The management of children with Down syndrome and profound hearing loss.

INTRODUCTION: Although, the association between Down syndrome (DS) and conductive hearing loss is well recognized, the fact that a small proportion of these children may have a severe to profound sensorineural hearing loss that could benefit from cochlear implantation (CI) is less well understood. The management of significant co-morbidities in children with DS can delay initial diagnosis of hearing impairment and assessment of suitability for CI can likewise be challenging, due to difficulties conditioning to behavioural hearing tests. METHODS: We performed a retrospective case note review of three children with DS referred to the Manchester Cochlear Implant Programme. RESULTS: Three illustrative cases are described including CI in a 4 years old. Using conventional outcome measurement instruments, the outcome could be considered to be suboptimal with a Categories of Auditory Performance score of 4 at 6 months post-op and at last follow up. In part, this is likely to reflect the delay in implantation, but the role of cognitive impairment must be considered. The cases described emphasize the importance of comprehensive radiological and audiological assessment in children with DS being considered for CI. CONCLUSION: The influence of cognitive impairment upon outcome of CI must be taken into account, but should not be considered a contra-indication to implantation in children with DS. Benefit that might be considered limited when quantified using existing general outcome measurement instruments, may have a significant impact upon psychosocial development and quality of life in children with significant cognitive impairment, or other additional needs.

Bone conduction implants - a rapidly developing field.

BACKGROUND: Since their introduction in 1977, the technology and surgical techniques surrounding the use and application of bone-anchored hearing devices have developed considerably. OBJECTIVE: This article reviews current developments in the use of bone-anchored hearing devices, looking at the possible options for patients, complications encountered and future possibilities. CONCLUSION: Advances in surgical technique are described, with the move towards the use of linear incisions and no soft tissue reduction. Methods for preventing complications are analysed, with review of different abutments and the introduction of the active bone conduction implant.

Bone-anchored hearing aids and unilateral sensorineural hearing loss: why do patients reject them?

OBJECTIVES: This study aimed to report the bone-anchored hearing aid uptake and the reasons for their rejection by unilateral sensorineural deafness patients. METHODS: A retrospective review of 90 consecutive unilateral sensorineural deafness patients referred to the Greater Manchester Bone-Anchored Hearing Aid Programme between September 2008 and August 2011 was performed. RESULTS: In all, 79 (87.8 per cent) were deemed audiologically suitable: 24 (30.3 per cent) eventually had a bone-anchored hearing aid implanted and 55 (69.6 per cent) patients declined. Of those who declined, 26 (47.3 per cent) cited perceived limited benefits, 18 (32.7 per cent) cited reservations regarding surgery, 13 (23.6 per cent) preferred a wireless contralateral routing of sound device and 12 (21.8 per cent) cited cosmetic reasons. In all, 32 (40.5 per cent) suitable patients eventually chose the wireless contralateral routing of sound device. CONCLUSION: The uptake rate was 30 per cent for audiologically suitable patients. Almost half of suitable patients did not perceive a sufficient benefit to proceed to device implantation and a significant proportion rejected it. It is therefore important that clinicians do not to rush to implant all unilateral sensorineural hearing loss patients with a bone-anchored hearing aid.

Feasibility of cochlear implantation in Mucopolysaccharidosis.

UNLABELLED: Mucopolysaccharidoses (MPS) are a group of rare inherited metabolic disorders resulting from deficiencies of particular enzymes involved in the breakdown of glycosaminoglycans. Amongst the manifestations of MPS within the head and neck patients may develop conductive, mixed or sensorineural hearing loss. OBJECTIVE: The main objective of this paper is to describe the management of profound sensorineural hearing loss in children with Mucopolysaccaridosis. The primary outcome measures for this case series were improvement in auditory performance and speech perception scores following cochlear implantation. Secondary outcome measures included surgical complications. METHODS: We carried out a casenote review of the first two cases of cochlear implantation (CI) to rehabilitate profound sensory neural hearing loss in Mucopolysaccharidoses. Improvement in auditory performance was measured by categories of auditory performance (CAP) score, speech reception score (SRS) and the IHR McCormick toy discrimination test. RESULTS: Both patients with MPS had demonstrable benefit from CI in terms of auditory performance and speech perception. The first patient improved from pre-operatively only managing to recognise environmental sounds to understanding conversation without lip-reading with a familiar talker. Following CI, the second patient can discriminate speech in noisy environments to a degree, without lip-reading. No peri-operative complications were noted in either patient. CONCLUSION: As the medical management of the MPS has progressed there is likely to be a corresponding increase in survival. This increased life-expectancy will likely lead to greater numbers of patients with MPS surviving long enough to develop profound hearing loss. Likewise, when considering the risks and benefits of quality of life interventions such as CI in patients with MPS, it is more likely that the risks of surgery and general anaesthesia will be considered acceptable. Clinicians managing such patients will need to be aware of these developments.

