A Retrospective Cohort Study of Glossopharyngeal Nerve Taste in Children with Recurrent Acute Tonsillitis.

Objective To compare glossopharyngeal taste between healthy children and those with recurrent acute tonsillitis. Study Design Retrospective cohort study. Setting Pediatric clinics in a tertiary care medical center and satellite location. Subjects and Methods Smell and taste testing was administered to 80 well children and 64 children with recurrent acute tonsillitis (age range, 6-17 years). Smell testing was performed with the NIH Toolbox Odor Identification Test, with scores based on national averages for age and sex. Validated Taste Strips were placed on the midline of the tongue at the circumvallate papillae in random tastant order and in increasing concentrations to test sweet, salty, sour, and bitter. Ordinal logistic regression was used for multivariate analysis. Results The healthy and tonsillitis groups were similar, with mean ages of 11.3 and 10.8 years ( P = .34), respectively. The tonsillitis group had fewer boys (n = 18 vs 43, P = .002), higher mean body mass index (BMI) percentile (n = 72.2 vs 59.8, P = .01), and more subjects with public or no insurance (n = 24 vs 13, P = .004). Univariate analysis revealed no statistically significant differences in rate of normal overall taste (67.2% vs 60%, P = .39) and in sweet (79.7% vs 82.5%, P = .67), salty (85.9% vs 82.8%, P = .82), sour (64.1% vs 70%, P = .48), and bitter (90.6% vs 86.3%, P = .45). In multivariate analysis, smell ability, sex, BMI percentile, parent BMI, and insurance type did not affect overall taste or sweet, salty, sour, or bitter alone. Conclusion Despite controlling for potential intrinsic (sex, smell, BMI) and extrinsic (parent BMI, insurance type) confounders, there was no statistically significant difference in taste among children with recurrent acute tonsillitis as compared with healthy children.

Incidence of and Factors Associated With Hypogeusia in Healthy Children.

IMPORTANCE: There are currently no measures of isolated glossopharyngeal taste in healthy children, to our knowledge. OBJECTIVE: To define the taste characteristics of an otherwise healthy pediatric population that could serve as a control group for further investigations. DESIGN, SETTING, AND PARTICIPANTS: A prospective study of taste and smell was conducted from August 4 to 29, 2014, at a general pediatrics clinic in a tertiary care medical center in 80 healthy children aged 6 to 17 years who were receiving well-child examinations or vaccinations or in their healthy siblings. EXPOSURES: Testing of smell and taste. MAIN OUTCOMES AND MEASURES: Demographic data were gathered on age, sex, and body mass index as well as type of insurance. Smell testing was performed with the National Institutes of Health Toolbox Odor Identification Test, with scores based on national averages for age and sex. Validated Taste Strips were used for testing sweet, salty, sour, and bitter tastes. One strip at a time was placed on the midline of the tongue at the circumvallate papillae in random tastant order and in increasing concentrations. Correct identification of the tastant earned 1 point; of 16 possible points, a score of less than 9 signified hypogeusia. Fisher exact test was used for statistical analysis. RESULTS: The mean (SD) age of the 80 children in this study was 11.3 (3.2) years, and 43 were boys (54%). Hypogeusia was identified in 32 (40%) of the 80 children. Overweight or obesity was identified in 23 children (29%) (15 [31%] with a normal sense of taste and 8 [25%] with hypogeusia; P = .62), and 12 (15%) used public insurance (7 [15%] with a normal sense of taste and 5 [16%] with hypogeusia; P > .99). Age younger than 12 years (24 [50%] with a normal sense of taste and 19 [59%] with hypogeusia; P = .50), male sex (25 [52%] with a normal sense of taste and 18 [56%] with hypogeusia; P = .39), overweight or obesity (15 [31%] with a normal sense of taste and 8 [25%] with hypogeusia; P = .62), insurance type (P > .99), and olfaction less than the 50th percentile (29 [60%] with a normal sense of taste and 17 [53%] with hypogeusia; P = .65) or hyposmia (<10th percentile; P = .47) were not statistically significantly correlated with overall hypogeusia. CONCLUSIONS AND RELEVANCE: A significant proportion of otherwise healthy children have hypogeusia according to previously published criteria. This study will provide baseline data from which future investigations studying taste disturbances in patients with chronic tonsillitis and after tonsillectomy can be compared.

