Jeanne Oiticica

Population epidemiological study on the prevalence of dizziness in the city of São Paulo

UNLABELLED The epidemiology of dizziness is essential in clinical practice. OBJECTIVE To establish the prevalence of dizziness in the adult population of São Paulo, its clinical characteristics and level of discomfort. METHOD A prospective cross-sectional study ran from April to October of 2012 by a field questionnaire, totaling 1,960 interviews. The predictor variables assessed were age, gender, type of dizziness and the dizziness disability index. The statistical tools used to assess the significance between variables were the chi-square test, Students t-test and logistic regression. We used a 95% confidence interval for estimated values. RESULTS The prevalence of dizziness in the city of São Paulo was established at 42%. We found two peak of complaints, 49% in the range of 46-55 years and 44% in the elderly. Vestibular-related dizziness was estimated to affect 8.3% of the population, mainly women (p < 0.001). The symptoms caused disability in 27% of symptomatic interviewees and it is more bothersome to females (p < 0.001), who more frequently seek medical care (p < 0.001). CONCLUSION The prevalence of dizziness in São Paulo was found to be 42%. It affects daily activities in 67% of symptomatic patients, but only 46% of them seek medical help.

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.

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

BackgroundCulturing 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.MethodsOrgans 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.ResultsThe 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.ConclusionsDissociated 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.

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.

Pegylated interferon/ribavirin-associated sudden hearing loss in a patient with chronic hepatitis C in Brazil

Sudden hearing loss is defined as a sensorineural hearing loss, equal to or greater than 30 dB, at three or more consecutive frequencies, which takes place within 72 hours. Both peginterferon and ribavirin are well-known to be associated with significant adverse effects, but sudden hearing loss is uncommon. We report a 65-year-old male patient who developed sudden-onset hearing loss during combination therapy with pegylated interferon-alpha and ribavirin for chronic hepatitis C. Peginterferon and ribavirin may cause sudden hearing loss that may not recover after discontinuation of therapy. Immediate treatment for all possible etiologies is essential, along with targeted investigations and early referral for an ear, nose and throat specialist. Physicians should be aware of the possible ototoxic effects of peginterferon and ribavirin combination therapy requiring appropriate surveillance.

Genomic copy number alterations in non-syndromic hearing loss

Genetic heterogeneity has made the identification of genes related to hearing impairment a challenge. In the absence of a clear phenotypic aetiology, recurrence risk estimates are often based on family segregation and may be imprecise. We profiled by oligonucleotide array‐CGH patients presenting non‐syndromic hearing loss with presumptive autosomal recessive (n = 50) or autosomal dominant (n = 50) patterns of inheritance. Rare copy number variants (CNVs) were detected in 12 probands; four of the detected CNVs comprised genes previously associated with hearing loss (POU4F3, EYA4, USH2A, and BCAP31) and were considered causative, stressing the contribution of genomic imbalance to non‐syndromic deafness. In six cases, segregation of the CNVs in pedigrees excluded them as causative. In one case, segregation could not be investigated, while in another case, a point mutation likely explains the phenotype. These findings show that the presumptive patterns of inheritance were incorrect in at least two cases, thereby impacting genetic counselling. In addition, we report the first duplication reciprocal to the rare ABCD1, BCAP31, and SLC6A8 contiguous deletion syndrome; as with most microduplication syndromes, the associated phenotype is much milder than the respective microdeletion and, in this case, was restricted to hearing impairment.

Short Report – Clinical Genetics Genomic copy number alterations in non‐syndromic hearing loss

Genetic heterogeneity has made the identification of genes related to hearing impairment a challenge. In the absence of a clear phenotypic aetiology, recurrence risk estimates are often based on family segregation and may be imprecise. We profiled by oligonucleotide array‐CGH patients presenting non‐syndromic hearing loss with presumptive autosomal recessive (n = 50) or autosomal dominant (n = 50) patterns of inheritance. Rare copy number variants (CNVs) were detected in 12 probands; four of the detected CNVs comprised genes previously associated with hearing loss (POU4F3, EYA4, USH2A, and BCAP31) and were considered causative, stressing the contribution of genomic imbalance to non‐syndromic deafness. In six cases, segregation of the CNVs in pedigrees excluded them as causative. In one case, segregation could not be investigated, while in another case, a point mutation likely explains the phenotype. These findings show that the presumptive patterns of inheritance were incorrect in at least two cases, thereby impacting genetic counselling. In addition, we report the first duplication reciprocal to the rare ABCD1, BCAP31, and SLC6A8 contiguous deletion syndrome; as with most microduplication syndromes, the associated phenotype is much milder than the respective microdeletion and, in this case, was restricted to hearing impairment.

