Audiometric and Otologic Findings in Children and Young Adults with Neurofibromatosis Type 1 and Plexiform Neurofibromas.

OBJECTIVES: To characterize otologic and audiologic manifestations in our NF1 cohort and explore the relationship between otologic and audiologic findings in a subset of patients with ear-related plexiform neurofibromas (PNs). METHODS: Audiologic and otologic clinical evaluations were conducted on 102 patients with NF1 in a natural history study (5-45 years; M = 14.4 years; Mdn = 14). Testing included pure tone and speech audiometry, middle ear function, neurodiagnostic auditory brainstem response (ABR), auditory processing, and MRIs of the head and neck region. Patients referred to this study had an overall higher incidence and burden of PNs than the overall NF1 population. RESULTS: The majority of subjects in this cohort had normal hearing sensitivity (81%) and normal middle ear function (78%). Nineteen participants had hearing loss that ranged in degree from mild to profound, with the majority in the mild range. Hearing loss was twice as likely to be conductive than sensorineural. In patients with ear-related PNs (n = 12), hearing loss was predominantly conductive (60%). Seventy-five percent of ears with PNs had atypical tympanometric tracings that could not be characterized by the classic categories. In all 20 patients with a PN in the temporal bone, the ear canal was affected, and the PNs often extended to the surrounding soft tissue regions. CONCLUSIONS: People with NF1-related PNs in the temporal bone and adjacent skull base should have audiometric and otologic monitoring. Addressing hearing concerns should be part of routine clinical evaluations in patients with NF1. Magnetic resonance imaging (MRI) should be performed in patients with NF1 who have hearing loss. LEVEL OF EVIDENCE: 3 Laryngoscope, 133:2770-2778, 2023.

The Impact of Intratympanic Steroid Dosage on Hearing Recovery in Sudden Sensorineural Hearing Loss.

OBJECTIVE: To investigate how dexamethasone dosage impacts intratympanic steroid therapy (IST) for treatment of sudden sensorineural hearing loss (SSNHL). STUDY DESIGN: Retrospective review. METHODS: Inclusion criteria identified subjects who received IST between January 1, 2010 and June 1, 2020 for iSSNHL. Subjects with Meniere's disease, autoimmune inner ear disease, subjects who received injections of non-dexamethasone steroid formulations, and subjects with missing audiogram data were excluded. Subjects were stratified by dexamethasone dosage: low-dose (10 mg/ml) versus high-dose (24 mg/ml), time-to-treatment and oral corticosteroid use. Outcome measures included post-treatment improvement in 4-frequency pure tone average (4F-PTA [500, 1000, 2000,4000 Hz]), low- and high-frequency PTA (250-1000 Hz and 2000-8000 Hz, respectively). RESULTS: Of the 55 included subjects (50.9% male, mean age 48.9 ± 16.4 years), 31 received high-dose while 24 received low-dose injections. 90.9% of subjects were treated with oral steroids prior to or during IST. No significant differences in hearing outcomes were observed between low- and high-dose cohorts or when stratifying by oral steroid use. Time-to-treatment analysis comparing ≤1 month (67.3%) versus >1 month (32.7%) groups demonstrated a significant improvement in post-treatment 4F-PTA (P = .01) in the ≤1 month group. CONCLUSIONS: Hearing recovery was not significantly different between the 10 mg/ml versus 24 mg/ml doses of intratympanic dexamethasone, suggesting that steroid dose may not impact the efficacy of IST. A shorter time-to-treatment was observed to be favorable for hearing improvement.

The Relationship Between Interaural Insertion-Depth Differences, Scalar Location, and Interaural Time-Difference Processing in Adult Bilateral Cochlear-Implant Listeners.

