Anne-Laure Mansbach

Auditory Neuropathy with Preserved Cochlear Microphonics and Secondary Loss of Otoacoustic Emissions

Auditory neuropathy is defined as absent or severely distorted auditory brainstem responses with preserved otoacoustic emissions and cochlear microphonics. This entity can be found in various circumstances including pre-lingual children. An almost universal characteristic reported from adult patients is the ineffectiveness of traditional hearing aids. Adequate management of pre-lingual cases therefore remains an open problem. This paper describes two pre-lingual children whose follow-up data demonstrated a selective loss of the otoacoustic emissions, whereas the cochlear microphonics remained preserved. In one of the patients, hearing aid fitting as soon as she lost her otoacoustic emissions proved successful. These findings have important implications for the operational definition of the condition, since one must be prepared to encounter cases with absent otoacoustic emissions. The present data also demonstrate that conventional amplification can benefit pre-lingual auditory neuropathy cases, at least once they have lost their otoacoustic emissions.

Familial CHARGE syndrome because of CHD7 mutation: Clinical intra- and interfamilial variability

CHARGE syndrome (OMIM #214800) is a multiple malformation syndrome with distinctive diagnostic criteria, usually because of CHD7 (chromodomain helicase DNA binding 7) haploinsufficiency. Familial occurrence of CHARGE syndrome is rare. We report six patients from two Caucasian families (both with one parent and two children) affected by mild to severe CHARGE syndrome. Direct sequencing of the CHD7 gene was performed in these two unrelated families. A mutation in exon 8 (c.2501C>T – p.S834F) in first chromodomain was found in family A and a nonsense mutation in exon 2 (c.469C>T – p.R157X) in family B. Both mutations are de novo in the parents. In family A, the elder son had bilateral cleft lip and palate, esophageal atresia with fistula, complex heart defect and vertebral abnormalities, while the younger had a posterior coloboma. Their mother had asymptomatic vestibular dysfunction and retinal coloboma, identified after the molecular diagnosis of her children. In family B, both affected children had severe expression of CHARGE syndrome. The father carrying the mutation only had asymmetric anomaly of the pinnae. These familial reports describe the intrafamilial variability of CHARGE syndrome, and underline the presence of CHD7 mutations in patients who do not fit the ‘classical clinical criteria’ for CHARGE syndrome.

Safety of MR Imaging at 1.5 T in Fetuses: A Retrospective Case-Control Study of Birth Weights and the Effects of Acoustic Noise

PURPOSE To evaluate the effects of exposure to routine magnetic resonance (MR) imaging at 1.5 T during pregnancy on fetal growth and neonatal hearing function in relation to the dose and timing of in utero exposure in a group of newborns at low risk for congenital hearing impairment or deafness. MATERIALS AND METHODS This retrospective case-control study was approved by the local ethics committee, and written informed consent was waived. Between January 2008 and December 2012, a group of 751 neonates exposed to MR imaging in utero and a group of control subjects comprising 10 042 nonexposed neonates, both groups with no risk factors for hearing impairment at birth, were included. Neonatal hearing screening was performed by means of otoacoustic emission testing and auditory brain stem response according to national guidelines, and the prevalence of hearing impairment in the two groups was compared by using a noninferiority test with Wilson score confidence intervals. The effect of MR exposure on birth weight percentile was examined between the singleton neonates in the exposed group and a randomly chosen subset of 1805 singleton newborns of the nonexposed group by performing an analysis of variance. RESULTS The rate of hearing impairment or deafness was found to be 0% (0 of 751) in the neonates in the exposed group and was not inferior to that in the nonexposed group (34 of 10 042 [0.34%], P < .05). There was no between-group difference in birth weight percentiles (50.6% for exposed vs 48.4% for nonexposed; P = .22). CONCLUSION This study showed no adverse effects of exposure to 1.5-T MR imaging in utero on neonatal hearing function or birth weight percentiles.

Effects of click polarity on brainstem auditory-evoked potentials in cochlear hearing loss: a working hypothesis.

The rarefaction-condensation differential potential (RCDP) obtained by subtracting brainstem auditory-evoked potentials (BAEPs) to C clicks from those to R clicks has been studied in 32 normal subjects and 31 cases of cochlear hearing loss. In normal subjects, no RCDP was recorded along the lower 30-55 dB of the JV latency-intensity function, thus defining the pre-RCDP range. The pre-RCDP range was always abolished in losses unmasking BAEPs from lower ( < 1 kHz) tonotopic regions. When the BAEP originated from higher ( > 1 kHz) tonotopic regions, the pre-RCDP range was either reduced or abolished. These results led to a working hypothesis based on single-unit data and stating a dual dependence of polarity effects on variables distributed along the tonotopic and intensity dimensions, with respective break-points at 1 kHz, and at the junction of the tip and tail of unit frequency tuning curves. The 1 kHz break-point could represent the upper frequency limit for phase locking in man.

