Cortical Auditory Evoked Potential Testing in Children With Auditory Neuropathy Spectrum Disorder.

PURPOSE: In the present report, we reviewed the role of cortical auditory evoked potentials (CAEPs) as an objective measure during the evaluation and management process in children with auditory neuropathy spectrum disorder (ANSD). METHOD: We reviewed the results of CAEP recordings in 66 patients with ANSD aged between 2 months and 12 years and assessed the relationship between their characteristics (prevalence, morphology, latencies, and amplitudes) and various clinical features, including the mode of medical management. RESULTS: Overall, the CAEPs were present in 85.2% of the ears tested. Factors such as prematurity, medical complexity, neuronal issues, or presence of syndromes did not have an effect on the presence or absence of CAEPs. CAEP latencies were significantly shorter in ears with cochlear nerve deficiency than in ears with a normal caliber nerve. Three different patterns of CAEP responses were observed in patients with bilateral ANSD and present cochlear nerves: (a) responses with normal morphology and presence of both P1-P2complex and N2 components, (b) responses with abnormal morphology and presence of the N2 component but undefined P1-P2complex peak, and (c) entirely absent responses. None of the patients with normal, mild, or moderate degree of hearing loss had a complete absence of CAEP responses. No significant differences were uncovered when comparing the latencies across unaided and aided children and children who later received cochlear implants. CONCLUSIONS: The CAEP protocol used in our ANSD program did inform about the presence or absence of central auditory stimulation. Absent responses typically fit into an overall picture of complete auditory deprivation and all of these children were ultimately offered cochlear implants after failing to develop oral language. Present responses, on the other hand, were acknowledged as a sign of some degree of auditory stimulation but always interpreted with caution given that prognostic implications remain unclear.

Asymmetric Ocular Vestibular Evoked Myogenic Potentials in Pediatric Vestibular Migraine.

OBJECTIVE: Although ocular vestibular evoked myogenic potentials (oVEMP) abnormalities have been associated with vestibular migraine (VM) in adults, no studies have evaluated this in pediatric patients with VM. oVEMP asymmetry with normal cervical VEMP (cVEMP) findings may be a reliable VM biomarker in adults. We characterize VEMP results among pediatric patients with VM and benign recurrent vertigo of childhood (BRVC), a migraine precursor, and compare these results with VEMP findings from pediatric patients with nonmigrainous vestibular diagnoses. METHODS: Four hundred seventy-four pediatric patients were evaluated over a 3-year period in a multidisciplinary pediatric vestibular clinic, 139 of whom met the inclusion criteria. Records were reviewed for history, audiometry, and vestibular testing results. VEMP testing was performed with a 500-Hz tone burst. Based on adult normative data, oVEMP asymmetry was defined as greater than 33% interaural difference; cVEMP asymmetry was defined as greater than 41%. RESULTS: Eighty subjects had VM or BRVC (mean [standard deviation] 12.8 [3.8] yr; range, 4.3-18.2 yr). Fifty-nine subjects received vestibular diagnoses other than VM or BRVC (nonmigrainous group; mean [standard deviation] age, 13.0 [3.6] yr; range, 5.14-18.9 yr). A greater proportion of the VM/BRVC group demonstrated oVEMP asymmetry with normal cVEMP as compared with the nonmigrainous group (22.5% versus 10.1%; p < 0.05). Zero subjects in the VM/BRVC group demonstrated cVEMP asymmetry versus three subjects (4.9%) of the nonmigrainous group. CONCLUSIONS: VM and BRVC are notable causes of migraine-related vertigo among pediatric patients. Of VM/BRVC patients, 22.5% had oVEMP asymmetry with normal cVEMP. Similar to the adult VM population, this finding may be a useful biomarker in the right clinical setting for pediatric VM. LEVEL OF EVIDENCE: 4.

A 15-Year Review of 260 Children With Auditory Neuropathy Spectrum Disorder: I. Demographic and Diagnostic Characteristics.

