Diffusion Tensor Imaging of Auditory Pathway in Patients With Crigler-Najjar Syndrome Type I: Correlation With Auditory Brainstem Response.

AIM: To evaluate the role of diffusion tensor imaging of the auditory pathway in patients with Crigler Najjar syndrome type I and its relation to auditory brainstem response. METHODS: Prospective study was done including 12 patients with Crigler Najjar syndrome type I and 10 age- and sex-matched controls that underwent diffusion tensor imaging of brain. Mean diffusivity and fractional anisotropy at 4 regions of the brain and brainstem on each side were measured and correlated with the results of auditory brainstem response for patients. RESULTS: There was significantly higher mean diffusivity of cochlear nucleus, superior olivary nucleus, inferior colliculus, and auditory cortex of patients versus controls on both sides for all regions (P = .001). The fractional anisotropy of cochlear nucleus, superior olivary nucleus, inferior colliculus, and auditory cortex of patients versus controls was significantly lower, with P values of, respectively, .001, .001, .003, and .001 on the right side and .001, .001, .003, and .001 on left side, respectively. Also, a negative correlation was found between the maximum bilirubin level and fractional anisotropy of the left superior olivary nucleus and inferior colliculus of both sides. A positive correlation was found between the mean diffusivity and auditory brainstem response wave latency of the right inferior colliculus and left cochlear nucleus. The fractional anisotropy and auditory brainstem response wave latency of the right superior olivary nucleus, left cochlear nucleus, and inferior colliculus of both sides were negatively correlated. CONCLUSION: Diffusion tensor imaging can detect microstructural changes in the auditory pathway in Crigler Najjar syndrome type I that can be correlated with auditory brainstem response.

Hipoacusia unilateral: bases neurobiológicas de la ambliaudia / Unilateral hearing loss: neurobiological basis of amblyaudia

Resumen La hipoacusia unilateral es una alteración prevalente e importante en la población infantil que puede llevar a un deterioro del procesamiento auditivo. Cualquier patología que cause hipoacusia asimétrica (conductiva o sensorioneural) durante ventanas críticas del desarrollo cerebral, puede dar lugar a déficits del procesamiento auditivo que podrían persistir incluso después de la rehabilitación audiológica. Este proceso fisiopatológico se ha denominado "ambliaudia" y los niños que la presentan tienen un mayor riesgo de sufrir retraso en el desarrollo del lenguaje, así como de padecer dificultades académicas, sociales y cognitivas. Por esto, la ambliaudia se presenta como un desafío en audiología, siendo necesario comprender los mecanismos neurobiológicos que la subyacen. Entender de mejor manera cuáles son las consecuencias que tiene la pérdida auditiva asimétrica sobre el desarrollo del sistema nervioso podría ser clave para guiar de mejor forma las intervenciones terapéuticas. En este artículo se revisan trabajos en humanos y en modelos animales que describen las consecuencias neurobiológicas de la deprivación auditiva unilateral durante el desarrollo del sistema nervioso y su posible aplicación a la práctica clínica.

Abstract Unilateral hearing loss is a prevalent and important disorder in children that can lead to an impairment of auditory processing. Any pathology that causes asymmetric (conductive or sensorineural) hearing loss during critical brain development windows can lead to hearing deficits that may persist even after audiological rehabilitation. This pathophysiological process has been referred to as amblyaudia, and children are at greater risk of experiencing language developmental delays as well as academic, social and cognitive impairments. For this reason, amblyaudia presents itself as a challenge in audiology, and it has become necessary to understand its neurobiological mechanisms. A better understanding of the consequences of asymmetric hearing loss on the development of the nervous system may be key to better guiding therapeutic interventions. This article reviews studies performed in humans and animal models that describe the neurobiological consequences of unilateral hearing deprivation during the development of the nervous system and its possible applications to clinical practice.