Sensitivity to interaural time differences (ITDs) in acoustic hearing involves comparison of interaurally frequency-matched inputs. Bilateral cochlear-implant arrays are, however, only approximately aligned in angular insertion depth and scalar location across the cochleae. Interaural place-of-stimulation mismatch therefore has the potential to impact binaural perception. ITD left-right discrimination thresholds were examined in 23 postlingually-deafened adult bilateral cochlear-implant listeners, using low-rate constant-amplitude pulse trains presented via direct stimulation to single electrodes in each ear. Angular insertion depth and scalar location measured from computed-tomography (CT) scans were used to quantify interaural mismatch, and their association with binaural performance was assessed. Number-matched electrodes displayed a median interaural insertion-depth mismatch of 18° and generally yielded best or near-best ITD discrimination thresholds. Two listeners whose discrimination thresholds did not show this pattern were confirmed via CT to have atypical array placement. Listeners with more number-matched electrode pairs located in the scala tympani displayed better thresholds than listeners with fewer such pairs. ITD tuning curves as a function of interaural electrode separation were broad; bandwidths at twice the threshold minimum averaged 10.5 electrodes (equivalent to 5.9 mm for a Cochlear-brand pre-curved array). Larger angular insertion-depth differences were associated with wider bandwidths. Wide ITD tuning curve bandwidths appear to be a product of both monopolar stimulation and angular insertion-depth mismatch. Cases of good ITD sensitivity with very wide bandwidths suggest that precise matching of insertion depth is not critical for discrimination thresholds. Further prioritizing scala tympani location at implantation should, however, benefit ITD sensitivity.

Computed-Tomography Estimates of Interaural Mismatch in Insertion Depth and Scalar Location in Bilateral Cochlear-Implant Users.

HYPOTHESIS: Bilateral cochlear-implant (BI-CI) users will have a range of interaural insertion-depth mismatch because of different array placement or characteristics. Mismatch will be larger for electrodes located near the apex or outside scala tympani, or for arrays that are a mix of precurved and straight types. BACKGROUND: Brainstem superior olivary-complex neurons are exquisitely sensitive to interaural-difference cues for sound localization. Because these neurons rely on interaurally place-of-stimulation-matched inputs, interaural insertion-depth or scalar-location differences for BI-CI users could cause interaural place-of-stimulation mismatch that impairs binaural abilities. METHODS: Insertion depths and scalar locations were calculated from temporal-bone computed-tomography scans for 107 BI-CI users (27 Advanced Bionics, 62 Cochlear, 18 MED-EL). RESULTS: Median interaural insertion-depth mismatch was 23.4 degrees or 1.3 mm. Mismatch in the estimated clinically relevant range expected to impair binaural processing (>75 degrees or 3 mm) occurred for 13 to 19% of electrode pairs overall, and for at least three electrode pairs for 23 to 37% of subjects. There was a significant three-way interaction between insertion depth, scalar location, and array type. Interaural insertion-depth mismatch was largest for apical electrodes, for electrode pairs in two different scala, and for arrays that were both-precurved. CONCLUSION: Average BI-CI interaural insertion-depth mismatch was small; however, large interaural insertion-depth mismatch-with the potential to degrade spatial hearing-occurred frequently enough to warrant attention. For new BICI users, improved surgical techniques to avoid interaural insertion-depth and scalar mismatch are recommended. For existing BI-CI users with interaural insertion-depth mismatch, interaural alignment of clinical frequency tables might reduce negative spatial-hearing consequences.

Audiologic and Otologic Clinical Manifestations of Loeys-Dietz Syndrome: A Heritable Connective Tissue Disorder.

