LINE-1 global DNA methylation, iron homeostasis genes, sex and age in sudden sensorineural hearing loss (SSNHL).

BACKGROUND: Sudden sensorineural hearing loss (SSNHL) is an abrupt loss of hearing, still idiopathic in most of cases. Several mechanisms have been proposed including genetic and epigenetic interrelationships also considering iron homeostasis genes, ferroptosis and cellular stressors such as iron excess and dysfunctional mitochondrial superoxide dismutase activity. RESULTS: We investigated 206 SSNHL patients and 420 healthy controls for the following genetic variants in the iron pathway: SLC40A1 - 8CG (ferroportin; FPN1), HAMP - 582AG (hepcidin; HEPC), HFE C282Y and H63D (homeostatic iron regulator), TF P570S (transferrin) and SOD2 A16V in the mitochondrial superoxide dismutase-2 gene. Among patients, SLC40A1 - 8GG homozygotes were overrepresented (8.25% vs 2.62%; P = 0.0015) as well SOD2 16VV genotype (32.0% vs 24.3%; P = 0.037) accounting for increased SSNHL risk (OR = 3.34; 1.54-7.29 and OR = 1.47; 1.02-2.12, respectively). Moreover, LINE-1 methylation was inversely related (r2 = 0.042; P = 0.001) with hearing loss score assessed as pure tone average (PTA, dB HL), and the trend was maintained after SLC40A1 - 8CG and HAMP - 582AG genotype stratification (ΔSLC40A1 = + 8.99 dB HL and ΔHAMP = - 6.07 dB HL). In multivariate investigations, principal component analysis (PCA) yielded PC1 (PTA, age, LINE-1, HAMP, SLC40A1) and PC2 (sex, HFEC282Y, SOD2, HAMP) among the five generated PCs, and logistic regression analysis ascribed to PC1 an inverse association with moderate/severe/profound HL (OR = 0.60; 0.42-0.86; P = 0.0006) and with severe/profound HL (OR = 0.52; 0.35-0.76; P = 0.001). CONCLUSION: Recognizing genetic and epigenetic biomarkers and their mutual interactions in SSNHL is of great value and can help pharmacy science to design by pharmacogenomic data classical or advanced molecules, such as epidrugs, to target new pathways for a better prognosis and treatment of SSNHL.

Newborn hearing screening at the Neonatal Intensive Care Unit and Auditory Brainstem Maturation in preterm infants.

OBJECTIVES: Aim of this study is to report and discuss the results of 4 years of Newborn hearing screening (NHS) program at the Neonatal Intensive Care Unit (NICU), particularly evaluating the clinical ABR results. METHODS: Retrospective study. NHS data from NICU newborns, admitted for ≥5 days, in the period from January 1st, 2013 and December 31st, 2016, were retrieved and analyzed. NHS results were classified as following: (i) "pass" when both ears for both the a-TEOAE (automated Transient-Evoked Otoacoustic Emissions) and the a-ABR (automated Auditory Brainstem Response) protocol resulted as "pass"; (ii) "fail" when one ear, at either one of the two performed tests resulted as "fail"; (iii) "missing" when the newborns were not tested with both protocols. All "fail" and "missing" newborns were retested (with both tests): in the case of a second "fail" result, a clinical ABR was performed within a period of 3 months. RESULTS: A total of 1191 newborns were screened. From those, 1044/1191 resulted as "pass", 108/1191 as "fail", and 39/1191 as "missing". During the re-testing of these 147 newborns, 43 were assigned as "missing", 63 were assigned as "pass" (showing bilaterally a wave V identifiable within 30 dB nHL) and 25 failed the retest and/or did not present an identifiable wave V within 30 dB nHL. Among the 147 retested infants, we identified a group of 16 subjects who resulted as NHS "refer" and who, during the audiological follow-up, showed either: (i) a unilateral or bilateral wave V identifiable over 30 dB nHL, at the first clinical ABR assessment; or (ii) a bilateral wave V identifiable within 30 dB nHL, in a following clinical ABR test during the first year of life. These 16 subjects were defined to have an 'Auditory Brainstem Maturation' issue. CONCLUSIONS: A possible "maturation" of the ABR response (and therefore of the auditory pathway) has been hypothesised in 16 out of 1191 infants (1.3%). A delay of the auditory pathway maturation in preterm babies compared to term newborns has already been suggested in the literature. A possible delay of the NHS retest could be considered, in selected cases, with significant savings in economic resources and parental anxiety.

