Inner Ear Dysfunction Research Articles

RBM24 is localized to stress granules in cells under various stress conditions

Stress granules (SGs) are formed when untranslated messenger ribonucleoproteins (mRNPs) accumulate in cells under stress, and are thought to minimize stress-induced damage and promote cell survival. RBM24 (RNA-binding motif protein 24) is an RNA-binding protein that plays pivotal roles in regulating the stability or translation initiation of target mRNAs as well as alternative splicing of target pre-mRNAs. Its important physiological functions are highlighted by the fact that Rbm24 knockout mice or zebrafish suffer from dysfunction of heart, eye, and inner ear. Here we show that RBM24 is recruited into SGs under various stress conditions, suggesting that it might protect its target RNAs in cells under stress. However, SG formation is unaffected when Rbm24 expression is down-regulated. Nevertheless, RBM24 overexpression in cultured cells is sufficient to induce SG formation, suggesting that RBM24 might play an important role in SG formation. In conclusion, our present work reveals that RBM24 is a SG component, which implies that RBM24 could protect its target mRNAs in stressed cells.

Inner ear drug delivery using liposomes.

Dysfunction of inner ear can result in from several disease procedures and introduce a possibility for therapeutic intervention. The existence of a blood-cochlear obstacle and round window membrane restricts direct access into the inner ear and following inner ear drug, gene, protein and cell delivery. Several strategies have designed to increase drug delivery to the inner ear. One of main particles for inner ear drug delivery is liposome. Here we reviewed the application of liposomes in inner ear drug delivery.

Pig’s ear: Streptococcus suis Meningitis and its associated inner ear implications

Streptococcus suis (S. suis) is a zoonotic pathogen commonly found in Asian countries. Infection with this bacterium typically clinically presents as meningitis and individuals whom handle swine are at increased risk of developing infections.We present a case of a patient with a S. suis meningitis who worked as a butcher. The 48-year-old man was admitted to our department with headaches, fevers, nausea and bilateral hearing loss. According to his medical history, the patient had sustained a cut on his finger while preparing pork meat. A microbiological examination of the cerebrospinal fluid and blood revealed S. suis. The patient was empirically treated with ceftriaxone, vancomycin and dexamethasone. The patient made a complete recovery from the meningitic process and inflammatory markers. However, the hearing and vestibular loss persisted with considerable functional impact upon his daily life. He was elected for a right cochlear implant, 7 weeks after the presentation with a poor outcome. It is important to remember that inner-ear dysfunction can occur frequently in S. suis meningitis surviving patients. Physicians should have a high index of suspicion if risk factors are present and initiate urgent treatment to prevent serious long-term consequences.

Inner ear lesion and the differential roles of hypoxia and hypercarbia in triggering active movements: Potential implication for the Sudden Infant Death Syndrome

Infants that succumb to Sudden Infant Death Syndrome (SIDS) have been identified with inner ear dysfunction (IED) at birth and on autopsy. We previously investigated whether IED could play a mechanistic role in SIDS. We discovered that animals with IED displayed significant suppression of movement arousal to a hypoxic–hypercarbic gas mixture under light anesthesia. In the current study we investigated the role of each gas in triggering movements and the response to hypercarbia during natural sleep without anesthesia. Seventeen-day-old CD-1 mice received intra-tympanic gentamicin (IT-Gent) injections to precipitate IED. The movement response to hypercarbia, hypoxia and hypoxia-hypercarbia was compared to controls under light anesthesia. Hypercarbia did not stimulate vigorous movements in any animals under either sleep condition. Hypoxia triggered vigorous movements in controls (p<0.05) and a decreased response in IT-Gent animals under light anesthesia. This contrasted with combined hypoxia-hypercarbia, in which IT-Gent animals displaced significantly suppressed movements compared to controls (p<0.05). Our findings portray that a degree of intact inner ear function is necessary for instigating the movement response. Additionally, hypoxia is the trigger for the movement response while carbon dioxide (CO2) suppresses it. The finding that carbon dioxide did not stimulate movement during natural sleep is an important finding. This contrasts with other studies that have identified hypercarbia as an arousal stimulus with EEG. Further studies are warranted to evaluate the precise role of the inner ear in the movement response and potential association with SIDS. The early detection of IED in SIDS predisposed cases could be invaluable.

