CNTN6 mutations are risk factors for abnormal auditory sensory perception in autism spectrum disorders.

Contactin genes CNTN5 and CNTN6 code for neuronal cell adhesion molecules that promote neurite outgrowth in sensory-motor neuronal pathways. Mutations of CNTN5 and CNTN6 have previously been reported in individuals with autism spectrum disorders (ASDs), but very little is known on their prevalence and clinical impact. In this study, we identified CNTN5 and CNTN6 deleterious variants in individuals with ASD. Among the carriers, a girl with ASD and attention-deficit/hyperactivity disorder was carrying five copies of CNTN5. For CNTN6, both deletions (6/1534 ASD vs 1/8936 controls; P=0.00006) and private coding sequence variants (18/501 ASD vs 535/33480 controls; P=0.0005) were enriched in individuals with ASD. Among the rare CNTN6 variants, two deletions were transmitted by fathers diagnosed with ASD, one stop mutation CNTN6W923X was transmitted by a mother to her two sons with ASD and one variant CNTN6P770L was found de novo in a boy with ASD. Clinical investigations of the patients carrying CNTN5 or CNTN6 variants showed that they were hypersensitive to sounds (a condition called hyperacusis) and displayed changes in wave latency within the auditory pathway. These results reinforce the hypothesis of abnormal neuronal connectivity in the pathophysiology of ASD and shed new light on the genes that increase risk for abnormal sensory perception in ASD.

Fetal airway management on placental support: limitations and ethical considerations in seven cases.

The aim of this study was to evaluate the paediatric and maternal outcome after ex utero intrapartum treatment (EXIT). A retrospective review was carried out of the medical charts (gestational age, circumstances of diagnosis, multidisciplinary prenatal decision, date of surgery, paediatric and maternal outcome) of all the fetuses eligible for/delivered via the EXIT procedure in our paediatrics and obstetrics tertiary care and teaching centre, between October 2004 and May 2011. Seven fetuses with cervical teratoma, epignathus tumour or congenital high airway obstruction syndrome (CHAOS) were included in our study. Two pregnancies were terminated and five fetuses were delivered alive. The airway was secured in all five cases (two endotracheal intubations and three tracheostomies). No maternal complications were observed. On average, babies were delivered at 32 gestational weeks, and spent 31 days in the intensive care unit. All but one baby were ventilated for 18 days. Long-term paediatric outcome was favourable. It is concluded that airway management by the EXIT procedure has become an efficient technique. A multidisciplinary prenatal assessment is essential in order to select appropriate cases.

Endonasal endoscopic approach for removal of intranasal nasal glial heterotopias.

BACKGROUND: Nasal Glial Heterotopias also called Nasal Gliomas (NG) are rare congenital tumours of the midline frontonasal space arising from a normal neurectodermal tissue entrapped during the closure of the anterior neuropore. Historically, such tumours were approached using a frontal craniotomy. The study aims to evaluate a fully endonasal endoscopic approach for intranasal NG removal. METHODS: We report a retrospective study of intranasal and mixed NG treated using endonasal endoscopic techniques and computer assisted navigation system from 1997 to 2010 in two tertiary referral centres of Paediatric Otolaryngology. All tumours were investigated using two imaging modalities: craniofacial MRI and CT-scan. RESULTS: Fifteen patients were included (0 to 14 years of age). All tumours were totally removed and no recurrence was observed after a mean follow-up of 32 months. A skull base plasty was done in 13 cases to cover a bony defect or to treat a cerebrospinal leak. Nasal packing was usually removed 24 hours after surgery and all children were discharged home after 2 to 4 days. CONCLUSION: Removal of intranasal NGs using an endonasal endoscopic approach and a dedicated computer assisted navigation system is a safe and efficient procedure. Early management is recommended to treat neonatal airway obstruction.

Recurrent laryngeal nerve monitoring during thyroidectomy and parathyroidectomy in children.

