Metabolic disorders prevalence in sudden deafness

OBJECTIVES: The aim of the present study was to establish the frequency of metabolic disorders among patients with sudden deafness and to compare this frequency with data from population surveys. INTRODUCTION: No consensus has been reached regarding the prevalence of metabolic disorders among sudden deafness patients or their influence as associated risk factors. METHODS: This cross-sectional study enrolled all sudden deafness patients treated in the Otolaryngology Department of the University of São Paulo between January 1996 and December 2006. Patients were subjected to laboratory exams including glucose and cholesterol levels, low-density lipoprotein cholesterol fraction, triglycerides, free T4 and TSH. RESULTS: The sample comprised 166 patients. We observed normal glucose levels in 101 (81.5%) patients and hyperglycemia in 23 (18.5%) patients, which is significantly different (p < 0.0001) compared to the diabetes mellitus prevalence (7.6%) in the Brazilian population. Cholesterol levels were normal in 78 patients (49.7%) and abnormal in 79 (50.3%) patients, which is significantly different compared to the Brazilian population (p = 0.0093). However, no differences were observed in low-density lipoprotein cholesterol fraction (p = 0.1087) or triglyceride levels (p = 0.1474) between sudden hearing loss patients and the Brazilian population. Normal levels of thyroid hormones were observed in 116 patients (78.4%), and abnormal levels were observed in 32 (21.6%) patients. Compared with the prevalence of thyroid disorders in the general population (10%), statistical analysis revealed a significant difference (p = 0.0132) between these two groups. DISCUSSION: Among sudden deafness patients, we observed frequencies of hyperglycemia and thyroid disorders that were more than twice those of the general population. CONCLUSIONS: Hyperglycemia and thyroid disorders are much more frequent in patients with sudden deafness than in the general population and should be considered as important associated risk factors

Evidence of progenitor cells in the adult human cochlea: sphere formation and identification of ABCG2

OBJECTIVES: The aim of this study was to search for evidence of stem or progenitor cells in the adult human cochlea by testing for sphere formation capacity and the presence of the stem cell marker ABCG2. METHODS: Cochleas removed from patients undergoing vestibular schwannoma resection (n=2) and from brain-dead organ donors (n=4) were dissociated for either flow cytometry analysis for the stem cell marker ABCG2 or a sphere formation assay that is widely used to test the sphere-forming capacity of cells from mouse inner ear tissue. RESULTS: Spheres were identified after 2-5 days in vitro, and the stem cell marker ABCG2 was detected using flow cytometric analysis after cochlear dissociation. CONCLUSIONS: Evidence suggests that there may be progenitor cells in the adult human cochlea, although further studies are required

Caloric test and video head impulse test sensitivity as vestibular impairment predictors before cochlear implant surgery

OBJECTIVES: Currently, cochlear implant procedures are becoming increasingly broad and have greatly expanded. Bilateral cochlear implants and cochlear implants are more frequently applied in children. Our hypothesis is that the video head impulse test may be more sensitive than the caloric test in detecting abnormal vestibular function before cochlear implant surgery. The objective of this study was to compare the video head impulse test and caloric test results of patients selected for cochlear implant procedures before surgery. METHODS: The patients selected for cochlear implant surgery were submitted to a bithermal caloric test and video head impulse test. RESULTS: By comparing angular slow phase velocity values below 5o in the bithermal caloric test (hypofunction) and video head impulse test with a gain lower than 0.8, we identified 37 (64.9%) patients with vestibular hypofunction or canal paresis and 21 (36.8%) patients with abnormal video head impulse test gain before the cochlear implant procedure. Of the 37 patients with caloric test vestibular hypofunction, 20 (54%) patients exhibited an abnormal gain in the video head impulse test. CONCLUSION: The caloric test is more sensitive than the video head impulse test (Fisher’s exact test, p=0.0002) in detecting the impaired ear before cochlear implant delivery. The proportion of caloric test/video head impulse test positive identification of abnormal vestibular function or caloric test/video head impulse test sensitivity was 1.8:1

Caloric test and video head impulse test sensitivity as vestibular impairment predictors before cochlear implant surgery

OBJECTIVES: Currently, cochlear implant procedures are becoming increasingly broad and have greatly expanded. Bilateral cochlear implants and cochlear implants are more frequently applied in children. Our hypothesis is that the video head impulse test may be more sensitive than the caloric test in detecting abnormal vestibular function before cochlear implant surgery. The objective of this study was to compare the video head impulse test and caloric test results of patients selected for cochlear implant procedures before surgery. METHODS: The patients selected for cochlear implant surgery were submitted to a bithermal caloric test and video head impulse test. RESULTS: By comparing angular slow phase velocity values below 5o in the bithermal caloric test (hypofunction) and video head impulse test with a gain lower than 0.8, we identified 37 (64.9%) patients with vestibular hypofunction or canal paresis and 21 (36.8%) patients with abnormal video head impulse test gain before the cochlear implant procedure. Of the 37 patients with caloric test vestibular hypofunction, 20 (54%) patients exhibited an abnormal gain in the video head impulse test. CONCLUSION: The caloric test is more sensitive than the video head impulse test (Fisher’s exact test, p=0.0002) in detecting the impaired ear before cochlear implant delivery. The proportion of caloric test/video head impulse test positive identification of abnormal vestibular function or caloric test/video head impulse test sensitivity was 1.8:1

