the fourth day after pump implantation, exposed to 120 dB SPL octave band noise, centered at 4 kHz, for 24 h. Animals receiving DEX demonstrated a dose-dependent reduction in noise-induced outer hair cell loss (significant at 1, 10 and 100 ng/ml DEX animals compared to AP control animals) and a similar attenuation of the noise-induced ABR threshold shifts, observed 7 days following exposure (significant at 100 ng/ml DEX animals compared to AP control animals). These physiological and morphological results indicate that direct infusion of DEX into the perilymphatic space has protective effects against noise-induced trauma in the guinea pig cochlea.

Intra-cochlear administration of dexamethasone attenuates aminoglycoside ototoxicity in the guinea pig.

This study demonstrates the attenuation of aminoglycoside ototoxicity by cochlear infusion of dexamethasone (Dex) using a microcannulation-osmotic pump delivery system. The results indicate that treating the cochlea with Dex both before and after kanamycin administration was more effective in preventing ototoxicity than Dex treatment only after kanamycin administration. A concentration of 1 ng/ml Dex showed the greatest protective effect on both kanamycin-induced threshold shift of the auditory brainstem response and outer hair cell survival. These results show that the Dex treatment attenuates both functional and structural damage of the inner ear from aminoglycoside toxicity.