Importance of early objective auditory testing in the presentation of sudden sensorineural hearing loss in children.

BACKGROUND: Functional hearing loss can be due to an auditory manifestation of functional neurological disorder, previously known as conversion disorder. METHODS: This is a case series of 3 pediatric patients with a diagnosis of idiopathic SSNHL who ultimately were found to have functional neurological disorder. RESULTS: Average age was 12.7 years at presentation (range 10-14 years). All three patients underwent invasive interventions prior to their initial clinic visit. All patients demonstrated profound SNHL on behavioural audiogram, but normal otoacoustic emissions (OAE) and auditory brainstem response testing. With counselling, both patients demonstrated significant hearing improvement. CONCLUSIONS: Early use of OAE's in the workup of SSNHL can avoid unnecessary and potentially harmful therapies and expedite access to counselling services which may help lead to symptom resolution.

The Importance of Access to Bilateral Hearing through Cochlear Implants in Children.

Children with hearing loss require early access to sound in both ears to support their development. In this article, we describe barriers to providing bilateral hearing and developmental consequences of delays during early sensitive periods. Barriers include late identification of hearing loss in one or both ears and delayed access to intervention with hearing devices such as cochlear implants. Effects of delayed bilateral input on the auditory pathways and brain are discussed as well as behavioral effects on speech perception and other developmental outcomes including language and academics. Evidence for these effects has supported an evolution in cochlear implant candidacy in children that was started with unilateral implantation in children with profound deafness bilaterally to bilateral implantation to implantation of children with asymmetric hearing loss including children with single-side deafness. Opportunities to enhance the developmental benefits of bilateral hearing in children with hearing loss are also discussed including efforts to improve binaural/spatial hearing and consideration of concurrent vestibular deficits which are common in children with hearing loss.

Hearing Loss After Radiation and Chemotherapy for CNS and Head-and-Neck Tumors in Children.

PURPOSE: Hearing loss (HL) is a serious secondary effect of treatment for CNS and head-and-neck tumors in children. The goal of this study was to evaluate incidence and risk factors for HL in patients with multiple ototoxic exposures. PATIENTS AND METHODS: We evaluated 340 ears from 171 patients with CNS or head-and-neck tumors treated with radiation, with or without chemotherapy, who had longitudinal audiologic evaluation. International Society of Pediatric Oncology-Boston grades were assigned to 2,420 hearing assessments. Multivariable weighted ordinal logistic regression was fitted to evaluate the effect of clinicopathologic features on HL. RESULTS: Mean cochlea dose (odds ratio [OR] 1.04 per Gy, P < .001), time since radiotherapy (RT; OR 1.21 per year, P < .001), cisplatin dose (OR 1.48 per 100 mg/m2, P < .001), and carboplatin dose (OR 1.41 per 1,000 mg/m2, P = .002) were associated with increasing International Society of Pediatric Oncology-Boston grade of HL. There was no synergistic effect of RT and cisplatin (interaction term, P = .53) or RT and carboplatin (interaction term, P = .85). Cumulative incidence of high-frequency HL (> 4 kHz) was 50% or greater at 5 years after RT if mean cochlea dose was > 30 Gy, while incidence of HL across all frequencies continued to increase beyond 5 years after RT. CONCLUSION: Children treated with radiation and chemotherapy experience a high incidence of HL over time, with associations found between more severe HL and cisplatin or carboplatin dose as well as mean cochlea dose. Mean cochlea dose of ≤ 30 Gy is proposed as a goal to reduce the risk of HL; a lower threshold (20-25 Gy) may be considered in patients receiving platinum chemotherapy to reduce cumulative HL burden.

Hearing loss and intellectual outcome in children treated for embryonal brain tumors: Implications for young children treated with radiation sparing approaches.