Deletion of the entire POU4F3 gene in a familial case of autosomal dominant non-syndromic hearing loss

In 20% of cases, hereditary non-syndromic hearing loss has an autosomal dominant inheritance (ADNSHL). To date, more than 50 loci for ADNSHL have been mapped to different chromosomal regions. In order to verify whether genomic alterations contribute to the hearing loss etiology and to search for novel deafness candidate loci, we investigated probands from families with ADNSHL by oligonucleotide array-CGH. A deletion in the 5q32 region encompassing only one gene, POU4F3, which corresponds to DFNA15, was detected in one family. POU4F3 protein has an important role in the maturation, differentiation and survival of cochlear hair cells. Defects in these cells may therefore explain sensorineural hearing loss. Mutations in this gene have already been associated with autosomal dominant hearing loss but this is the first description of a germline POUF4F3 deletion associated with hearing impairment.The authors are grateful to the family members for their enrollment in this study and would like to thank laboratory fellows for their collaboration, especially Maria Teresa de Mello Auricchio for technical support. This work was financially supported by Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Investigating deafness genes as a cause of sudden sensorineural hearing loss

Hearing loss is a very heterogeneous genetic condition, meaning that identical or similar phenotypes result from \ud mutations in many di erent genes, with diverse inheritance mechanisms. Sudden sensorineural hearing loss (SSNHL) \ud is an emergency de ned as sensorineural hearing loss (SNHL) equal to or greater than 30 dB HL, a ecting at least \ud three consecutive tonal frequencies, with sudden onset and occurring within three days. e estimate incidence \ud is 5 to 20 within 100.000 people by year, but despite the extensive list of potentially etiologic factors described, \ud its pathophysiology is poorly understood. Some individuals with deafness due to mitochondrial mutations were \ud described as having SSNHL. In mitochondrial DNA, genes encoding for transporter and ribosome RNA are hot \ud candidates to explain hearing loss due to the large number of mutations associated with deafness already described \ud in them. e main mitochondrial mutations associated with non-syndromic deafness are A1555G, ΔT961insCn, \ud T1095C, C1494T in MTRNR1 gene, that encodes the 12S subunit of rRNA; and A7445G, 7472insC, T7510C and \ud T7511C in MTTS1 gene, that encodes the tRNASer(UCN). Regarding the MTTL1 gene, mutations are more frequently \ud associated to mitochondrial syndroms that can include deafness as a symptom. Besides, mutations c.35delG and \ud c.167delT in the GJB2 gene, del(GJB6-D13S1830) and del(GJB6-D13S1854) deletions near the GJB6 gene and the \ud A1555G mitochondrial mutation in the 12S rRNA gene are described as the most frequently molecular diagnosis \ud among individuals with hearing loss. e aim of this work was to investigate the role of genetic factor in the etiology \ud of SSNHL. In order to achieve this, the screened the mutations in the GJB2 and GJB6 gene and sequenced the \ud mitochondrial genes MTRNR1, MTTS1 and MTTL1 in 53 individuals with SSNHL, associated or not with other \ud symptoms. Mutations c.35delG, c.167delT, the deletions del(GJB6-D13S1830) and del(GJB6-D13S1854) were not \ud found in the sample. Variants in MTTS1 and MTTL1 genes were not detected, either. Regarding the MTRNR1 \ud gene, 15 di erent variants were found, 13 of which were already described as having no phenotypic e ect. Two novel \ud mutations (m.806C>T and m.986G>A) were not reported in SNP database. ey were not found in a Brazilian \ud control sample of 104 normal hearing individuals (Abreu-Silva et al., Ann Hum Biol, 2011, 38(2):210-8), and \ud their meaning still needs to be clari ed through population studies. Although molecular screening did not point \ud to a signi cant role of the tested genes in SSNHL, it is noteworthy that 20 (37,7%) of the 53 subjects reported a \ud positive familial history of hearing loss. while 18% of people in the control sample reported a ected relatives. ese \ud data suggest genetic susceptibility to hearing loss in this group, probably resulting from multifactorial mechanism.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) – CEPID, and Conselho Nacional de Desenvolvimento Cientí co e Tecnológico (CNPQ)

Retention of progenitor cell phenotype in otospheres from guinea pig and mouse cochlea