White matter lesions and sudden sensorineural hearing loss.

Aim of this paper is to investigate the presence of White Matter Lesions (WMLs) in subjects affected by Sudden Sensorineural Hearing Loss (SSNHL) and possibly to evaluate the significance of WMLs in SSNHL patients. A total of 64 patients (cases) affected by SSNHL were included in this case-control study. Hearing tests were performed at SSNHL onset, after 7 days and after 30 days. Cerebral MRI sequences were performed to rule out retrocochlear pathology, and WMLs were evaluated if present. MRI control group included 32 subjects, without hearing loss, affected by pituitary adenoma, who underwent cerebral MRI of follow-up. WML presence in those affected by SSNHL resulted having a similar distribution to that of the control group; however, we observed complete hearing recovery in 42,9% of patients without WML and in 11,6% of patients with WML >1 (p = 0,017*). The incidence of WML in patients with SSNHL was not different compared to that of the control group; however, MRI could have a prognostic role for SSNHL patients, as the presence of WMLs can been linked to a poorer hearing recovery rate.

Clinical features of benign paroxysmal positional vertigo of the posterior semicircular canal.

OBJECTIVE: The aim of this study was to evaluate the relationship between age, gender and affected ear, in patients presenting benign paroxysmal positional vertigo. METHODS: This was a retrospective study. Data from benign paroxysmal positional vertigo clinical reports (January 2009-December 2014) were analysed. A total of 174 patients affected by benign paroxysmal positional vertigo of the posterior semicircular canal have been identified. Pearson chi-square test has been used to evaluate the probability of benign paroxysmal positional vertigo occurrence in relation to gender and side, within the studied groups. The level of significance was set at a p < 0.05. RESULTS: Considering age as a discriminant factor, three groups of patients were identified: group 1: 16 patients with an age <40 years; group 2: 79 patients with an age between 40 and 65 years and group 3: 79 patients with an age >65 years. In each group, the right posterior semicircular canal was involved in the majority of cases (group 1 incidence: 12/16; group 2 incidence: 49/79 and group 3 incidence: 52/79). In all three groups, female patients were significantly more affected (9/16 in group 1, 61/79 in group 2 and 55/79 in group 3). CONCLUSION: Benign paroxysmal positional vertigo is most prevalent in female subjects having an age>40 years and mainly involves the right posterior semicircular canal.

Autoimmune inner ear disease (AIED): A diagnostic challenge.

Autoimmune inner ear disease (AIED) has been defined as a condition of bilateral sensorineural hearing loss (SNHL), caused by an 'uncontrolled' immune system response. The inner ear can be the direct target of the immune response, but it can be additionally damaged by a deposition of circulating immune complexes or by systemic immune-mediated diseases. The clinical expression of immune-mediated inner ear disease shows a progressive bilateral and asymmetric SNHL profile, which typically benefits from a steroid and immunosuppressive therapy. The onset of AIED is between 3 and 90 days. Cochlear symptoms can be associated with vestibular disorders and in 15%-30% of cases, AIED occurs in the contest of a systemic autoimmune disease. Currently, the onset of immune-mediated SNHL is not a well-understood process and the pathogenetic mechanisms of AIED remain unclear. Furthermore, there are no standardized diagnostic criteria or reliable diagnostic tests for the diagnosis of AIED. Hence, the definition of immune-mediated cochleovestibular disorders is a challenging diagnosis based on exclusion. A close collaboration between otolaryngologists, audiologists and rheumatologists is recommended, in order to achieve the multidisciplinary management of this rare entity, since an early AIED identification and a prompt medical treatment might result in acceptable hearing outcomes. The paper describes the clinical features of AIED and offers a diagnostic flow-chart to use in the clinical assessment of this condition.