PURPOSE: We investigate the impact of severe sensorineural hearing loss (SNHL) and for the first time evaluate the effect of unilateral versus bilateral SNHL on intellectual outcome in a cohort of children with embryonal brain tumors treated with and without radiation. METHODS: Data were from 94 childhood survivors of posterior fossa (PF) embryonal brain tumors who were treated with either: (1) chemotherapy alone (n = 16, 7.11 [3.41] years, 11M/5F), (2) standard-dose craniospinal irradiation (CSI) and/or large boost volumes (n = 44, 13.05 [3.26] years, 29M/15F), or (3) reduced-dose CSI with a boost restricted to the tumor bed (n = 34, 11.07 [3.80] years, 19M/15F). We compared intellectual outcome between children who: (1) did and did not develop SNHL and (2) developed unilateral versus bilateral SNHL. A Chang grade of ≥2b that required the use of a hearing aid was considered severe SNHL. Comparisons were made overall and within each treatment group separately. RESULTS: Patients who developed SNHL had lower full scale IQ (p = 0.007), verbal comprehension (p = 0.003), and working memory (p = 0.02) than patients without SNHL. No differences were observed between patients who had unilateral versus bilateral SNHL (all p > 0.05). Patients treated with chemotherapy alone who developed SNHL had lower mean working memory (p = 0.03) than patients who did not develop SNHL. Among patients treated with CSI, no IQ indices differed between those with and without SNHL (all p > 0.05). CONCLUSIONS: Children treated for embryonal brain tumors who develop severe SNHL have lower intellectual outcome than patients with preserved hearing: this association is especially profound in young children treated with radiation sparing approaches. We also demonstrate that intellectual outcome is similarly impaired in patients who develop unilateral versus bilateral SNHL. These findings suggest that early intervention to preserve hearing is critical.

The Effect of Music and White Noise on Electroencephalographic (EEG) Functional Connectivity in Neonates in the Neonatal Intensive Care Unit.

The purpose of this study is to investigate whether listening to music and white noise affects functional connectivity on scalp electroencephalography (EEG) in neonates in the neonatal intensive care unit.Nine neonates of ≥34 weeks' gestational age, who were already undergoing clinical continuous EEG monitoring in the neonatal intensive care unit, listened to lullaby-like music and white noise for 1 hour each separated by a 2-hour interval of no intervention. EEG segments during periods of music, white noise, and no intervention were band-pass filtered as delta (0.5-4 Hz), theta (4-8 Hz), lower alpha (8-10 Hz), upper alpha (10-13 Hz), beta (13-30 Hz), and gamma (30-45 Hz). Synchronization likelihood was used as a measure of connectivity between any 2 electrodes.In theta, lower alpha, and upper alpha frequency bands, the synchronization likelihood values yielded statistical significance with sound (music, white noise and no intervention) and with edge (between any 2 electrodes) factors. In theta, lower alpha, and upper alpha frequency bands, statistical significance was obtained between music and white noise (t = 3.12, 3.32, and 3.68, respectively; P < .017), and between white noise and no intervention (t = 4.51, 3.09, and 2.95, respectively, P < .017). However, there was no difference between music and no intervention.Although limited by a small sample size and the 1-time only auditory intervention, these preliminary results demonstrate the feasibility of EEG connectivity analyses even at bedside in neonates on continuous EEG monitoring in the neonatal intensive care unit. They also point to the possibility of detecting significant changes in functional connectivity related to the theta and alpha bands using auditory interventions.

The limitation of risk factors as a means of prognostication in auditory neuropathy spectrum disorder of perinatal onset.

OBJECTIVE: The management of hearing loss due to auditory neuropathy spectrum disorder (ANSD) in neonates and infants is challenging because speech and language development prognosis cannot be directly inferred from early audiometric hearing thresholds. Consequently, appropriate intervention with hearing aids or cochlear implantation (CI) can be delayed. Our objective was to determine whether any features of patient history could be used to identify CI candidates with ANSD at an earlier age. METHOD: A database was maintained over 11 years to monitor cases of perinatal onset ANSD. Risk factors associated with the perinatal time period considered pertinent to hearing outcomes were assessed, including prematurity, birth weight, APGAR score, ototoxic drugs, and hyperbilirubinemia. Children with cochlear nerve aplasia and genetic mutations were excluded. Hearing outcome was determined according to mode of auditory rehabilitation beyond 30 months of age: A) no hearing device; B) hearing aid; C) CI. RESULTS: Of twenty-eight children with ANSD, nine (32%) had behavioural thresholds and language development sufficient to require no assistive device, 9 (32%) were fitted with hearing aids and 10 (36%) had CIs. The average age at CI (3.45 ± 2.07 years) was significantly older than the age at CI of other children in our program with prelingual hearing loss (2.05 ± 1.14 years; p = 0.01 Mann-Witney U Test). None of the putative risk factors for hearing loss reliably predicted the need for subsequent CI. CONCLUSION: The small sample size in this study is sufficient to confirm that clinical history alone does not reliably predict which young children with perinatal-onset ANSD will require CI. Consequently, timing for CI remains delayed in these children, potentially affecting speech and language outcome. The pathogenesis of perinatal-onset ANSD remains undetermined and novel means of assessment are required for prognostication in affected infants.

