Red flags alerting a posterior cranial fossa tumor from audiovestibular perspectives - a review.

BACKGROUND: There is no comprehensive and up-to-date overview of audiovestibular approach to the posterior fossa tumors in the literature. OBJECTIVE: This paper reviewed the literature relating to tumors at the posterior cranial fossa to find red flags alerting a posterior fossa lesion from audiovestibular perspectives. METHODS: This review was developed from articles published in those journals listed on the journal citation reports. Through the PubMed database, Embase, Google Scholar, and Cochrane library, 60 articles were finally obtained based on the PRISMA guidelines for reporting reviews. RESULTS: The presence of one red flag indicates a positive predictive value of 33% for detecting a posterior fossa lesion. Clinical features, namely, 1) mid-frequency sudden sensorineural hearing loss (SNHL), 2) bilateral sudden SNHL, and 3) rebound nystagmus may indicate a posterior fossa lesion, representing one, two, and three red flags, respectively. CONCLUSION: Those with 1) mid-frequency sudden SNHL, 2) bilateral sudden SNHL, and 3) rebound nystagmus trigger one, two, and three red flags, respectively, alerting clinicians the possibility of a posterior fossa lesion, which warrant MR imaging to exclude life-threatening or treatable conditions. SIGNIFICANCE: Patients with posterior fossa tumors may have potential life-threatening outcome.

A case of sudden hearing loss in a patient with chronic myelomonocytic leukemia.

Chronic myelomonocytic leukemia is a myeloid stem cell disease characterized by an abnormal production and accumulation of monocytic cells in association with other signs of myeloproliferation. Extramedullary manifestations of CMML are common and can affect the spleen, liver skin, and lymph nodes. However, otologic manifestations are extremely rare and could have occurred from either direct leukemic infiltration, hemorrhage of the cochlea, labyrinth, leukostasis, or infection. There is no standard treatment protocol for sensorineural hearing loss in CMML patients. More research is needed to improve the understanding of the pathogenesis of this condition, in order to provide better treatment options.

The Clinical Value of Periventricular White Matter Hyperintensity on MRI in Sudden Sensorineural Hearing Loss.

OBJECTIVES: To assess the clinical value of periventricular white matter hyperintensity (PWMH) found on brain magnetic resonance imaging (MRI) in patients with sudden sensorineural hearing loss (SSNHL). METHODS: In this prospective study, 115 patients who were diagnosed with SSNHL aged between 55 and 75 years were analyzed. All subjects underwent brain MRI and were divided into a PWMH and control groups, depending on the presence of PWMH on MRI. PWMH was subdivided into 3 groups according to severity. Pure-tone average results and hearing gain were compared between the 2 groups before treatment and 2 months after treatment. Hearing improvement was assessed using Sigel's criteria. RESULTS: A total of 106 patients (43 in the PWMH group and 63 in the control group) finally completed the 2-month follow-up. Average hearing gain in the PWMH group was significantly higher than in the control group (34.8 ± 20.3 and 25.9 ± 20.3, respectively, P = .029). PWMH score 1 showed significantly better hearing levels and hearing gain compared to PWMH score 3 and the control group. Multivariate analysis revealed that younger age, better initial hearing level, and the presence of PVWM score 1 were associated with good recovery. CONCLUSIONS: The presence of PWMH score 1 on brain MRI in patients with SSNHL was associated with better treatment response and was a good prognostic factor in a multivariate analysis while the hearing recovery in more severe PWMH (scores 2, 3) was not different from the control group.

[SENSORINEURAL HEARING LOSS AND VERTIGO DUE TO INTRA-COCHLEAR HEMORRHAGE].

INTRODUCTION: Intra-cochlear hemorrhage is a rare cause of sudden sensorineural hearing loss (SSNHL) which may be accompanied by diverse labyrinthine symptoms. In these cases, we expect magnetic resonance imaging (MRI) to demonstrate a high signal intensity in the labyrinth on unenhanced T1-weighted images as well as in fluid-attenuated inversion recovery (FLAIR) images. AIMS: To describe an experience with a case of intra-cochlear hemorrhage in a patient treated with anticoagulation, causing SSNHL and vertigo. METHODS: Case report and literature review. RESULTS: An 85-year old patient treated with anticoagulation therapy presented with right SSNHL, tinnitus and vertigo. Physical examination revealed: bilateral normal otoscopic examination, lateralized left Weber tuning fork test and a spontaneous left horizontal nystagmus. MRI performed demonstrated a high signal intensity inside the cochlea on unenhanced T1-weighted images. CONCLUSIONS: Performing an MRI is necessary in order to rule out frequent causes of SSNHL including benign as well as malignant tumors, malformations, trauma and more. The finding of an intra-labyrinthine hemorrhage causing SSNHL is rare, and should be taken into consideration when treated by anticoagulation therapy.