Incidence of Visualization of the Glossopharyngeal Nerve after Pediatric Tonsillectomy.

The objective was to determine the incidence of exposure of the lingual branch of the glossopharyngeal nerve during tonsillectomy with a retrospective review of surgical findings in 138 children who underwent total tonsillectomy at a tertiary medical center. Age, sex, surgical indication, tonsil size, congenital abnormalities, operative time, and surgical findings indicating the presence or absence of the glossopharyngeal nerve in the tonsillar fossa were recorded. Statistical analysis was performed with z test, t test, and Fisher's exact test. Thirty-seven nerves were observed in 28 patients, with preponderance for the left fossa (24 of 37 vs 13 of 37; P = .01). In a comparison of children with and without exposed nerves, there was no statistically significant difference in mean age (6.89 vs 7.08; P = .84), proportion of males (14 of 28 vs 54 of 110; P = 1), or proportion of 3 to 4+ tonsils (20 of 28 vs 73 of 110; P = .66). In approximately 20% of children undergoing tonsillectomy, the lateral pharyngeal musculature incompletely protected the lingual branch of the glossopharyngeal nerve from the tonsil capsule.

Effects of inter-alpha inhibitor proteins on neonatal brain injury: Age, task and treatment dependent neurobehavioral outcomes.

Hypoxic-ischemic (HI) brain injury is frequently associated with premature and/or full term birth related complications. HI injury often results in learning and processing deficits that reflect widespread damage to an extensive range of cortical and sub-cortical brain structures. Further, inflammation has been implicated in the long-term progression and severity of HI injury. Recently, inter-alpha inhibitor proteins (IAIPs) have been shown to attenuate inflammation in models of systemic infection. Importantly, preclinical studies of neonatal HI injury and neuroprotection often focus on single time windows of assessment or single behavioral domains. This approach limits translational validity, given evidence for a diverse spectrum of neurobehavioral deficits that may change across developmental windows following neonatal brain injury. Therefore, the aims of this research were to assess the effects of human IAIPs on early neocortical cell death (72h post-insult), adult regional brain volume measurements (cerebral cortex, hippocampus, striatum, corpus callosum) and long-term behavioral outcomes in juvenile (P38-50) and adult (P80+) periods across two independent learning domains (spatial and non-spatial learning), after postnatal day 7 HI injury in rats. Here, for the first time, we show that IAIPs reduce acute neocortical neuronal cell death and improve brain weight outcome 72h following HI injury in the neonatal rat. Further, these longitudinal studies are the first to show age, task and treatment dependent improvements in behavioral outcome for both spatial and non-spatial learning following systemic administration of IAIPs in neonatal HI injured rats. Finally, results also show sparing of brain regions critical for spatial and non-spatial learning in adult animals treated with IAIPs at the time of injury onset. These data support the proposal that inter-alpha inhibitor proteins may serve as novel therapeutics for brain injury associated with premature birth and/or neonatal brain injury and highlight the importance of assessing multiple ages, brain regions and behavioral domains when investigating experimental treatment efficacy.

Spatial working memory deficits in male rats following neonatal hypoxic ischemic brain injury can be attenuated by task modifications.

Hypoxia-ischemia (HI; reduction in blood/oxygen supply) is common in infants with serious birth complications, such as prolonged labor and cord prolapse, as well as in infants born prematurely (<37 weeks gestational age; GA). Most often, HI can lead to brain injury in the form of cortical and subcortical damage, as well as later cognitive/behavioral deficits. A common domain of impairment is working memory, which can be associated with heightened incidence of developmental disorders. To further characterize these clinical issues, the current investigation describes data from a rodent model of HI induced on postnatal (P)7, an age comparable to a term (GA 36-38) human. Specifically, we sought to assess working memory using an eight-arm radial water maze paradigm. Study 1 used a modified version of the paradigm, which requires a step-wise change in spatial memory via progressively more difficult tasks, as well as multiple daily trials for extra learning opportunity. Results were surprising and revealed a small HI deficit only for the final and most difficult condition, when a delay before test trial was introduced. Study 2 again used the modified radial arm maze, but presented the most difficult condition from the start, and only one daily test trial. Here, results were expected and revealed a robust and consistent HI deficit across all weeks. Combined results indicate that male HI rats can learn a difficult spatial working memory task if it is presented in a graded multi-trial format, but performance is poor and does not appear to remediate if the task is presented with high initial memory demand. Male HI rats in both studies displayed impulsive characteristics throughout testing evidenced as reduced choice latencies despite more errors. This aspect of behavioral results is consistent with impulsiveness as a core symptom of ADHD-a diagnosis common in children with HI insult. Overall findings suggest that task specific behavioral modifications are crucial to accommodating memory deficits in children suffering from cognitive impairments following neonatal HI.

