Joseph B. Roberson

GJB2 Mutations and Degree of Hearing Loss: A Multicenter Study

Hearing impairment (HI) affects 1 in 650 newborns, which makes it the most common congenital sensory impairment. Despite extraordinary genetic heterogeneity, mutations in one gene, GJB2, which encodes the connexin 26 protein and is involved in inner ear homeostasis, are found in up to 50% of patients with autosomal recessive nonsyndromic hearing loss. Because of the high frequency of GJB2 mutations, mutation analysis of this gene is widely available as a diagnostic test. In this study, we assessed the association between genotype and degree of hearing loss in persons with HI and biallelic GJB2 mutations. We performed cross-sectional analyses of GJB2 genotype and audiometric data from 1,531 persons, from 16 different countries, with autosomal recessive, mild-to-profound nonsyndromic HI. The median age of all participants was 8 years; 90% of persons were within the age range of 0-26 years. Of the 83 different mutations identified, 47 were classified as nontruncating, and 36 as truncating. A total of 153 different genotypes were found, of which 56 were homozygous truncating (T/T), 30 were homozygous nontruncating (NT/NT), and 67 were compound heterozygous truncating/nontruncating (T/NT). The degree of HI associated with biallelic truncating mutations was significantly more severe than the HI associated with biallelic nontruncating mutations (P<.0001). The HI of 48 different genotypes was less severe than that of 35delG homozygotes. Several common mutations (M34T, V37I, and L90P) were associated with mild-to-moderate HI (median 25-40 dB). Two genotypes--35delG/R143W (median 105 dB) and 35delG/dela(GJB6-D13S1830) (median 108 dB)--had significantly more-severe HI than that of 35delG homozygotes.

Cochleostomy site: Implications for electrode placement and hearing preservation

Conclusions. With recent increased interest in minimizing intracochlear trauma and preserving residual hearing during cochlear implantation, increased attention must be paid to the cochleostomy site. The results of this paper demonstrate that the cochleostomy must be made inferior, rather than anterior, to the round window to ensure scala tympani insertion and to decrease the likelihood of insertion-induced intracochlear damage during electrode insertion. Objective. To describe the complex anatomy of the hook region of the cochlea, specifically in relation to the optimal placement of the cochleostomy for cochlear implant electrode insertion to potentially achieve hearing preservation. The authors believe that previous industry recommendations and described surgical techniques have resulted in cochleostomies being placed in anatomical positions that possibly result in electrode insertions that damage the basilar membrane and/or other cochlear structures. Material and methods. The results of a number of temporal bone studies were reviewed with attention being paid to the anatomical relationship of the basilar membrane and spiral ligament to the round window membrane. For different cochleostomy sites the potential for damage to intracochlear structures, particularly the basilar membrane and organ of Corti, was assessed. Results. The review of electrode insertion studies into human temporal bones, as well as a post-mortem anatomical study of implanted temporal bones, showed an increased risk of scala vestibuli insertions and insertion-induced damage to intracochlear structures when the cochleostomy was performed more anterior to the round window. These results were endorsed by studies detailing the anatomy of the hook region of the cochlea.

Nucleus Freedom North American clinical trial

OBJECTIVE: To evaluate hearing outcomes and effects of stimulation rate on performance with the Nucleus Freedom cochlear implant (Cochlear Americas, Denver, CO). STUDY DESIGN AND SETTING: Randomized, controlled, prospective, single-blind clinical study using single-subject repeated measures (A-B-A-B) design at 14 academic centers in the United States and Canada and comparison with outcomes of a prior device by the same manufacturer. PATIENTS: Seventy-one severely/profoundly hearing impaired adults. RESULTS: Seventy-one adult recipients were randomly programmed in two different sets of rate: ACE or higher rate ACE RE. Mean scores for Consonant Nucleus Consonant words is 57%, Hearing in Noise Test (HINT) sentences in quiet 78%, and HINT sentences in noise 64%. Sixty-seven percent of subjects preferred slower rates of stimulation, and performance did not improve with higher rates of stimulation using this device. CONCLUSIONS: Subjects performed well, and there was no advantage to higher stimulation rates with this device. SIGNIFICANCE: Higher stimulation rates do not necessarily result in improved performance.