Utilizing Single Cell RNA-Sequencing to Implicate Cell Types and Therapeutic Targets for SSNHL in the Adult Cochlea.

OBJECTIVE: To identify genes implicated in sudden sensorineural hearing loss (SSNHL) and localize their expression in the cochlea to further explore potential pathogenic mechanisms and therapeutic targets. STUDY DESIGN: Systematic literature review and bioinformatics analysis. DATA SOURCES: The following sources were searched from inception through July 2, 2020: PubMed-NCBI, MEDLINE, Embase, CINAHL, Cochrane Library, ClinicalTrials.gov, OpenGrey, GreyNet, GreyLiterature Report, and European Union Clinical Trials Registry. PubMed-NCBI and MEDLINE were additionally searched for human temporal bone histopathologic studies related to SSNHL. METHODS: Literature review of candidate SSNHL genes was conducted according to PRISMA guidelines. Existing temporal bone studies from SSNHL patients were analyzed to identify the most commonly affected inner ear structures. Previously published single-cell and single-nucleus RNA-Seq datasets of the adult mouse stria vascularis, as well as postnatal day 7 and 15 mouse cochlear hair cells and supporting cells, were utilized for localization of the SSNHL-related genes curated through literature review. CONCLUSIONS: We report 92 unique single nucleotide polymorphisms (SNPs) in 76 different genes that have been investigated in relation to SSNHL in the literature. We demonstrate that a subset of these genes are expressed by cell types in the adult mouse stria vascularis and organ of Corti, consistent with findings from temporal bone studies in human subjects with SSNHL. We highlight several potential genetic targets relevant to current and possible future SSNHL treatments.

Genetic Susceptibility Study of Chinese Sudden Sensorineural Hearing Loss Patients with Vertigo.

OBJECTIVE: To investigate the genetic causes of sudden sensorineural hearing loss (SSNHL) patients in China. This study focused on analyzing variations of coding sequence of common genes related to deafness, revealing the molecular pathogenesis of sudden deafness from a genomics perspective, discovering molecular markers associated with the onset of deafness, and then supplying prevention to high-risk populations, classifying disease according to accurate etiology, and choosing a much more precision therapy. METHODS: We retrospectively analyzed the clinical characteristics of 51 patients diagnosed as SSNHL with vertigo treated in the Chinese PLA General Hospital. In this study, mutation screening of 307 nuclear genes and mitochondrial genome responsible for human or mouse deafness was performed on the 51 cases of unilateral sudden deafness patients with vertigo. RESULTS: We identified 51 cases of unilateral sudden deafness, including 2 cases of low-mid frequency hearing impairment, 18 cases of mid-high frequency hearing loss, 11 cases of flat-type hearing loss, and 20 cases of all frequency hearing loss. Among the 51 cases, 8 (15.69%) cases of GJB2 heterozygous variations, 1 (1.96%) case of GJB3 heterozygous variations, 5 (9.8%) cases of SLC26A4 heterozygous variations, 2 (3.92%) cases of COCH heterozygous variations, 14 (27.45%) cases of CDH23 heterozygous variations, 14 (27.45%) cases of OTOF heterozygous variations, 1 (1.96%) case of SLC17A8 heterozygous variations and 2 (3.92%) cases of KCNE1 heterozygous variations. No mtDNA gene variations were identified. CONCLUSION: SSNHL has some relationship with hereditary in Chinese population, but its complex genetic pathogenic mechanisms need further study.

Migraine and Cochlear Symptoms.

Migraine is one of the most common and highest burdens of disease. As a primary cerebral dysfunction illness, migraine might exhibit other system-related symptoms, including vestibular and cochlear symptoms. With the publication of the diagnostic criteria of vestibular migraine, the link between migraine and vestibular symptoms became clear. However, the relationship between migraine and cochlear symptoms is far from straightforward. Therefore, we focus on the correlation between migraine and deafness, sudden sensorineural hearing loss, acute tinnitus, and chronic tinnitus to better understand the relationship between migraine and cochlear symptoms.

Oral Corticosteroid Therapy For Sudden Sensorineural Hearing Loss And Factors Affecting Prognosis.

