Philip Bird

Intratympanic Versus Intravenous Delivery of Methylprednisolone to Cochlear Perilymph

Objective: To compare methylprednisolone concentrations in the perilymph of the human ear and in plasma after intratympanic (IT) or intravenous (IV) administration. Methods: Methylprednisolone concentrations in the perilymph of patients during cochlear implantation were compared after 3 dosing strategies of methylprednisolone solution for injection (40 mg/ml): 1) IT administration of up to 40 mg was injected into the middle ear through the external auditory canal via a 27-gauge needle passed through a small anterosuperior myringotomy; 2) IV administration of 1 mg/kg was given as a single injection over 30 seconds; 3) IV administration of 10 mg/kg was infused over 30 minutes. Perilymph (single sample, ~20 μL) was sampled using a needle passed through the round window membrane, from 0.5 to 3 hours after dosing. In most patients, simultaneous blood sampling was performed. Methylprednisolone concentrations were measured by high-performance liquid chromatography with a limit of quantification of 0.001 mg/L. Results: In 39 patients studied, 33 perilymph samples were suitable for measurement, along with 26 plasma samples. Median perilymph concentrations were 6.7 mg/L (n = 18; range, 0.2-89.4 mg/L) after IT administration, 0.053 mg/L (n = 8; range, 0-0.47 mg/L) after IV injection of 1 mg/kg, and 0.2 mg/L (n = 7; range, 0.067-3.1 mg/L) after IV infusion of 10 mg/kg. The median perilymph concentrations were 126-fold higher after the IT administration than after 1 mg/kg IV (p = 0.0003) and 33-fold higher than after 10 mg/kg IV infusion (p = 0.0045). Plasma concentrations after IT administration were 16-fold lower than after IV administration of 1 mg/kg (p = 0.0006), and 136-fold lower than after IV infusion of 10 mg/kg (p = 0.0006). Conclusion: IT administration of methylprednisolone in humans results in much higher perilymph concentrations and much lower systemic concentrations than IV administration.

Intratympanic Versus Intravenous Delivery of Dexamethasone and Dexamethasone Sodium Phosphate to Cochlear Perilymph

Objective: To measure dexamethasone concentrations in the plasma and perilymph of the human ear after intravenous (IV) and intratympanic (IT) administration and to compare these with previous studies with methylprednisolone. Methods: Patients were administered dexamethasone by the IT or IV routes approximately 0.5 to 2 hours before cochlear implantation. The IT dose of 1.6 to 7.2 mg (0.4-1.8 ml of a 4 mg/ml solution) of dexamethasone sodium phosphate was administered by injection into the middle ear cavity through the external auditory canal via a 27-gauge needle passed through a small anterosuperior myringotomy. The IV dose of dexamethasone sodium phosphate was 0.17 mg/kg given as a single injection for 30 seconds. A sample of perilymph (approximately 20 &mgr;l) was collected using a needle passed through the round window, and blood was sampled simultaneously. Concentrations of free dexamethasone and dexamethasone sodium phosphate were measured using a validated liquid chromatography-tandem mass spectrometry method. Results: In the 22 patients studied, 22 perilymph samples and 19 plasma samples were available and suitable for measurement. The median perilymph concentration of dexamethasone after IV injection of 0.17 mg/kg was 0.016 mg/L (n = 9; range, 0.008-0.17), and 1.4 mg/L (n = 13; range, 0.1-16.3) after IT administration of approximately 4 mg. Perilymph concentrations were approximately 88-fold higher after IT compared with IV administration (p = 0.0004) or approximately 260 fold after correction for dosage. The median plasma concentration of dexamethasone after IV injection was 0.12 mg/L (n = 7; range, 0.07-0.14) and 0.003 mg/L (n = 12; range, <0.0005-0.005) after IT injection. Plasma concentrations were approximately 40-fold lower (p = 0.0005) or approximately 13-fold lower after dose correction. Concentrations of dexamethasone sodium phosphate were more variable and were even higher in perilymph and lower in plasma. Conclusion: Administration of dexamethasone IT results in much higher perilymph concentrations and much lower plasma concentrations compared with IV administration.

