Progressive Sensorineural Hearing Loss Research Articles

A Case of Vitiligo Associated with Meniere’s Disease

Vitiligo is a pigmentary skin disorder characterized by chronic and progressive loss of melanocytes. Although the etiology of vitiligo is still unknown, the most convincing theory is thought to an interaction between genetic and unknown environmental factors, resulting in autoimmune melanocyte destruction. Meniere's disease is characterized by recurrent vertigo, fluctuating or progressive sensorineural hearing loss and tinnitus, and it is associated with an accumulation of endolymph in the inner ear. Although its etiology is not known, genetic or epigenetic factors have a significant contribution. And recently many articles support the hypothesis that Meniere's disease is an autoimmune disorderand associated with immune-mediated disorder. Loss of otic melanocytes may occur in patients with vitiligo and, evidences of sensorineural hearing loss in vitiligo patients have been reported over the last decade. However, there have been no reports of Meniere's disease associated wth vitiligo patients. We report an interesting case of vitiligo on the face with Meniere's disease.

Association of PRPS1 Mutations with Disease Phenotypes.

Phosphoribosylpyrophosphate synthetase 1 (PRPS1) codes for PRS-I enzyme that catalyzes the first step of nucleotide synthesis. PRPS1 gene mutations have been implicated in a number of human diseases. Recently, new mutations in PRPS1 have been identified that have been associated with novel phenotypes like diabetes insipidus expanding the spectrum of PRPS1-related diseases. The purpose of this review is to evaluate current literature on PRPS1-related syndromes and summarize potential therapies. The overexpression of PRPS1 results in PRS-I superactivity resulting in purine overproduction. Patients with PRS-I superactivity demonstrate uric acid overproduction, hypotonia, ataxia, neurodevelopment abnormalities, and postlingual hearing impairment. On the other hand, decreased activity leads to X-linked nonsyndromic sensorineural deafness (DFNX-2), Charcot-Marie-Tooth disease-5 (CMTX5), and Arts syndrome depending on the residual activity of PRS-I. Mild PRS-I deficiency (DFNX-2) results in non-syndromic progressive hearing loss whereas moderate PRS-I deficiency (CMTX5) and severe PRS-I deficiency (Arts syndrome) present with peripheral or optic neuropathy, prelingual progressive sensorineural hearing loss, and central nervous system impairment. Currently, purine replacement via S-adenosylmethionine (SAM) supplementation in patients with Arts syndrome appears to improve their condition. This suggests that SAM supplementation can alleviate symptoms of PRPS1 deficient patients and open new avenues of therapeutic intervention.

Congenital HCMV and assisted reproduction: Why not use the chance for primary screening?

HCMV is the leading cause of congenital infection, with 0.5-0.9% of infants affected in Europe, and primary maternal infection from the preconceptional phase to the first half of pregnancy bears the highest risk for long-term sequelae-like mental retardation, visual impairment, and progressive sensorineural hearing loss. As compared to couples conceiving spontaneously those under infertility treatment are well accessible to primary HCMV prevention. Since they face higher risk pregnancies this chance should be considered. The concept comprises serological screening for HCMV-IgG, including the partner where appropriate, defining individual risk factors, and counselling on hygiene at the initial assessment of infertility treatment. If seroconversion occurs, the subsequent treatment cycles should be postponed by 6 months. Uncertainties of diagnosis in early pregnancy which may lead to precautious elective termination can be prevented. A newborn at risk of congenital HCMV infection can be identified and scheduled for laboratory and paediatric evaluation within the first 2 weeks of life.

Congenital cytomegalovirus: what the otolaryngologist should know.

Cytomegalovirus (CMV) is an important cause of congenital sensorineural hearing loss (SNHL) that may represent up to 20% of nonsyndromic cases. Congenital CMV is an unrecognized cause of SNHL that all otolaryngologists should be aware of as it represents the only treatable cause of congenital SNHL. The current review highlights the recent advances on congenital CMV, including methods of diagnosis and prevention of progression of hearing loss with valganciclovir treatment. A recent study has shown that 6 months of oral valganciclovir treatment of infants with congenital CMV disease improves audiologic and neurodevelopmental outcomes to at least 2 years of age. Early treatment could, thus, have an important impact on these children. Increased awareness of congenital CMV SNHL by an otolaryngologist should lead to increased testing, and thus diagnosis, of this condition in newborns diagnosed with congenital SNHL. Prompt treatment with valganciclovir in these patients may consequently lead to prevention of progressive SNHL. Further research toward a CMV vaccine is hoped to eventually lead to prevention of congenital CMV.