BACKGROUND: Sudden sensorineural hearing loss (SSNHL) is considered an otologic emergency globally. Aetiology is unknown in most cases but still the disease is believed to be caused by inflammation of the cochlea; therefore, steroids are considered beneficial due to their anti-inflammatory effect. METHODS: This study was conducted on 62 patients of sudden sensorineural hearing loss (SSNHL) in Ayub Medical Complex, Abbottabad. The patients were given prednisolone and their response to the therapy was monitored. Factors like age of the patient, gender, degree of hearing loss and duration of symptoms at initial presentation were recorded and their effect of response of the patient was also noted. RESULTS: The research subjects were 62 patients. Majority of the patients suffered from moderate to moderately severe hearing loss. Age and gender did not influence the response to the treatment. While the patients who presented earlier after the onset of disease and the patients who had milder degree of hearing loss at presentation had a better response to therapy. CONCLUSIONS: Oral corticosteroid therapy is a good therapeutic option for the treatment of sudden sensorineural hearing loss (SSHNL). The response to therapy is better in patients with milder hearing loss and those who present early to the otologist for treatment.

Global and local brain connectivity changes associated with sudden unilateral sensorineural hearing loss.

Recent studies suggest that even moderate sudden sensorineural hearing loss (SSNHL) causes reduction of gray matter volume in the primary auditory cortex, diminishing its ability to react to sound stimulation, as well as reorganization of functional brain networks. We employed resting-state functional MRI (rs-fMRI), in conjunction with graph-theoretical analysis and a newly developed functional "disruption index," to study whole-brain as well as local functional changes in patients with unilateral SSNHL. We also assessed the potential of graph-theoretical measures as biomarkers of disease, in terms of their relationship to clinically relevant audiological parameters. Eight patients with moderate or severe unilateral SSNHL and 15 healthy controls were included in this prospective pilot study. All patients underwent rs-fMRI to study potential changes in brain connectivity. From rs-fMRI data, global and local graph-theoretical measures, disruption index, and audiological examinations were estimated. Mann-Whitney U tests were used to study the differences between SSNHL patients and healthy controls. Associations between brain metrics and clinical variables were studied using multiple linear regressions, and the presence or absence of brain network hubs was assessed using Fisher's exact test. No statistically significant differences between SSNHL patients and healthy controls were found in global or local network measures. However, when analyzing brain networks through the disruption index, we found a brain-wide functional network reorganization (p < 0.001 as compared with controls), whose extent was associated with clinical impairment (p < 0.05). We also observed several functional hubs in SSNHL patients that were not present in healthy controls and vice versa. Our results demonstrate a brain involvement in SSNHL patients, not detectable using conventional graph-theoretical analysis, which may yield subtle disease clues and possibly aid in monitoring disease progression in clinical trials.

Investigational Medicinal Products for the Inner Ear: Review of Clinical Trial Characteristics in ClinicalTrials.gov.

BACKGROUND: The previous 30 years have provided information on the mechanisms of cell death in the inner ear after noise exposure, ototoxic drug injury, and during aging, and clinical trials have emerged for all of these acquired forms of hearing loss. Sudden hearing loss is less well understood, but restoration of hearing after sudden hearing loss is also a long-standing drug target, typically using steroids as an intervention but with other agents of interest as well. PURPOSE: The purpose of this review was to describe the state of the science regarding clinical testing of investigational medicinal products for the inner ear with respect to treatment or prevention of acquired hearing loss. DATA COLLECTION AND ANALYSIS: Comprehensive search and summary of clinical trials listed in the National Library of Medicine (www. CLINICALTRIALS: gov) database identified 61 clinical trials. RESULTS: Study phase, status, intervention, and primary, secondary, and other outcomes are summarized for studies assessing prevention of noise-induced hearing loss, prevention of drug-induced hearing loss, treatment of stable sensorineural hearing loss, and treatment of sudden sensorineural hearing loss. CONCLUSION: This review provides a comprehensive summary of the state of the science with respect to investigational medicinal products for the inner ear evaluated in human clinical trials, and the current challenges for the field.

Biomarkers Suggesting Favorable Prognostic Outcomes in Sudden Sensorineural Hearing Loss.

