Yael Raz

Malignant Otitis Externa: Evolving Pathogens and Implications for Diagnosis and Treatment

Objective Malignant otitis externa (MOE) is an invasive infection of the temporal bone that is classically caused by Pseudomonas aeruginosa. Increasingly, however, nonpseudomonal cases are being reported. The goal of this study was to evaluate and compare the clinical presentation and outcomes of cases of MOE caused by Pseudomonas versus non-Pseudomonas organisms. Study Design Retrospective case series with chart review. Setting Tertiary care institution. Subjects and Methods Adult patients with diagnoses of MOE between 1995 and 2012 were identified. Charts were reviewed for history, clinical presentation, laboratory data, treatment, and outcomes. Results Twenty patients diagnosed with and treated for MOE at the University of Pittsburgh Medical Center between 1995 and 2012 were identified. Nine patients (45%) had cultures that grew P aeruginosa. Three patients (15%) had cultures that grew methicillin-resistant Staphylococcus aureus (MRSA). Signs and symptoms at presentation were similar across groups. However, all of the patients with Pseudomonas had diabetes, compared with 33% of MRSA-infected patients (P = .046) and 55% of all non-Pseudomonas-infected patients (P = .04). Patients infected with MRSA were treated for an average total of 4.7 more weeks of antibiotic therapy than Pseudomonas-infected patients (P = .10). Overall, patients with non-Pseudomonas infections were treated for a total of 2.4 more weeks than Pseudomonas-infected patients (P = .25). Conclusions A high index of suspicion for nonpseudomonal organisms should be maintained in patients with signs and symptoms of MOE, especially in those without diabetes. MRSA is an increasingly implicated organism in MOE.

Challenges and opportunities in managing the dizzy older adult.

Balance disorders are common in elderly people, not only resulting in distressing sensations but also leading to reduced activity levels and quality of life. It has been estimated that 30% of elderly patients experience a balance disorder. Managing these disorders is a substantial challenge for patients and their caregivers and physicians. Moreover, abnormalities in balance are associated with falls, a major cause of morbidity and mortality for elderly people. Management is complicated by the inherent difficulties in assessing the generic complaint of dizziness, as well as the likelihood of multiple, often nonvestibular causes. The authors of this mini-seminar review both vestibular and nonvestibular causes of balance disorders in elderly people, emphasizing practical therapeutic maneuvers that can be used.

ICP, BMI, surgical repair, and CSF diversion in patients presenting with spontaneous CSF otorrhea.

Objective To assess intracranial pressure (ICP), body mass index (BMI), surgical repair, and cerebrospinal fluid (CSF) diversion in patients presenting with spontaneous CSF otorrhea. Study Design Retrospective series review. Setting Tertiary referral center. Patients Thirty-two patients were treated surgically from 2004 to 2013 for spontaneous CSF otorrhea by the principal investigators. Patients with a history of chronic ear disease and cholesteatoma, previous mastoid surgery, head trauma, or iatrogenic injury were excluded. Average age was 56 years. Twenty-two patients (69%) were female. Intervention(s) Middle fossa repair, transmastoid repair, lumbar puncture, V-P shunt, L-P shunt, and magnetic resonance imaging. Main Outcome Measure(s) Patients underwent middle fossa or transmastoid repair of tegmen defects. Intracranial pressures were determined with lumbar puncture at time of surgical repair or shortly after surgery. CSF diversion procedures were performed in patients who were found to have elevated ICP, which was not controlled medically, presented with recurrent leak or had ICP of 25 cm or greater of H2O. Preoperative BMI was calculated. Results Thirty-two patients underwent 37 operations. Average BMI was 35.0 kg/m2 (median, 34.7; range, 18.7–53.2 kg/m2). There were 21 repairs on the left and 16 on the right. The majority underwent a middle fossa craniotomy for repair (27/32). Two patients had bilateral repairs. Three patients (8%) underwent revision surgery, of which, 2 had untreated intracranial hypertension (ICP 24.5 and 24 cm H2O). ICP measurements were available for 29 patients. The mean ICP was 23.4 cm H2O (median, 24; range, 13–36 cm H20). Twenty-two patients (69%) had ICP of 20 cm or greater of H20; of those, 13 had an ICP of 25 cm or greater of H20. Seventeen patients (53%) underwent CSF diversion procedures. Conclusion Our findings of elevated ICP and BMI in patients presenting with spontaneous CSF otorrhea are consistent with previous reports in the literature. The percentage of patients that underwent CSF diversion procedures was high at 53% and represents an aggressive stance in managing elevated ICP in a population that may be at risk for subsequent leaks.