Cerebral Inflow and Outflow Discrepancies in Severe Sudden Sensorineural Hearing Loss.

The aim of this study is to evaluate whether cerebral inflow and outflow abnormalities, assessed by the means of a validated ultrasound model, could be associated with Sudden Sensorineural Hearing Loss (SSNHL). According to Clark, a total of 42 patients affected by severe SSNHL and 19 healthy volunteers matched by gender without any history of sudden hearing impairment have been included in this study. Patients and controls underwent EchocolorDoppler assessment of brain hemodynamics. All subjects affected by SSNHL were also assessed with Auditory Brainstem Responses (ABR) and Magnetic Resonance Imaging (MRI) in order to exclude retrocochlear pathology. The head inflow through the common carotid artery was practically equivalent between groups, but at the level of the carotid bifurcation, the external carotid artery showed a highly significant flow rate in SSNHL 5.4±2 vs 3.9±1.1 ml/s in controls (p=0.01). The brain inflow was similar between patients and controls, but interestingly the flow rate of the vertebral artery was significantly reduced in SSNHL 1.6±0.8 vs 2.8±0.9 ml/s (p=0.01). The brain outflow was found significantly restricted at the level of the jugular outlet 6.6±6 vs 9.9±6 ml/s (p=0.002); consequently, the collateral flow index was significantly increased in SSNHL (p=0.001). The present study shows a discrepant distribution of the brain inflow which seems to penalize the posterior segments of the Willis polygon in patients affected by severe SSNHL. In addition, our study confirms the presence of chronic cerebrospinal venous insufficiency in SSNHL with significant activation of venous collateral circulation.

A Multicenter Clinical Evaluation of Data Logging in Cochlear Implant Recipients Using Automated Scene Classification Technologies.

Currently, there are no studies assessing everyday use of cochlear implant (CI) processors by recipients by means of objective tools. The Nucleus 6 sound processor features a data logging system capable of real-time recording of CI use in different acoustic environments and under various categories of loudness levels. In this study, we report data logged for the different scenes and different loudness levels of 1,366 CI patients, as recorded by SCAN. Monitoring device use in cochlear implant recipients of all ages provides important information about the listening conditions encountered in recipients' daily lives that may support counseling and assist in the further management of their device settings. The findings for this large cohort of active CI users confirm differences between age groups concerning device use and exposure to various noise environments, especially between the youngest and oldest age groups, while similar levels of loudness were observed.

Assessment Tools for Use in Patients with Ménière Disease: An Update.

A number of electrophysiological tests have been proposed for the initial diagnostic assessment or for the follow-up phase of patients affected by Ménière disease. The most common are: (i) vestibular evoked myogenic potentials (VEMPs); (ii) electrocochleography (ECochG); and (iii) otoacoustic emissions (OAEs). This paper presents the latest clinical developments with these 3 testing modalities. The PubMed, Embase, and Cinahl databases were searched from 2006 to December 2016. Full-text articles were obtained in cases where the title, abstract, or key words suggested that the study may be eligible for this review. The medical subject heading (MeSH) terms included the following: Ménière, hearing threshold, vestibule, otoacoustic emissions, inner ear, ECochG, VEMPs. There were 368 identified papers, out of which 87 were eligible for inclusion. Overall the data in the literature are still limited and the recommended procedures have not reached an international consensus. From the available data, one can conclude that none of the electrophysiological tests could be considered as pathognomonic, for the diagnosis of Ménière disease: presently, the tests could be mostly used in a supportive role to the clinical diagnosis. Hopefully, in the future, improved technology in electrophysiological testing could contribute to the development of better strategies for the diagnosis of Ménière disease.