Malleus-to-footplate versus malleus-to-stapes-head ossicular reconstruction prostheses: temporal bone pressure gain measurements and clinical audiological data.

Hypothesis: Several clinical reports suggest that if the stapes superstructure is intact, ossicular reconstruction should be made to the stapes head rather than the footplate to achieve a better hearing outcome. To test this hypothesis, we compared the in situ mechanical performance of hydroxylapatite (HA) malleus-to-stapes-head (MSH) ossicular reconstruction prosthesis (ORP) with malleus-to-footplate (MFP) ORP, both manufactured by Project HEAR. Background: ORPs are commonly used to replace a missing or deficient incus. However, hearing outcomes are highly variable, depending on the ORP material, design, surgical technique, and ORP positioning. Methods: Cochleo-vestibular pressure measurements in human cadaveric temporal bones for the HA MFP ORP have been reported by Puria et al. (2005). In the present study, the ear canal pressure Pe and cochleovestibular pressure Pv were measured in cadaveric temporal bones with intact incus, removed incus, and MSH ORP reconstruction. The relative loss in gain, Lmsh, is defined as the ratio of Pv with reconstructed MSH ORP to intact incus and compared with Lmfp. A retrospective clinical audit of the pre- and postoperative audiologic results of patients who had undergone ossiculoplasty with either MSH or MFP ORP was conducted for comparison. Results: For the 0.5 to 3 kHz frequency range, Lmsh magnitude is 6.2 dB lower than the Lmfp magnitude (p = 0.05). The retrospective audit of audiologic results after ossiculoplasty with either MSH or MFP ORP revealed a similar difference in gain between the two ORP designs with air-bone gap differences of 7.6 dB (p = 0.04) and air conduction threshold differences of 8.0 dB (p = 0.13) for these patients. Conclusion: The MFP ORP showed better average pressure gain compared with the MSH ORP across the speech frequencies. Surgeons performing ossiculoplasty with designs similar to Project HEAR HA ORPs, where there is direct columella-like connection between the malleus and stapes, should consider using the MFP ORP design to achieve a better postoperative audiologic result, even when the stapes superstructure is intact.

Mastoid obliteration: autogenous cranial bone pAte reconstruction.

Objective To review the outcome in consecutive patients who have undergone complete epitympanic and mastoid obliteration and concurrent tympanic membrane reconstruction over a 53-month period. Study Design Retrospective review. Setting Tertiary referral center. Patients Sixty-two ears in 56 sequential patients undergoing mastoid obliteration with major indications including recurrent infection, debris trapping in the canal wall-down cavity, intolerance of water exposure, calorically induced vertigo in an existing cavity, a semicircular canal fistula, and inability to wear a hearing device. Thirty-six ears in 33 patients who underwent second-stage surgery for ossicular reconstruction during the same time period are also reviewed. Intervention Transplanted autogenous cranial bone is used to induce osteoneogenesis resulting in complete obliteration of the epitympanic and mastoid spaces while maintaining a mesotympanic space. Main Outcome Measures Success of obliteration, incidence of symptoms prompting intervention, hearing outcome, incidence of recurrent cholesteatoma, and incidence of eustachian tube dysfunction necessitating treatment and need for revision surgical procedures. Results Complete take of the bony obliteration occurs in over 95% of cases; 90% of treated patients enjoy complete absence of original symptoms, whereas symptoms improved in the remainder. For over 95% of patients, existing eustachian tube function has been adequate after obliteration. To date, no patient has required revision surgical intervention. Conclusion Mastoid obliteration with autogenous cranial bone is a safe and extremely effective option for treatment of problematic canal wall-down mastoid cavities. Surgical techniques that include sterile harvest of the cranial bone graft mixed with antibiotic, revision of the cavity to expose viable native bone, inclusion of the epitympanic spaces in the obliteration, and complete coverage of the pÂte with autogenous fascia have proven critical to successful outcome.

Malleus-to-footplate ossicular reconstruction prosthesis positioning: cochleovestibular pressure optimization.