The management of cochlear nerve deficiency.

The assessment process is critical in deciding whether a profoundly deaf child with cochlear nerve deficiency (CND) will be suitable for a cochlear or auditory brainstem implant (ABI). Magnetic resonance imaging (MRI) using submillimetric T2 weighted gradient echo or turbo spin echo sequences is mandatory for all profoundly deaf children to diagnose CND. Evidence of audition on behavioural or electrophysiological tests following both auditory and electrical stimulation sometimes allows identification of significant auditory tissue not visible on MRI. In particular electric auditory brainstem response (EABR) testing may allow some quantification of auditory tissue and help decide whether a cochlear implant will be beneficial. Age and cognitive development are the most critical factors in determining ABI benefit. Hearing outcomes from both cochlear implants and ABIs are variable and likely to be limited in children with CND. A proportion of children will get no benefit. Usually the implants would be expected to provide recognition of environmental sounds and understanding of simple phonetics. Most children will not develop normal speech and they will often need to learn to communicate with sign language. The ABI involves a major neurosurgical procedure and at present the long term outcomes are unknown. It is therefore essential that parents who are considering this intervention have plenty of time to consider all aspects and the opportunity for in depth discussion.

Cochlear implants and positron emission tomography.

OBJECTIVE: This review aimed to summarise present knowledge surrounding cochlear implants and neuroplasticity using positron emission tomography. OVERVIEW: Cochlear implants are an established device for severe sensorineural hearing loss. However, the outcomes following a cochlear implant are variable and unpredictable. Furthermore, despite increasing numbers of implantations taking place, there are still uncertainties regarding how individuals learn to process speech using an implant. Functional neuroimaging studies using techniques such as positron emission tomography provide an insight into the cortical changes that take place in patients with cochlear implants. CONCLUSION: Only when the underlying mechanisms responsible for speech processing in implantees are understood can appropriate rehabilitation for those with poor speech perception be provided and outcomes improved.

Bone-anchored hearing aids and chronic pain: a long-term complication and a cause for elective implant removal.

OBJECTIVES: To report a case series of elective removal of bone-anchored hearing aid implants, and reasons for removal. DESIGN: Retrospective review of a prospectively collected database. SETTING: Two tertiary referral centres in the Manchester area: Manchester Royal Infirmary and Salford Royal University Hospital. PARTICIPANTS: A series of 499 adults and children who had undergone a total of 602 implant insertions (1984-2008). MAIN OUTCOME MEASURES: Implant removal rates, and reasons. RESULTS: Twenty-seven of the 602 implants (4.5 per cent) required removal. Of these, 12 were due to pain (2.0 per cent), seven to persistent infection (1.2 per cent), three to failure of osseointegration (0.5 per cent), three to trauma (0.5 per cent) and two to other reasons (0.4 per cent). CONCLUSION: Chronic implant site pain represents the main reason why implants are removed electively, and affects 2 per cent of all implants. This complication has important medico-legal implications and should be discussed when obtaining informed consent for implantation.

Cochlear implantation in a child with CINCA syndrome who also has wide vestibular aqueducts.

Chronic infantile neurological cutaneous and articular (CINCA) syndrome is a severe auto-inflammatory disease, due to mutation of the CIAS1 gene. CINCA syndrome should be considered the most severe of a spectrum of three disorders all due to mutation of the CIAS1 gene. CINCA syndrome produces a triad of symptoms of neonatal onset: maculopapular urticarial rash, chronic meningitis, and chronic non-inflammatory arthropathy with recurrent fever. CINCA syndrome is also associated with sensory organ damage, especially progressive hearing loss and loss of vision. In this case report, we present the first case of cochlear implantation in a 13-year-old child with CINCA syndrome. Cochlear implantation was successful at rehabilitating the hearing loss with the child able to continue mainstream education, with her academic performance and speech discrimination both showing marked improvement. Anakinra (an interleukin 1 receptor antagonist) is now in widespread use to treat CINCA syndrome and is known to rapidly reverse the inflammatory features of CINCA syndrome. However, current evidence suggests that anakinra has limited effectiveness in reversing the sensorineural hearing loss seen in CINCA syndrome. We therefore propose that cochlear implantation is a viable treatment option in this rare yet severe auto-inflammatory disease, if the patient has failed to respond to anakinra. Owing to the unknown pathogenesis of the progressive hearing loss seen in CINCA syndrome and the limited effectiveness of anakinra in reversing the progressive hearing loss, we suggest that cochlear implantation is the modality of choice in rehabilitating severe-to-profound hearing loss not responsive to anakinra.

