Macrophage depletion attenuates degeneration of spiral ganglion neurons in kanamycin-induced unilateral hearing loss model.

Pathological conditions in cochlea, such as ototoxicity, acoustic trauma, and age-related cochlear degeneration, induce cell death in the organ of Corti and degeneration of the spiral ganglion neurons (SGNs). Although macrophages play an essential role after cochlear injury, its role in the SGNs is limitedly understood. We analyzed the status of macrophage activation and neuronal damage in the spiral ganglion after kanamycin-induced unilateral hearing loss in mice. The number of ionized calcium-binding adapter molecule 1 (Iba1)-positive macrophages increased 3 days after unilateral kanamycin injection. Macrophages showed larger cell bodies, suggesting activation status. Interestingly, the number of activating transcription factor 3 (ATF3)-positive-neurons, an indicator of early neuronal damage, also increased at the same timing. In the later stages, the number of macrophages decreased, and the cell bodies became smaller, although the number of neuronal deaths increased. To understand their role in neuronal damage, macrophages were depleted via intraperitoneal injection of clodronate liposome 24 h after kanamycin injection. Macrophage depletion decreased the number of ATF3-positive neurons at day 3 and neuronal death at day 28 in the spiral ganglion following kanamycin injection. Our results suggest that suppression of inflammation by clodronate at early timing can protect spiral ganglion damage following cochlear insult.

Sudden unilateral hearing loss and vertigo following isolated cerebellar hypoperfusion without infarction due to vertebral artery dissection.

BACKGROUND: The definition of sudden sensorineural hearing loss (SSNHL) is broadly accepted as acute sensorineural hearing loss of more than 30 dB over at least three consecutive frequencies in a pure-tone audiogram (PTA). Acute audiovestibular loss is common with ischaemic stroke in the territory of the anterior inferior cerebellar artery (AICA). However, cases in which SSNHL and vertigo occur with hypoperfusion alone are very rare. We describe a patient who developed unilateral SSNHL and vertigo as initial symptoms caused by cerebellar hypoperfusion by vertebral artery (VA) dissection without the occurrence of infarction. CASE PRESENTATION: A 51-year-old man suddenly developed acute hearing loss (AHL) in his left ear and vertigo. On neurological examination, he had vibration-induced right-beating nystagmus and left-beating nystagmus after a head-shaking test. Additionally, he had apogeotropic nystagmus during head turns to either side. The head impulse test (HIT) was normal. PTA showed mild unilateral SSNHL in the left ear. Diffusion-weighted imaging (DWI) and perfusion-weighted imaging (PWI) showed territorial perfusion deficits in the left posterior inferior cerebellar artery (PICA) and anterior inferior cerebellar artery (AICA) without infarction. Two months later, the patient had no vertigo but still had hearing impairment in his left ear. A follow-up PTA documented persistent unilateral SSNHL in the left ear. Additionally, perfusion computed tomography (CT) showed that perfusion deficits remained in the left cerebellum along the PICA and AICA territories. CONCLUSIONS: Our case highlights a case of AHL and vertigo presented by isolated cerebellar hypoperfusion without infarction. It is necessary to consider the possibility of a central cause in patients with AHL and vertigo, and it is important to confirm this possibility through brain magnetic resonance imaging (MRI), including PWI, and magnetic resonance angiography (MRA).

A review of the effects of unilateral hearing loss on spatial hearing.

The capacity of the auditory system to extract spatial information relies principally on the detection and interpretation of binaural cues, i.e., differences in the time of arrival or level of the sound between the two ears. In this review, we consider the effects of unilateral or asymmetric hearing loss on spatial hearing, with a focus on the adaptive changes in the brain that may help to compensate for an imbalance in input between the ears. Unilateral hearing loss during development weakens the brain's representation of the deprived ear, and this may outlast the restoration of function in that ear and therefore impair performance on tasks such as sound localization and spatial release from masking that rely on binaural processing. However, loss of hearing in one ear also triggers a reweighting of the cues used for sound localization, resulting in increased dependence on the spectral cues provided by the other ear for localization in azimuth, as well as adjustments in binaural sensitivity that help to offset the imbalance in inputs between the two ears. These adaptive strategies enable the developing auditory system to compensate to a large degree for asymmetric hearing loss, thereby maintaining accurate sound localization. They can also be leveraged by training following hearing loss in adulthood. Although further research is needed to determine whether this plasticity can generalize to more realistic listening conditions and to other tasks, such as spatial unmasking, the capacity of the auditory system to undergo these adaptive changes has important implications for rehabilitation strategies in the hearing impaired.