MRI Inner Ear Imaging and Tone Burst Electrocochleography in the Diagnosis of Ménière's Disease.

Objective To compare the sensitivity of gadolinium MRI inner imaging with tone burst electrocochleography (EcochG) for diagnosing endolymphatic hydrops. Study Design A prospective study on patients who were to have an MRI scan to exclude retrocochlear pathology. Setting Tertiary care center. Patients One hundred and two patients: 57 patients with Possible, Probable, or Definite Ménière’s Disease, 25 with asymmetrical hearing loss, 18 with sudden sensorineural hearing loss, and 2 with unilateral tinnitus had additional MRI inner ear imaging and click and tone burst stimulus EcochG testing. Intervention Diagnostic. Main Outcome Measure To compare the sensitivity of the two techniques. Results In 30 patients with symptom-based Definite Ménière’s Disease, tone burst EcochG was positive in 25 (83%) and the click EcochG was positive in 9/30 (30%), and gadolinium MRI imaging diagnosed hydrops in 14 (47%). A positive result for either MRI imaging or tone burst EcochG was seen in 26 patients (87%). In 14 subjects with symptom-based Probable Ménière’s Disease, 10 (71%) had either a positive EcochG or MRI. In 13 with Possible Ménière’s Disease, four (31%) had a positive EcochG or MRI. Conclusion This study confirms the greatly enhanced diagnostic sensitivity of tone burst EcochG over click response in diagnosing endolymphatic hydrops in Ménière’s disease. Even though adequate MRI imaging was achieved in 90%, tone burst EcochG was a more sensitive test.

Unsuccessful cochlear implantation in two patients with superficial siderosis of the central nervous system.

Objective: To highlight the potential adverse outcomes with cochlear implantation (CI) in patients with superficial siderosis. Patients: Two patients with superficial siderosis of the central nervous system with secondary sensorineural hearing loss. Intervention: Cochlear implantation. Main Outcome Measure: Postimplantation speech discrimination scores. Results: In both cases, initial results after implantation were promising. However, in 1 case, their ability to use the CI rapidly declined after 1 week because of major difficulties adapting to electrical stimulation. For the other case, hearing rapidly declined over a 6-month period. Conclusion: The 2 patients reported did not benefit from CI in superficial siderosis that is in contrast to several previously published cases. Adequate counseling of patients with superficial siderosis is important when considering cochlear implantation as results are variable.

Determination of dexamethasone and dexamethasone sodium phosphate in human plasma and cochlear perilymph by liquid chromatography/tandem mass spectrometry.

A rapid, simple and sensitive liquid chromatography/tandem mass spectrometry (LC-MS/MS) assay was developed for the determination of dexamethasone (Dex) and dexamethasone sodium phosphate (Dex SP) in plasma and human cochlear perilymph. After proteins were precipitated with a mixture of acetonitrile and methanol, Dex, Dex SP and flumethasone, the internal standard, were resolved on a C18 column using gradient elution of 5 mM ammonium acetate and methanol. The three compounds were detected using electrospray ionisation in the positive mode. Standard curves were linear over the concentration range 0.5-500 μg/L (r>0.99), bias was <±10%, intra- and inter-day coefficients of variation (imprecision) were <10%, and the limit of quantification was 0.5 μg/L for both Dex and Dex SP. The assay has been used successfully in a clinical pharmacokinetics study of Dex and Dex SP in cochlear perilymph and plasma.

Facial nerve function and hearing preservation after retrosigmoid excision of vestibular schwannoma: Christchurch Hospital experience with 97 patients.

Background:  Between January 1988 and December 2002, 97 patients underwent surgery for excision of vestibular schwannoma via the retrosigmoid approach at Christchurch Hospital.

Giant cell reparative granuloma of the temporal bone treated with calcitonin.