OBJECTIVES: The aim of the study was to review the demographic and clinical characteristics of all pediatric patients diagnosed with auditory neuropathy spectrum disorder (ANSD) by a pediatric health care system from 2005 to 2020 and examine whether or not our diagnostic capabilities in an ANSD population have evolved as our institutional experience has grown and knowledge in the field has expanded. DESIGN: This was a retrospective study reviewing the demographic data, medical history, imaging studies, audiological and speech-language data, type of audiological intervention and mode of communication in 260 pediatric patients diagnosed with ANSD over a 15-year period. RESULTS: The study revealed that male and female children were equally affected with all levels of hearing detection being represented and that about 40% of affected children were premature and most were admitted to the neonatal intensive care unit. More than a third of our patients presented with a complex medical history and/or neural involvement while about 30% were full-term newborns with normal pregnancy, no prenatal complications or infections, normal birth weight, no neonatal intensive care unit need, no hyperbilirubinemia, no respiratory distress requiring ventilation, and no known syndrome. Review of audiological findings confirms that otoacoustic emissions are not always present in ANSD cases, and that the presence of an abnormal wave V on the auditory brainstem response tracings (only present at high intensities and with an absent intensity/latency function) is not a rare finding and should not immediately be dismissed as not being a case of ANSD. CONCLUSIONS: This review of ANSD diagnosis over a 15-year period clearly reveals the drastic improvements made in the identification of ANSD, with a drastic decrease in the age at diagnosis and a reduction in the percentage of misdiagnosed patients. The study also stresses the need for continued improvement in different areas such as genetic studies and physiological measures to help clinicians distinguish between pre- and postsynaptic ANSD.

Congenital soft tissue stenosis of the external auditory canal with canal cholesteatoma: Case report and literature review.

Congenital external auditory canal stenosis (EACS) is a spectrum of abnormalities affecting the external and middle ear. We report a 6 year-old patient with EACS affecting the lateral fibrocartilaginous canal that was successfully repaired. This patient highlights a variant of EACS characterized by lateral soft tissue narrowing with normal osseous development. Most previous studies of CAA have described severe forms associated with complete atresia, bony stenosis, and middle ear malformations. Stenosis affecting only the fibrocartilaginous canal is a milder form resulting from premature arrest of the canalization process during embryologic development, and may predispose to cholesteatoma formation.

Cochlear Nerve Deficiency and Brain Abnormalities in Pediatric Patients.

HYPOTHESIS: To investigate the intracranial abnormalities present in children with cochlear nerve deficiency (CND), including abnormalities of other cranial nerves, and to describe their auditory abilities. BACKGROUND: The prevalence of CND has increased with the development of high resolution magnetic resonance imaging (MRI). There are varying degrees of CND from true aplasia to hypoplasia. The etiology of CND remains unclear and it may be associated with intracranial abnormalities in some instances. CND needs to be identified as early as possible to ensure prompt and adequate management of hearing loss since hearing aids and cochlear implants may not be an option. METHODS: A retrospective chart review of 56 ears of pediatric patients with CND was conducted between August 2006 and November 2014 at a tertiary care pediatric hospital. RESULTS: 27.6% of children had cochlear abnormalities and 48.9.8% had concomitant vestibular anomalies. Five patients had absent or abnormal facial nerves and two patients had aplastic bilateral olfactory nerves. In the 27 ears with an absent nerve that were functionally tested, eight (29.6%) had partial hearing which indicates the presence of an extremely small nerve whose size is below the limits of spatial resolution of the MRI. CONCLUSION: MRI is becoming the initial imaging choice for children with sensorineural hearing loss to identify CND and other brain anomalies. Concomitant vestibular and cochlear abnormalities were observed in respectively half and one-third of the pediatric patients with CND. The incidence of vestibular malformation suggests that balance testing should be recommended for most if not all CND patients.

A pearl in the ear: Intracranial complications of pediatric cholesteatomas.