Progression of Unilateral Hearing Loss in Children With and Without Ipsilateral Cochlear Nerve Canal Stenosis: A Hazard Analysis.

OBJECTIVE: To investigate the risk of hearing loss progression in each ear among children with unilateral hearing loss associated with ipsilateral bony cochlear nerve canal (BCNC) stenosis. SETTING: Tertiary pediatric referral center. PATIENTS: Children diagnosed with unilateral hearing loss who had undergone temporal bone computed tomography imaging and had at least 6 months of follow-up audiometric testing were identified from a prospective audiological database. INTERVENTIONS: Two pediatric radiologists blinded to affected ear evaluated imaging for temporal bone anomalies and measured bony cochlear canal width independently. All available audiograms were reviewed, and air conduction thresholds were documented. MAIN OUTCOME MEASURE: Progression of hearing loss was defined by a 10 dB increase in air conduction pure-tone average. RESULTS: One hundred twenty eight children met inclusion criteria. Of these, 54 (42%) had a temporal bone anomaly, and 22 (17%) had ipsilateral BCNC stenosis. At 12 months, rates of progression in the ipsilateral ear were as follows: 12% among those without a temporal bone anomaly, 13% among those with a temporal bone anomaly, and 17% among those with BCNC stenosis. Children with BCNC stenosis had a significantly greater risk of progression in their ipsilateral ear compared with children with no stenosis: hazard ratio (HR) 2.17, 95% confidence interval (CI) (1.01, 4.66), p value 0.046. When we compared children with BCNC stenosis to those with normal temporal bone imaging, we found that the children with stenosis had nearly two times greater risk estimate for progression, but this difference did not reach significance, HR 1.9, CI (0.8, 4.3), p = 0.1. No children with BCNC stenosis developed hearing loss in their contralateral year by 12 months of follow-up. CONCLUSION: Children with bony cochlear nerve canal stenosis may be at increased risk for progression in their ipsilateral ear. Audiometric and medical follow-up for these children should be considered.

Detection of Unilateral Hearing Loss by Stationary Wavelet Entropy.

AIM: Sensorineural hearing loss is correlated to massive neurological or psychiatric disease. MATERIALS: T1-weighted volumetric images were acquired from fourteen subjects with right-sided hearing loss (RHL), fifteen subjects with left-sided hearing loss (LHL), and twenty healthy controls (HC). METHOD: We treated a three-class classification problem: HC, LHL, and RHL. Stationary wavelet entropy was employed to extract global features from magnetic resonance images of each subject. Those stationary wavelet entropy features were used as input to a single-hidden layer feedforward neuralnetwork classifier. RESULTS: The 10 repetition results of 10-fold cross validation show that the accuracies of HC, LHL, and RHL are 96.94%, 97.14%, and 97.35%, respectively. CONCLUSION: Our developed system is promising and effective in detecting hearing loss.

Alterations in gray matter volume due to unilateral hearing loss.

Although extensive research on neural plasticity resulting from hearing deprivation has been conducted, the direct influence of compromised audition on the auditory cortex and the potential impact of long durations of incomplete sensory stimulation on the adult cortex are still not fully understood. In this study, using voxel-based morphometry, we evaluated gray matter (GM) volume changes that may be associated with reduced hearing ability and the duration of hearing impairment in 42 unilateral hearing loss (UHL) patients with acoustic neuromas compared to 24 normal controls. We found significant GM volume increases in the somatosensory and motor systems and GM volume decreases in the auditory (i.e., Heschl's gyrus) and visual systems (i.e., the calcarine cortex) in UHL patients. The GM volume decreases in the primary auditory cortex (i.e., superior temporal gyrus and Heschl's gyrus) correlated with reduced hearing ability. Meanwhile, the GM volume decreases in structures involving high-level cognitive control functions (i.e., dorsolateral prefrontal cortex and anterior cingulate cortex) correlated positively with hearing loss duration. Our findings demonstrated that the severity and duration of UHL may contribute to the dissociated morphology of auditory and high-level neural structures, providing insight into the brain's plasticity related to chronic, persistent partial sensory loss.