OBJECTIVE: Injury of the recurrent laryngeal nerve (RLN) is the most frequent complication of thyroid and parathyroid (TP) surgery. Monitoring of the RLN in children is not widely studied as this is not a common disease in the pediatric population. The aim of our study was to evaluate the reliability, feasibility and benefits of RLN monitoring during TP surgery in children. METHODS: We analyzed all children who underwent TP surgery in our department between January 2009 and March 2018. Patients were classified into three groups: without monitoring (group 1), monitoring with an endotracheal tube (group 2) and monitoring with a double-needle electrode placed through the cricothyroid ligament (group 3). RESULTS: We performed 53 surgeries (77 RLNs at risk) on 47 patients aged between 6 months and 18 years. Fourteen RLNs were in group 1, 47 in group 2 and 16 in group 3. We found one transient lesion of the RLN in group 1, three in group 2 and two in group 3. Seven patients in group 3 could not undergo monitoring with the tube because they need an orotracheal tube smaller than the smallest monitoring tube size available. The sensitivity and specificity values of the monitoring methods were 33% and 97% in group 2 and 67% and 100% in group 3, respectively. The positive and negative predictive values were 50% and 95% in group 2 and 100% and 92% in group 3, respectively. No complications arose during insertion of the electrode through the cricothyroid ligament. CONCLUSION: Monitoring of the RLN with a double-needle electrode inserted through the cricothyroid ligament is a reliable method with no associated complication, which is achievable at any age.

Recurrent laryngeal nerve monitoring in children using cricothyroid membrane needle electrodes.

AIMS: Thyroid pathology is rare in children and the rate of malignancy is higher than in adults. Thyroid surgery in children is therefore particularly at risk of causing recurrent laryngeal nerve (RLN) palsies. The classical technique for monitoring the RLN is not always adapted to children due to the large size of the dedicated endotracheal tubes. MATERIAL AND METHODS: Double-needle electrodes (NIM 3.0) were placed medially or paramedially through the cricothyroid membrane and carefully kept submucosal just below the level of the vocal folds. Before identification of the RLN, the vagal nerve was dissected on the side of the concerned lobe and stimulated. The thyroid surgery was then performed with the routine identification of the RLN. The response of the RLN is periodically checked using a stimulating probe. The main outcomes were the identification and stimulation of the RLN, quality of the voice in post-operative time. OBJECTIVE: The main objective of our study is to present a simple and efficient method, available for children of all ages, in order to perform monitoring of the recurrent laryngeal nerves during thyroid surgery. RESULTS: We present the results of our retrospective series, in a tertiary-care university pediatric hospital. We included nine children, corresponding to 15 nerves. In all cases, the RLN was identified, stimulated and a positive response was obtained via monitoring. CONCLUSIONS: This technique of monitoring is safe, feasible at any age, even in neonates, and, as the electrode stays in the operation field, its position is easily controlled.

Otologic disorders in Turner syndrome.

INTRODUCTION: Patients with Turner syndrome (TS) have craniofacial malformations, such as Eustachian tube hypoplasia and dysfunction and velar dysfunction, which foster acute otitis media. The aim of this study was to inventory pediatric otologic disorders in patients with TS at their first ENT consultation in our center. PATIENTS AND METHODS: We reviewed the ENT consultation data of pediatric TS patients followed in our center between 2005 and 2015: otoscopy, hearing threshold, and history of acute otitis media or ENT surgery. Data were compared according to karyotype: X monosomy (45,X), mosaic (45,X/46,XX), isochromosome (46,Xi [Xq]), X ring chromosome X (XrX), with Y material, and "other". RESULTS: Ninety patients, with mean age 11.9years (±4.8years) at first ENT consultation, were included: 29% showed tympanic abnormality on otoscopy, 21% had hearing loss, 24% had history of recurrent acute otitis media; 18% had undergone adenoidectomy, 24% T-tube insertion, and 5.6% tympanoplasty. No particular karyotype was associated with higher risk of hearing loss or acute otitis media. CONCLUSION: Patients with TS showed high prevalence of pediatric otologic disorders; they therefore require close and prolonged ENT follow-up.

[Rectal pentobarbital sedation for children undergoing auditory brainstem response testing]. / Sédation au pentobarbital par voie rectale pour enregistrement des PEA chez l'enfant.

OBJECTIVES: The aim of our study was to determine if rectal sedation with pentobarbital sodium provides safe and effective sedation for children undergoing auditory brainstem response (ABR) testing. MATERIAL AND METHODS: A prospective study was conducted in the ENT pediatric department of Robert Debre's hospital (APHP, Paris). 68 children under 8 years of age were given rectal pentobarbital for ABR testing at a dosage of about 5 mg/kg. RESULTS: 61 children of 68 (89.7%) were adequately sedated with rectal pentobarbital. The mean elapsed time from drug administration to full sedation was 36,1 minutes. No adverse event was reported in 84.1% of children. CONCLUSION: Pentobarbital provides safe and effective sedation. Rectal administration is easy, painless and with brief duration of action. It's a good alternative to general anesthesia for young children undergoing ABR testing.