Identifying microRNAs involved in aging of the lateral wall of the cochlear duct.

Age-related hearing loss is a progressive sensorineural hearing loss that occurs during aging. Degeneration of the organ of Corti and atrophy of the lateral wall of the cochlear duct (or scala media) in the inner ear are the two primary causes. MicroRNAs (miRNAs), a class of short non-coding RNAs that regulate the expression of mRNA/protein targets, are important regulators of cellular senescence and aging. We examined miRNA gene expression profiles in the lateral wall of two mouse strains, along with exploration of the potential targets of those miRNAs that showed dynamic expression during aging. We show that 95 and 60 miRNAs exhibited differential expression in C57 and CBA mice during aging, respectively. A majority of downregulated miRNAs are known to regulate pathways of cell proliferation and differentiation, while all upregulated miRNAs are known regulators in the pro-apoptotic pathways. By using apoptosis-related gene array and bioinformatic approaches to predict miRNA targets, we identify candidate miRNA-regulated genes that regulate apoptosis pathways in the lateral wall of C57 and CBA mice during aging.

SYMPTOMS OF MITOCHONDRIAL DISEASE FALLING ON DEAF EARS

<h3>Case report</h3> Mitochondrial diseases show a broad phenotypic spectrum and are underdiagnosed. We present a 37-year-old woman referred to our neurology clinic after an incidental finding of bilateral caudate, lentiform and pulvinar calcification during workup for cochlear implant surgery. She was born at 30 weeks9 gestation with her identical twin sister and was found to have progressive sensorineural hearing loss from eight years of age. She had had no seizures, ataxia, weakness, psychosis or involuntary movements. Her mother had diabetes mellitus. On examination, she was areflexic but otherwise normal. Neurophysiology showed a mild sensory neuropathy. Mitochondrial gene testing showed heteroplasmy for m.3243A&gt;G mutation. <h3>Discussion</h3> Our patient was seen by a number of different specialists for her deafness and the possibility of mitochondrial diseases was never explored. Pathogenic mitochondrial gene mutations are present in up to 0.5% of the general population. The m.3243A&gt;G mutation is associated with deafness and diabetes mellitus. Neurologists see it in MELAS syndrome. Radiologically, it is associated with basal ganglia calcification. Reaching a diagnosis allows the patient and family to understand their illness and prognosis, to undergo predictive testing if wished and to undergo screening for other affected organ systems.

Progressive, reversible sensorineural hearing loss caused by azathioprine.

This paper describes the first reported case of progressive sensorineural hearing loss caused by azathioprine, which was reversed on stoppage of the drug. A female patient with previously normal hearing presented with progressive sensorineural hearing loss after being started on azathioprine. Otological and neurological examination findings were unremarkable. After stopping the drug, the patient reported an improvement in hearing, which was confirmed on pure tone audiometry. This previously unreported side effect of azathioprine is highlighted in order to increase clinical awareness. Early recognition of this adverse effect is important to minimise the possibility of permanent sensorineural hearing loss.

IL-1β inhibition in autoimmune inner ear disease: can you hear me now?

Clinical vignette: A 51-year-old man with right-sided sudden hearing loss presents to the otology clinic. He has a 4-year history of episodic vertigo of several hours' duration and fluctuating, progressive sensorineural hearing loss in his left ear. The vertigo attacks have not occurred for the last 18 months, and the left ear hearing is consistently poor. The patient's right ear hearing has dropped in the last 36 hours. MRI imaging of brain and temporal bone are normal. A 2-week "burst and taper" of oral prednisone is administered with no effect. Over the next 3 months, serial audiograms show rapidly progressive loss of threshold and word recognition scores on the right side. A trial of high-dose prednisone (60 mg/d for 30 days) results in full recovery of the right ear hearing and substantial improvement in the left ear. As the prednisone dose is slowly tapered over several months, the hearing drops again.

Targeted high-throughput sequencing identifies pathogenic mutations in KCNQ4 in two large Chinese families with autosomal dominant hearing loss.