Induction of single-sided deafness in the newborn rat and its consequence for cochlear nucleus volume development.

Aim of this study was to induce a single-sided deafness (SSD) in rats before hearing onset. Rats were operated at postnatal day 10 by approaching the tympanic cavity along a retroauricular path without manipulating ossicles or tympanic membrane. The ototoxic aminoglycoside neomycin was injected intracochlearly through the round window membrane on one side. When the animals have reached young adult stages, their hearing threshold was determined by their auditory brainstem response (ABR). Monaural deafening was considered successful when the hearing threshold was at least 95 dB above the threshold of the normal hearing ear. Growing up with one non-functional ear, rats developed a striking anatomical asymmetry of their cochlear nuclei (CN). The CN from age-matched normal hearing brains and from both sides of single-sided deaf brains were cut into series of frontal sections and their volumes calculated. No difference was detected between the volume of the normal hearing CN and the contralateral CN in SSD rats. By contrast, growth retardation was found for the ventral CN on the deaf side to result in a volume of only 57% compared to the normal hearing side. Marginal growth retardation was also observed for the dorsal CN on the deaf side. Thus, loss of sensory activation leads mainly, but not exclusively, to a reduction of tissue volume in the ventral CN of the deaf side, leaving the contralateral side apparently unaffected.

Allelic Mutations of KITLG, Encoding KIT Ligand, Cause Asymmetric and Unilateral Hearing Loss and Waardenburg Syndrome Type 2.

Linkage analysis combined with whole-exome sequencing in a large family with congenital and stable non-syndromic unilateral and asymmetric hearing loss (NS-UHL/AHL) revealed a heterozygous truncating mutation, c.286_303delinsT (p.Ser96Ter), in KITLG. This mutation co-segregated with NS-UHL/AHL as a dominant trait with reduced penetrance. By screening a panel of probands with NS-UHL/AHL, we found an additional mutation, c.200_202del (p.His67_Cys68delinsArg). In vitro studies revealed that the p.His67_Cys68delinsArg transmembrane isoform of KITLG is not detectable at the cell membrane, supporting pathogenicity. KITLG encodes a ligand for the KIT receptor. Also, KITLG-KIT signaling and MITF are suggested to mutually interact in melanocyte development. Because mutations in MITF are causative of Waardenburg syndrome type 2 (WS2), we screened KITLG in suspected WS2-affected probands. A heterozygous missense mutation, c.310C>G (p.Leu104Val), that segregated with WS2 was identified in a small family. In vitro studies revealed that the p.Leu104Val transmembrane isoform of KITLG is located at the cell membrane, as is wild-type KITLG. However, in culture media of transfected cells, the p.Leu104Val soluble isoform of KITLG was reduced, and no soluble p.His67_Cys68delinsArg and p.Ser96Ter KITLG could be detected. These data suggest that mutations in KITLG associated with NS-UHL/AHL have a loss-of-function effect. We speculate that the mechanism of the mutation underlying WS2 and leading to membrane incorporation and reduced secretion of KITLG occurs via a dominant-negative or gain-of-function effect. Our study unveils different phenotypes associated with KITLG, previously associated with pigmentation abnormalities, and will thereby improve the genetic counseling given to individuals with KITLG variants.

Vulnerability to acoustic trauma in the normal hearing ear with contralateral hearing loss.

OBJECTIVES: We undertook an animal study to investigate the functional and histological changes that occur in the normal hearing ear of following acoustic trauma. METHODS: As an animal model of unilateral hearing loss, the right ears of CBA mice were deafened by cochlear destruction at 6 weeks of age (SSD group). The control groups included mice that underwent a sham surgery, and mice that were exposed to noise binaurally and monaurally (by plugging the right ear completely). At 10 weeks of age, all mice were exposed to acoustic trauma (110 dB sound pressure level for 1 hour) that induced a transient threshold shift (TTS). Changes in the hearing thresholds of the left ear were assessed over the next 4 weeks by measuring the auditory brainstem responses (ABRs) and distortion product otoacoustic emissions (DPOAEs). RESULTS: Following the noise exposure, the SSD group showed a permanent threshold shift (PTS) of about 10 dB, whereas the other groups showed full recovery from the TTS. The threshold of the DPOAEs of the left ears were increased after noise exposure but returned to normal in all groups, with no significant differences among the groups. Histological evaluation showed no apparent cellular loss or apoptosis in the left ears of all groups, including the SSD group. CONCLUSIONS: These results suggest that normal hearing ears are more vulnerable to acoustic trauma following contralateral unilateral cochlear ablation. This increased vulnerability may be due to damaged neural structures.