Hearing performance as a predictor of postural recovery in cochlear implant users

OBJECTIVE This study aimed to evaluate if hearing performance is a predictor of postural control in cochlear implant (CI) users at least six months after surgery. METHODS Cross-sectional study including (CI) recipients with post-lingual deafness and controls who were divided into the following groups: nine CI users with good hearing performance (G+), five CI users with poor hearing performance (G-), and seven controls (CG). For each patient, computerized dynamic posturography (CDP) tests, a sensory organization test (SOT), and an adaptation test (ADT) were applied as dual task performance, with first test (FT) and re-test (RT) on the same day, including a 40-60min interval between them to evaluate the short-term learning ability on postural recovery strategies. The results of the groups were compared. RESULTS Comparing the dual task performance on CDP and the weighted average between all test conditions, the G+ group showed better performance on RT in SOT4, SOT5, SOT6, and CS, which was not observed for G- and CG. The G- group had significantly lower levels of short-term learning ability than the other two groups in SOT5 (p=0.021), SOT6 (p=0.025), and CS (p=0.031). CONCLUSION The CI users with good hearing performance had a higher index of postural recovery when compared to CI users with poor hearing performance.

Transplantation and survival of mouse inner ear progenitor/stem cells in the organ of Corti after cochleostomy of hearing-impaired guinea pigs: preliminary results

In mammals, damage to sensory receptor cells (hair cells) of the inner ear results in permanent sensorineural hearing loss. Here, we investigated whether postnatal mouse inner ear progenitor/stem cells (mIESCs) are viable after transplantation into the basal turns of neomycin-injured guinea pig cochleas. We also examined the effects of mIESC transplantation on auditory functions. Eight adult female Cavia porcellus guinea pigs (250-350g) were deafened by intratympanic neomycin delivery. After 7 days, the animals were randomly divided in two groups. The study group (n=4) received transplantation of LacZ-positive mIESCs in culture medium into the scala tympani. The control group (n=4) received culture medium only. At 2 weeks after transplantation, functional analyses were performed by auditory brainstem response measurement, and the animals were sacrificed. The presence of mIESCs was evaluated by immunohistochemistry of sections of the cochlea from the study group. Non-parametric tests were used for statistical analysis of the data. Intratympanic neomycin delivery damaged hair cells and increased auditory thresholds prior to cell transplantation. There were no significant differences between auditory brainstem thresholds before and after transplantation in individual guinea pigs. Some mIESCs were observed in all scalae of the basal turns of the injured cochleas, and a proportion of these cells expressed the hair cell marker myosin VIIa. Some transplanted mIESCs engrafted in the cochlear basilar membrane. Our study demonstrates that transplanted cells survived and engrafted in the organ of Corti after cochleostomy.

Contribution of audiovestibular tests to the topographic diagnosis of sudden deafness

Summary Introduction: Sudden hearing loss (SHL) is an ENT emergency defined as sensorineural hearing loss (SNHL) ≥ 30 dB HL affecting at least 3 consecutive tonal frequencies, showing a sudden onset, and occurring within 3 days. In cases of SHL, a detailed investigation should be performed in order to determine the etiology and provide the best treatment. Otoacoustic emission (OAE) analysis, electronystagmography (ENG), bithermal caloric test (BCT), and vestibular evoked myogenic potential (VEMP) assessments may be used in addition to a number of auxiliary methods to determine the topographic diagnosis. Objective To evaluate the contribution of OAE analysis, BCT, VEMP assessment, and magnetic resonance imaging (MRI) to the topographic diagnosis of SHL. Method Cross-sectional and retrospective studies of 21 patients with SHL, as defined above, were performed. The patients underwent the following exams: audiometry, tympanometry, OAE analysis, BCT, VEMP assessment, and MRI. Sex, affected side, degree of hearing loss, and cochleovestibular test results were described and correlated with MRI findings. Students t-test was used for analysis of qualitative variables (p < 0.05). Results The mean age of the 21 patients assessed was 52.5 ± 15.3 years; 13 (61.9%) were women and 8 (38.1%) were men. Most (55%) had severe hearing loss. MRI changes were found in 20% of the cases. When the audiovestibular test results were added to the MRI findings, the topographic SHL diagnosis rate increased from 20% to 45%. Conclusion Only combined analysis via several examinations provides a precise topographic diagnosis. Isolated data do not provide sufficient evidence to establish the extent of involvement and, hence, a possible etiology.