Autosomal dominant non-syndromic hearing loss (ADNSHL) is highly heterogeneous, among them, KCNQ4 is one of the most frequent disease-causing genes. More than twenty KCNQ4 mutations have been reported, but none of them were detected in Chinese mainland families. In this study, we identified a novel KCNQ4 mutation in a five generation Chinese family with 84 members and a known KCNQ4 mutation in a six generation Chinese family with 66 members. Mutation screening of 30 genes for ADNSHL was performed in the probands from thirty large Chinese families with ADNSHL by targeted region capture and high-throughput sequencing. The candidate variants and the co-segregation of the phenotype were verified by polymerase chain reaction (PCR) amplification and Sanger sequencing in all ascertained family members. Then we identified a novel KCNQ4 mutation p.W275R in exon 5 and a known KCNQ4 mutation p.G285S in exon 6 in two large Chinese ADNSHL families segregating with post-lingual high frequency-involved and progressive sensorineural hearing loss. This is the first report of KCNQ4 mutation in Chinese mainland families. KCNQ4, a member of voltage-gated potassium channel family, is likely to be a common gene in Chinese patients with ADNSHL. The results also support that the combination of targeted enrichment and high-throughput sequencing is a valuable molecular diagnostic tool for autosomal dominant hereditary deafness.

Investigation of clinical features and detection of 79 known deafness genes in a large Chinese family with dominant non-syndromic hearing loss

To investigate the clinical and genetic characteristics of a large family with late-onset, progressive autosomal dominant non-syndromic hearing loss. Collections of detail history hereditary features, physical and audiological examination were performed. After mutation screening of GJB2, SLC26A4, MTRNR1 (12SrRNA) genes by Sanger sequencing, the proband was investigated by targeted next-generation sequencing of 79 deafness genes. This family included seven generations and 73 members. Eleven persons with hearing loss and 11 normal-hearing persons participated in this study. All affected members but one exhibited late-onset, progressive non-syndromic sensorineural hearing loss; the ages of onset were between 9 and 30 years. Mutation screening by sanger-sequencing and targeted next-generation sequencing excluded the possibility of pathogenic mutations within known deafness gene. A Chinese family with late-onset progressive non-syndromic sensorineural hearing loss was investigated clinically and genetically. By candidate gene approach and targeted next-generation sequencing, this family was preliminary proved to be caused by unknown deafness gene.

A novel DFNA36 mutation in TMC1 orthologous to the Beethoven (Bth) mouse associated with autosomal dominant hearing loss in a Chinese family.

Mutations in the transmembrane channel-like gene 1 (TMC1) can cause both DFNA36 and DFNB7/11 hearing loss. More than thirty DFNB7/11 mutations have been reported, but only three DFNA36 mutations were reported previously. In this study, we found a large Chinese family with 222 family members showing post-lingual, progressive sensorineural hearing loss which were consistent with DFNA36 hearing loss. Auditory brainstem response (ABR) test of the youngest patient showed a special result with nearly normal threshold but prolonged latency, decreased amplitude, and the abnormal waveform morphology. Exome sequencing of the proband found four candidate variants in known hearing loss genes. Sanger sequencing in all family members found a novel variant c.1253T>A (p.M418K) in TMC1 at DFNA36 that co-segregated with the phenotype. This mutation in TMC1 is orthologous to the mutation found in the hearing loss mouse model named Bth ten years ago. In another 51 Chinese autosomal dominant hearing loss families, we screened the segments containing the dominant mutations of TMC1 and no functional variants were found. TMC1 is expressed in the hair cells in inner ear. Given the already known roles of TMC1 in the mechanotransduction in the cochlea and its expression in inner ear, our results may provide an interesting perspective into its function in inner ear.

Mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) in the older adult

A 70-year-old woman presented to the hospital's general physicians with a 3-week exacerbation of pre-existing migrainous headache, speech and behavioural change. There was a 20-year history of slowly progressive bilateral...

Acetaminophen and NAPQI are toxic to auditory cells via oxidative and endoplasmic reticulum stress-dependent pathways

Pain relievers containing N-acetyl-para-aminophenol, also called APAP, acetaminophen or paracetamol, in combination with opioid narcotics are top-selling pharmaceuticals in the U.S. Individuals who abuse these drugs for as little as sixty days can develop tinnitus and progressive bilateral sensorineural hearing loss. Recently published studies indicate that APAP and its metabolic product N-acetyl-p-benzoquinoneimine (NAPQI) are the primary ototoxic agents in this type of pain relievers. However, the mechanisms underlying the deleterious effects of these drugs on auditory cells remain to be fully characterized. In this study, we report cellular, genomic, and proteomic experiments revealing that cytotoxicity by APAP and NAPQI involves two different pathways in Immortomouse™-derived HEI-OC1 cells, implicating ROS overproduction, alterations in ER morphology, redistribution of intra-cisternal chaperones, activation of the eIF2α-CHOP pathway, as well as changes in ER stress and protein folding response markers. Thus, both oxidative and ER stress are part of the cellular and molecular mechanisms that contribute to the cytotoxic effects of APAP and NAPQI in these cells. We suggest that these in vitro findings should be taken into consideration when designing pharmacological strategies aimed at preventing the toxic effects of these drugs on the auditory system.