Prevalence of eosinophilic esophagitis in children with refractory aerodigestive symptoms.

IMPORTANCE: Eosinophilic esophagitis (EoE) is an increasingly important diagnosis for children; it has a remarkable impact on their quality of life and can present with aerodigestive symptoms commonly evaluated by otolaryngologists. OBJECTIVES: To evaluate the prevalence of EoE in children presenting to a pediatric aerodigestive clinic, to describe their presentation, and to review the role of subsequent food allergy evaluation and treatment. DESIGN: Review of a prospective database. SETTING: Tertiary pediatric multispecialty aerodigestive center. PATIENTS: Children with aerodigestive symptoms refractory to medical treatment who underwent direct laryngoscopy with rigid or flexible bronchoscopy and esophagoscopy with or without pH probe study. MAIN OUTCOMES AND MEASURES: Diagnosis of EoE. RESULTS: Between 2003 and 2012, 376 of 1540 children seen in the center (mean [range] age, 4.54 [0-18.6] years; male to female ratio, 1.72:1) remained symptomatic despite medical therapy and thus underwent triple endoscopic evaluation. Of the 376 children, 14 (3.7%) were eventually diagnosed as having EoE, as defined by 15 or more eosinophils per high-power field on esophageal biopsy and either a negative pH study result or nonresponse to a trial of high-dose proton pump inhibitors. The subpopulation with EoE presented with airway symptoms and diagnoses, most commonly cough (n = 6; 42.9%). Inflammatory subglottic stenosis due to EoE was identified in 1 patient. Of the 14 children with EoE, 6 presented with gastrointestinal symptomatology, most commonly choking or gagging. Subsequent treatment including food allergy challenge and elimination diet resulted in a clinical improvement in half of the cases identified. CONCLUSIONS AND RELEVANCE: This represents the largest multispecialty clinic epidemiologic study evaluating the prevalence of EoE in children presenting not strictly with gastrointestinal symptoms but rather with aerodigestive symptoms that are frequently evaluated by pediatric otolaryngologists. Although the prevalence is low, EoE should be considered for children with appropriate symptoms in whom other medical therapies fail.

Consistency of voice frequency and perturbation measures in children.

OBJECTIVE: Evaluate normal pediatric voice frequency and perturbation measures with Voice Evaluation Suite (VES) and Multi Dimensional Voice Program (MDVP), determine the consistency of these measures over time, and understand which measures might be most useful for evaluating children with voice disorders. STUDY DESIGN: Prospective, longitudinal study of normal voices of 50 children aged 4 to 17 years. SETTING: Pediatric otolaryngology clinic within tertiary hospital. SUBJECTS AND METHODS: Two tests of sustained utterances from each child were evaluated by 2 computerized voice analysis programs for frequency and perturbation. Intraclass correlation coefficient (ICC) was used to assess the reliability between the samples. RESULTS: Children (male/female, 1.08:1) with a mean age of 8.34 years were tested on an average of 54.2 minutes apart. Each test included 4 utterances; 1 was analyzed by MDVP, and 3 grouped utterances were averaged and evaluated by VES. Fundamental frequency had excellent reliability (ICC = 0.95) in both VES and MDVP. Jitter, shimmer, and noise to harmonic ratio were poorly reliable (ICC ≤ 0.4) in MDVP but had good to excellent reliability (ICC 0.66-0.8) in VES. CONCLUSION: Single, sustained utterances in children provide consistent measures of frequency. Perturbation is not reliably measured by such testing, but averaging multiple samples yields improved consistency. Evaluating acoustic measure stability in spontaneous speech and in sustained utterances cued by a tuning frequency can provide further insight on pediatric voice consistency.