Cortical activations in sequential bilateral cochlear implant users.

This study aimed to examine auditory and visual cortical activations in bilateral cochlear implant recipients using [(18)F]-FDG positron emission tomography. We aimed to compare the activations from use of the first implant alone, the second implant alone, and both implants together. When both implants were activated simultaneously, summation of cortical activity did not occur. The first and second implants demonstrated evidence of developing distinct neural networks. The first implants show stronger bilateral recruitment of the auditory areas than the second implants. Visual cortical activations occur in response to stimulation of the second but not the first implants. When both implants were activated together, there were no visual activations suggesting interaction between the first- and second-implant networks. These findings add to the existing knowledge of plasticity following cochlear implantation and demonstrate a variability of these processes that was previously unreported.

Complications of bone-anchored hearing aid implantation.

INTRODUCTION: Bone-anchored hearing aid implantations have been performed in Manchester for over 20 years. This study examined a range of variables that can occur during the implantation process, and the effect they may have on successful outcome. METHOD: Retrospective study and literature review. LOCATION: Tertiary referral centre in central Manchester. RESULTS: Details of 602 bone-anchored hearing aid implantation procedures were retrieved from the departmental database. The overall complication rate was 23.9 per cent. The rate of revision surgery was 12.1 per cent. CONCLUSION: This study involved a significantly larger number of patients than any previously reported, similar study. Possible reasons for differences in outcomes, and recommendations for best practice, are discussed.

Proinsulin peptide immunotherapy in type 1 diabetes: report of a first-in-man Phase I safety study.

Immunotherapeutic strategies under consideration for type 1 diabetes include modification of the autoimmune response through antigen-specific routes. Administration of short peptides representing T cell epitopes targeted by patients with the disease represents one approach. This study evaluated safety and mechanistic outcomes during first-in-man intradermal administration of a human leucocyte antigen-DR4 (HLA-DR4)-restricted peptide epitope of proinsulin (C19-A3). This randomized, open-label study assessed two major theoretical risks of peptide immunotherapy, namely induction of allergic hypersensitivity and exacerbation of the proinflammatory autoimmune response, using clinical assessment and mechanistic assays in vitro. Patients with long-standing type 1 diabetes and HLA-DRB1*0401 genotype received 30 microg (n = 18) or 300 microg (n = 18) of peptide in three equal doses at 0, 1 and 2 months or no intervention (n = 12). Proinsulin peptide immunotherapy in the dosing regimen used is well tolerated and free from risk of systemic hypersensitivity and induction/reactivation of proinsulin-specific, proinflammatory T cells. Peptide-specific T cells secreting the immune suppressive cytokine interleukin (IL)-10 were observed at month 3 in four of 18 patients in the low-dose group (versus one of 12 in the control group; P = not significant). Mean IL-10 response to peptide in the low-dose group increased between 0 and 3 months (P = 0.05 after stimulation with 5 microM peptide in vitro) and then declined to baseline levels between 3 and 6 months (P = 0.01 at 10 microM peptide in vitro). These studies pave the way for future investigations in new-onset patients designed to examine whether proinsulin peptide immunotherapy has beneficial effects on markers of T cell autoimmunity and preservation of beta cell mass.

Can keratinocytes cause failure of osseointegration?

AIM: Bone-anchored hearing aids are well established, implanted devices. We present two patients who suffered mixed hearing loss and who underwent titanium implant placement in the temporal bone to enable attachment of bone-anchored hearing aids. Osseointegration is necessary for such implants to function. We report these two cases to highlight how such osseointegration may be disrupted. METHOD: Attached tissue from the explanted or removed titanium implants was examined by transmission electron microscopy and histopathological analysis. RESULTS: Attached tissue from both implants showed the presence of keratinocytes at the titanium implant and living bone interface. This was confirmed by histopathological analysis. In one case, there was frank keratinocyte proliferation, which had led to osseointegration failure; in the other case, such proliferation was present but not so advanced. CONCLUSION: These findings suggest that, in the cases reported, keratinocytes implanted between the titanium and the living bone, leading to disruption of osseointegration.

Cortical plasticity in the first year after cochlear implantation.

This study aimed to investigate changes in auditory and visual cortical activity over the first year following cochlear implantation using (18)F-fluorodeoxyglucose positron emission tomography. Subjects underwent scanning prior to the initial implant activation (control), after one to two months of implant use (early activation) and after one year of implant use (late activation). All subjects had activation of the auditory cortices. Group analysis using Statistical Parametric Mapping package SPM99 showed these became more focused over the first year of implant use. There was no evidence of left hemispheric dominance at any stage post implantation.Visual cortical activations were highly variable between patients and did not increase significantly between early and late activations. Taken together, our results lead us to suggest that the neural processes that occur during the first year of auditory rehabilitation following cochlear implantation vary between individuals to a greater extent than previously reported.