Aims: To determine 1) the best position for hydroxylapatite malleus-to-footplate (MFP), ossicular replacement prosthesis (ORP) in reconstructed ears, and 2) whether preserving the stapes superstructure (SS), when present, has acoustic advantages. Background: Positioning of the MFP-ORP head beneath the neck of the malleus may produce maximal force, whereas positioning beneath the manubrium of the malleus may produce the greatest displacement. It is not clear which is the optimal placement position. In addition, we look at the effect of the SS on sound transmission to the inner ear in ossicular reconstruction. Methods: The ear-canal air pressure and vestibular hydro-pressure were measured in human cadaver temporal bones with incus intact, removed, and replaced with the MFP-ORP; the ORP head was placed at three different positions on the malleus (head, mid-manubrium, and umbo) while keeping its base at the center of stapes footplate with intact or removed stapes SS. The vestibular pressure ratio between the ear with intact incus and MFP-ORP reconstructed ear is defined as Lmfp, the loss caused by the prosthesis in relation to the normal ossicular chain. Results: The mean magnitude of Lmfp, averaged in the important speech frequency region of 0.5 to 3 kHz, is approximately 7.8 dB at the neck with stapes SS. In comparison, mean magnitude of Lmfp for mid-manubrium without stapes SS is 15 dB (p = 0.04), and with the stapes SS it is 16 dB (p = 0.05), whereas at the umbo without SS it is 15 dB (p = 0.03). In the 8 kHz region, the mean magnitude of Lmfp is approximately 1 dB with the stapes SS intact and approximately 8.5 dB when it was removed (p < 0.09). Conclusion: There are significant physiologic advantages to placing the hydroxylapatite MFP-ORP beneath the neck of the malleus and preserving the SS.

Silicone allergy: A new cause for cochlear implant extrusion and its management.

Objective: We introduce silicone allergy as a rare cause for cochlear implant extrusion and discuss its management. Study Design: Retrospective case series and literature review. Setting: Tertiary referral centers. Patients: Primary eligibility criteria included patients who experienced a delayed extrusion of their cochlear implants with negative wound cultures and had a suspected or a test-proven allergy to silicone components of an implant. Interventions: Silicone allergy testing, explantation of a cochlear implant containing allergenic silicone materials, reimplantation with a custom-made cochlear implant excluding an allergenic silicone component. Outcome Measures: Uneventful wound healing and extrusion-free long-term follow-up after the reimplantation with a custom-made cochlear implant excluding an allergenic silicone component. Results: Three known cases of cochlear implant extrusion as a result of silicone allergy have been noted from 1991 through 2004 in three cochlear implant programs in the United States. All three devices extruded, resulting in explantation of the old device and reimplantation with a new custom-made device eliminating the allergenic silicone component. Wound cultures were negative in all cases. All three patients experienced a delayed extrusion of their devices. Two of these patients had a test-proven allergy to the implants silicone components, whereas the third patient was presumed to have a hypersensitivity solely on the basis of a clinical presentation. Conclusion: We propose that silicone allergy is a rare cause of cochlear implant extrusion. Patients experiencing cochlear implant extrusion, particularly with a delayed onset and negative wound culture results, should be tested for silicone allergy.

Preoperative marijuana inhalation--an airway concern.

PurposeCannabis Sativa (marijuana) may cause a variety of respiratory disorders including uvular oedema. This case illustrates that uvular oedema secondary to marijuana inhalation may cause a potentially serious postoperative clinical problem.Clinical featuresA healthy 17-yr-old man who inhaled marijuana prior to general anaesthesia. In the recovery room, after an uneventful general anaesthetic, acute uvular oedema resulted in post operative airway obstruction and admission to hospital. The uvular oedema was treated successfully with dexamethasone.ConclusionRecent inhalation of marijuana before general anaesthesia may cause acute uvular oedema and post operative airway obstruction. The uvular oedema can be easily diagnosed and treated.RésuméObjectifLe cannabis sativa (marijuana) peut provoquer plusieurs problèmes respiratoires dont l’oedème de la luette. Cette observation montre que l’oedème de la luette secondaire à l’inhalation de marijuana peut être à l’origine d’un problème clinique postopératoire grave.Caractéristiques cliniquesUn jeune homme de 17 ans ayant inhalé depuis peu de la marijuana subit une anesthésie générale. À la salle de réveil, après une anesthésie générale sans incident, un oedème de la luette provoque une obstruction des voies respiratoires et son admission à l’hôpital. L’oedème se dissipe avec le dexométhasone.ConclusionL’inhalation récente de marijuana avant une anesthésie générale peut provoquer un oedème aigu de la luette avec obstruction des voies respiratoires. Cette affection est facile à diagnostiquer et à traiter.