Rinne Revisited: Steel versus Aluminum Tuning Forks

Objective (1) Determine whether tuning fork material (aluminum vs stainless steel) affects Rinne testing in the clinical assessment of conductive hearing loss (CHL). (2) Determine the relative acoustic and mechanical outputs of 512-Hz tuning forks made of aluminum and stainless steel. Study Design Prospective, observational. Setting Outpatient otology clinic. Subjects and Methods Fifty subjects presenting May 2011 to May 2012 with negative or equivocal Rinne in at least 1 ear and same-day audiometry. Rinne test results using aluminum and steel forks were compared and correlated with the audiometric air-bone gap. Bench top measurements using sound-level meter, microphone, and artificial mastoid. Results Patients with CHL were more likely to produce a negative Rinne test with a steel fork than with an aluminum fork. Logistic regression revealed that the probability of a negative Rinne reached 50% at a 19 dB air-bone gap for stainless steel versus 27 dB with aluminum. Bench top testing revealed that steel forks demonstrate, in effect, more comparable air and bone conduction efficiencies while aluminum forks have relatively lower bone conduction efficiency. Conclusion We have found that steel tuning forks can detect a lesser air-bone gap compared to aluminum tuning forks. This is substantiated by observations of clear differences in the relative acoustic versus mechanical outputs of steel and aluminum forks, reflecting underlying inevitable differences in acoustic versus mechanical impedances of these devices, and thus efficiency of coupling sound/vibratory energy to the auditory system. These findings have clinical implications for using tuning forks to determine candidacy for stapes surgery.

Hearing Preservation: Does Electrode Choice Matter?:

Objective Evaluate if electrode design affects hearing preservation (HP) following cochlear implantation (CI) with full-length electrodes. Study Design Case series with chart review. Setting Tertiary referral academic center. Subjects and Methods Forty-five adults with low-frequency hearing (≤85 dB at 250 and 500 Hz) who underwent unilateral CI with full-length electrode arrays made by 1 manufacturer were included. HP was calculated with (1) mean low-frequency pure-tone average (LFPTA) at 250 and 500 Hz (MEAN method), (2) a percentile method across the audiometric frequency spectrum generating an S-value (HEARRING method), and (3) functional if hearing remained ≤85 dB at 250 and 500 Hz. Audiometric testing was performed approximately 1 month and 1 year postoperatively, yielding short-term and long-term results, respectively. Results Of 45 patients who underwent CI, 46.7% received lateral wall (LW) and 53.3% received perimodiolar (PM) electrodes. At short-term follow-up, LW electrodes were associated with significantly better HP than PM (LFPTA method: 27.7 vs 39.3 dB, P < .05; S-value method: 48.2 vs 21.8%, P < .05). In multivariate regression of short-term outcomes, LW electrode use was a significant predictor of better HP (P < .05). At long-term follow-up, electrode type was not associated with HP. Younger patient age was the only significant predictor of long-term HP on multivariate analysis (P < .05). Conclusion The LW electrode is associated with short-term HP, suggesting its design is favorable for limiting trauma to the cochlea during and directly following CI. Other factors, including age, are relevant for maintaining HP over the long term. The data support further investigation into what modifiable factors may promote long-term HP.

Radiographic Mastoid and Middle Ear Effusions in Intensive Care Unit Subjects.