[The deaf child: anatomy, etiologies and management]. / Le sourd est un enfant: qu'est-ce que ça change. Anatomie, pathologie, prise en charge.

Temporal bone imaging in children shows radioanatomical aspects and diseases distinct from the imaging and pathology results found in adults. Imaging modalities such as CT and MR bring out these differences. The aim of this study is to present the CT and MR particularities of the temporal bone during postnatal growth. The mastoid air cells form mostly in the postnatal period and the course of pneumatization is directly correlated with middle ear successive inflammatory episodes. The most frequent etiologies of hearing loss in children are reviewed, emphasizing their specificities in clinical presentation, radiological aspects, and treatment. In children, conductive hearing loss with normal tympanic membrane is mostly caused by minor aplasia rather than otosclerosis. Sensorineural hearing loss, even when unilateral, is predominantly due to malformation or infection and in rare cases to posterior fossa tumor.

Audiovestibular consequences of congenital cytomegalovirus infection.

Congenital cytomegalovirus (CMV) infection is the second most frequent cause of mental retardation and sensorineural hearing loss, after genetic factors. Recently, pediatric forensic and fetopathological studies have led to progress in understanding the pathophysiological mechanisms underlying the various neurosensory sequelae. Thanks to the identification of certain prognostic factors of hearing loss, therapeutic protocols based on antiviral molecules are now proposed for target populations. This treatment has shown efficacy in limiting hearing threshold deterioration and even, in some cases, seems to provide partial recovery of hearing in symptomatic congenitally infected CMV neonates. However, optimal treatment duration and administration modalities are not clearly defined. This article reviews recent data concerning audiovestibular sequelae and their management in children congenitally infected by CMV.

Inlay butterfly cartilage tympanoplasty in children.

OBJECTIVE: To assess the results of inlay butterfly cartilage tympanoplasty in children. STUDY DESIGN: Before-and-after trial; follow-up duration, 26.6 +/- 19.9 months (mean +/- standard deviation). SETTING: Tertiary referral center. PATIENTS: Fifty-nine pediatric cases of tympanic membrane perforation. INTERVENTION: Inlay butterfly cartilage tympanoplasty was performed under general anesthesia according to the technique originally described by Eavey and modified by Lubianca-Neto (i.e., without any associated split-thickness skin graft). MAIN OUTCOME MEASURES: Percentage of perforation closures, surgical complications, preoperative and postoperative puretone hearing thresholds; the results of inlay butterfly cartilage tympanoplasty were compared with those obtained in a retrospective series of 29 underlay fascia temporalis myringoplasties. RESULTS: The 71% "take rate" of inlay butterfly cartilage tympanoplasty was not significantly different from the 83% take rate obtained with underlay fascia temporalis tympanoplasty (p = 0.23, chi test). The anatomic results were improved when the graft diameter was at least 2 mm larger than the size of the perforation (81% take rate) (p = 0.009, chi test). No iatrogenic cholesteatoma was observed. Pure-tone hearing thresholds were improved at 0.5, 1, and 2 kHz, and stable at 4 kHz. Hearing levels were not different from those obtained with underlay fascia temporalis tympanoplasty. CONCLUSION: Inlay butterfly cartilage tympanoplasty is a safe, efficient, time-saving, and easy technique of tympanoplasty in children. Anatomic results may be improved by associating a split-thickness skin graft and/or by trimming a tragal graft much larger than the size of the perforation.

Tracheotomy in children: A series of 57 consecutive cases.

OBJECTIVES: With medical improvements in pediatrics, the role of tracheotomy has evolved. The aim of this study was to specify the indications for and complications of tracheotomy performed on children in a teaching hospital containing a level-3 maternity department and pediatric intensive care unit. MATERIAL AND METHODS: A retrospective study was conducted in pediatric tracheotomies performed from 2004 to 2014. Indications, early and late complications and the number and timing of decannulations were collated. RESULTS: Fifty-seven patients were included. Tracheotomy was motivated by upper airway obstruction in 39 children (68%) (median age, 4.9 months) or the need for prolonged ventilation in 18 children (32%) (median age, 6 months). There were 4 early complications (7%) (2 decannulations, including 1 fatal; an obstructive plug, responsible for another death; and 1 pneumothorax during an EXIT procedure), and 15 secondary complications requiring further surgery (26%). Twenty-seven patients (47%) were decannulated, with a mean tracheotomy duration of 26 months. In 9 cases (33% of decannulations), persistence of tracheocutaneous fistula required surgical repair. CONCLUSION: Tracheotomy for infection is almost a thing of the past; tracheotomy for airway obstruction is also likely to decrease, thanks to medical treatment (for hemangioma) and surgical techniques (for congenital stenosis). Tracheotomy for prolonged ventilation, on the other hand, remains. Complications of tracheotomy in children are rare but potentially serious, requiring care in a specialized center within a multidisciplinary team with defined care protocols.

