Investigation of inner ear drug delivery with a cochlear catheter in piglets as a representative model for human cochlear pharmacokinetics.

Hearing impairment is the most common sensory disorder in humans, and yet hardly any medications are licensed for the treatment of inner ear pathologies. Intricate pharmacokinetic examinations to better understand drug distribution within this complex organ could facilitate the development of novel therapeutics. For such translational research projects, animal models are indispensable, but differences in inner ear dimensions and other anatomical features complicate the transfer of experimental results to the clinic. The gap between rodents and humans may be bridged using larger animal models such as non-human primates. However, their use is challenging and impeded by administrative, regulatory, and financial hurdles. Other large animal models with more human-like inner ear dimensions are scarce. In this study, we analyzed the inner ears of piglets as a potential representative model for the human inner ear and established a surgical approach for intracochlear drug application and subsequent apical sampling. Further, controlled intracochlear delivery of fluorescein isothiocyanate-dextran (FITC-d) was carried out after the insertion of a novel, clinically applicable CE-marked cochlear catheter through the round window membrane. Two, six, and 24 hours after a single injection with this device, the intracochlear FITC-d distribution was determined in sequential perilymph samples. The fluorometrically assessed concentrations two hours after injection were compared to the FITC-d content in control groups, which either had been injected with a simple needle puncture through the round window membrane or the cochlear catheter in combination with a stapes vent hole. Our findings demonstrate not only significantly increased apical FITC-d concentrations when using the cochlear catheter but also higher total concentrations in all perilymph samples. Additionally, the concentration decreased after six and 24 hours and showed a more homogenous distribution compared to shorter observation times.

Microvascular decompression for tinnitus: systematic review.

OBJECTIVE The objective of this study was to examine operative outcomes in cases of microvascular decompression (MVD) of cranial nerve (CN) VIII for tinnitus through a critical review of the literature. METHODS Forty-three English-language articles were gathered from PubMed and analyzed. In this review, two different case types were distinguished: 1) tinnitus-only symptomatology, which was defined as a patient with tinnitus with or without sensorineural hearing loss; and 2) mixed symptomatology, which was defined as tinnitus with symptoms of other CN dysfunction. This review reports outcomes of those with tinnitus-only symptoms. RESULTS Forty-three tinnitus-only cases were found in the literature with a 60% positive outcome rate following MVD. Analysis revealed a 5-year cutoff of preoperative symptom duration before which a good outcome can be predicted with 78.6% sensitivity, and after which a poor outcome can be predicted with 80% specificity. CONCLUSIONS As the 60% success rate is more promising than several other therapeutic options open to the chronic tinnitus sufferer, future research into this field is warranted.

Reduction in high-frequency hearing loss following technical modifications to microvascular decompression for hemifacial spasm.

OBJECT: Microvascular decompression is a safe and effective procedure to treat hemifacial spasm, but the operation poses some risk to the patient's hearing. While severe sensorineural hearing loss across all frequencies occurs at a low rate in experienced hands, a recent study suggests that as many as one-half of patients who undergo this procedure may experience ipsilateral high-frequency hearing loss (HFHL), and as many as one-quarter may experience contralateral HFHL. While it has been suggested that drill-related noise may account for this finding, this study was designed to examine the effect of a number of techniques designed to protect the vestibulocochlear nerve from operative manipulation on the incidence of HFHL. METHODS: Pure-tone audiometry was performed both preoperatively and postoperatively on 67 patients who underwent microvascular decompression for hemifacial spasm during the study period. A change of greater than 10 dB at either 4 kHz or 8 kHz was considered to be HFHL. Additionally, the authors analyzed intraoperative brainstem auditory evoked potentials from this patient cohort. RESULTS: The incidence of ipsilateral HFHL in this cohort was 7.4%, while the incidence of contralateral HFHL was 4.5%. One patient (1.5%; also included in the HFHL group) experienced an ipsilateral nonserviceable hearing loss. CONCLUSIONS: The reduced incidence of HFHL in this study suggests that technical modifications including performing the procedure without the use of fixed retraction may greatly reduce, but not eliminate, the occurrence of HFHL following microvascular decompression for hemifacial spasm.