Patent Foramen Ovale as Possible Cause of Sudden Sensorineural Hearing Loss: A Case Report.

OBJECTIVE: To present a case of sudden sensorineural hearing loss (SSNHL) and the related diagnostic workup. CLINICAL PRESENTATION AND INTERVENTION: A 54-year-old man presented with a unilateral SSNHL episode and vertigo. A severe patent foramen ovale (PFO) that included a complete ear nose and throat, audiological, and neurological examination was discovered during the diagnostic workup. Audiometry, blood, and serological tests were performed. Magnetic resonance imaging and color Doppler echography of the supra-aortic trunks and lower limbs were carried out. Finally, transthoracic followed by transesophageal echocardiography and transcranial Doppler were performed in order to confirm the diagnosis of PFO. Medical therapy with systemic steroid and antiplatelet drugs was administered. CONCLUSIONS: This case showed a small PFO associated with an aneurysmatic interatrial septum. The PFO and paradoxical thromboembolism could be involved in the pathogenesis of SSNHL.

The impact of dizziness on quality-of-life in the elderly.

Dizziness is a common medical condition that has been related to falls in the elderly, and it is, therefore, considered a severe social health problem. Particularly in the elderly, the impact of dizziness may be relevant, as it has been linked to several conditions, such as isolation, depression, reduced self autonomy, and self control. The social, functional, and psychological well-being of those affected can be hampered significantly, thus reducing the quality-of-life (QoL) perception. In addition, due to the aging of the population in the developed world, dizziness is becoming a growing public health problem; an optimal management of this condition includes, nowadays, the improvement of rehabilitative programs, as well as the evaluation of QoL status and its management. The aim of this paper is to evaluate the impact of dizziness on the QoL in the elderly, also analyzing the instruments available, nowadays, to evaluate QoL of dizzy patients.

Moderate-Severe Hearing Loss in Children: A Diagnostic and Rehabilitative Challenge.

Hearing loss in children represents a relevant topic, which needs an increasing attention by clinicians and researchers. Unfortunately, most cases of hearing loss still remain idiopathic (most frequently reported causes are genetic, infectious, toxic). An early diagnosis is crucial, as if not properly recognized, hearing disorders may impact negatively on children development and on quality of life. Literature data show that also children with mild-moderate, or even monolateral, hearing loss may present learning or verbal language disorders, if not adequately managed. The diagnostic work-up of hearing loss in children, which starts with universal neonatal hearing screening at birth, is complex, has to define hearing threshold, and, when possible, its etiology, often by multidisciplinary approach. At the same time, the audiological follow-up of those affected by moderate-severe hearing loss must be tight, as it is necessary to verify constantly: (i) hearing threshold levels, (ii) adequateness of hearing aids fitting, and (iii) language development. This review focuses specifically on the diagnostic work-up and the rehabilitative features of moderate-severe hearing loss in children.

Sudden sensorineural hearing loss: Is there a connection with inner ear electrolytic disorders? A literature review.

Electrolytic disorders of the inner ear represent a model that could be implicated in partially explaining the pathogenesis of sudden sensorineural hearing loss (SSNHL). Different types of electrolytes and different inner-ear loci are involved in cochlear homeostasis physiologically, to ensure the maintenance of an ion-balanced cochlear environment allowing a normal hair cell function. It has been hypothesized that a sudden loss of endocochlear potential, due to a rapid disruption of the inner ear fluid osmolality, could be responsible for a deterioration of the hearing function caused by damaged hair cells. The aim of this paper was to review the current literature and identify sources which might validate/fortify the hypothesis that inner ear electrolytic disorders have a role in the etiopathogenesis of SSNHL. The data in the literature underline the importance of ionic homeostasis in the inner ear, but they do not support a direct link between SSNHL and electrolyte disorders/imbalances. There is marginal evidence from otoacoustic emissions research that an indirect link might be present.

Cochlear Implants in Subjects Over Age 65: Quality of Life and Audiological Outcomes.