Alterações auditivas em recém-nascidos e lactentes com mielomeningocele / Hearing impairment in newborns and infants with myelomeningocele

RESUMO Objetivo Verificar a ocorrência de alterações auditivas em recém-nascidos e lactentes com mielomeningocele e/ou Síndrome de Arnold Chiari tipo II. Métodos Foram incluídos na amostra 160 neonatos atendidos em unidade de terapia intensiva neonatal, distribuídos em três grupos: Grupo Estudo 1, formado por 42 neonatos com Síndrome de Arnold Chiari tipo II; Grupo Estudo 2, constituído por 38 neonatos com mielomeningocele e Grupo Controle, com 80 recém-nascidos sem síndromes, malformações e/ou riscos para alteração auditiva. Todos os pacientes realizaram a triagem auditiva neonatal com emissões otoacústicas evocadas por estímulo transiente e foram submetidos à pesquisa do potencial evocado auditivo de tronco encefálico com estímulo clique. Quando houve falha nas emissões, a pesquisa dos limiares eletrofisiológicos foi realizada mediante potencial evocado auditivo de tronco encefálico com tone burst . A análise estatística foi feita por meio de testes paramétricos e os dados encontrados foram descritos nos resultados, considerando o nível de significância p<0,05. Resultados Houve maior ocorrência de perda coclear, alteração central e neuropatia auditiva nos grupos estudados. No que se refere aos valores médios das latências absolutas e dos intervalos interpicos, nos três grupos, por orelha, houve aumento das latências absolutas das ondas III e V e dos intervalos interpicos III-V e I-V , no grupo de lactentes com Síndrome de Arnold Chiari tipo II. Conclusão Recém-nascidos e lactentes com Síndrome de Arnold Chiari tipo II e mielomeningocele apresentaram maior ocorrência de perda coclear, espectro da neuropatia auditiva e alterações centrais.

ABSTRACT Purpose To characterize Auditory and oral language performance in children under 2 years of age with Hearing and Language Development Scale (EDAL-1) and to compare the results to those of hearing children up to two years of age. Methods This is an experimental study of descriptive nature. A total of 141 children were divided into two groups: control group with 92 normal hearing, and the experimental group with 49 deaf children followed audiologically during the first two years after implantation. Normal hearing children underwent auditory assessment and parents responded to EDAL-1. The children implanted, every three months, underwent otorhinolaryngological and speech-language evaluation, and the parents answered EDAL-1. Results In both groups we observed upward responses, with improvement as chronological and auditory age increases. Results obtained in the study group are statistically worse than in the control group, but with a tendency to grow. EDAL-1 was easy to apply and allowed to monitor the performance of the implanted children. Conclusion Oral and auditory performance in deaf children with cochlear implants was characterized by EDAL-1, and it was shown to be growing as the time of auditory stimulation increased, a fact also seen in hearing children. Despite this, the results of the hearing children were better than those of the deaf children implanted.

Dcc Mediates Functional Assembly of Peripheral Auditory Circuits.

Proper structural organization of spiral ganglion (SG) innervation is crucial for normal hearing function. However, molecular mechanisms underlying the developmental formation of this precise organization remain not well understood. Here, we report in the developing mouse cochlea that deleted in colorectal cancer (Dcc) contributes to the proper organization of spiral ganglion neurons (SGNs) within the Rosenthal's canal and of SGN projections toward both the peripheral and central auditory targets. In Dcc mutant embryos, mispositioning of SGNs occurred along the peripheral auditory pathway with misrouted afferent fibers and reduced synaptic contacts with hair cells. The central auditory pathway simultaneously exhibited similar defective phenotypes as in the periphery with abnormal exit of SGNs from the Rosenthal's canal towards central nuclei. Furthermore, the axons of SGNs ascending into the cochlear nucleus had disrupted bifurcation patterns. Thus, Dcc is necessary for establishing the proper spatial organization of SGNs and their fibers in both peripheral and central auditory pathways, through controlling axon targeting and cell migration. Our results suggest that Dcc plays an important role in the developmental formation of peripheral and central auditory circuits, and its mutation may contribute to sensorineural hearing loss.