A Case of Acute Inner Ear Dysfunction as a Prodrome of Transient Ischemic Attack Caused by Vertebral Artery Stenosis

일과성 허혈발작(transient ischemic attack)은 국소적으로 뇌나 망막에 허혈이 발생해서 일시적인 신경학적 이상이 생기 는 질환으로 정의할 수 있는데, 신경학적 증상은 한 시간 이상 지속되지 않으며 급성 뇌경색의 소견은 없어야 한다. 그동안 일과성 허혈발작은 뇌의 허혈이 완전하게 회복할 수 있기 때 문에 신경학적 증상이 24시간 이내에 좋아지게 되는 양성 질 환이며 영구적인 뇌손상은 발생하지 않는다고 알려져 왔다. 그러나 일과성 허혈발작이 생긴 환자의 10~20%는 90일 이내 에 허혈성 뇌경색이 발생하고, 허혈성 뇌경색 환자의 7~40% 는 일과성 허혈발작이 선행하게 된다. 그러므로 최근에는 일과성 허혈발작을 뇌경색의 중요한 위험 인자로 생각하고 신 속한 재관류를 통해 뇌세포 보호(neuroprotection)가 필요한 질환으로 여기고 있다. 일과성 허혈발작의 증상으로는 편측 마비, 연하곤란, 복시, 입 주위 감각이상, 운동마비, 구음장애 등을 보이게 되는데, 이 경우 뇌 영상 검사를 통해 초기 뇌경 색이나 다른 신경학적 원인에 대한 확인이 필요하며 특히 뇌 혈관에 대한 평가가 중요하다. 대부분의 증상은 30분 이내에 사라지기 때문에 간과되어 방치될 수 있는데, 특히 초기에 전 형적인 신경학적 증상이 없는 경우는 진단에 어려움이 많다. 다른 신경학적 이상 소견 없이 어지럼증과 돌발성 난청 소견 만 보이는 환자에서는 중추성 원인의 감별 진단을 위해 뇌 자 기공명영상(magnetic resonance imaging, MRI)에 의존하게 되는데, 확산 강조 MRI 검사에서 초기 뇌경색이 발견될 수도 있지만, 초기 MRI에서 정상 소견을 보였던 환자에서 시간이 Case Report Korean J Otorhinolaryngol-Head Neck Surg 2016;59(1):58-63 / pISSN 2092-5859 / eISSN 2092-6529 http://dx.doi.org/10.3342/kjorl-hns.2016.59.1.58

Gravity-dependent Nystagmus and Inner-Ear Dysfunction Suggest Anterior and Posterior Inferior Cerebellar Artery Infarct

Cerebellar lesions may present with gravity-dependent nystagmus, where the direction and velocity of the drifts change with alterations in head position. Two patients had acute onset of hearing loss, vertigo, oscillopsia, nausea, and vomiting. Examination revealed gravity-dependent nystagmus, unilateral hypoactive vestibulo-ocular reflex (VOR), and hearing loss ipsilateral to the VOR hypofunction. Traditionally, the hypoactive VOR and hearing loss suggest inner-ear dysfunction. Vertigo, nausea, vomiting, and nystagmus may suggest peripheral or central vestibulopathy. The gravity-dependent modulation of nystagmus, however, localizes to the posterior cerebellar vermis. Magnetic resonance imaging in our patients revealed acute cerebellar infarct affecting posterior cerebellar vermis, in the vascular distribution of the posterior inferior cerebellar artery (PICA). This lesion explains the gravity-dependent nystagmus, nausea, and vomiting. Acute onset of unilateral hearing loss and VOR hypofunction could be the manifestation of inner-ear ischemic injury secondary to the anterior inferior cerebellar artery (AICA) compromise. In cases of combined AICA and PICA infarction, the symptoms of peripheral vestibulopathy might masquerade the central vestibular syndrome and harbor a cerebellar stroke. However, the gravity-dependent nystagmus allows prompt identification of acute cerebellar infarct.

Local and systemic effects of low-dose transtympanic methotrexate: in vivo animal study

To evaluate the safety of low-dose transtympanic methotrexate in a rat model. Experimental animal study. Tertiary training and research hospital. Twenty-four rats were randomly divided into three study groups. Diluted methotrexate solution was administered transtympanically to fill the middle-ear cavity, twice a week in group one and three times a week in group two. Ringer lactate solution was administered transtympanically three times a week in the control group. Local and systemic effects of low-dose transtympanic methotrexate. In the methotrexate groups, middle-ear mucosal oedema was present in all animals. Auditory brainstem response thresholds indicated no inner-ear dysfunction in any group. Liver function and serum haemoglobin levels showed no statistically significant difference in any group. However, liver biopsies from groups one and two showed mild portal hyperaemia. These findings are encouraging, and support further investigation of the topical application of methotrexate in autoimmune hearing diseases, as an alternative or adjunct to transtympanic steroids.