A nine-year-old male had a cholesteatoma of the mastoid and middle ear found incidentally after myringotomy tube placement. Associated asymptomatic sigmoid plate dehiscence with sinus invasion or thrombosis and ossicular chain destruction complicated his case. He had canal wall down tympanomastoidectomy and was followed for 4.5 years. Disease recurrence necessitated revision. Our case highlights an unusual clinical presentation, possible complications, and the aggressive quality of a benign lesion common in the pediatric population. To our knowledge, this is the first report of an asymptomatic lateral sinus obstruction secondary to an invasive cholesteatoma in this population.

The role of gastric pepsin in the inflammatory cascade of pediatric otitis media.

IMPORTANCE: Otitis media is characterized as an ongoing inflammation with accumulation of an effusion in the middle ear cleft. The molecular mechanisms underlying the pathogenesis, particularly the inflammatory response, remain largely unknown. We hypothesize that aspiration of gastric contents into the nasopharynx may be responsible for the initiation of the inflammatory process or aggravate a preexisting condition. OBJECTIVE: To investigate the correlation of gastric pepsin A with inflammatory cytokines, bacterial infection, and clinical outcomes. DESIGN, SETTING, AND PARTICIPANTS: Prospective study of 129 pediatric patients undergoing myringotomy with tube placement for otitis media at a tertiary care pediatric hospital. MAIN OUTCOMES AND MEASURES: Ear samples were tested for pepsin A; cytokines interleukin (IL)-6, IL-8, and tumor necrosis factor; and bacterial culture inoculation. Data were analyzed by descriptive statistics and regression analysis to identify risk factors for the presence of pepsin A and to correlate pepsin A levels with cytokine levels, infection status, and clinical outcomes. RESULTS: Of the 129 patients, 199 ear samples were obtained; 82 samples (41%) and 64 patients (50%) were positive for pepsin A as measured by immunoassay. Pepsin A positivity correlated with age younger than 3.0 years (mean [SD], 2.3 [2.1] years in the positive group vs 3.3 [3.0] years in the negative group) and with all 3 cytokine levels (mean [SD] tumor necrosis factor, 29.5 [45.9] pg/mL in the positive group vs 13.2 [21.6] pg/mL in the negative group; IL-6, 6791.7 [9389.1] pg/mL in the positive group vs 2849.9 [4066.3] pg/mL in the negative group; and IL-8, 6828.2 [8122.3] pg/mL in the positive group vs 2925.1 [3364.5] pg/mL in the negative group [all P < .05]); however, logistic regression analysis showed that only IL-8 (odds ratio, 3.96; 95% CI, 1.3-12.0; P = .02) and age (odds ratio, 3.83; 95% CI, 1.2-12.7; P = .03) were significant independent variables. No statistically significant association was found with other parameters. Multiple linear regressions revealed that the levels of pepsin A were correlated with IL-8 levels (R2 = 0.248; P < .001) and the need for second or third tubes 6 to 12 months after the first (R2 = 0.102; P = .006). The presence of pepsin A in the middle ear was not associated with increased bacterial infection. Interleukin 8 was independent and significantly associated with both pepsin A levels and bacterial infection (R2 = 0.144 and 0.263, respectively; P = .001 for both). CONCLUSIONS AND RELEVANCE: Extraesophageal reflux as indicated by the presence of pepsin A is closely involved in the middle ear inflammatory process and may worsen the disease in some children; however, a proof of cause and effect between extraesophageal reflux and middle ear inflammation requires further investigation.

A homozygous SLITRK6 nonsense mutation is associated with progressive auditory neuropathy in humans.