Mutation of Npr2 leads to blurred tonotopic organization of central auditory circuits in mice.

Tonotopy is a fundamental organizational feature of the auditory system. Sounds are encoded by the spatial and temporal patterns of electrical activity in spiral ganglion neurons (SGNs) and are transmitted via tonotopically ordered processes from the cochlea through the eighth nerve to the cochlear nuclei. Upon reaching the brainstem, SGN axons bifurcate in a stereotyped pattern, innervating target neurons in the anteroventral cochlear nucleus (aVCN) with one branch and in the posteroventral and dorsal cochlear nuclei (pVCN and DCN) with the other. Each branch is tonotopically organized, thereby distributing acoustic information systematically along multiple parallel pathways for processing in the brainstem. In mice with a mutation in the receptor guanylyl cyclase Npr2, this spatial organization is disrupted. Peripheral SGN processes appear normal, but central SGN processes fail to bifurcate and are disorganized as they exit the auditory nerve. Within the cochlear nuclei, the tonotopic organization of the SGN terminal arbors is blurred and the aVCN is underinnervated with a reduced convergence of SGN inputs onto target neurons. The tonotopy of circuitry within the cochlear nuclei is also degraded, as revealed by changes in the topographic mapping of tuberculoventral cell projections from DCN to VCN. Nonetheless, Npr2 mutant SGN axons are able to transmit acoustic information with normal sensitivity and timing, as revealed by auditory brainstem responses and electrophysiological recordings from VCN neurons. Although most features of signal transmission are normal, intermittent failures were observed in responses to trains of shocks, likely due to a failure in action potential conduction at branch points in Npr2 mutant afferent fibers. Our results show that Npr2 is necessary for the precise spatial organization typical of central auditory circuits, but that signals are still transmitted with normal timing, and that mutant mice can hear even with these deficits.

Hipoacusia en niños con conducto auditivo interno agrandado / Hearing loss and enlarged internal auditory canal in children

Introducción: Entre las anomalías del hueso temporal que pueden encontrarse en el estudio etiológico de la hipoacusia neurosensorial (HANS) infantil mediante pruebas de imagen, las relacionadas con el conducto auditivo interno (CAI) se hallan entre las menos frecuentes. De ellas, la más prevalente y relacionada con HANS es el CAI estenótico por su asociación a deficiencias del nervio coclear. Menos frecuente y menos concomitante con HANS es el hallazgo de un CAI agrandado (> 8 mm). Métodos: Estudio retrospectivo y descriptivo de las asociaciones clínicas, estudios de imagen, patrones audiológicos y opciones de tratamiento de 9 niños diagnosticados de hipoacusia en el periodo 1999-2012 con un CAI agrandado. Resultados: Se describen 2 grupos de pacientes. El primero, sin asociación con displasias cocleovestibulares: 2 pacientes con HANS sin otras alteraciones de hueso temporal o sistémicas, una hipoacusia mixta bilateral con cromosomopatía por deleción 18q, una hipoacusia genética DFN 3 ligada a X, una hipoacusia unilateral en neurofibromatosis tipo 2 con neurinoma del acústico bilateral, y una hipoacusia unilateral con déficit de nervio coclear unilateral; y un segundo grupo con asociación a displasias cocleovestibulares: una hipoacusia mixta bilateral moderada en síndrome branquio-oto-renal, una HANS profunda unilateral con meningitis recurrentes, y una HANS bilateral profunda con hipotiroidismo congénito. Conclusiones: La presencia de un CAI agrandado en niños puede encontrarse en diferentes contextos clínicos y audiológicos, con relevancias que pueden variar desde situaciones con riesgo vital como en meningitis recurrentes, hasta hipoacusias aisladas sin otras asociaciones (AU)