Abstract\ud \ud Background\ud Culturing otospheres from dissociated organ of Corti is an appropriate starting point aiming at the development of cell therapy for hair cell loss. Although guinea pigs have been widely used as an excellent experimental model for studying the biology of the inner ear, the mouse cochlea has been more suitable for yielding otospheres in vitro. The aim of this study was to compare conditions and outcomes of otosphere suspension cultures from dissociated organ of Corti of either mouse or guinea pig at postnatal day three (P3), and to evaluate the guinea pig as a potential cochlea donor for preclinical cell therapy.\ud \ud \ud Methods\ud Organs of Corti were surgically isolated from P3 guinea pig or mouse cochlea, dissociated and cultivated under non-adherent conditions. Cultures were maintained in serum-free DMEM:F12 medium, supplemented with epidermal growth factor (EGF) plus either basic fibroblast growth factor (bFGF) or transforming growth factor alpha (TGFα). Immunofluorescence assays were conducted for phenotype characterization.\ud \ud \ud Results\ud The TGFα group presented a number of spheres significantly higher than the bFGF group. Although mouse cultures yielded more cells per sphere than guinea pig cultures, sox2 and nestin distributed similarly in otosphere cells from both organisms. We present evidence that otospheres retain properties of inner ear progenitor cells such as self-renewal, proliferation, and differentiation into hair cells or supporting cells.\ud \ud \ud Conclusions\ud Dissociated guinea pig cochlea produced otospheres in vitro, expressing sox2 and nestin similarly to mouse otospheres. Our data is supporting evidence for the presence of inner ear progenitor cells in the postnatal guinea pig. However, there is limited viability for these cells in neonatal guinea pig cochlea when compared to the differentiation potential observed for the mouse organ of Corti at the same developmental stage

Zumbido e intolerância a sons : evidência e experiência de um grupo brasileiro

Introdução Zumbido e intolerância a sons são queixas frequentes e subjetivas que podem ter impacto na qualidade de vida do paciente. Objetivo Apresentar uma revisão dos principais pontos, inclusive conceitos, fisiopatologia, diagnóstico e abordagem do paciente com zumbido e sensibilidade a sons. Método Revisão da literatura com levantamento bibliográfico na base de dados da LILACS, SciELO, Pubmed e MEDLINE. Foram selecionados artigos e capítulos de livros sobre zumbido e sensibilidade a sons. Os diversos tópicos foram discutidos por um grupo de profissionais brasileiros e as conclusões, descritas. Resultado A prevalência de zumbido tem aumentado ao longo dos anos, muitas vezes associado a perda auditiva, fatores metabólicos e erros alimentares. A avaliação médica deve ser feita minuciosamente no sentido de orientar a solicitação de exames subsidiários. Os tratamentos disponíveis atualmente variam de medicamentos ao uso de sons com características específicas e técnicas de meditação, com resultados variáveis. Conclusão Foi apresentada uma revisão sobre os temas que permitindo ao leitor uma visão ampla da abordagem dos pacientes com zumbido e sensibilidade auditiva baseada em evidências científicas e experiência nacional.Introduction Tinnitus and sound intolerance are frequent and subjective complaints that may have an impact on a patient's quality of life. Objective To present a review of the salient points including concepts, pathophysiology, diagnosis and approach of the patient with tinnitus and sensitivity to sounds. Methods Literature review with bibliographic survey in LILACS, SciELO, Pubmed and MEDLINE database. Articles and book chapters on tinnitus and sound sensitivity were selected. The several topics were discussed by a group of Brazilian professionals and the conclusions were described. Results The prevalence of tinnitus has increased over the years, often associated with hearing loss, metabolic factors and inadequate diet. Medical evaluation should be performed carefully to guide the request of subsidiary exams. Currently available treatments range from medications to the use of sounds with specific characteristics and meditation techniques, with variable results. Conclusion A review on tinnitus and auditory sensitivity was presented, allowing the reader a broad view of the approach to these patients, based on scientific evidence and national experience

Tinnitus Neural Mechanisms and Structural Changes in the Brain: The Contribution of Neuroimaging Research

Introduction Tinnitus is an abnormal perception of sound in the absence of an external stimulus. Chronic tinnitus usually has a high impact in many aspects of patients' lives, such as emotional stress, sleep disturbance, concentration difficulties, and so on. These strong reactions are usually attributed to central nervous system involvement. Neuroimaging has revealed the implication of brain structures in the auditory system. Objective This systematic review points out neuroimaging studies that contribute to identifying the structures involved in the pathophysiological mechanism of generation and persistence of various forms of tinnitus. Data Synthesis Functional imaging research reveals that tinnitus perception is associated with the involvement of the nonauditory brain areas, including the front parietal area; the limbic system, which consists of the anterior cingulate cortex, anterior insula, and amygdala; and the hippocampal and parahippocampal area. Conclusion The neuroimaging research confirms the involvement of the mechanisms of memory and cognition in the persistence of perception, anxiety, distress, and suffering associated with tinnitus