OBJECTIVES/HYPOTHESIS: SLITRK family proteins control neurite outgrowth and regulate synaptic development. In mice, Slitrk6 plays a role in the survival and innervation of sensory neurons in the inner ear, vestibular apparatus, and retina, and also influences axial eye length. We provide the first detailed description of the auditory phenotype in humans with recessive SLITRK6 deficiency. STUDY DESIGN: Prospective observational case study. METHODS: Nine closely related Amish subjects from an endogamous Amish community of Pennsylvania underwent audiologic and vestibular testing. Single nucleotide polymorphism microarrays were used to map the chromosome locus, and Sanger sequencing or high-resolution melt analysis were used to confirm the allelic variant. RESULTS: All nine subjects were homozygous for a novel nonsense variant of SLITRK6 (c.1240C>T, p.Gln414Ter). Adult patients had high myopia. The 4 oldest SLITRK6 c.1240C>T homozygotes had absent ipsilateral middle ear muscle reflexes (MEMRs). Distortion product otoacoustic emissions (DPOAEs) were absent in all ears tested and the cochlear microphonic (CM) was increased in amplitude and duration in young patients and absent in the two oldest subjects. Auditory brainstem responses (ABRs) were dys-synchronised bilaterally with no reproducible waves I, III, or V at high intensities. Hearing loss and speech reception thresholds deteriorated symmetrically with age, which resulted in severe-to-profound hearing impairment by early adulthood. Vestibular evoked myogenic potentials were normal in three ears and absent in one. CONCLUSION: Homozygous SLITRK6 c.1240C>T (p.Gln414Ter) nonsense mutations are associated with high myopia, cochlear dysfunction attributed to outer hair cell disease, and progressive auditory neuropathy.

Clinical characteristics of pediatric granular myringitis.

OBJECTIVE: To determine the clinical characteristics of children with granular myringitis. STUDY DESIGN: Case series with chart review of children with granular myringitis. SETTING: Tertiary care children's hospitals in Delaware and Florida. SUBJECTS AND METHODS: From July 1, 2006, to June 30, 2011, 15 patients were identified with granular myringitis based on International Classification of Diseases, Ninth Revision code 384.1 (10 male, 5 female; 10 left-sided, 5 right-sided). RESULTS: Average age at onset was 10 years (range, 4-18 years). Average length of symptoms was 21 months (range, 3-48 months). Thirteen of the 15 patients (87%) had myringotomy tube placement prior to diagnosis of myringitis, and 11 had a previous perforation (73%). Eleven myringoplasties were performed on 8 (53%) patients prior to the onset of granular myringitis (5 fascia, 2 fat, 2 cartilage, 1 paper patch, and 1 at an outside hospital that was unknown). A total of 27 otolaryngologic surgical procedures were done on 14 of 15 patients. Ten patients (67%) had audiometry performed, and 6 (40%) had ear cultures. Medical treatment included ciprofloxacin and dexamethasone otic drops in all patients, oral antibiotics in 4 patients, and additional topical agents in 8 patients. Two patients had laser resurfacing, and 1 patient had surgical curettage. Five patients had long-term remission, 8 had intermittent remission, and 2 had no remission of their symptoms. CONCLUSION: Granular myringitis is a chronic, recalcitrant disease typically preceded by myringotomy and tube placement or myringoplasty/tympanoplasty. Medical and surgical intervention is varied and often does not lead to permanent resolution of the disease.

Clinical characteristics of children with cochlear nerve dysplasias.

OBJECTIVES/HYPOTHESIS: To describe the clinical and audiometric characteristics of children with cochlear nerve dysplasia (CND). STUDY DESIGN: Retrospective chart review of clinical database of children with inner ear anomalies treated at a tertiary care children's hospital. METHODS: Institutional review board-approved retrospective review from June 30, 2006, to July 1, 2011; 18 children were identified with magnetic resonance imaging (MRI) evidence of CND defined as a cochlear nerve 50% smaller than the adjacent facial nerve. RESULTS: Of the 18 patients, nine were girls and nine were boys. Average age at time of MRI diagnosis of CND was 4.6 years. Twelve children had cochlear nerve aplasia, and six had hypoplasia. Three were affected bilaterally: two with aplasia and one with hypoplasia. Unilateral dysplasia was found in 15 children; of these, 60% occurred on the left side. Other inner ear anomalies were found in 50%, including all patients with bilateral CND. Severe-to-profound hearing loss was found in the involved ear(s) in 14 of 18 patients, including all bilateral patients. Of the 18 patients tested, 13 (72%) had an audiometric profile of auditory neuropathy/dys-synchrony syndrome (auditory neuropathy spectrum disorder [ANSD]). Comorbid conditions were present in 56% of patients. Two patients were syndromic. Family history of hearing loss was present in 11% of patients. CONCLUSIONS: Many patients with CND have ANSD, and more than half have comorbidities. Approximately half of affected patients have other inner ear anomalies in the involved ears. Unilateral CND may be more common on the left side.