Remodelling at the calyx of Held-MNTB synapse in mice developing with unilateral conductive hearing loss.

Structure and function of central synapses are profoundly influenced by experience during developmental sensitive periods. Sensory synapses, which are the indispensable interface for the developing brain to interact with its environment, are particularly plastic. In the auditory system, moderate forms of unilateral hearing loss during development are prevalent but the pre- and postsynaptic modifications that occur when hearing symmetry is perturbed are not well understood. We investigated this issue by performing experiments at the large calyx of Held synapse. Principal neurons of the medial nucleus of the trapezoid body (MNTB) are innervated by calyx of Held terminals that originate from the axons of globular bushy cells located in the contralateral ventral cochlear nucleus. We compared populations of synapses in the same animal that were either sound deprived (SD) or sound experienced (SE) after unilateral conductive hearing loss (CHL). Middle ear ossicles were removed 1 week prior to hearing onset (approx. postnatal day (P) 12) and morphological and electrophysiological approaches were applied to auditory brainstem slices taken from these mice at P17-19. Calyces in the SD and SE MNTB acquired their mature digitated morphology but these were structurally more complex than those in normal hearing mice. This was accompanied by bilateral decreases in initial EPSC amplitude and synaptic conductance despite the CHL being unilateral. During high-frequency stimulation, some SD synapses displayed short-term depression whereas others displayed short-term facilitation followed by slow depression similar to the heterogeneities observed in normal hearing mice. However SE synapses predominantly displayed short-term facilitation followed by slow depression which could be explained in part by the decrease in release probability. Furthermore, the excitability of principal cells in the SD MNTB had increased significantly. Despite these unilateral changes in short-term plasticity and excitability, heterogeneities in the spiking fidelity among the population of both SD and SE synapses showed similar continuums to those in normal hearing mice. Our study suggests that preservations in the heterogeneity in spiking fidelity via synaptic remodelling ensures symmetric functional stability which is probably important for retaining the capability to maximally code sound localization cues despite moderate asymmetries in hearing experience.

Ectopic pituitary adenoma associated with an empty sella presenting with hearing loss: case report with literature review.

Ectopic pituitary adenomas are uncommon entities that may pose substantial diagnostic challenges. In the majority of these cases, patients present with endocrine and/or nasal obstruction symptoms. We report the case of an ectopic pituitary adenoma in a 76-year-old man with an empty sella who initially presented with right-sided hearing loss progressing to bilateral hearing loss over the next 4 years. Neuroimaging studies revealed a large, expansile central skull base mass replacing the clivus and sphenoid sinus, and invading the internal auditory canals and inner ear bilaterally. The tumor also involved the floor of the middle cranial fossae and bilateral medial temporal and occipital bones. Histopathologic examination, including immunohistochemical studies, revealed a sparsely granulated lactotroph adenoma. Hearing loss in a patient with ectopic pituitary adenoma constitutes an extremely unusual presentation. This case was further complicated by the presence of an empty sella and the absence of symptoms related to hyperprolactinemia.

Sudden unilateral hearing loss as first sign of cerebral sinus venous thrombosis? A 3-year retrospective analysis.

INTRODUCTION: Recently, several studies and case reports have dealt with the topic of cerebral sinus venous thrombosis (CSVT) and focused on sudden hearing loss as an early and rare symptom, to diminish the delay in diagnosing this serious disease. MATERIALS AND METHODS: We conducted a retrospective analysis over 3 years and investigated MRIs of all inpatients who were treated for sudden sensorineural hearing loss. The aim of the study was to evaluate whether sudden hearing loss could be an early indicator, or the first sign, of CSVT. RESULTS: In total, 554 patients were included. Only 2 patients with CSVT could be identified. In both, sudden unilateral sensorineural hearing loss was not the only symptom. They also reported headache, and 1 patient also reported tinnitus and vertigo. CONCLUSION: In our opinion, sudden unilateral sensorineural hearing loss alone is not a reliable indicator of CSVT. In combination with headache or visual impairment, this rare vascular disease should be taken into account.