Introduction: Among the temporal bone abnormalities that can be found in the etiological study of paediatric sensorineural hearing loss (SNHL) by imaging techniques, those related to the internal auditory canal (IAC) are the least frequent. The most prevalent of these abnormalities that is associated with SNHL is stenotic IAC due to its association with cochlear nerve deficiencies. Less frequent and less concomitant with SNHL is the finding of an enlarged IAC (> 8 mm). Methods: Retrospective and descriptive review of clinical associations, imaging, audiological patterns and treatment of 9 children with hearing loss and enlarged IAC in the period 1999 to 2012. Results: Two groups of patients are described. The first, without association with vestibulocochlear dysplasias, consisted of: 2 patients with SNHL without other temporal bone or systemic abnormalities, one with bilateral mixed HL from chromosome 18q deletion, one with a genetic X-linked DFN3 hearing loss, one with unilateral hearing loss in neurofibromatosis type 2 with bilateral acoustic neuroma, and one with unilateral hearing loss with cochlear nerve deficiency. The second group, with association with vestibulocochlear dysplasias, was comprised of: one patient with moderate bilateral mixed hearing loss in branchio-oto-renal syndrome, one with profound unilateral SNHL with recurrent meningitis, and another with profound bilateral SNHL with congenital hypothyroidism. Conclusions: The presence of an enlarged IAC in children can be found in different clinical and audiological settings with relevancies that can range from life-threatening situations, such as recurrent meningitis, to isolated hearing loss with no other associations (AU)

Otitis media crónica complicada en un adolescente con malformación auditiva / Complicated chronic otitis media in an adolescent with auditory malformation

Se describe el caso clínico de un adolescente de 17 años de edad, multimalformado, con agenesia del pabellón auricular, así como en el oído externo y medio, quien presentó otitis media crónica complicada. Fue ingresado en el Servicio de Otorrinolaringología del Hospital Provincial Docente Clinicoquirúrgico Saturnino Lora Torres y se le indicó antibioticoterapia triple. Posteriormente se realizó una incisión en la región mastoidea del lado izquierdo, se drenó abundante pus, se colocó drenaje y se mantuvo la medicación con antibióticos. El paciente evolucionó favorablemente y egresó a los 10 días. Se concluyó el caso como una otitis media crónica con mastoiditis aguda(AU)

The case report of a 17 year-old adolescent, with multiple malformations, agenesia of pinna as well as of the external and middle ear who presented with complicated chronic otitis media is described. He was admitted to the Otorhinolaryngology Service of Saturnino Lora Torres Clinical Surgical Teaching Provincial Hospital and he was indicated triple antibiotic therapy. Later an incision in the mastoid region of his left side was carried out, abundant pus was drained, drainage was placed and the medication with antibiotics was maintained. The patient had a favorable clinical course and he was discharged 10 days later. It was concluded that the case was a chronic otitis media with acute mastoiditis(AU)

MRI during cochlear implant assessment: Should we image the whole brain?

OBJECTIVES: Magnetic resonance imaging (MRI) is a standard part of a cochlear implant assessment in most centres. While there is ample literature on the temporal bone-specific imaging that is required, the role of whole brain imaging has not been as fully studied. We present the first report of the incidence of associated brain abnormalities in the whole cochlear implant population, including adults and consider their significance. METHODS: We retrospectively reviewed 51 (12 adults and 39 children) sequential cases since we added whole brain MRI sequences to our cochlear implant assessment protocol. We reviewed the scans for abnormalities of the cochlea and cochlear nerve and a neuroradiologist reviewed the images of the whole brain sequences for further abnormalities. RESULTS: We identified abnormalities on the whole brain sequences in 21 (41%) of these patients, 5 of 12 adults (42%) and 16 of 39 children (41%). Thirty-six (71%) patients subsequently had at least one implant inserted, 13 with abnormalities on whole brain MRI (36%) and 23 without. Of the 15 patients who did not undergo subsequent implantation, 8 had positive findings on their whole brain MRI sequence (53%). There was no statistical difference in the probability of finding an abnormality on the whole brain MRI between those who did and those who did not go on to have an implant (P = 0.35). There were abnormalities within the inner ear in five patients. DISCUSSION: The abnormalities detected on the whole brain images are heterogenous and of wide ranging clinical significance ranging from truly incidental findings to abnormalities that are so severe that they may predict a very poor prognosis such that an implant may contribute little.