Sudden sensorineural hearing loss (SSNHL) is a medical emergency, making detailed examination to determine possible causes and early treatment important. However, etiological examinations in SSNHL do not always reveal a cause, and several factors have been found to affect treatment outcomes. Various studies are being performed to determine the prognosis and effects of treatment in patients who experience sudden hearing loss, and to identify biomarkers associated with this condition. Embase, PubMed, and the Cochrane database were searched using the key words SSNHL, prognostic, and biomarker. This search identified 4 articles in Embase, 28 articles in PubMed, and 36 in the Cochrane database. Of these 68 articles, 3 were duplicates and 37 were unrelated to the research topic. After excluding these articles, the remaining 28 articles were reviewed. Factors associated with SSNHL were divided into six categories: metabolic, hemostatic, inflammatory, immunologic, oxidative, and other factors. The associations between these factors with the occurrence of SSNHL and with patient prognosis were analyzed. Low monocyte counts, low neutrophil/lymphocyte ratio (NLR) and monocyte/high-density lipoproteins (HDL) cholesterol ratio (MHR), and low concentrations of fibrinogen, platelet glycoprotein (GP) IIIa, and TNF-α were found to be associated with good prognosis. However, these factors alone could not completely determine the onset of and recovery from SSNHL, suggesting the need for future basic and clinical studies.

Topography of the lesion in idiopathic sudden sensorineural hearing loss.

INTRODUCTION: Etiology of ISSNHL includes cessation of vascular perfusion, viral infection and cochlear membrane injury. Precise location of injury should be defined for a target-oriented treatment. Vestibular complaints in ISSNHL are hypothesized as involvement of vestibule. Vestibular complaints can be either due to involvement of inner ear or neural tract at any level. OBJECTIVES: In the present study we aimed to demonstrate involvement of vestibular organs in the absence of vestibular symptoms. It was aimed to evaluate superior and inferior vestibular neural pathways. METHODS: c-vemp and o-vemp were applied to patients suffering ISSNHL without vertigo. Pure tone averages, audiogram configurations, degree of hearing loss were analyzed. Latencies of P1 and N1 waves, amplitudes of P1-N1 waves were evaluated. Asymmetrical vemp wave patterns were compared between two ears regarding difference of PTA. RESULTS: Latencies of c-vemp waves were longer and amplitudes were smaller. o-vemp parameters were similar on both sides. Positive correlation was observed between c-vemp latencies and degree hearing loss. CONCLUSION: Inferior vestibular nerve pathway is affected in the absence of vertigo in ISSNHL with spared superior vestibular nerve pathway. Damage in IVN pathway correlates with degree of ISSNHL.

Early Magnetic Resonance Imaging for Patients With Idiopathic Sudden Sensorineural Hearing Loss in an Emergency Setting.

OBJECTIVE: The role of magnetic resonance (MR) imaging in idiopathic sudden sensorineural hearing loss (ISSHL) is controversial due to the inhomogeneity of clinical and MR protocols. The aim of this work is to relate early MR findings obtained immediately after the admission, with the clinical presentation, the audiological findings, and the outcomes of treatment. STUDY DESIGN: Prospective observational study. SETTING: Tertiary referral university center. PATIENTS: Forty-seven patients (22 M, 25 F; age: 54.4 ±â€Š17.5 yr) consecutively referred to the Department of Emergency for ISSHL. INTERVENTIONS: All patients underwent the diagnostic and therapeutic work-up for ISSHL, and MR imaging within 72 hours from the admission, independently of the symptoms onset. All patients received the same treatment (systemic steroid therapy, intratympanic steroid injection, and hyperbaric oxygen therapy). MAIN OUTCOME MEASURE(S): MR patterns, clinical, and laboratory findings. RESULTS: MR imaging was positive in 25 of 47 cases (53%), with a perfect agreement between clinical and MR examinations (Cohen K = 1) upon the affected ear. Three different radiological patterns were observed: labyrinthine haemorrhage (n = 5), acute inflammatory process (n = 14), isolated blood-labyrinth barrier breakdown (n = 6). By binary logistic regression, only vertigo was associated with a positive MR imaging [B = 2.8; p = 0.011; OR = 9.5 (95% CI: 2.2-40.8)] and the latter was the only variable associated with an unfavorable outcome [(B = 2.8; p = 0.02 OR = 12.8 (95% CI: 2.9-56.7)]. CONCLUSION: Patients affected by ISSHL with associated vertigo show a higher likelihood of having a positive MR imaging, which, in turn, seems to predict an unfavorable outcome.

Sudden Sensorineural Hearing Loss in Children: Clinical Characteristics, Etiology, Treatment Outcomes, and Prognostic Factors.