OBJECTIVE: Loeys-Dietz syndrome (LDS) is a rare genetic connective tissue disorder resulting from TGF-ß signaling pathway defects and characterized by a wide spectrum of aortic aneurysm, arterial tortuosity, and various extravascular abnormalities. This study describes the audiologic, otologic, and craniofacial manifestations of LDS. STUDY DESIGN: Consecutive cross-sectional study. SETTING: Tertiary medical research institute. METHODS: Audiologic and clinical evaluations were conducted among 36 patients (mean ± SD age, 24 ± 17 years; 54% female) with genetically confirmed LDS. Cases were categorized into genetically based LDS types 1 to 4 (TGFBR1, TGFBR2, SMAD3, TGFB2, respectively). Audiometric characteristics included degree and type of hearing loss: subclinical, conductive, mixed, and sensorineural. RESULTS: LDS types 1 to 4 included 11, 13, 5, and 7 patients, respectively. In LDS-1, 27% had bilateral conductive hearing loss; 9%, unilateral mixed; and 36%, subclinical. In LDS-2, 38% had conductive hearing loss and 38% subclinical. In LDS-3 and LDS-4, 40% and 43% had bilateral sensorineural hearing loss, respectively. Degree of hearing loss ranged from mild to moderate. Bifid uvula was observed only in LDS-1 (55%) and LDS-2 (62%). Submucosal/hard cleft palates were primarily in LDS-1 and LDS-2. Posttympanostomy tympanic membrane perforations occurred in 45% (10/22 ears) of LDS-1 and LDS-2. There were 4 cases of cholesteatoma: 3 middle ear (LDS-1 and LDS-2) and 1 external ear canal (LDS-3). CONCLUSION: Conductive hearing loss, bifid uvula/cleft palate, and posttympanostomy tympanic membrane perforation are more common in LDS-1 and LDS-2 than LDS-3 and LDS-4, while sensorineural hearing loss was present only in LDS-3 and LDS-4. These LDS-associated key clinical presentations may facilitate an early diagnosis of LDS and thus prompt intervention to prevent related detrimental outcomes.

Increased Radiosurgery Toxicity Associated With Treatment of Vestibular Schwannoma in Multiple Sclerosis.

OBJECTIVE: Explore the risk of radiation-induced neurotoxicity in patients with multiple sclerosis (MS) treated with stereotactic radiosurgery (SRS) and better understand the pathophysiology of radiation-induced injury in the central nervous system (CNS). PATIENTS/INTERVENTION: We present the clinical course and magnetic resonance imaging (MRI) findings of a 52-year-old woman with a history of relapsing remitting MS, who developed radiation-induced neurotoxicity following CyberKnife SRS (25 Gy in five fractions) for a left-sided vestibular schwannoma (VS). MAIN OUTCOME MEASURE: Risk of radiation-induced damage following SRS to the CNS, including radiation type and dose, toxicity, and time to symptom onset, in patients with MS. RESULTS: Our patient developed increased imbalance (grade 2 toxicity) 3 months following CyberKnife SRS. Brain MRI showed new fluid-attenuated inversion recovery (FLAIR) hyperintensity in the pons and cerebellum. Neurotoxicity from SRS is rare. However, our literature review showed that 19 patients with MS who underwent intracranial radiation therapy sustained radiation-induced toxicity. The potential mechanisms for increased toxicity in MS could be due to a combination of demyelination, inflammatory, and/or vascular changes. Efficacy of treatments including steroids, bevacizumab, and hyperbaric oxygen therapy is currently unknown. CONCLUSION: Treatment options of SRS and surgery for VS should be carefully considered as patients with known MS may be at increased risk for radiation-induced damage following SRS to the CNS. Thoughtful radiosurgical planning and dosing accounting for this inherent risk is essential for managing patients with MS and VS.

Nasal chondromesenchymal hamartomas in a cohort with pathogenic germline variation in DICER1.

BACKGROUND: Nasal chondromesenchymal hamartomas are benign, rare nasal tumors associated with DICER1 pathogenic germline variation. They can be locally destructive and recurrent if not completely resected. METHODOLOGY: In this single-center, case-control study, otorhinolaryngology evaluations and review of systems questionnaires of DICER1-carriers and controls enrolled in the DICER1 Natural History Study at the National Cancer Institute were collected. Review of these medical records were analyzed to determine if DICER1-carriers experienced different sinonasal clinical manifestations compared to controls. Additionally, the number of diagnoses of nasal chondromesenchymal hamartoma cases in the NCI DICER1 study was compared against the total person years of observation of DICER1-carriers in the study to determine the total number of cases per person-years of observation. Lastly, both the NCI DICER1 study and the International Pleuropulmonary Blastoma/DICER1 Registry were queried for unpublished cases of nasal chondromesenchymal hamartomas. RESULTS: There were no clinical differences in sinonasal symptomatology between DICER1-carriers and control patients seen in the ENT clinic. We observed of two cases of nasal chondromesenchymal hamartoma in a total of 555 person-years of monitoring DICER1-carriers. We include six unpublished nasal chondromesenchymal hamartoma cases. When combined with a comprehensive literature review, 38% of nasal chondromesenchymal hamartoma cases had at least one additional DICER1-associated tumor and 24% of the NCMH were found in the ethmoid sinus, the most commonly involved paranasal sinus. CONCLUSIONS: We quantify the risk of developing nasal chondromesenchymal hamartomas in our cohort of 236 DICER1-carriers, report six unpublished cases, and provide an updated review of the literature.