Cochlear electrical stimulation: influence of age of implantation on Fos immunocytochemical reactions in inferior colliculi and dorsal cochlear nuclei of the rat.

The influence of age at the time of implantation of a stimulating electrode unilaterally in the inner ear on central auditory pathways was investigated in rats deafened shortly after birth. Immunoreactivity for Fos served as a functional marker of neuronal activity. Electrodes were implanted in the left cochlea of rats aged 3 weeks or 4 months. Stimulation lasted 45 minutes, then rats were sacrificed and tissues processed for immunocytochemistry. The younger animals showed significantly more neurons with Fos immunoreactivity bilaterally in the dorsal cochlear nuclei (DCN) and inferior colliculi (IC) than the older rats or control animals with normal hearing receiving the same stimulation. Activity was more prominent in the left DCN and right IC. The results show that electrical stimulation of the inner ear is more effective in younger animals in eliciting gene expression associated with development of a functional network in the auditory pathways. This suggests that deaf children should be provided with cochlear implants as early as possible.

Mismatch negativity: a tool for the assessment of stimuli discrimination in cochlear implant subjects.

OBJECTIVES: The performance of cochlear implants varies among users. This variability may be due to the ability to process auditory information. The mismatch negativity should provide an index of discrimination in cochlear implantees (Kraus N, McGee T, Carrell T, Sharma A. Neurophysiologic bases of speech discrimination. Ear Hear. 1995;16:19-37). Our aim was to analyze MMN in cochlear implant (Digisonic) subjects to assess electrode discrimination and to study the relationship between MMN and speech performance. METHODS: The mismatch was determined by stimulating three pairs of different electrodes. Two sessions were performed with both standard and deviant stimuli reversed. Speech recognition abilities were evaluated using 4 speech tests. The statistics included the results of 6 subjects. They indicated that MMN may be obtained when stimulating two different electrodes. A difference occurred between standard and deviant stimuli within a session but also when the response to the deviant stimulus was compared to the response of the same stimulus in a standard condition, validating the discrimination process. MMN latency was about 140 ms, and amplitude about -2.8 microV. No differences were shown with respect to electrode spacing. No relationship between MMN and speech performance was found. A clinical application of this method might be to assess the auditory processing of electrical stimuli in congenitally deaf subjects at the pre-implantation stage.

Traumatic luxation of the stapes evidenced by high-resolution CT.

We encountered a case of acquired perilymphatic fistula in which the origin of the disease, namely, the stapes begin medially displaced into the vestibule, was shown by thin-section CT. Accordingly, we recommend that every patient with suspected perilymphatic fistula of traumatic origin undergo high-resolution CT of the petrous bone.

Bronchial trifurcation in a congenital pulmonary venolobar syndrome.

Congenital malformations of the tracheobronchal tree and the related arterial blood supply are a complex group of lesions in which there are abnormalities of the venous drainage and lung parenchyma. These malformations are examples of congenital pulmonary venolobar syndrome (CPVS). Tracheal trifurcation is an extremely rare anomaly associated with CPVS. We report on an unusual case of lower right extralobar sequestration connected to the trachea, plus a type I posterior laryngeal cleft, an aberrant systemic artery, and an anomalous route of the phrenic nerve. This paper discusses the place of this unusual abnormality in the spectrum of congenital bronchopulmonary vascular malformations.

Potassium channel ether à go-go mRNA expression in the spiral ligament of the rat.