Treatment of Traumatic Stapediovestibular Luxation

Stapediovestibular luxations are rare lesions that are most commonly caused by direct, penetrating trauma to the external ear canal. In this type of ossicular dislocation, disruption of the annular ligament or footplate fracture may lead to a perilymphatic fistula (PLF) presenting with cochleovestibular symptoms including (progressive) sensorineural hearing loss, tinnitus, and vestibular symptoms. The objective of this article is to define the optimal treatment of stapediovestibular luxations and review the literature on this topic. We present a case of internal stapediovestibular dislocation and pneumolabyrinth after penetrating trauma with predominantly conductive hearing loss and incapacitating vertigo. Middle ear inspection with removal of the luxated incus, repositioning of the stapes with a "stapedial strut" and closure of the tympanic membrane. Hearing outcome and vestibular symptoms of this patient are presented, and all comparable cases in the literature are reviewed. Complete resolution of the vestibular symptoms and stabilization of the bone conduction thresholds. In patients with pneumolabyrinth after middle ear trauma with mild symptoms, we recommend initial conservative treatment with close monitoring of hearing. In patients with severe, persisting, or progressive vestibulocochlear symptoms, exploratory tympanotomy should be performed to check for and treat PLF. Oval window fistula repair is reported to have variable hearing outcomes but offers complete resolution of vestibular symptoms in most cases. The stapedial strut is one of the possible surgical techniques in case of an internally luxated stapes.

Evidence for genotype–phenotype correlation for OTOF mutations

ObjectivesThe aim of this study is to evaluate the auditory phenotype in subjects with OTOF gene mutations to describe genotype–phenotype correlations. MethodsTwenty-two affected members from three families with homozygous OTOF mutations were included. Nine subjects were evaluated audiologically with otoscopic examination, pure-tone audiometry, tympanometry with acoustic reflex testing, auditory brain stem responses, and otoacoustic emission tests. ResultsHomozygous c.4718T>C (p.Ile1573Thr) mutation was associated with the auditory neuropathy/auditory dys-synchrony (AN/AD) phenotype and with progressive sensorineural hearing loss in four siblings in one family, while homozygous c.4467dupC (p.I1490HfsX19) was associated with severe to profound sensorineural hearing loss without AN/AD in four relatives in another family. Homozygous c.1958delC (p.Pro653LeufsX13) mutation was associated with moderate sensorineural hearing loss without AN/AD in one affected person in an additional family. ConclusionsThe audiological phenotype associated with different OTOF mutations appears to be consistently different suggesting the presence of a genotype–phenotype correlation.

Combined Occurrence of Alström Syndrome and Bronchiectasis

Alström syndrome (Online Mendelian Inheritance in Man ALMS #203800) is a rare hereditary disorder caused by mutations in the gene ALMS1. This rare disorder's characteristics are cone-rod dystrophy resulting in blindness in childhood, insulin-resistant type 2 diabetes mellitus, truncal obesity, progressive sensorineural hearing loss, dilated cardiomyopathy, craniofacial features, hypothyroidism, elevation in liver transaminases, renal insufficiency, gonadal dysfunction, and menstrual irregularities. A 13.5-year-old girl was admitted to the hospital for complaints of excessive water consumption and urination over the previous 2 years. The patient's parents were third-degree relatives. At physical examination, hyperpigmentation was present over the areola and acanthosis nigricans under the arms and on the neck. Audiologic examination revealed bilateral sensorineural hearing loss, and bilateral cataract was determined at ocular examination. The patient was monitored by the chest diseases department due to bronchiectasis. HbA1c was 13.1%. In mutation screening study, 2 novel mutations c.5586T>G; p.Tyr1862* and c.2905insT; p.L968fs*4 were detected in the ALMS1 gene. Saccharin test was positive. We emphasize that Alström syndrome may be complicated by bronchiectasis.