Auditory nerve function following cochleitis.

We present a case of temporary cochlear nerve dysfunction due to endocochlear inflammation with subsequent recovery. Retrospective case review at a pediatric tertiary care hospital. A nine-year-old male presented seven years post-cochlear implantation with an electrode array extruded into the external auditory canal. Upon exploration in the operating room, turbid perilymph from the scala tympani was discovered. A new electrode array was implanted. The patient had no discernible neural response telemetry (NRT) responses or auditory perception immediately following the procedure. Continuous but varying stimulation was continued postoperatively. Two months after implantation, he began having some auditory awareness; subsequent mapping resulted in the activation of a limited number of channels. Nine months following reimplantation, NRT demonstrated responses in three channels. Additionally, functional gain testing revealed sound awareness levels in the mild-hearing-loss range and the patient was able to detect and repeat all six Ling sounds. Continuous cochlear nerve stimulation at various levels may aid in function recovery after endocochlear inflammation.

Atypical presentation of geniculate ganglion venous malformation in a child: conductive hearing loss without facial weakness.

We describe an unusual presentation of geniculate ganglion venous malformation, a rare facial nerve lesion, emphasizing the importance of the differential diagnosis, imaging characteristics, and controversies in management. A child presented with moderate right-sided conductive hearing loss and a House-Brackmann grade I facial nerve function bilaterally. Computed tomography and magnetic resonance imaging showed a mass demonstrating features consistent with a geniculate ganglion venous malformation. To our knowledge, this is the first pediatric case of geniculate ganglion venous malformation presenting solely with conductive hearing loss. Proper management requires differentiating this condition from other geniculate and temporal bone lesions.

Complications of otitis media.

Otitis media is the most common reason for antibiotic prescription in the United States. Whether due to disease virulence or growing antimicrobial resistance, complications of otitis media seem to be seen more frequently. These complications may be difficult to identify and treat. This article focuses on the pathophysiology of these complications and address medical and surgical approaches to safe treatment.

Hearing loss in children with mitochondrial disorders.

OBJECTIVE: At least 1-5 children per 1000 suffer from congenital hearing loss, and 50% of these cases can be attributed to genetic causes. It has been estimated that 1% of pre-lingual hearing loss is due to mutations in mitochondrial DNA. Previous literature reports audiometric data for few patients, usually less than 20 per study. The goal of this study was to characterize the hearing loss associated with mitochondrial mutations and determine whether previously characterized patterns of hearing loss in these patients (progressive, sensorineural, high frequency losses) are found in our population as well. METHODS: An IRB-approved retrospective chart review of the electronic medical records in the Nemours/Alfred I. dupont Hospital for Children system from January 2004 to October 2009 (a five-year period) was undertaken using ICD-9 codes 277.87 (mitochondrial disorder) and 359.89BA (mitochondrial myopathy). These 149 records were then evaluated for audiologic data, resulting in 26 charts with both a mitochondrial disorder and hearing evaluation. RESULTS: Of 26 patients with known mitochondrial disorders and audiometric documentation, 15 (58%) had hearing loss, and 11 patients had normal hearing (42%). Ten patients had sensorineural hearing loss (38%), two patients had conductive hearing loss (7.7%), one patient had a mixed hearing loss (3.8%), and two patients had an as yet undefined hearing loss (ABR had not yet been performed at the time of this study) (7.7%). CONCLUSION: In comparison with previous studies, generally including less than 20 patients, this is one of the largest collections of audiometric data on children with mitochondrial disorders. Unlike prior studies describing a progressive, sensorineural loss across all frequencies or mainly affecting high frequencies, the hearing loss in our patients was more variable including low frequency losses, mid-frequency losses, and conductive losses and was often not progressive or even improved. Our overall 38% rate of sensorineural hearing loss correlates well with previous case series; this study clearly justifies the use of routine audiometric screening in children with mitochondrial disorders, including use of ABR and OAEs as ASND can be seen in this population, as well as repeat testing over time to evaluate for progression.