OBJECTIVE: To investigate the clinical characteristics, etiology, treatment outcomes, and prognostic factors of sudden sensorineural hearing loss (SSNHL) in children to guide the clinical diagnosis and treatment of SSNHL in the pediatric population. STUDY DESIGN: Retrospective case review. SETTING: Tertiary referral center. PATIENTS: Patients diagnosed with SSNHL from November 2011 to December 2017 with relatively complete clinical data. INTERVENTION: Diagnosis and systemic treatment of SSNHL. MAIN OUTCOME MEASURES: Patients' clinical characteristics, etiology, laboratory tests, imaging, pure-tone audiometry at admission, and discharge were analyzed. RESULTS: A total of 25 children and 149 adults with SSNHL were included. Recent or previous viral infection rates (81.8%) and fasting blood glucose level (5.23 + 1.47 mmol/L) in children with SSNHL were lower than those in adult SSNHL patients (p = 0.033, p = 0.033). Autoimmune abnormalities (90.0%) and plasma fibrinogen abnormalities (27.3%) were higher in children with SSNHL than those in adult SSNHL patients (40.0%, 8.8%, respectively, p < 0.05). The recovery rate in children (38.4%) with SSNHL is comparable to that in adults (22.6%), but children have a higher complete rate compared to adults (26.9%, 11.3%, respectively, p < 0.05). Children with a profound audiometric curve had a worse prognosis in comparison to other types of audiometric curves (p = 0.041). CONCLUSIONS: Children with SSNHL have a lower rate of viral infection in comparison to adults with SSNHL. Fasting blood glucose levels, complement C3, C4, and fibrinogen may be closely related to childhood SSNHL. The recovery rate in children with SSNHL is comparable to that in adults, but children have a higher complete rate compared to adults. A profound hearing curve is an unfavorable prognostic factor in both children and adults with SSNHL.

Three-Tesla magnetic resonance imaging of the vestibular endolymphatic space: A systematic qualitative description in healthy ears.

BACKGROUND AND PURPOSE: A detailed knowledge of the normal Magnetic Resonance (MR) anatomy of the vestibular endolymphatic space (ES) could be useful to understand the linkage between endolymphatic hydrops (EH) and Ménière's disease (MD). Our aim was to describe the MR anatomy of the vestibular ES as depicted by MR imaging in healthy ears. METHODS: This report describes a single-center retrospective study. Three readers analyzed the healthy ears of 22 consecutive patients who had undergone MRI for unilateral sudden hearing loss. The readers described the vestibular ES based on a delayed post-contrast 3D-FLAIR sequence according to six well-defined planes, three oblique sagittal (lateral, intermediate and medial) planes and three axial (superior, intermediate and inferior) planes. RESULTS: On sagittal lateral and intermediate planes, we identified the SSC ampulla combined with the utricle in 22/22 ears. On the sagittal medial plane, the saccule was detectable in 15/22 (68%) ears, having a club shape with the long axis oriented cranio-caudally; in 7/22 (32%) ears, the saccule presented an oval/round shape that appeared more conspicuously on the axial intermediate plane. The ES occupied the half superior portion of the vestibule in 22/22 ears, never contacting the round and oval windows. On the axial plane, in 17/22 cases, the ES showed a Y-shaped arrangement, while in 5/22 ears (23%), the ES presented a more globular shape. CONCLUSION: MR imaging represents a valid tool to explore the in vivo anatomy of the vestibular ES and to highlight its variability in normal ears.

Rate of Spiral Ganglion Cell Loss in Idiopathic Sudden Sensorineural Hearing Loss.

OBJECTIVE: To calculate the spiral ganglion neural decay rate among patients diagnosed with idiopathic sudden sensorineural hearing loss (ISSNHL). STUDY DESIGN: Retrospective. SETTING: Temporal bone histopathology bank. PATIENTS: Subjects diagnosed during life with unrecovered unilateral ISSNHL. INTERVENTION(S): Spiral ganglion cell count in the bilateral reconstructed Rosenthal canal. MAIN OUTCOME MEASURE(S): Decay rate of spiral ganglion cells. RESULTS: Nine patients were enrolled. The average age of ISSNHL diagnosis and death was 52 and 63 years, respectively. The total and segmental SGCC decay shows a temporal dependency. The time lag between the ISSNHL event and death was linearly proportional to the SGCC decay. Subjects who died less than 5 years from diagnosis of ISSNHL had no more than 13% loss of their total SGCC, and no more than 14% of SGCC per Rosenthal canal segment. When a longer period passed from ISSNHL diagnosis to death (19-20 yr), a loss of 16% and 13 to 18% of total and segmental SGCC occurred, respectively. CONCLUSIONS: SGCC decline from ISSNHL diagnosis through life.