Cochlear implantation in a patient with Paget’s disease

Paget’s disease of the temporal bone can cause hearing loss that eventually develops into profound deafness. However, the treatment options for hearing loss associated with Paget’s disease are limited. Thus far, only 3 cases of cochlear implantation in patients with Paget’s disease have been reported. In this study, we describe a 62-year-old woman who underwent cochlear implantation for progressive bilateral sensorineural hearing loss. The patient gained useful open-set speech perception over a 5-year postoperative period. Cochlear implantation can be beneficial in patients with profound hearing loss associated with Paget’s disease.

Adult progressive sensorineural hearing loss: is preoperative imaging necessary before cochlear implantation?

Preoperative evaluation of cochlear implant candidate includes routine imaging to identify anatomic abnormalities that may preclude or complicate implantation, such as cochlear aplasia, absent/narrowed internal auditory canals, cochlear ossificans, or significant traumatic fracture. The aim of this study is to determine if preoperative imaging is necessary in select cochlear implant candidates, thus defraying cost and ionizing radiation. Retrospective chart review. Tertiary referral facility. Adult patients with progressive sensorineural hearing loss without evidence of head trauma, meningitis, or congenital hearing loss who underwent cochlear implantation. Diagnostic and therapeutic. Preoperative radiologic abnormalities, deviation from standard cochlear implant operation. One hundred eighteen cochlear implants met inclusion criteria; 23.7% of CT scans had a documented abnormality, including chronic otitis media (14.4%), otosclerosis (4.2%), and an enlarged vestibular aqueduct (3.4%). There were 6 eventful surgeries in patients with normal documented CT scan. Events included multiple insertion attempts (3.4%), CSF leak (2.5%), and no apparent round window (2.5%). In every case, a cochlear implant was able to be placed successfully. In the appropriately selected patient, preoperative imaging is not necessary as it does not impact the cochlear implant surgery and will defray cost and ionizing radiation.

A clinical study of age related hearing loss among diabetes patients

Background: Age related hearing loss is one of the most common chronic health conditions affecting the elderly people. With aging, risk of presbycusis and diabetes increases. Our study aims at evaluating auditory dysfunction in patients with diabetes mellitus aged above 50 years as compared to non-diabetic patient. We also tried to find the relation between duration of diabetes and severity of hearing loss and whether HbA1c and blood sugars levels affected the type and severity of hearing loss. Materials and Methods: A cross-sectional study on 106 patients with type 2 diabetes mellitus and 90 non-diabetic patients with age and sex matched (controls) was carried out during November 2011 to October 2013. All patients were evaluated for hearing loss by subjecting to pure tone audiometry and blood investigations like glycated hemoglobin, fasting and postprandial blood sugars and serum creatinine levels. Results: A prevalence of 73% hearing loss was seen in diabetics. The degree of hearing loss increased with age. There was bilateral progressive sensory neural hearing loss with right sloping curve in both diabetics as well as controls but with significantly (P < 0.001) higher loss in diabetics (at 4 KHz and 8 KHz). A significant relationship between duration of the diabetes, HbA1c and severity of hearing loss was observed. Conclusion: Diabetes mellitus was associated with higher hearing loss compared to presbycusis and hearing threshold was seen to affect all frequencies, but significantly the higher frequencies in diabetics. As duration of diabetes increased, the severity also increased. Poorer the HbA1c, more severe was the hearing loss.

Conventional Audiometry, Extended High-Frequency Audiometry, and DPOAE for Early Diagnosis of NIHL

Background:Noise most frequently affects hearing system, as it may typically cause a bilateral, progressive sensorineural hearing loss at high frequencies.Objectives:This study was designed to compare three different methods to evaluate noise-induced hearing loss (conventional audiometry, high-frequency audiometry, and distortion product otoacoustic emission).Material and Methods:This was a cross-sectional study. Data was analyzed by SPSS (ver. 19) using chi square, T test and repeated measures analysis. Study samples were workers from tile and ceramic industry.Results:We found that conventional audiometry, extended high-frequency audiometry, low-tone distortion product otoacoustic emission and high-tone distortion product otoacoustic emission had abnormal findings in 29 %, 69 %, 22 %, and 52 % of participants. Most frequently affected frequencies were 4000 and 6000Hz in conventional audiometry, and 14000 and 16000 in extended high-frequency audiometry.Conclusions:Extended high-frequency audiometry was the most sensitive test for detection of hearing loss in workers exposed to hazardous noise compared with conventional audiometry and distortion product otoacoustic.