Can Differences in Early Hearing Development Be Distinguished by the LittlEARs Auditory Questionnaire?

OBJECTIVE: This study asks whether the LittlEARs Auditory Questionnaire (LEAQ), a caregiver measure, can differentiate between the early auditory development of children with bilateral cochlear implants (CIs), bilateral hearing aids (HAs), and children with Auditory Neuropathy Spectrum Disorder (ANSD) who wear CIs or HAs. The LEAQ is sensitive to impaired auditory development but has not previously been used to distinguish developmental changes between groups of children using different hearing technologies or with different types of hearing loss. DESIGN: We collected retrospective longitudinal LEAQ results from 43 children with HAs, 43 with CIs, and 18 with ANSD. The children with ANSD wore hearing technology. They were a similar age to the children without ANSD (23 months; SD = 15), while the CI group (14 months; SD = 8) was younger than the HA group (24 months; SD = 18) [F(2,98.48) = 3.4; p = 0.04]. The CI group often participated in their first LEAQ pretreatment. Participants completed between one and seven LEAQs. Scores ranged between zero and 35 (mean = 18.36). We conducted a linear mixed-effects analysis, which included age or time since device fitting, hearing type (HA, CI, or ANSD), and presence of a comorbidity as fixed effects. A secondary analysis assessed effects of device audibility, measured by the Speech Intelligibility Index or Articulation Index, and consistency of device use obtained from device datalogs. RESULTS: Children with CIs progressed faster than their peers with HAs or ANSD [χ2(8) = 24.51; p = 0.002]. However, within a subsample that included consistency of device use (ß7 = -0.20 ± 0.38, t = -0.52; ß8 = 0.93 ± 0.82, t = 1.13) and audibility (ß6 = -0.70 ± 1.45, t = -1.87; ß7 = 0.87 ± 0.89, t = 0.98), study group did not significantly influence rate of improvement on the LEAQ. In addition, children with developmental delays in all three study groups demonstrated significantly slower LEAQ score improvement [χ2(6) = 23.60; p < 0.001] and a trend toward decreased consistency of device use [F(1) = 3.31; p = 0.07]. As we expected, children in the CI and HA groups were more likely to achieve auditory skills indicated in early rather than later LEAQ questions. There was less variability in the responses of the ANSD group [CI: interquartile range (IQR) = 9; HA: IQR = 8; ANSD: IQR = 1]. There was no connection between LEAQ growth and speech perception outcomes in a subsample [r(6) = 0.42; p = 0.30]. CONCLUSIONS: The LEAQ is a useful tool for monitoring initial auditory development in very young children and can inform early treatment decisions.

Dose derivation of once-daily dosing guidelines for gentamicin in critically ill pediatric patients.

OBJECTIVES: To determine dose and eligibility criteria for once-daily dosing (ODD) of gentamicin in critically ill pediatric patients. METHODS: Retrospective chart review of patients admitted to the Pediatric Intensive Care Unit or Cardiac Critical Care Unit at The Hospital for Sick Children (SickKids) who received traditionally dosed intravenous (IV) gentamicin (January 2008 to June 2010). Statistically significant patient characteristics associated with gentamicin pharmacokinetic (PK) parameters were determined by multiple linear regression. Binary partitioning was used to set critical values for these characteristics to derive dose for ODD of gentamicin. Feasibility of implementing ODD of gentamicin in critically ill children was assessed using individualized PK parameters to simulate area under the concentration-time curves and drug-free intervals while targeting a maximum concentration (C(max)) of 16-20 mg/L. Eligibility criteria were determined by patient characteristics that had a statistically significant impact on gentamicin PK. RESULTS: Volume of distribution (V(d)) and elimination rate constant (k(e)) were calculated for 140 patients. Weight and admission unit were significantly associated with weight-normalized V(d) (Vd/kg), whereas age and serum creatinine (SCr) were significantly associated with k(e). Weight <5 kg and SCr ≥20% over age-specific upper normal limit before gentamicin initiation were associated with prolonged gentamicin elimination. Gentamicin 6 mg/kg IV every 24 hours, the dose at which the highest percentage of patients achieved C(max), area under the curve, and drug-free interval within target ranges simultaneously, was selected as the proposed ODD regimen. CONCLUSIONS: A regimen of gentamicin 6 mg/kg IV every 24 hours for Pediatric Intensive Care Unit/Cardiac Critical Care Unit patients at SickKids weighing ≥5 kg with SCr <20% above age-specific upper normal limit before initiation of gentamicin is proposed.