Objective: A case report of a giant cell reparative granuloma involving the temporal bone successfully treated with calcitonin. Study design: Case report. Setting: Teaching hospital, tertiary referral center. Patient, Intervention, and Results: A 62-year-old man was referred to the otolaryngology department with an extensive temporal bone lesion confirmed by biopsy to be a giant cell reparative granuloma. As an alternative to surgery, calcitonin therapy was commenced. After 12 months of treatment, clinical and audiological parameters had returned to normal, and radiological appearances had shown significant bony remodeling. These parameters remain stable 24 months after cessation of treatment. Conclusion: Calcitonin is a safe and economical medical treatment, which should be considered for destructive giant cell granulomas of the temporal bone.

Cochlear Implantation in Children with CHARGE Syndrome

UNLABELLED CHARGE syndrome is a rare congenital condition that manifests with anomalies of coloboma, heart defects, choanal atresia, mental retardation, genitourinary and ear anomalies that can affect almost any part of the auditory pathway. In those patients with a significant sensorineural hearing loss, cochlear implantation has become a potential therapeutic option. METHODS Chart review of three cases from the Southern Cochlear Implant Programme. OUTCOMES All patients met clinical diagnostic criteria of CHARGE syndrome, and had abnormal inner ear anatomy with profound sensorineural hearing loss. One child had previously undergone cochlear implantation which was unsuccessful due to increasing non-auditory stimulation. All patients had successful cochlear implantation with full insertion of a Nucleus Freedom Implant with contour Advance. All patients showed improvement in their audiological function; one child has high functioning verbal communication, one child uses both sign and verbal communication with improved speech quality and ability to speech read, and one child responds reliably to sound, understands short phrases and attempts to vocalize, but this is limited by tracheostomy. CONCLUSION Cochlear implantation faces numerous challenges in children with CHARGE syndrome, but with appropriate patient selection can result in successful audiologic and quality of life outcomes.

Measuring the forces of middle ear surgery; evaluating a novel force-detection instrument.

Hypothesis The forces applied to the middle ear structures during surgery are measurable. Background Surgical forces applied to the middle ear are often cited as a cause of postoperative sensorineural hearing loss; however, no literature exists on how much total force is applied during common middle ear procedures. Methods Using our novel middle ear surgical force sensor, we took measurements from 6 temporal bones of common middle ear manipulations. Results Temporal bones of 3 males and 3 females yielded 72 measurements for an average peak applied force and 68 measurements for total applied force across 3 levels of operator experience. Statistically significant differences were seen between different levels of operator and how much force was applied, with senior operators using less force. Conclusion We show it is possible to measure the applied forces in middle ear surgery and that some of these forces are very large. Larger forces are seen in destructive procedures and in procedures performed by inexperienced operators. This project is an important first step in investigating the association between surgically applied middle ear forces and postoperative sensorineural hearing loss.

Magnetic resonance imaging for Ménière's disease: correlation with tone burst electrocochleography.

The newly developed use of magnetic resonance imaging of the human inner ear, on a 3 Tesla scanner with intratympanically administered gadolinium, can now reliably distinguish perilymph from endolymph and visually confirm the presence or absence of endolymphatic hydrops. Transtympanic tone burst electrocochleography is an established, and under-utilised evoked response electrophysiological test for hydrops, but it relies on a symptom score to indicate the likelihood of hydrops being present. The current diagnostic criteria for Ménières disease make no allowance for any in vivo test, making diagnostic errors likely. In this small pilot study of three patients undergoing tone burst electrocochleography, subsequent magnetic resonance imaging confirmed or excluded the hydrops that the electrocochleography predicted. Magnetic resonance imaging of the inner ear is a safe technique that can be performed in conjunction with imaging of the VIIIth cranial nerves. As this report comprised only three patients in a pilot study, rigorous clinical studies are required to define the possible role of magnetic resonance imaging in the diagnosis of Ménières disease.