BACKGROUND: This study was conducted to determine the incidence of and risk factors associated with the development of radiographic mastoid and middle ear effusions (ME/MEE) in ICU patients. METHODS: Head computed tomography or magnetic resonance images of 300 subjects admitted to the University of Pittsburgh Medical Center neurologic ICU from April 2013 through April 2014 were retrospectively reviewed. Images were reviewed for absent, partial, or complete opacification of the mastoid air cells and middle ear space. Exclusion criteria were temporal bone or facial fractures, transmastoid surgery, prior sinus or skull base surgery, history of sinonasal malignancy, ICU admission < 3 days or inadequate imaging. RESULTS: At the time of admission, 3.7% of subjects had radiographic evidence of ME/MEE; 10.3% (n = 31) of subjects subsequently developed new or worsening ME/MEE during their ICU stay. ME/MEE was a late finding and was found to be most prevalent in subjects with a prolonged stay (P < .001). Variables associated with ME/MEE included younger age, the use of antibiotics, and development of radiographic sinus opacification. The proportion of subjects with ME/MEE was significantly higher in the presence of an endotracheal tube (22.7% vs 0.6%, P < .001) or a nasogastric tube (21.4% vs 0.6%, P < .001). CONCLUSIONS: Radiographic ME/MEE was identified in 10.3% of ICU subjects and should be considered especially in patients with prolonged stay, presence of an endotracheal tube or nasogastric tube, and concomitant sinusitis. ME/MEE is a potential source of fever and sensory impairment that may contribute to delirium and perceived depressed consciousness in ICU patients.

Response to “Management and Outcomes in Patients Affected by Malignant Otitis Externa”

We read with great interest the recent article from Hobson et al, who studied a retrospective case series of patients diagnosed with the rare manifestations of malignant otitis externa (MOE). We commend the authors for their efforts in trying to identify a sample as homogeneously as possible. However, we highlight some important methodological issues that unfortunately may undermine the scientific rigor of the study, and therefore the clinical evidence provided, more so in light of the very limited sample size (only 15 eyes at final follow-up). While a strict adherence to the Cohen criteria may be no longer fundamental to the diagnosis of MOE, given the use of computed tomography (CT) that documents the presence of bone erosion (osteomyelitis), we feel that it is nowadays mandatory to avoid CT for assessing the progression and documenting the resolution as bone changes persist after treatment of the disease. We would have expected that the authors had provided information regarding their changed practice during the study period if it really occurred, or at least suggested that readers adopt Ga-67 scintigraphy, whether or not combined with single-photon emission computed tomography (SPECT)/CT, for the follow-up of these patients. We also point out that some of the patients included were not treated for at least 6 weeks, as per current recommendations of best practice guidelines. Lastly, perhaps it would have been more appropriate to exclude the 3 patients who underwent combined medical and surgical treatment.

Malignant Otitis Externa: An Evolving Disease

Objectives: 1) Compare the clinical presentations and outcomes of patients with MOE caused by Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus (MRSA). 2) Recognize the evolving trend of atypical and drug-resistant organisms causing malignant otitis externa (MOE). Methods: A retrospective review of disease course and outcome was performed of patients diagnosed with MOE at a tertiary referral center between 1995 and 2012. Results: Forty-four patients with a diagnosis of MOE were identified. Eighteen patients were excluded due to insufficient or inconsistent clinical data, leaving 26 patients for analysis. Forty-six percent of patient cultures grew Pseudomonas and 12% grew MRSA. All patients infected with Pseudomonas had diabetes mellitus, compared to 33% of MRSA-infected patients (P < 0.05). Twenty-five percent of Pseudomonas-infected patients presented with at least one cranial nerve palsy, as compared to none of the MRSA-infected patients (ns). Duration of therapy for Pseudomonas-infected patients lasted an average of 7.2 weeks, while MRSA-infected patients lasted 10 weeks (ns). Excluding failed initial treatment courses, the average treatment durations were 5.0 and 7.7 weeks for Pseudomonas and MRSA infections, respectively. Other atypical pathogenic organisms isolated in culture include Candida, Aspergillus, and Enterococcus species. Conclusions: Increasingly, MOE is being caused by organisms other than Pseudomonas, including MRSA. Empiric treatment, without culture, can lead to delays in definitive therapy. A high index of suspicion for atypical or drug resistant organisms should be maintained in MOE patients who are not diabetic. Culture directed therapy for treatment of MOE is paramount.