Auditory cortical activation and speech perception in cochlear implant users.

Cochlear implantation is generally accepted as a successful means of restoring auditory sensation to profoundly deaf individuals. Although most patients can expect a satisfactory outcome following implantation, some have poor speech perception outcomes. This investigation used [18F]-fluorodeoxyglucose positron emission tomography to measure cortical activity resulting from auditory stimulation in seven 'good' and four 'poor' cochlear implant recipients. Activations were significantly greater in both the primary and association cortices in the good compared with the poor implant users. We suggest that the ability to access the more specialised speech processing abilities of the auditory association cortices helps determine outcome following cochlear implantation.

Predictors of audiological outcome following cochlear implantation in adults.

The objective of this study was to examine variables that may predict open set speech discrimination following cochlear implantation. It consisted of a retrospective case review conducted in a tertiary referral centre with a cochlear implant programme. The patients were 117 postlingually deafened adult cochlear implant recipients. The main outcome measures were Bench, Kowal, Bamford (BKB) sentence scores recorded nine months following implant activation. The variables studied were age at the time of surgery, sex, duration of hearing loss, aetiology of hearing loss, residual hearing, implant type, speech processor strategy, number of active electrodes inserted. Variables found to have a significant effect on BKB following univariate analysis were entered into a multivariate analysis to determine independent predictors. Multivariate ordinal regression analysis gave an odds ration of 1.09 for each additional year of deafness prior to implantation (confidence interval 1.06-1.13; p < 0.001). Duration of deafness prior to implantation is an independent predictor of implant outcome. It accounted for 9% of the variability. Other factors must influence implant performance.

Nasal fracture reduction: local versus general anaesthesia.

OBJECTIVE: To investigate the outcomes from nasal fracture reduction performed under local anaesthesia (LA) and general anaesthesia (GA). METHOD: A randomised multi-centred prospective trial and cohort analysis. Patients were randomised into two groups, 74 (53%) underwent closed reduction under LA, 65 (47%) patients underwent closed reduction under GA. MAIN OUTCOME MEASURES: Pain scores and patient toleration of local or general nasal manipulation was noted. RESULTS: The pain score ranged from 0 (no pain) to 10 (unbearable pain). The mean pain score in the LA group was 3, compared to 2 in the GA group. LA manipulation was tolerated equally well as GA manipulation by 85% of the patients in each group. The number of patients requiring a septorhinoplasty was compared between LA 19/74 (26%), and GA 21/65 (32%). This failed to demonstrate a significant difference with a p value of 0.50. The absolute risk difference was 5% with a 95% confidence interval of (20% to -10%). CONCLUSION: This trial clearly shows LA to be as effective as GA in the first line management of nasal fractures. The degree of septal displacement and presence of nasal tip deviation were associated with persistent nasal deformity following nasal fracture reduction.

Proteomic analysis of human meibomian gland secretions.

BACKGROUND/AIM: Human tears contain hundreds of proteins that may exert a significant influence on tear film stability, ocular surface integrity, and visual function. The authors hypothesise that many of these proteins originate from the meibomian gland. This study's aim was to begin to develop the proteomic methodology to permit the testing of their hypothesis. METHODS: Meibomian gland secretions were collected from the lower eyelids of adult volunteers and placed in a chloroform-methanol mixture. Samples were partitioned in a biphasic system and non-lipid phase materials were reduced, alkylated, and trypsin digested to obtain peptides for protein identification. This peptide mixture was separated by micro-capillary reverse phase chromatography and the effluent examined by nano-electrospray MS and data dependent MS/MS. SEQUEST software was used to identify proteins from the MS/MS spectra. RESULTS: The methodological approach to date has permitted the identification of more than 90 proteins in human meibomian gland secretions. Proteins include the alpha2-macroglobulin receptor, IgA alpha chain, farnesoid X activated receptor, interferon regulatory factor 3, lacritin precursor, lactotransferrin, lipocalin 1, lysozyme C precursor, potential phospholipid transporting ATPase IK, seven transmembrane helix receptor (also termed somatostatin receptor type 4), testes development related NYD-SP21 (also termed high affinity IgE receptor beta subunit), and TrkC tyrosine kinase. CONCLUSIONS: These findings indicate that the meibomian gland secretes a number of proteins into the tear film. It is quite possible that these proteins contribute to the dynamics of the tear film in both health and disease.