Comprehensive vestibular and balance testing in the dizzy pediatric population.

OBJECTIVE: To describe the spectrum of balance disease in a large population of children presenting to a tertiary care vestibular and balance laboratory. STUDY DESIGN: Case series with chart review. SETTING: Tertiary care pediatric hospital. MAIN OUTCOME MEASURES: Results of audiometric, vestibular, and balance tests and final diagnosis. SUBJECTS AND METHODS: Retrospective review of audiometric, vestibular, balance testing, and final diagnosis from a patient database. RESULTS: Between September 2003 and September 2007, 132 children were evaluated at the Alfred I. duPont Hospital for Children Vestibular Disorders Program. Sixty-nine of the patients were boys and 63 were girls. The average age was 9.7 ± 5.0 years (range, 1-17 years). Although not all were able to complete the entire test battery (99 children completed at least 50% of the tests in the protocol), a diagnosis was achieved in most cases. The most common diagnoses were peripheral vestibulopathy (29.5%), migraine/benign recurrent vertigo of childhood (24.2%), motor/developmental delay (10.6%), traumatic brain injury (9.8%), and central nervous system structural lesion (9.1%). CONCLUSIONS: Peripheral vestibular deficits and migraine disease account for most of the pathology in the pediatric population. With a multidisciplinary approach, diagnosis of the source of vertigo and imbalance is possible in most children.

Prevalence of vestibular and balance disorders in children.

OBJECTIVE: Determine the prevalence of vestibular and balance disorders in children, rate of complaints of imbalance, and odds ratio of related diagnoses. PATIENTS AND METHODS: Retrospective review of pediatric health system during a 4-year period for International Classification of Diseases, 9th Revision, codes related to balance disorders. Identified records were searched for chief complaints related to balance and for codes of related otologic and neuro-otologic diagnoses. RESULTS: A total of 561,151 distinct patient encounters were found. Unspecified dizziness was diagnosed in 2,283 patients (0.4%). Also, 22% presented with balance complaints. Peripheral disorders were diagnosed in 159, and central disturbances were diagnosed in 109 (prevalence < 0.0002%). Cumulative prevalence of diagnoses related to balance was 0.45% (2,546/561,151). Of all patients, 5,793 (1.03%) had chief complaint related to balance, and 2,076 (35.84%) were also diagnosed with vestibular disorder. Moreover, 38% with peripheral disturbances and 21% with central disturbances had balance complaints. Odds ratio of syncope was 21× higher than the general pediatric population in patients with unspecified dizziness, and sensorineural hearing loss was 43 times higher in those with peripheral vestibular disorders. In patients with central disorders headache was 16× higher (p < 0.05). CONCLUSION: The prevalence of balance disorders in children is low. Children diagnosed with these disorders typically do not present with chief complaint related to balance. Significant associations exist between sensorineural hearing loss, syncope, and headache in children diagnosed with balance disorders.

Inflammatory pseudotumor of the inner ear: are computed tomography changes pathognomonic?

This case study presents a report of inflammatory pseudotumor of the inner ear in a child, discusses radiographic findings and clinical management, and reviews the current literature on this rare disease. A 2.5-year-old presented with otalgia, transient vertigo, and fluctuating facial palsy partially responsive to myringotomy with tube. Work-up for infectious and neoplastic processes was negative. Computed tomography (CT) of the temporal bone showed a very unusual, expansile, erosive appearance to the otic capsule, and magnetic resonance imaging of the temporal bone revealed soft tissue enhancement of the middle ear, mastoid, and inner ear. The patient's symptoms were transiently responsive to tympanomastoidectomy. Inner ear histopathology after labyrinthectomy revealed changes consistent with pseudotumor. Inflammatory pseudotumor of the inner ear is extremely rare but needs to be considered in cases of refractory otitis media with facial palsy, particularly when certain changes appear on CT of the temporal bone.