Identification of the K+ transporters located in the lateral wall of the cochlea is essential for a better understanding of the mechanisms by which a positive endocochlear potential and a high K+ concentration are achieved in endolymph. In this study, we have determined the distribution of the K+ channel rat ether à go-go (eag) mRNA in the cochlea. After reverse transcription of adult rat cochlear tissues, cDNA was amplified with primers specific to eag channel. The eag mRNA was localized in cochlear tissues by in situ hybridization using specific oligonucleotide probes tailed with digoxigenin conjugated UTP. Eag mRNA was detected in the organ of Corti but mainly in the fibrocytes of the spiral ligament but not in spiral prominence or in stria vascularis. The expression pattern of rat eag transcript in spiral ligament is complementary to the Na+,K+-ATPase distribution in the cochlear lateral wall. The localization of eag mRNA suggests that eag potassium channel may be produced in the corresponding cells. Considering the importance of the K+ gradient in the cochlea, the result reported here suggests that eag channel may play a role in the control of K+ fluxes in the spiral ligament.

Luminal non-selective cation and outwardly rectifying chloride channels in cultured strial marginal cells from gerbil.

Ionic channels located on the luminal side of strial marginal cells (MCs) of gerbil in culture were investigated using the patch-clamp technique. Two types of channels were identified. The most frequently recorded single-channel activity corresponded to a non-selective cation (NSC) channel with a conductance of 23.7 +/- 0.2 pS (n = 18) in symmetrical NaCl conditions. The channel was activated by internal Ca2+ and inhibited by internal adenine nucleotides and flufenamic acid. Spontaneous activity of NSC channels was found in 16% of the cell-attached patches and with a very high density (9 +/- 2 levels/patch, n = 28) in 100% of the excised patches. An outwardly rectifying chloride (ORC) channel was also identified in 14% of the patches but only after excision. The channel exhibited at 0 mV a unit conductance of 26.8 +/- 1.3 pS (n = 8) and a strong outward rectification in symmetrical NaCl conditions, and the open probability increased with depolarization. The luminal NSC channel and the ORC channel evidenced in this study might participate in the production of endolymph. Although extrapolation of the presents results to the in vivo situation should be made with caution, this study suggests that culture of strial MCs may be a suitable model for investigation of endolymph physiology.

Expression of NMDA, AMPA and GABA(A) receptor subunit mRNAs in the rat auditory brainstem. I. Influence of early auditory deprivation.

Impact of early post-natal deafening on auditory pathways was investigated in newborn rats deafened by daily amikacin injections from P7 to P16 inducing a complete destruction of the organ of Corti. The expression of mRNAs encoding N-methyl-D-aspartate (NMDA), alpha-amino-3-hydroxy-5-methyl-4-isoxazole (AMPA) and gamma-aminobutyric acid type A (GABA(A)) receptor subunits was then studied by in situ hybridization in the dorsal and ventral cochlear nucleus and in the central nucleus of the inferior colliculus (CNIC). Early post-natal deafening decreased bilaterally the expression of mRNAs encoding NR1, NR2a, NR2b and flop isoforms of AMPA receptors. On the contrary, it increased the expression of mRNAs encoding some GABA(A) subunits (alpha1, beta1, gamma2) and flip isoforms of AMPA receptors. These changes were more pronounced in cochlear nuclei than in CNIC. They suggest that auditory sensation is essential in the normal development of central auditory pathways.

Expression of NMDA, AMPA and GABA(A) receptor subunit mRNAs in the rat auditory brainstem. II. Influence of intracochlear electrical stimulation.

We investigated the effects of intracochlear electrical stimulation (ICES) on auditory pathways of neonatal rat deafened by daily amikacin injections. Expression of mRNAs encoding ionotropic glutamate receptor subunits such as alpha-amino-3-hydroxy-5-methyl-4-isoxazole (AMPA) and N-methyl-D-aspartate (NMDA), and gamma-aminobutyric acid type A (GABA(A)) receptor subunits was assessed by in situ hybridization in the dorsal (DCN) and the ventral cochlear nucleus (VCN) and in the central nucleus of the inferior colliculus (CNIC). After 15 days of daily unilateral ICES, the expressions of NR1, NR2b and NR2c subunits of NMDA receptor, that of GluRA, B, C, D flop isoforms of AMPA receptor and that of some GABA(A) subunits (alpha1, beta1, gamma1, gamma2) were increased bilaterally in the DCN, VCN and the CNIC. These changes last over a week after stimulation for only NR1 and NR2c. These modifications might be related to long lasting synaptic plasticity of brainstem auditory pathways. As far as analogy to deaf children can be made, early electrical stimulation might be of interest to maintain neuronal networks.