Audiologic Natural History of Small Volume Cochleovestibular Schwannomas in Neurofibromatosis Type 2.

OBJECTIVE: To characterize the audiometric natural progression in patient-ears with small volume (<1,000 mm), treatment-naïve cochleovestibular schwannomas (CVSs) in Neurofibromatosis Type 2 (NF2). STUDY DESIGN: Prospective, longitudinal cohort study. SETTING: Quaternary medical research institute. PATIENTS: One hundred eleven ears in 71 NF2 patients with small, treatment-naïve CVSs observed from July 2006 to July 2016. INTERVENTION: Serial audiometric testing, including pure tone audiometry, speech audiometry, and magnetic resonance imaging (MRI). OUTCOME MEASURES: Four-frequency pure tone average (4f-PTA) of 0.5, 1, 2, and 4 kHz and word recognition score (WRS) were recorded. Their changes were compared with MRI changes in CVS volume over time. Times to significant hearing loss (10 dB loss in 4f-PTA) and WRS based on 95% critical difference were measured. RESULTS: Linear regression analysis showed a significant correlation with baseline hearing level (4f-PTA) and internal auditory canal (IAC) tumor volume to annual hearing decrease rate (AHDR) (p = 0.003, p = 0.0004). Hearing level at baseline and tumor volume correlate with AHDR while tumor volume growth rate does not. Two-way analysis of variance found significant differences in AHDR, risk of significant hearing loss, and risk of critical difference in WRS based on baseline hearing level (abnormal or normal) and IAC tumor volume (greater or less than 200 mm). CONCLUSION: Subjects with normal baseline hearing and small IAC tumor component had a low AHDR and low risk of significant hearing loss and may warrant conservative management while the presence of baseline hearing loss and large IAC volume resulted in higher ADHR and greater risk for further hearing loss and may benefit from early treatment interventions.

Auditory and otologic profile of Alström syndrome: Comprehensive single center data on 38 patients.

Alström syndrome (AS) is a rare autosomal recessive ciliopathy caused by mutations in the ALMS1 gene. Hallmark characteristics include childhood onset of severe retinal degeneration, sensorineural hearing loss, obesity, insulin-resistant diabetes, and cardiomyopathy. Here we comprehensively characterize the auditory and otologic manifestations in a prospective case series of 38 individuals, aged 1.7-37.9 years, with genetically confirmed AS. Hearing loss was preceded by retinal dystrophy in all cases, and had an average age of detection of 7.45 years (range 1.5-15). Audiometric assessments showed mean pure tone averages (0.5, 1, 2, 4 kHz) of 48.6 and 47.5 dB HL in the right and left ears, respectively. Hearing was within normal limits for only 8/74 ears (11%). For the 66 ears with hearing loss, the degree was mild (12%), moderate (54%), or severe (8%). Type of hearing loss was predominantly sensorineural (77%), while three ears had mixed loss, no ears had conductive loss, and type of hearing loss was indeterminate for the remaining 12 ears. Serial audiograms available for 33 patients showed hearing loss progression of approximately 10-15 dB/decade. Our data show that hearing loss associated with AS begins in childhood and is a predominantly symmetric, sensory hearing loss that may progress to a severe degree. Absent otoacoustic emissions, intact speech discrimination, and disproportionately normal auditory brainstem responses suggest an outer hair cell site of lesion. These findings indicate that individuals with AS would benefit from sound amplification and if necessary, cochlear implantation.