Early cisplatin induced ototoxicity profile may predict the need for hearing support in children with medulloblastoma.

BACKGROUND: Cisplatin (CDDP) ototoxicity is a significant side effect of the current treatment of medulloblastoma (MB). Cumulative dose of CDDP and age are recognized risk factors for hearing loss, but inter-individual susceptibility limits our ability to identify patients at risk for hearing loss. We describe the kinetics of early audiometric changes during therapy and identify profiles associated with a higher risk of needing hearing aids. PROCEDURE: Serial audiometric evaluations were performed during and after completion of therapy in children with average risk (AR) and high-risk (HR) MB. Each audiogram was scored according to five grading systems. Variations of pure tone thresholds were analyzed at each frequency for each consecutive audiogram. CDDP dose modifications and hearing outcome were recorded. RESULTS: A total of 258 audiograms from 35 patients (22 AR, 13 HR) were analyzed. Eighteen AR patients (81.3%) required dose reduction and the median cumulative dose of CDDP administered was 412.5 mg/m(2) (150-600), corresponding to 68% of the intended dose. Three HR patients (23.0%) required dose reduction. At a median follow-up of 67 months (11-117), nine patients (25.7%) required hearing support: After two cycles of CDDP (150 mg/m(2) ), the average hearing loss at 8,000 Hz was twice higher in the group that eventually required hearing support. CONCLUSION: Early alteration of high-frequency thresholds may help identify individuals who will require hearing support. In the MB population, alternative strategies should be developed to limit the cumulative dose of CDDP to prevent significant ototoxicity.

Low pediatric cochlear implant failure rate: contributing factors in large-volume practice.

OBJECTIVE: To evaluate the rate of cochlear implant (CI) failure and CI reimplantation (CIri) in our population of children receiving implants by means of a technique that includes device fixation with suture to cortical bone. DESIGN: Retrospective analysis from January 1990 to June 2010. SETTING: Tertiary pediatric hospital. PATIENTS: A total of 971 devices were provided to 738 children (5575 implant-years). INTERVENTIONS: Cochlear implant explants and CIri. MAIN OUTCOME MEASURES: Surgical findings at CIri were assessed by device model. The Pediatric Ranked Order Speech Perception score and the Phonetically Balanced Kindergarten score were used to make comparisons of hearing ability before and after CIri. RESULTS: Thirty-four patients have undergone CIri in our pediatric center during the past 20 years. Excluding 7 of these patients who received their initial implant at other centers, our rate of CIri was 2.9%. Mean (SD) time to device failure was 61 (43) months. A disproportionately high number of patients (7 of 35 [20%]) requiring CIri had meningitis before implantation. After CIri, children maintained or improved their best speech performance measured before device failure, with only 2 children showing a significant reduction in speech perception after CIri. CONCLUSIONS: A very low rate of failure occurs in children who receive CI devices, and several factors may account for this low rate. Children who develop meningitis before CI appear to be at an increased risk of device failure.

Parental and program's decision making in paediatric simultaneous bilateral cochlear implantation: who says no and why?

OBJECTIVE: To evaluate initial candidacy for bilateral simultaneous cochlear implantation in children. DESIGN: Prospective case series. SETTING: Tertiary academic pediatric hospital. PARTICIPANTS: As part of our research protocol all children eligible for cochlear implantation were assessed for suitability to receive a simultaneous bilateral implant. Over a 12-month period (January to December 2007) 78 children received a total of 95 cochlear implants. Children with sequential second implants (24), revision cases (4), and out of province recipients (4) were excluded. The remaining 46 patients were assessed for bilateral simultaneous implantation. MAIN OUTCOME MEASURES: Team/parental decision to proceed with bilateral simultaneous implantation. RESULTS: 17 children (37%) received simultaneous bilateral implants. 29 children (63%) were not considered suitable for simultaneous bilateral implantation. Reasons included developmental delay (10), residual borderline hearing in the second ear (9), parental/patient refusal (6), abnormally poor speech development for age (2), and abnormal cochlear anatomy precluding implantation (2). None were considered unsuitable for the more prolonged operative procedure on medical grounds. CONCLUSIONS: Although bilateral implantation is thought to produce the optimal auditory outcome, not all patients are suitable, nor do all parents wish to proceed, when assessed for simultaneous implantation. Some of these patients are likely to be candidates for sequential bilateral implantation in due course.