BACKGROUND Cochlear implants (CIs) have been recognized as a safe and effective means for profound hearing loss rehabilitation in children and adults and recently their use has been extended to subjects over 65 years of age. The aim of this paper was to assess indices related to changes in the quality of life (QoL) in elderly CI recipients. MATERIAL AND METHODS A case-control paradigm was used to assess the effects of CIs on the QoL. Forty-two subjects were assigned to the Case group and 15 subjects to the Control group. All 57 subjects were affected by profound hearing loss and had received a CI. Audiological data were collected from both groups at: (i) 1 month pre-implantation [T1]; (ii) 1 day pre- implantation [T2]; (iii) 30 days post-implantation, with CI used in free field [T3]; and (iv) 12 months post-implantation, with CI used in a free field [T4]. The QoL was assessed via a Glasgow Benefit Inventory (GBI) questionnaire, adapted to otolaryngology. To compare subjects across different ages with varying degrees of speech development, a perception parameter was used from the Speech Perception Categories test developed by Geers and Moog. RESULTS Hearing performance was considerably improved after CI. In relation to the hearing performance at time T1, statistically significant threshold gains were observed in both groups in the T3 and T4 observation windows. At time T4, a threshold gain of 70 dB HL in the Case group and a gain of 84 dB HL in the Control group were observed. With speech therapy rehabilitation, a perception level of 6 was reached by 80.0% of patients in the Case group and by 100% of patients in the Control group. In terms of QoL, both groups showed improved post-CI scores. Statistical differences were observed between the 2 groups, with the Control group outperforming the Case group in all but the social section. CONCLUSIONS Despite age-related changes in auditory system and prolonged hearing deprivation, CIs offer audiological and QoL benefits in the elderly.

Head and neck cancer patients: impact of diabetes mellitus on surgical outcomes.

PURPOSE: Cancer patients with significant comorbidities undergoing major surgical intervention are at high risk for peri/postoperative complications and a prolonged hospital stay. Diabetes mellitus is a prevalent chronic metabolic disease, reported to affect surgery outcomes of malignancies. The purpose of this article was to evaluate the impact of diabetes mellitus on the development of local and systemic complications as well as the length of the hospital stay, after major surgery for Head and Neck (H&N) cancer. METHODS: A total of 168 patients suffering from H&N cancer, surgically treated between 2004 and 2013 at our ENT Department, were included. Clinical records were examined, particularly focusing on the onset of local and systemic complications and on the length of the hospital stay. The subjects considered as diabetics were the ones with a history of physician-diagnosed diabetes or those who were taking oral hypoglycemic drugs or insulin. For those without a diagnosis of diabetes and not taking any antidiabetic medications, the value of fasting blood glucose was used to assess the presence of diabetes, according to the American Diabetes Association guidelines (glycaemia >126 mg/dl). The occurrence of local and systemic postoperative complications, as well as the length of the hospital stay, were statistically compared between the diabetic and non-diabetic group of patients. RESULTS: 31 of 168 (18.5%) patients, surgically treated for H&N cancer, had also been diagnosed with diabetes mellitus. Episodes of postoperative complications in non-diabetic patients were 50.4%, whereas in diabetics 45.2%. The mean length of hospital stay for non-diabetics was 28.1±14.8 days and for diabetics 32.2±24. In univariate and multivariate analysis, no statistically significant differences were found when comparing the diabetic to the non-diabetic group, in terms of occurrence of postoperative complications in respect to cancer stage and length of hospitalization. In univariate and multivariate analyses none of the variables studied was a risk factor for postoperative complications. CONCLUSIONS: This study provides evidence that a good metabolic control of diabetes mellitus does not have impact on the occurrence of peri/postoperative complications and therefore on the length of hospital stay of H&N cancer patients.

Facial nerve paralysis in children.