Hearing loss is part of the clinical picture of ENPP1 loss of function mutation

Background: Ecto/nucleotide pyrophosphatase/phosphodiesterase-1 (ENPP1) loss-of-function mutations have been described in patients with autosomal recessive hypophosphatemic rickets (HR), in patients with generalized arterial calcification of infancy (GACI) and in several patients with both conditions. Out of more than 50 cases of homozygous or compound heterozygous ENPP1 loss-of-function mutations published so far, 1 case with labyrinthine deafness probably due to occlusion of inner ear supplying arteries and 2 cases of conductive hearing loss due to stapedovestibular calcification diagnosed in childhood have been reported. Aims: To report a case of ENPP1 loss-of-function novel mutation presenting with HR and very early onset and severe hearing loss. Methods: Case report and review of the literature. Results: We report on a patient homozygous for a novel 1-bp deletion in ENPP1 that presented with GACI evolving towards HR associated with a mixed hearing loss (both labyrinthine and conductive) diagnosed at 9 days of life that evolved towards profound labyrinthine deafness. Conclusion: Hearing loss is a rare finding in patients with ENPP1 loss-of-function mutations. Interestingly, it has already been described in other affected patients, in ENPP1 knock-out mice and in other diseases of pyrophosphate metabolism. Conversely it seems to be absent in children with the X-linked form of HR.

Interest of vestibular evaluation in sequentially implanted children: Preliminary results

INTRODUCTION An early acquired or congenital absence of sensory input of the vestibule will lead to severe delayed posturomotor milestones. Previous studies have proven modifications and even complete ipsilateral loss of vestibular function after unilateral cochlear implantation. The objective of this study was to evaluate whether sequential cochlear implantation has an impact on vestibular function. METHODS Retrospective study from January 2012 to January 2015 including 26 patients. The first stage consisted of determining the vestibular status of 26 hearing impaired children who were candidates for a second cochlear implant. Three months after contralateral implantation, we reevaluated the vestibular function of the same patients. The vestibular evaluation consisted of multiple tests for canal and otolith function. A complete clinical vestibular evaluation was performed, including the head thrust test. This was followed by an instrumental assessment composed of the classic bicaloric test and vestibular evoked myogenic potentials testing with tone bursts. RESULTS A high prevalence of vestibular dysfunction (69%) was found in our group of unilaterally implanted children. Three patients had a unique functional vestibule at the not yet implanted ear. Vestibular evoked myogenic potentials responses stayed present in 15 of the 19 patients with a VEMP-response before contralateral implantation. Results of the caloric test changed for 6 patients after contralateral implantation. CONCLUSIONS After contralateral implantation, 37% of our patients manifested modifications of their vestibular status. Intrasubject comparison of bicaloric and vestibular evoked myogenic potentials testing before and after contralateral cochlear implantation showed that canal function was better preserved than saccular function. Seeing the high prevalence of vestibular dysfunction in our test group of unilateral implanted children, sequential implantation must be preceded by a vestibular assessment to prevent complete bilateral vestibular areflexia and its potential consequences. Presence of hyporeflexia at the yet-to-be implanted ear seems to be a situation particularly at risk.

Group A Streptococcus Colonies from a Single Throat Swab Can Have Heterogeneous Antimicrobial Susceptibility Patterns.

This study describes for the first time heterogeneity of antibiotic resistance profiles among group A Streptococcus isolates originating from a single throat swab in patients with acute pharyngitis. For each throat swab, 10 group A Streptococcus colonies were randomly selected from the primary plate and subcultured to a secondary plate. These isolates were characterized by various phenotypic and genotypic methods. Our results demonstrated that differing antibiotic resistance profiles were present in 19% of pediatric patients with acute pharyngitis before antimicrobial treatment. This heterogeneity likely resulted from horizontal gene transfer among streptococcal isolates sharing the same genetic background. As only a minority of colonies displayed antibiotic resistance among these heterogeneous samples, a classical diagnostic antibiogram would have classified them in most instances as “susceptible,” although therapeutic failure could be caused by the proliferation of resistant strains after initiation of antibiotic treatment.

Clinical findings and PDS mutations in 15 patients with hearing loss and dilatation of the vestibular aqueduct

Following systematic skull imaging of hundred and sixty seven individuals attending a medical referral centre for the deaf in Brussels, Belgium, fifteen patients (9 per cent) aged between two and 25 years were diagnosed with dilatation of the vestibular aqueduct. Careful audiological study, with a baseline assessment then longitudinal follow up, indicated mild to profound deafness with a progressive course (i.e. an average loss of 3.3 dB per year) and frequent dizziness. Sequencing of PDS was performed in all individuals. Alterations of this gene (either homozygous, heterozygous or compound heterozygous base changes) were found in 53 per cent of patients with a large vestibular aqueduct. Four new mutations (two missense, a splice site and a four base pair insertion) were described. We were unable to confirm a correlation between homozygosity, heterozygosity and a Pendred or deafness-only phenotype.

Immunization against cow's milk in infants with cleft lip and/or palate.

70 pg/day) for 10 days from 8 to 17 November. Abdominal distention and pain increased markedly. Watery diarrhoea contaminated with fresh blood developed on 11 November. Plain abdominal radiograph showed marked dilatation of the small intestine. Computed tomography on 13 November showed thickening of the intestinal wall but no pneumatosis. A diagnosis of neutropenic enterocolitis was made. Intravenous hyperalimentation was instituted. No neutrophils were found in the peripheral blood count until 16 November when they increased to 0.33 x 109/1. Fever disappeared 2 days later. On 24 November, neutrophils reached 1 • 109/I and examination of iliac bone marrow showed complete remission. Computed tomography on 28 November showed normal intestinal wall size. The mainstay of treatment for neutropenic enterocolitis is an appropriate use of antibiotics and careful regulation of water and electrolyte balance until the return of functioning neutrophils. In our patient rG-CSF treatment was initiated 2 days after development of profound neutropenia. Though there was no dramatic response, the favourable course is slightly suggestive of a positive effect of rG-CSF.