Speech perception outcome in multiply disabled children following cochlear implantation: investigating a predictive score.

BACKGROUND: Children with multiple disabilities account for a small percentage of implantees in a cochlear implant program, but they remain the most challenging group for which to predict benefit from the implant and for cooperation with habilitation postoperatively. PURPOSE: To assess the relationship of pre-implant functional disabilities with postoperative speech perception scores and determine the feasibility of predicting outcome with a cochlear implant in a multiply disabled pediatric population. RESEARCH DESIGN: Retrospective cohort study. STUDY SAMPLE: Sixty-six children with a cochlear implant and at least one additional disability. DATA COLLECTION AND ANALYSIS: We retrospectively examined the relationship between pre-implant Graded Profile Analysis (GPA) scores and postimplant speech perception scores. A pre-implant functional disability score (based on the Battelle developmental screen) was applied to the same cohort of patients and its association with postimplant speech perception scores was examined. RESULTS: The functional disability score significantly predicted high (k > 24) and low (k < 7) speech perception scores (p < 0.001 and p < .0001) and had excellent discrimination ability (c statistic = 0.88 and 0.93 respectively). The GPA score was not significantly associated with speech perception scores (p = 0.519 and p = 0.146) and demonstrated no ability to discriminate postimplant speech perception scores in this implant population (c statistic = 0.49 and c = 0.57). CONCLUSIONS: Prediction of outcomes following cochlear implantation in multiply disabled children can be facilitated using this newly developed functional disability score as an adjunct to traditional candidacy assessments.

Hearing in children with fetal alcohol spectrum disorder (FASD).

BACKGROUND: Alcohol is the most prevalent human teratogen affected by early exposure of the fetus. Although not listed as a major part of the fetal alcohol spectrum disorder (FASD), different texts list hearing loss as a characteristic of the FASD, based on several small studies. OBJECTIVE: To characterize hearing in children with FASD, diagnosed in the Motherisk Program in Toronto. DESIGN: Cross sectional cohort study. SETTING: Academic referral center. PATIENTS: Children 4-16 years of age that met criteria for FASD, with no other known risk factor for sensorineural hearing loss. A consecutive sample of 41 children (13 girls, mean age 8.9 +/-3 years) was collected. INTERVENTION: Physical examination, audiometry and tympanometry. OUTCOME MEASURES: External and middle ear pathology on physical examination, pure tone average (PTA), speech reception threshold (SRT), discrimination and tympanometry. Results were compared to reference values in the normal population. Hearing loss equal or greater than 16dB hearing-level in each frequency tested was considered to be clinically significant. RESULTS: A total of 5 (11.2%) of children had hearing loss of at least 16dB hearing-level, mostly unilateral. SRT was within the normal range in 40 (98%) of children with FASD and discrimination was normal in all children. None had auricular or external canal dysmorphology. 14.7% of the children had frequent episodes of acute otitis media. Middle ear effusion was detected in 8 ears (9.8%). CONCLUSIONS: The prevalence of mild sensorineural hearing loss in children diagnosed with FASD (16dB hearing-level or greater) was not higher than expected in this age group. However, because children with FASD are academically and behaviorally challenged, early detection of hearing loss and early intervention is warranted.

Low incidence of ototoxicity with continuous infusion of cisplatin in the treatment of pediatric germ cell tumors.

Cisplatin is an important chemotherapeutic agent in the treatment of many pediatric malignancies, but its use is limited in part by ototoxicity. The authors' institution has been administering standard-dose cisplatin by continuous infusion rather than bolus administration in germ cell tumors. The authors retrospectively reviewed 39 patients with germ cell tumors requiring chemotherapy over the past 20 years and recorded data including demographics, cumulative cisplatin dose, degree of ototoxicity (by the Brock grading system), and disease outcome. The median age was 9.4 years and the majority of children (48.7%) had endodermal sinus tumor. Twenty-one children received 400 mg/m of cisplatin or more. One child had evidence of significant ototoxicity at last follow-up (6.64 years after diagnosis). This patient received a total cumulative dose of 500 mg/m of cisplatin. Eighty-two percent of children achieved clinical remission of their disease. The authors conclude that continuous administration of cisplatin is associated with minimal ototoxicity while maintaining good tumoricidal efficacy, and further studies using this regimen are warranted.