Low surgical complication rates in cochlear implantation for young children less than 1 year of age.

OBJECTIVE: To identify risk factors for perioperative morbidity among a large national cohort of pediatric patients undergoing cochlear implantation. STUDY DESIGN: Retrospective study utilizing the American College of Surgeons National Surgical Quality Improvement Program Pediatric database (2012-2013). METHODS: Pediatric cochlear implantation cases were identified using current procedural terminology 69930. Patients were categorized by age, and operative characteristics along with 30-day perioperative outcomes were analyzed. RESULTS: We identified 1,351 cases of pediatric cochlear implantation. The median age was 3.6 years, and 73 patients were less than 1 year of age. Of 21 complication occurrences (1.55%), superficial incisional surgical site infection (SSI) was the most common (n = 13, 61.9%). Thirty-nine patients (2.9%) required readmission. The median operative time was 142 minutes, and the mean postoperative length of stay was 0.58 days. When comparing patients younger than 1 year old to those 1 year or older, no significant differences were noted in complication rate, postoperative length of stay, or reoperation rate. Patients less than 1 year of age were more likely to be readmitted (6.9% vs. 2.7%, P = 0.04) and had longer mean operative times (191 minutes vs. 160 minutes, P = 0.0015). Steroid use was a risk factor for unplanned reoperation, SSI, and readmission. CONCLUSION: Despite a slight increase in readmission rates and operative times among patients less than 1 year of age, cochlear implantation appears to be safe in this population, with complication rates, reoperation rates, and postoperative lengths of stay similar to children undergoing the procedure at the current U.S. Food and Drug Administration-approved age of 1 year and older. LEVEL OF EVIDENCE: 4. Laryngoscope, 127:720-724, 2017.

Audiovestibular Characteristics of Small Cochleovestibular Schwannomas in Neurofibromatosis Type 2.

OBJECTIVE: Describe the relationship between cochleovestibular schwannoma (CVS) volume, audiovestibular characteristics, and magnetic resonance imaging (MRI) findings in patients with neurofibromatosis type 2 (NF2). STUDY DESIGN: Subgroup analysis of NF2 prospective natural history study from 2008 to 2011. SETTING: Quaternary medical research institute. SUBJECTS AND METHODS: NF2 patients with small treatment-naive CVSs (volume <1000 mm(3)) by ear; N = 49 ears (32 patients). Cross-sectional analysis of the following parameters was performed: tumor size, auditory brainstem response (ABR), 4-frequency pure-tone average (4f-PTA; 0.5, 1, 2, and 4KHz), cervical vestibular evoked myogenic potential (cVEMP), caloric testing, 240° velocity step test (VST), and MRI findings. RESULTS: For all physiologic measures but the 4f-PTA, larger tumors correlated with abnormal responses (P < .05). For abnormal ABR, mean tumor volume was 405 vs 151 mm(3) (P = .0007) for normal ABR. Similarly, larger tumors correlated with weak caloric responses (mean 521 vs 165 mm(3); P = .0007) and weak cVEMP (mean 357 vs 192 mm(3); P = .0262). Tumor volume was not significantly correlated with 4f-PTA. Elevated intralabyrinthine protein on MRI fluid-attenuated inversion recovery sequences was correlated with larger tumor volume (mean 333 vs 55 mm(3); P = .001) and abnormal ABR and 4f-PTA (P < .05) but did not correlate with cVEMP, VST, or caloric responses. CONCLUSION: In our cohort, ABR, caloric response, cVEMP, and elevated intralabyrinthine protein correlated with tumor volume, but 4f-PTA did not. Abnormal ABR and 4f-PTA correlated with elevated intralabyrinthine protein. These findings may provide insight on the effect of small CVS on the inner ear and cochleovestibular nerves, which may aid in their optimal management.

Clinical presentation and imaging findings in patients with pulsatile tinnitus and sigmoid sinus diverticulum/dehiscence.