10:50: Axon Guidance Cues in the Developing Inner Ear

PROBLEM: Mutations in the Pendrin gene (SLC26A4) are associated with congenital autosomal recessive hearing loss (DFNB4), often with accompanying temporal bone and/or thyroid abnormalities (Pendred Syndrome, PS). Evidence to date indicates that different populations exhibit different patterns of mutations, suggesting that local clinical testing strategies should reflect these differences. METHODS: The authors used DHPLC–based mutation analysis and bidirectional DNA sequencing to detect all possible mutations in the open reading frame and flanking sequences of SLC26A4 in a population of patients referred for genetic testing in China, and a comparable group of patients in the United States. RESULTS: The relatively higher proportion of Chinese patients with temporal bone abnormalities and deafness who had SLC26A4 mutations (47 of 50 families) and the different spectrum of SLC26A4 mutations in these two populations were found, and 11 previously unreported SLC26A4 mutations were discovered: 5 in the Chinese population (E303Q, G316X, X329, X467, X573), and 6 in the U.S. population (V250A, D266N, F354S, D697A, K715N, E737D), in addition to 14 reported mutations. CONCLUSION: Since this approach worked well in both clinical laboratory settings, the authors propose a practical diagnostic strategy: In China, to screen the two prevalent mutations IVS7-2A G and H723R first as an effective and affordable alternative to CT examination; in the U.S., information on temporal bone and thyroid abnormalities to be included in the clinical information submitted with clinical samples from deaf patients who are undergoing genetic testing and use two-tier analyses for detection of SLC26A4 mutations. SIGNIFICANCE: This study provides appropriate, efficient, and cost effective molecular diagnostic strategies for EVAS in deaf populations from both China and the U.S. SUPPORT: This work was supported by the Chinese National Nature Science Foundation Research Grant 30572015, Beijing Nature Science Foundation Research Grant 7062062 to Pu Dai and Chinese Capital Medical Development Scientific Funding 2005-1032 to Dongyi Han. 10:50 Axon Guidance Cues in the Developing Inner Ear Alyssa M Hackett, MD (presenter); Wei Gao; Ashish R Shah; Sabrina Kadri; Audra M Webber, MD; Yael Raz, MD

09:30 AM: Slit/Robo Signaling in Auditory Development

ing to programmed hair cell death. Antioxidants such as N-acetylcysteine (NAC) and acetyl-L-carnitine (ALCAR) mitigate this process and spare auditory function. The objective of this prospective, randomized, controlled study was to establish the dose response effects of NAC and ALCAR on threshold shifts when given to chinchillas after acoustic trauma. This was a preliminary investigation exploring the use of these two agents as a combinatorial therapy for treating cochlear injury. METHODS: Chinchillas (n 42) received baseline auditory brainstem response (ABR) threshold testing at 2, 4, 6, and 8 kHz. All were exposed to 6 hours of continuous 105 dB SPL noise. Animals were randomly given saline, NAC (50, 100, or 200 mg/kg), or ALCAR (20, 30, or 50 mg/kg), with six animals per dose. Five intraperitoneal doses spaced every 12 hours were started 4 hours post-noise. The primary outcome was the 21-day post-noise ABR threshold shift at each frequency. RESULTS: NAC and ALCAR decreased permanent threshold shift (PTS) across all frequencies compared with saline (ANOVA, p 0.01), with a dose-dependent response (p 0.05), leveling at NAC 200 mg/kg and ALCAR 30 mg/kg. CONCLUSION: NAC and ALCAR reduced PTS from acute acoustic trauma in a dose-dependent fashion. Optimum doses were: NAC 200 mg/kg and ALCAR 30 mg/kg. As this study continues, combined therapy and varying treatment durations will be investigated along with analysis of cochlear hair cells counts and biochemical markers of oxidative stress and programmed cell death. SIGNIFICANCE: There is a window of opportunity for treating acoustic trauma, and an orally administered, safe, effective therapy will profoundly impact both military and civilian life. Human clinical trials with antioxidant compounds are needed. SUPPORT: Funded by the Office of Naval Research. The views expressed in this work are those of the authors and do not necessarily reflect the official policy or position of the Department of the Navy, Department of Defense, nor the U.S. Government.