An isolated vestibulocochlear symptom preceding brainstem infarction due to basilar artery occlusion.

OBJECTIVE: To describe unilateral hearing loss preceding brainstem infarction due to basilar artery occlusion. STUDY DESIGN: Clinical capsule report. SETTING: University hospital. PATIENT: A 67-year-old woman presented with unilateral acute hearing loss with dizziness as a sole prodromal manifestation of basilar artery occlusion for 2 weeks before the appearance of motor and oculomotor deficits. INTERVENTION: Otologic examinations and magnetic resonance imaging (MRI) were performed. RESULTS: A pure-tone audiogram showed unilateral profound sensorineural hearing loss preceding brainstem occlusion. Diffusion-weighted MR image demonstrated acute infarction around the paramedian area of the upper and middle pons, although T2-weighted MR image showed a normal brain image except for occlusion of the basilar artery. CONCLUSION: Acute unilateral hearing loss could be a prodrome of basilar artery occlusion. Clinicians must consider this possibility, especially in patients at high risk of brainstem infarction.

Screening of SLC26A4, FOXI1 and KCNJ10 genes in unilateral hearing impairment with ipsilateral enlarged vestibular aqueduct.

OBJECTIVE: To investigate the implication of SLC26A4, FOXI and KCNJ10 genes in unilateral hearing impairment associated with ipsilateral inner ear malformation (Enlargement of the vestibular aqueduct and/or Mondini dysplasia). METHODS: We have gathered 25 patients presenting unilateral hearing impairment and ipsilateral enlarged vestibular aqueduct. For each of the patients, we have analyzed SLC26A4, FOXI1 and KCNJ10 genes sequences. RESULTS: The analysis of SLC26A4 revealed only eight heterozygous SLC26A4 sequence variants, three of them being novel (p.Met147Ile, p.Asn538Asn and p.Leu627Arg). None of the patients carried a second mutation on the other allele. Moreover, the SLC26A4 locus was excluded by segregation analysis in two families. No mutations were present in FOXI1 and KCNJ10 genes. CONCLUSIONS: Together, these data suggest that SLC26A4, FOXI1 and KCNJ10 are not major determinants in unilateral deafness and enlarged vestibular aqueduct compared with their implication in Pendred syndrome and non-syndromic bilateral enlarged vestibular aqueduct.

Is there a correlation between vascular loops in the cerebellopontine angle and unexplained unilateral hearing loss?

OBJECTIVE: This study was a retrospective analysis of patients who had received magnetic resonance imaging scans of the internal auditory canal (IAC) to evaluate unexplained asymmetric hearing loss. The study aimed to correlate structural features of vascular loops formed by the anterior inferior cerebellar artery (AICA) within the cerebellopontine angle and IAC with asymmetric hearing loss. STUDY DESIGN: High-resolution thin-section T2 fast spin echo magnetic resonance imaging scans of 58 patients with asymmetric sensorineural hearing loss were obtained; the structure of the AICA was graded on both sides using 2 scoring systems. The grading senior head and neck radiologist was blinded to the clinical history. The first scoring system used was the Chavda classification, which is based on the anatomic location of the AICA loop. This system identified 92 loops within the cerebellopontine angle; 22 loops extending less than halfway into the IAC and 2 loops extending more than halfway into the IAC. A second classification system was used simultaneously to describe the extent of contact between the AICA loop and the vestibulocochlear nerve. The second system identified 24 loops that were not in contact with the nerve, 60 in which the loop was running adjacent to the nerve but not displacing it; 12 loops were identified that were displacing the vestibulocochlear nerve, and 24 loops were identified running between the facial and the vestibulocochlear nerve. Four loops were classified as both displacing the vestibulocochlear nerve and running between the facial and vestibulocochlear nerves. Tinnitus was present in addition to hearing loss. In 48 of the 58 patients, the statistical analysis was repeated for these patients. RESULTS: No statistically significant association was found between loops classified by the Chavda system and hearing loss. No statistically significant association was present between loops that made no contact with the nerve, ran adjacent to the nerve, or displaced the nerve. A statistically significant association was found between loops that ran between the facial and vestibulocochlear nerve and hearing loss, with a p value of 0.0162. The subset who had tinnitus in addition to hearing loss had similar results, with the only significant association being found between loops running between the facial nerve and the vestibulocochlear nerve, and a p value of 0.0433 was obtained. CONCLUSION: A correlation between vascular loops and hearing loss did not exist in the majority of the patients in this study. The subset of patients that had a vessel between the facial and vestibular cochlear nerves deserve further investigation.