Egr2::cre mediated conditional ablation of dicer disrupts histogenesis of mammalian central auditory nuclei.

Histogenesis of the auditory system requires extensive molecular orchestration. Recently, Dicer1, an essential gene for generation of microRNAs, and miR-96 were shown to be important for development of the peripheral auditory system. Here, we investigated their role for the formation of the auditory brainstem. Egr2::Cre-mediated early embryonic ablation of Dicer1 caused severe disruption of auditory brainstem structures. In adult animals, the volume of the cochlear nucleus complex (CNC) was reduced by 73.5%. This decrease is in part attributed to the lack of the microneuronal shell. In contrast, fusiform cells, which similar to the granular cells of the microneural shell are derived from Egr2 positive cells, were still present. The volume reduction of the CNC was already present at birth (67.2% decrease). The superior olivary complex was also drastically affected in these mice. Nissl staining as well as Vglut1 and Calbindin 1 immunolabeling revealed that principal SOC nuclei such as the medial nucleus of the trapezoid body and the lateral superior olive were absent. Only choline acetyltransferase positive neurons of the olivocochlear bundle were observed as a densely packed cell group in the ventrolateral area of the SOC. Mid-embryonic ablation of Dicer1 in the ventral cochlear nucleus by Atoh7::Cre-mediated recombination resulted in normal formation of the cochlear nucleus complex, indicating an early embryonic requirement of Dicer1. Quantitative RT-PCR analysis of miR-96 demonstrated low expression in the embryonic brainstem and up-regulation thereafter, suggesting that other microRNAs are required for proper histogenesis of the auditory brainstem. Together our data identify a critical role of Dicer activity during embryonic development of the auditory brainstem.

Structural abnormalities of the central auditory pathway in infants with nonsyndromic cleft lip and/or palate.

OBJECTIVE: To investigate possible structural abnormalities of the central auditory pathway in infants with nonsyndromic cleft lip and/or palate (NSCL/P). PARTICIPANTS: Twenty-seven Chinese infants with NSCL/P, aged from 6 to 24 months. INTERVENTION: Morphological magnetic resonance imaging (MRI) measurements of the central auditory nervous system (CANS) in infants with NSCL/P were analyzed and compared with those of age- and sex-matched normal controls. RESULTS: No significant group differences were found in general brain measurements, including volumes of the brain stem and right hemisphere. However, infants with NSCL/P had statistically significantly smaller volumes of the left thalamus and left auditory cortex and notably decreased thickness of the left auditory cortex. CONCLUSION: Cortical abnormalities were more marked compared with other MRI measurements. Structural CANS abnormalities in infants with NSCL/P may be located mainly in the left cerebral hemisphere. The development and maturation of the auditory cortex in infants with NSCL/P may be abnormal when compared with those of normal children.

Malformation of the superior olivary complex in an animal model of autism.

Autism is a neurodevelopmental disorder characterized by social difficulties, impaired communication skills and repetitive behavioral patterns. Additionally, there is evidence that auditory deficits are a common feature of the autism spectrum disorders. Despite the prevalence of autism, the neurobiology of this disorder is poorly understood. However, abnormalities in neuronal morphology, cell number and connectivity have been described throughout the autistic brain. Indeed, we have demonstrated significant dysmorphology in the superior olivary complex (SOC), a collection of auditory brainstem nuclei, in the autistic brain. Prenatal exposure to valproic acid (VPA) in humans has been associated with autism and in rodents prenatal VPA exposure produces many neuroanatomical and behavioral deficits associated with autism. Thus, in an effort to devise an animal model of the autistic auditory brainstem, we have investigated neuronal number and morphology in animals prenatally exposed to valproic acid (VPA). In VPA exposed rats, we find significantly fewer neurons and significant alterations in neuronal morphology. Thus, prenatal VPA exposure in rats appears to produce similar dysmorphology as we have reported in the autistic human brain.