Effects of test experience and neocortical microgyria on spatial and non-spatial learning in rats.

Neocortical neuronal migration anomalies such as microgyria and heterotopia have been associated with developmental language learning impairments in humans, and rapid auditory processing deficits in rodent models. Similar processing impairments have been suggested to play a causal role in human language impairment. Recent data from our group has shown spatial working memory deficits associated with neocortical microgyria in rats. Similar deficits have also been identified in humans with language learning impairments. To further explore the extent of learning deficits associated with cortical neuronal migration anomalies, we evaluated the effects of neocortical microgyria and test order experience using spatial (Morris water maze) and non-spatial water maze learning paradigms. Two independent groups were employed (G1 or G2) incorporating both microgyria and sham conditions. G1 received spatial testing for five days followed by non-spatial testing, while the reverse order was followed for G2. Initial analysis, including both test groups and both maze conditions, revealed a main effect of treatment, with microgyric rats performing significantly worse than shams. Overall analysis also revealed a task by order interaction, indicating that each group performed better on the second task as compared to the first, regardless of which task was presented first. Independent analyses of each task revealed a significant effect of treatment (microgyria worse than sham) only for the spatial water maze condition. Results indicate that prior maze experience (regardless of task type) leads to better subsequent performance. Results suggest that behavioral abnormalities associated with microgyria extend beyond auditory and working memory deficits seen in previous studies, to include spatial but not non-spatial learning impairments and that non-specific test experience may improve behavioral performance.

Sex differences in mechanisms and outcome of neonatal hypoxia-ischemia in rodent models: implications for sex-specific neuroprotection in clinical neonatal practice.

Clinical findings show that male infants with hypoxic-ischemic injury (HI) fare more poorly than matched females on cognitive outcomes. Rodent models of neonatal hypoxia-ischemia support this difference, with data showing that perinatal brain injury leads to long-term behavioral deficits primarily in male rodents and in female rodents treated with early androgens. Results support the idea that sex-specific gonadal hormones may modulate developmental response to injury and dovetail with overwhelming evidence of developmental androgen effects on typical brain morphology and behavior. However, mechanisms underlying sex differences in response to early brain injury may be more complicated. Specifically, activation of cell death pathways in response to HI may also differ by sex. In females, the preferential activation of the caspase-dependent apoptotic pathway may actually afford greater protection, potentially due to the actions of X-linked inhibitor of apoptosis (XIAP) within this pathway. This contrasts the pattern of preferential activation of the caspase-independent pathway in males. While an integrated model of sex-specific hormonal and genetic modulation of response to early injury remains to be fully elucidated, these findings suggest that infants might benefit from sex-specific neuroprotection following HI injury.

A pilot study to identify pre- and peri-operative risk factors for airway complications following adenotonsillectomy for treatment of severe pediatric OSA.

OBJECTIVE: A pilot study to identify risk factors predicting post-operative complications in children with severe OSA undergoing adenotonsillectomy. METHODS: Retrospective review in a tertiary care academic institution. Two-stage least squares regression analysis and instrumental variable analysis to allow for modeling of pre- and peri-operative risk factors as having significance in predicting post-operative morbidity. RESULTS: Eighty-three children (mean age 4.88 ± 3.09 years) with apnea-hypopnea index (AHI) ≥ 10 who were observed overnight following adenotonsillectomy were evaluated for rates of major (increased level of care, CPAP/BiPAP use, pulmonary edema and reintubation) and minor (oxygen saturation <90%) airway complications as well as total observation costs. Major and minor complications occurred in 4.8% and 19.3% of children, respectively. Age <2 years (p<0.01), AHI >24 (p<0.05), intra-operative laryngospasm requiring treatment (p<0.05), oxygen saturations <90% on room air in PACU (p<0.05) and PACU stay >100 min (p<0.01) independently predicted post-operative complications. Children with any one of these factors experienced a 38% complication rate versus 4% in all others. CONCLUSIONS: This pilot study identified pre- and peri-operative risk factors that collectively can be investigated as predictors of post-operative airway complications in a prospective study. By identifying preliminary results comparing the complication rates between those children with and without these risk factors, we will be able to calculate the sample size for a future prospective validation study. Such a study is necessary to understand the safety and potential significant cost savings of observing children without risk factors on the pediatric floor and not in an ICU setting. A best practice algorithm can be created for children with severe OSA only after completing this prospective study.