Evaluation of botulinum toxin A in treatment of tinnitus

OBJECTIVES: The purpose of this study was to evaluate the potential benefit of botulinum toxin A in treatment of tinnitus with a prospective, double-blinded study design. STUDY DESIGN : Double-blinded, prospective clinical study. METHODS : Thirty patients with tinnitus were randomly placed into 1 of 2 treatment arms. Patients either received botulinum toxin A (20 to 50 units) or saline injection at the first treatment, and the opposite treatment 4 months later. Prospective data including tinnitus matching test, tinnitus handicap inventory (THI), tinnitus rating scale (TRS), and patient questionnaires were obtained over a 4-month period after each injection. RESULTS : Twenty-six patients completed both injections and follow-up and were included in data analysis. After botulinum toxin A, subjective tinnitus changes included 7 patients improved, 3 worsened, and 16 unchanged. Following placebo, 2 patients were improved, 7 worsened, and 17 unchanged. Comparison of the treatment and placebo groups was statistically significant (P >0.005) when including better, worse, and same effects. A significant decrease in THI scores between pretreatment and 4 month postbotulinum toxin A injection (P = 0.0422) was recorded. None of the other comparisons of pretreatment to 1 month, or pretreatment to 4 months were significantly different. CONCLUSIONS : This small study found improvement in THI scores and patient subjective results after botulinum toxin A injection compared with placebo, suggesting a possible benefit of botulinum toxin A in tinnitus management. Larger studies need to be completed to further evaluate potential benefits of botulinum toxin A in treatment of this difficult problem.

Acoustic neuroma surgery: Absent auditory brainstem response does not contraindicate attempted hearing preservation†

Objective: Absence of auditory brainstem response (ABR) waveforms has been associated with a poor likelihood of hearing preservation following resection of acoustic neuromas. Our experience is reviewed for patients with absent preoperative ABR regarding hearing preservation, hearing improvement, and return of ABR. Study Design: Retrospective review of 22 cases of acoustic neuroma resection. Nine patients with absent preoperative ABR were identified. All underwent tumor resection utilizing intraoperative cochlear nerve action potential (CNAP) monitoring. Postoperative hearing results and ABR waveforms were examined. Methods: Charts were reviewed and tabulated for age, sex, tumor side, tumor size, preoperative and postoperative audiometric and ABR results, intraoperative monitoring results by ABR and CNAP, and surgical complications. Results: Hearing preservation was achieved in seven of nine patients (78%) with absent preoperative ABR, as well as six of seven patients (86%) with tumors less than or equal to 20 mm in greatest dimension. Although intraoperative ABR monitoring was not possible in any of these patients, CNAP monitoring was successful in all. Return of ABR waveforms was observed in four of the six patients (67%) tested from 3 to 22 months postoperatively. Four of the seven patients (57%) enjoyed improvement in hearing class as defined by the guidelines of the American Academy of Otolaryngology—Head and Neck Surgery. Conclusions: Absent ABR waveforms have not been a negative prognostic sign regarding hearing preservation. CNAP monitoring is possible in these patients and likely helps to minimize iatrogenic cochlear nerve trauma. Patients with no ABR waveforms have hope of hearing preservation and even improvement following acoustic neuroma resection performed utilizing CNAP monitoring and hearing preservation surgical techniques. Key Words: Acoustic neuroma, auditory brainstem response, cochlear nerve action potential, hearing preservation.