Facial nerve palsy is a condition with several implications, particularly when occurring in childhood. It represents a serious clinical problem as it causes significant concerns in doctors because of its etiology, its treatment options and its outcome, as well as in little patients and their parents, because of functional and aesthetic outcomes. There are several described causes of facial nerve paralysis in children, as it can be congenital (due to delivery traumas and genetic or malformative diseases) or acquired (due to infective, inflammatory, neoplastic, traumatic or iatrogenic causes). Nonetheless, in approximately 40%-75% of the cases, the cause of unilateral facial paralysis still remains idiopathic. A careful diagnostic workout and differential diagnosis are particularly recommended in case of pediatric facial nerve palsy, in order to establish the most appropriate treatment, as the therapeutic approach differs in relation to the etiology.

Cochlear Implant Outcomes and Genetic Mutations in Children with Ear and Brain Anomalies.

BACKGROUND: Specific clinical conditions could compromise cochlear implantation outcomes and drastically reduce the chance of an acceptable development of perceptual and linguistic capabilities. These conditions should certainly include the presence of inner ear malformations or brain abnormalities. The aims of this work were to study the diagnostic value of high resolution computed tomography (HRCT) and magnetic resonance imaging (MRI) in children with sensorineural hearing loss who were candidates for cochlear implants and to analyse the anatomic abnormalities of the ear and brain in patients who underwent cochlear implantation. We also analysed the effects of ear malformations and brain anomalies on the CI outcomes, speculating on their potential role in the management of language developmental disorders. METHODS: The present study is a retrospective observational review of cochlear implant outcomes among hearing-impaired children who presented ear and/or brain anomalies at neuroimaging investigations with MRI and HRCT. Furthermore, genetic results from molecular genetic investigations (GJB2/GJB6 and, additionally, in selected cases, SLC26A4 or mitochondrial-DNA mutations) on this study group were herein described. Longitudinal and cross-sectional analysis was conducted using statistical tests. RESULTS: Between January 1, 1996 and April 1, 2012, at the ENT-Audiology Department of the University Hospital of Ferrara, 620 cochlear implantations were performed. There were 426 implanted children at the time of the present study (who were <18 years). Among these, 143 patients (64 females and 79 males) presented ear and/or brain anomalies/lesions/malformations at neuroimaging investigations with MRI and HRCT. The age of the main study group (143 implanted children) ranged from 9 months and 16 years (average = 4.4; median = 3.0). CONCLUSIONS: Good outcomes with cochlear implants are possible in patients who present with inner ear or brain abnormalities, even if central nervous system anomalies represent a negative prognostic factor that is made worse by the concomitant presence of cochlear malformations. Common cavity and stenosis of the internal auditory canal (less than 2 mm) are negative prognostic factors even if brain lesions are absent.

Sudden sensorineural hearing loss and polymorphisms in iron homeostasis genes: new insights from a case-control study.

Background. Even if various pathophysiological events have been proposed as explanations, the putative cause of sudden hearing loss remains unclear. Objectives. To investigate and to reveal associations (if any) between the main iron-related gene variants and idiopathic sudden sensorineural hearing loss. Study Design. Case-control study. Materials and Methods. A total of 200 sudden sensorineural hearing loss patients (median age 63.65 years; range 10-92) were compared with 400 healthy control subjects. The following genetic variants were investigated: the polymorphism c.-8CG in the promoter of the ferroportin gene (FPN1; SLC40A1), the two isoforms C1 and C2 (p.P570S) of the transferrin protein (TF), the amino acidic substitutions p.H63D and p.C282Y in the hereditary hemochromatosis protein (HFE), and the polymorphism c.-582AG in the promoter of the HEPC gene, which encodes the protein hepcidin (HAMP). Results. The homozygous genotype c.-8GG of the SLC40A1 gene revealed an OR for ISSNHL risk of 4.27 (CI 95%, 2.65-6.89; P = 0.001), being overrepresented among cases. Conclusions. Our study indicates that the homozygous genotype FPN1 -8GG was significantly associated with increased risk of developing sudden hearing loss. These findings suggest new research should be conducted in the field of iron homeostasis in the inner ear.