Early acoustic discrimination experience ameliorates auditory processing deficits in male rats with cortical developmental disruption.

Auditory temporal processing deficits have been suggested to play a causal role in language learning impairments, and evidence of cortical developmental anomalies (microgyria (MG), ectopia) has been reported for language-impaired populations. Rodent models have linked these features, by showing deficits in auditory temporal discrimination for rats with neuronal migration anomalies (MG, ectopia). Since evidence from human studies suggests that training with both speech and non-speech acoustic stimuli may improve language performance in developmentally language-disabled populations, we were interested in whether/how maturation and early experience might influence auditory processing deficits seen in male rats with induced focal cortical MG. Results showed that for both simple (Normal single tone), as well as increasingly complex auditory discrimination tasks (silent gap in white noise and FM sweep), prior experience significantly improved acoustic discrimination performance--in fact, beyond improvements seen with maturation only. Further, we replicated evidence that young adult rats with MG were significantly impaired at discriminating FM sweeps compared to shams. However, these MG effects were no longer seen when experienced subjects were retested in adulthood (even though deficits in short duration FM sweep detection were seen for adult MG rats with no early experience). Thus while some improvements in auditory processing were seen with normal maturation, the effects of early experience were even more profound, in fact resulting in amelioration of MG effects seen at earlier ages. These findings support the clinical view that early training intervention with appropriate acoustic stimuli could similarly ameliorate long-term processing impairments seen in some language-impaired children.

Developmental learning impairments in a rodent model of nodular heterotopia.

Developmental malformations of neocortex-including microgyria, ectopias, and periventricular nodular heterotopia (PNH)-have been associated with language learning impairments in humans. Studies also show that developmental language impairments are frequently associated with deficits in processing rapid acoustic stimuli, and rodent models have linked cortical developmental disruption (microgyria, ectopia) with rapid auditory processing deficits. We sought to extend this neurodevelopmental model to evaluate the effects of embryonic (E) day 15 exposure to the anti-mitotic teratogen methylazoxymethanol acetate (MAM) on auditory processing and maze learning in rats. Extensive cortical anomalies were confirmed in MAM-treated rats post mortem. These included evidence of laminar disruption, PNH, and hippocampal dysplasia. Juvenile auditory testing (P21-42) revealed comparable silent gap detection performance for MAM-treated and control subjects, indicating normal hearing and basic auditory temporal processing in MAM subjects. Juvenile testing on a more complex two-tone oddball task, however, revealed a significant impairment in MAM-treated as compared to control subjects. Post hoc analysis also revealed a significant effect of PNH severity for MAM subjects, with more severe disruption associated with greater processing impairments. In adulthood (P60-100), only MAM subjects with the most severe PNH condition showed deficits in oddball two-tone processing as compared to controls. However, when presented with a more complex and novel FM sweep detection task, all MAM subjects showed significant processing deficits as compared to controls. Moreover, post hoc analysis revealed a significant effect of PNH severity on FM sweep processing. Water Maze testing results also showed a significant impairment for spatial but not non-spatial learning in MAM rats as compared to controls. Results lend further support to the notions that: (1) generalized cortical developmental disruption (stemming from injury, genetic or teratogenic insults) leads to auditory processing deficits, which in turn have been suggested to play a causal role in language impairment; (2) severity of cortical disruption is related to the severity of processing impairments; (3) juvenile auditory processing deficits appear to ameliorate with maturation, but can still be elicited in adulthood using increasingly complex acoustic stimuli; and (4) malformations induced with MAM are also associated with generalized spatial learning deficits. These cumulative findings contribute to our understanding of the behavioral consequences of cortical developmental pathology, which may in turn elucidate mechanisms contributing to developmental language learning impairment in humans.