Childhood autism and auditory system abnormalities.

Hearing disorders are common among children with autism, ranging from peripheral and sensorineural hearing deficit or loss to auditory hypersensitivity with bizarre reactions to sounds. The auditory abnormalities and consequent sensory deprivation exacerbate the communication deficit of autism, and early auditory assessment holds an important place in the planning of intervention and the overall prognosis of patients. Physiologic, pathologic, imaging, and neurochemical studies have revealed an array of aberrations in the perception and processing of the audiologic stimuli, including (among others) maturational defects, atypical lateralization, and serotonin dysfunction.

Functional reorganization of the auditory pathways (or lack thereof) in callosal agenesis is predicted by monaural sound localization performance.

Neuroimaging studies show that permanent peripheral lesions such as unilateral deafness cause functional reorganization in the auditory pathways. However, functional reorganization of the auditory pathways as a result of higher-level damage or abnormalities remains poorly investigated. A relatively recent behavioural study points to functional changes in the auditory pathways in some, but interestingly not in all, of the acallosal individuals that were tested. The present study uses fMRI to investigate auditory activities in both cerebral hemispheres in those same acallosal subjects in order to directly investigate the contributions of ipsilateral and contralateral functional pathways reorganization. Predictions were made that functional reorganization could be predicted from behavioural performance. As reported previously in a number of neuroimaging studies, results showed that in neurologically intact subjects, binaural stimulation induced balanced activities between both hemispheres, while monaural stimulation induced strong contralateral activities and weak ipsilateral activities. In accordance with behavioural predictions, some acallosal subjects showed patterns of auditory cortical activities that were similar to those observed in neurologically intact subjects while others showed functional reorganization of the auditory pathways. Essentially they showed a significant increase and a significant decrease of neural activities in the contralateral and/or ipsilateral pathways, respectively. These findings indicate that at least in some acallosal subjects, functional reorganization inside the auditory pathways does contribute to compensate for the absence of the corpus callosum.

Síndrome de Stickler: aspectos gerais / Stickler syndrome: general aspects

A síndrome de Stickler é a principal causa de descolamento de retina entre os fatores hereditários, sendo ainda pouco conhecida, apesar de comum na Europa. Constitui-se em doença autossômica dominante, progressiva, causada a partir de mutações em genes responsáveis pela síntese de colágeno, como COL2A1, COL11A1 e COL11A2. Possui variada sintomatologia, inclusive dentro de uma mesma família. Ocorrem alterações otorrinolaringológicas, oftalmológicas, ortopédicas e sistêmicas, como hipoacusia, fenda palatina, face plana, nariz achatado, miopia intensa, catarata, glaucoma, articulações hiperflexíveis e prolapso da valva mitral. Dentre as principais complicações dos indivíduos afetados se encontram surdez neurossensorial, descolamento da retina e cegueira. O artigo se constituiu em uma revisão bibliográfica sobre a síndrome de Stickler, abordando os principais sinais e sintomas clínicos, diagnóstico e tratamento, através da pesquisa e seleção de artigos científicos na biblioteca virtual BIREME, predominantemente de 2000 a 2006, associados a artigos clássicos sobre o tema. Devido a seu caráter progressivo, torna-se fundamental o diagnóstico precoce, na tentativa de evitar complicações que prejudiquem o desenvolvimento do indivíduo, havendo necessidade de tratamento multidisciplinar, devido ao acometimento de múltiplas estruturas.

Morphological features of the medial superior olive in autism.