EchoScan: A new system to objectively assess peripheral hearing disorders

Pure-tone air-conduction audiometry (PTA) is the reference clinical test used in Europe and the United States to measure the extent of hearing loss. It is a subjective, behavioral test, which measures thresholds of hearing sensations and perceptions based on patient responses to frequency-specific pure-tone stimuli. PTA can detect hearing problems due to cochlear or retro-cochlear impairment, without identifying the source of the problem. In contrast, cubic distortion product otoacoustic emissions (DPOAEs) detect inner-ear dysfunctions, particularly those involving the outer hair cells sensitive to noise and ototoxicants. Recently, ototoxicants were shown to have an action on the central nuclei driving the middle-ear acoustic reflex. Therefore, a new device, called EchoScan, was conceived to collect and measure performance both in the middle- and inner-ear. Its originality: the use of a battery of DPOAE measurements associated with contra-lateral acoustic stimulation. Changes in DPOAE amplitude due to ageing and gender were incidentally detected and EchoScan was more sensitive than impedancemetry to detect the stapedial reflex. EchoScan can be used both in clinical investigations and in occupational medicine, especially for the auditory follow-up of people exposed to noise or ototoxic agents. EchoScan could be promising to assess early detection in programs to prevent hearing loss.

Large vestibular aqueduct syndrome and endolymphatic hydrops: two presentations of a common primary inner-ear dysfunction?

To present the theory that large vestibular aqueduct syndrome (i.e. the recognised existence of an enlarged vestibular aqueduct with progressive sensorineural hearing loss) and endolymphatic hydrops are due to a common primary dysfunction of inner-ear fluid homeostasis. Case report and review of the world literature concerning large vestibular aqueduct syndrome and endolymphatic hydrops. We report a family in which one sibling suffered from large vestibular aqueduct syndrome while the other had classic Ménière's disease. This suggests that large vestibular aqueduct syndrome and endolymphatic hydrops, in some cases, may be due to a common primary dysfunction of inner-ear fluid homeostasis. To our knowledge, this is the first report in the world literature to postulate that variation in the relative compliance of inner-ear membranes could be the factor that determines the manifestation of the disorder as either endolymphatic hydrops or large vestibular aqueduct syndrome.

Vestibular Rehabilitation in Individuals with Inner-Ear Dysfunction: A Pilot Study

A randomised control prospective study was carried out examining patient outcomes after performing a 10-week vestibular home exercise programme. Thirty-two adults with vestibular dysfunction who reported vestibular symptoms negatively affecting daily life were enrolled. Test subjects were provided with an individualised vestibular rehabilitation programme designed by a physiotherapist. Control subjects received a set of strength and endurance exercises only. All subjects performed their exercises 3 times a day for 10 weeks. Subjective and objective patient measures were collected at 0, 6, 10 and 26 weeks. Results showed that both groups improved after beginning exercise, and that test subjects significantly benefited compared to the controls. These benefits were long term and measurable 6 months later. This study provides evidence that individualised vestibular exercises promote better outcomes for patients with vestibular dysfunction.

Late radiation effects on hearing, vestibular function, and taste in brain tumor patients

Purpose: To investigate late radiation effects on hearing, vestibular function, and taste after conventional radiotherapy in brain tumor patients. Methods and Materials: Hearing, vestibular function, and taste were assessed in 33 brain tumor patients irradiated unilaterally to the tumor-bearing hemisphere and the temporal bone. Median observation time after completion of radiotherapy was 13 years; the fraction dose was 1.8 Gy, and mean radiation dose was 53.1 Gy. Results: Deep ulceration in the external ear canal and osteoradionecrosis on the irradiated side was seen in three patients. Reduced hearing was found for air and bone conduction of the irradiated side compared to the opposite side (0.25–2 kHz: 6.1 dB, 4 kHz: 10.3 dB, 6 kHz: 15.6 dB, and 8 kHz: 16.5 dB). For bone conduction, the corresponding figures were 0.25–2 kHz: 5.5 dB and 4 kHz: 8.2 dB. Three patients had a canal paresis of the irradiated side, and three patients had affection of the chorda tympani. Conclusion: Irradiation of the temporal bone with doses usually given in the treatment of patients with brain tumors may cause osteoradionecrosis, sensorineural hearing loss, dysfunction of the vestibular inner ear, and loss of taste. Head-and-neck examination should be included in the follow-up of long-term survivors.