Endolymphatic space imaging in patients with delayed endolymphatic hydrops.

CONCLUSION: Magnetic resonance imaging (MRI) after intratympanic gadolinium injection can reveal endolymphatic hydrops (ELH) in patients with delayed ELH (DELH). Patients with contralateral DELH may have bilateral ELH. OBJECTIVE: DELH has previously been diagnosed based on clinical history, hearing and vestibular examinations. DELH is classified into three types: ipsilateral, contralateral and bilateral indicate the side with the longstanding hearing loss. Ipsilateral DELH occurs in the ear with a profound hearing loss, contralateral DELH in the better hearing ear and bilateral DELH in both ears. Imaging diagnosis of the endolymphatic space may add a new dimension to the diagnosis and treatment of DELH. PATIENTS AND METHODS: Gadodiamide hydrate was diluted eightfold with saline. The diluted gadodiamide hydrate was injected intratympanically through the tympanic membrane in two patients with ipsilateral DELH and five patients with contralateral DELH. One day after the injection, 3 Tesla MRI was performed to evaluate the endolymphatic space. RESULTS: ELH was observed in all patients. In three patients who underwent bilateral intratympanic injection of gadolinium and were diagnosed with contralateral DELH, ELH was observed bilaterally. In one of these three patients, ELH was observed in the cochlea on the left and in the vestibule on the right.

Response of the flat cochlear epithelium to forced expression of Atoh1.

Following hair cell elimination in severely traumatized cochleae, differentiated supporting cells are often replaced by a simple epithelium with cuboidal or flat appearance. Atoh1 (previously Math1) is a basic helix-loop-helix transcription factor critical to hair cell differentiation during mammalian embryogenesis. Forced expression of Atoh1 in the differentiated supporting cell population can induce transdifferentiation leading to hair cell regeneration. Here, we examined the outcome of adenovirus mediated over-expression of Atoh1 in the non-sensory cells of the flat epithelium. We determined that seven days after unilateral elimination of hair cells with neomycin, differentiated supporting cells are absent, replaced by a flat epithelium. Nerve processes were also missing from the auditory epithelium, with the exception of infrequent looping nerve processes above the habenula perforata. We then inoculated an adenovirus vector with Atoh1 insert into the scala media of the deafened cochlea. The inoculation resulted in upregulation of Atoh1 in the flat epithelium. However, two months after the inoculation, Atoh1-treated ears did not exhibit clear signs of hair cell regeneration. Combined with previous data on induction of supporting cell to hair cell transdifferentiation by forced expression of Atoh1, these results suggest that the presence of differentiated supporting cells in the organ of Corti is necessary for transdifferentiation to occur.

Consequences of unilateral hearing loss: time dependent regulation of protein synthesis in auditory brainstem nuclei.

Conductive hearing impairment results in marked changes in neuronal activity in the central auditory system, particularly in young animals [Tucci, D.L., Cant, N.B., Durham, D., 1999. Conductive hearing loss results in a decrease in central auditory system activity in the young gerbil. Laryngoscope 109, 1359-1371]. To better understand the effects of conductive hearing loss (CHL) on cellular metabolism, incorporation of (3)H-leucine was used as a measure of protein synthesis in immature postnatal day 21 gerbils subjected to either unilateral CHL by malleus removal or profound sensorineural hearing loss by cochlear ablation. (3)H-leucine uptake was measured after survival times of 6 or 48h. Protein synthesis values were standardized to measurements from the abducens nucleus and compared with measurements from sham animals at similar age/survival times. Protein synthesis in the medial superior olive (MSO) was found to be significantly down-regulated (bilaterally) after CHL in animals surviving 48h. However, 6h after CHL manipulation, protein synthesis is up-regulated in MSO (bilaterally) and in the ipsilateral medial nucleus of the trapezoid body.