OBJECTIVE: Sigmoid sinus diverticulum/dehiscence (SSDD) is an increasingly recognized venous cause for pulsatile tinnitus (PT). SSDD is amenable to surgical/endovascular intervention. We aim to understand the clinical and imaging features of patients with PT due to SSDD. STUDY DESIGN: Retrospective CT study and chart review. SETTING: Tertiary-care, academic center. PATIENTS: Cohort 1: 200 consecutive unique temporal bone CT were blindly reviewed for anatomic findings associated with PT. Cohort 2: 61 patients with PT were evaluated for otologic manifestations. INTERVENTION(S): All patients underwent a temporal bone CT for evaluation of PT. Clinical information was gathered using electronic medical records. MAIN OUTCOME MEASURE(S): Otologic symptoms and physical findings (including body mass index (BMI), mastoid/neck bruits) were analyzed. Temporal bone CT scans were evaluated for the presence of SSDD and other possible causes of PT. RESULTS: Cohort 1: 35 cases of SSDD were identified (18%); 10 (29%) true diverticula; and 25 (71%) dehiscence. Sixty-six percent were right sided. Twelve patients had PT (34%). Patients with SSDD are more likely to have PT (p = 0.003). A significant association between right SSDD and PT was found (p = 0.001). Cohort 2: 15 out of 61 patients had PT and CT-confirmed SSDD. All were female subjects; average age was 45 years (26-73 yr). Radiologic evaluation revealed 10 SSDD cases on the right (66.7%), 2 on the left (13.3%%), and 3 bilateral (20%). Sensorineural hearing loss was seen in 8 (53%), aural fullness in 12 (80%). Average BMI was 32.2 (21.0-59.82), and 4 (26%) had audible mastoid bruits. CONCLUSION: SSDD may be the most common identifiable cause for PT from venous origin and is potentially treatable. Temporal bone CT scans should be included in a complete evaluation of PT.

Sinonasal disease in polyostotic fibrous dysplasia and McCune-Albright Syndrome.

OBJECTIVES/HYPOTHESIS: To characterize the spectrum, symptoms, progression, and effects of endocrine dysfunction on sinonasal disease in polyostotic fibrous dysplasia (PFD) and McCune-Albright Syndrome (MAS). STUDY DESIGN: Retrospective review. METHODS: A prospectively followed cohort of subjects with PFD/MAS underwent a comprehensive evaluation that included otolaryngologic and endocrine evaluation, and imaging studies. Head and facial computed tomography scans were analyzed, and the degree of fibrous dysplasia (FD) was graded using a modified Lund-MacKay scale. Those followed for >4 years were analyzed for progression. RESULTS: A total of 106 patients meeting inclusion criteria were identified with craniofacial FD. A majority (92%) demonstrated sinonasal involvement. There were significant positive correlations between the sinonasal FD scale score and chronic congestion, hyposmia, growth hormone excess, and hyperthyroidism (P < .05 for all). Significant correlations were not found for headache/facial pain or recurrent/chronic sinusitis. Thirty-one subjects met the criteria for longitudinal analysis (follow-up mean, 6.3 years; range, 4.4-9 years). Those who demonstrated disease progression were significantly younger than those who did not (mean age, 11 vs. 25 years). Progression after age of 13 years was uncommon (n = 3) and minimal. Concomitant endocrinopathy or bisphosphonate use did not have any significant effect on progression of disease. CONCLUSIONS: Sinonasal involvement of fibrous dysplasia in PFD/MAS is common. Symptoms are usually few and mild, and disease progression occurs primarily in young subjects. Concomitant endocrinopathy is associated with disease severity, but not progression.

Otitis media.

Otitis media represents a broad spectrum of disease, which include acute otitis media and otitis media with effusion. As immunization with the pneumococcal conjugate vaccine has become more widespread, the microbiological landscape of otitis media has changed, which affects the treatment options facing clinicians worldwide. This review discusses the diagnosis and medical management of acute and chronic suppurative otitis media, the changes noted over the past decade, and briefly expounds on the surgical management of their severe complications.