Identification and Characterization of an Inner Ear-Expressed Human Melanoma Inhibitory Activity (MIA)-like Gene (MIAL) with a Frequent Polymorphism That Abolishes Translation

To discover new cochlea-specific genes as candidate genes for nonsyndromic hearing impairment, we searched in The Institute of Genome Research database for expressed sequence tags isolated from the cochlea only. This led to the cloning and characterization of a human gene named melanoma inhibitory activity-like (MIAL; HGMW-approved symbol OTOR alias MIAL) gene. In situ hybridization revealed MIAL expression in a cell layer beneath the sensory epithelium of cochlea and vestibule of human fetal inner ear. No other human tissue, except fetal brain, showed expression of MIAL when analyzed by in situ hybridization or reverse transcription-polymerase chain reaction. The cDNA of the mouse homologue was also cloned and mapped about 80 cM from the top of mouse chromosome 2. In mouse, Mial was also expressed in the cochlea and the vestibule of the inner ear, as well as in brain, eye, limb, and ovary. Expression in mammalian cell cultures showed that MIAL is translated as an ∼15-kDa polypeptide that is assembled into a covalently linked homodimer, modified by sulfation, and secreted from the cells via the Golgi apparatus. In the human MIAL gene, a frequent polymorphism was discovered in the translation initiation codon (ACG instead of ATG). Of 505 individuals, 48 (9.5%) were ATG/ACG heterozygous and 1 (0.2%) was homozygous for ACG. No MIAL protein was synthesized in cells transfected with cDNA of the ACG allele. The inner ear-restricted expression pattern and the existence of an inactive allele suggest that MIAL may contribute to inner-ear dysfunction in humans.

The role of serotonin as a mediator of emesis induced by different stimuli.

The aim of this work was to evaluate the impact of changes in serotonin metabolism on the pathophysiology of different types of emesis: pregnancy-induced emesis, emesis associated with inner-ear dysfunction, and cisplatin-induced emesis. The urinary excretion of 5-hydroxyindoleacetic acid (5-HIAA), the main metabolite of serotonin, was measured in 13 women with pregnancy-induced emesis, 12 patients who had nausea and vomiting following inner-ear dysfunctions, 27 patients with cisplatin-induced emesis and a control group of 21 women. 5-HIAA was measured with a fluorescence polarization immunoassay (Abbott) and corrected for varying urine concentrations. Both patients with emesis associated with inner-ear dysfunction and patients with pregnancy-associated emesis showed a similar 5-HIAA excretion pattern compared with the control group. No correlation between intensity of nausea or vomiting and changes in 5-HIAA excretion could be detected. In patients receiving cisplatin, the 5-HIAA excretion increased rapidly within the 12 h following cisplatin administration and returned to baseline levels after 24 h. There was a parallel increase of 5-HIAA excretion and numbers of emetic episodes in the first 12 h, but delayed emesis was not associated with elevated 5-HIAA excretion. Our results provide evidence that serotonin is involved in the pathophysiology of cisplatin-induced acute emesis. Cisplatin-induced delayed emesis, pregnancy-associated emesis, and emesis due to inner-ear dysfunction are not associated with elevated levels of 5-HIAA excretion. The serotonin pathway probably represents only one of many different afferent mechanisms capable of initiating the emesis cascade.

Hydrogen clearance and cochlear microcirculation at different levels of blood pressure.

To study the autoregulative capabilities of the cochlear vessels, hydrogen clearance (HC) measurements were carried out by means of various blood pressure levels in hemorrhagic hypotension. H2-sensitive platinum--needle electrode were applied and a polarographic microanalysis method was used. The measurements were performed in the scala media of anesthetized cats during measuring of blood pressure and blood gases. The statistical analysis of the experimental data shows that the relationship between the HC and aortic blood pressure represents a regression line. According to the regression line the half-life time of HC was delayed for 0.7 min, when the blood pressure was reduced by 10 mm Hg (40-150 mm Hg blood pressure range). This corresponds to a cochlea flow rate of 0.3 ml/100 g/min. By mean aortic blood pressure of 40 mm Hg, the speed of H2 exchange still remains about 50% of the initial clearance. This indicates that the cochlear vessels have autoregulative capability. This autoregulative capability differs from the saturation curves of most autoregulated blood flow in the brain, heart and kidney vessels. These findings are in accordance with the observations of other authors. As our experimental data show, and as long as an analogy can be drawn between man and cat, it is hardly possible to explain that the fall of the blood pressure alone could lead to a disturbance of the oxygen supply to the inner ear, as often discussed in certain inner-ear dysfunctions.