Autism is a psychosocial disorder clinically characterized by social difficulties, impairment in communication skills and repetitive behavioral patterns. Despite the increasing reported incidence of autism, the neurobiology of this disorder is poorly understood. However, researchers have uncovered numerous structural anomalies in the brainstem, cerebellum and forebrain of autistic individuals and there is substantial support for the association of hearing deficits with autism. In an effort to discover an anatomical correlate for the functional auditory deficits found in autism, we examined the SOC, a group of brainstem nuclei that function in sound source localization, in post-mortem brain tissue from autistic individuals. The neurons of the medial superior olive (MSO), an SOC nucleus, display a precise geometric organization essential for detection of timing differences between the two ears. We examined the architecture of the MSO in five autistic brains (ages 8 to 32 years) and two age-matched controls (ages 26 and 29 years) and found a significant disruption in the morphology of MSO neurons in autistic brains, involving cell body shape and orientation. The results from this study provide evidence on the cellular level that may help to explain the hearing difficulties associated with autism.

Auditory brainstem neural activation patterns are altered in EphA4- and ephrin-B2-deficient mice.

Auditory processing requires proper formation of tonotopically ordered projections. We have evaluated the role of an Eph receptor tyrosine kinase and an ephrin ligand in the development of these frequency maps. We demonstrated expression of EphA4 and ephrin-B2 in auditory nuclei and found expression gradients along the frequency axis in neonates. We tested the roles of EphA4 and ephrin-B2 in development of auditory projections by evaluating whether mutations result in altered patterns of expression of the immediate early gene c-fos after exposure to pure tone stimuli. We evaluated two nuclei, the dorsal cochlear nucleus (DCN) and the medial nucleus of the trapezoid body (MNTB), which project in two distinct auditory pathways. The mean number of c-fos-positive neurons in EphA4(-/-) DCN after 8-kHz pure tone stimulation was 42% lower than in wild-type DCN. Along the dorsoventral, tonotopic axis of DCN, the mean position of c-fos-positive neurons was similar for mutant and wild-type mice, but the spread of these neurons along the tonotopic axis was 35% greater for ephrin-B2(lacZ/+) mice than for wild-type mice. We also examined these parameters in MNTB after exposure to 40-kHz pure tones. Both EphA4(-/-) and ephrin-B2(lacZ/+) mice had significantly fewer c-fos-positive cells than wild-type littermates. The labeled band of cells was narrower and laterally shifted in EphA4(-/-) mice compared with wild-type mice. These differences in cell number and distribution suggest that EphA4 and ephrin-B2 signaling influence auditory activation patterns.

Auditory event-related responses in children with semi-lobar holoprosencephaly.

The purpose of this study was to evaluate auditory sensory and discrimination responses in children with semi-lobar holoprosencephaly (HPE). Event-related potential (ERP) signals were recorded to tone pair stimuli at 62 electrode sites from the scalp using an oddball paradigm (a two-block design, inter-stimulus interval=70 or 300 ms; frequency of tone pair=100 vs. 100 Hz for the frequent and 100 vs. 300 Hz for the infrequent). Latencies and amplitudes of P150, N250, and mismatch negativity (MMN)-like components were compared between children with HPE and controls. Our results revealed less organized ERP waveforms to both stimuli in children with HPE, with diminished P150 and N250 components across brain area. Robust and delayed MMN-like responses were elicited from the children with HPE, with decreased MMN amplitudes in the central, parietal, occipital, and posterior temporal areas. Our results suggest that while brain sensory responses to auditory tones may be impaired in children with semi-lobar HPE, subcomponents of auditory discrimination processes remain functional.

Perdas auditivas condutivas / Conductive hearing loss

O sistema auditivo é constituído pelas orelhas externa, média e interna e pelas vias auditivas no sistema nervoso central. A membrana timpânica tem como função amplificar a pressão sonora, permitindo uma amplificação de sons. A orelha média compreende a cavidade timpânica composta pela membrana timpânica (camadas intermediária e interna), cadeia ossicular com seus músculos e ligamentos, a tuba auditiva, o adito, o antro e as células mastóideas. Conhecendo-se as estruturas das orelhas externa e média e sua fisiologia na transmissão sonora, pode-se reconhecer o que alterações neste sistema trazem de prejuízos para a função auditiva no ser humano, constituindo assim quadros clínicos diversos que cursam com perdas auditivas condutivas.