A mouse model of autoimmune inner ear disease without endolymphatic hydrops.

Autoimmune inner ear disease (AIED) is an organ-specific disease characterized by irreversible, prolonged, and progressive hearing and equilibrium dysfunctions. The primary symptoms of AIED include asymmetric sensorineural hearing loss accompanied by vertigo, aural fullness, and tinnitus. AIED is divided into primary and secondary types. Research has been conducted using animal models of rheumatoid arthritis (RA), a cause of secondary AIED. However, current models are insufficient to accurately analyze vestibular function, and the mechanism underlying the onset of AIED has not yet been fully elucidated. Elucidation of the mechanism of AIED onset is urgently needed to develop effective treatments. In the present study, we analyzed the pathogenesis of vertigo in autoimmune diseases using a mouse model of type II collagen-induced RA. Auditory brain stem response analysis demonstrated that the RA mouse models exhibited hearing loss, which is the primary symptom of AIED. In addition, our vestibulo-oculomotor reflex analysis, which is an excellent vestibular function test, accurately captured vertigo symptoms in the RA mouse models. Moreover, our results revealed that the cause of hearing loss and vestibular dysfunction was not endolymphatic hydrops, but rather structural destruction of the organ of Corti and the lateral semicircular canal ampulla due to an autoimmune reaction against type II collagen. Overall, we were able to establish a mouse model of AIED without endolymphatic hydrops. Our findings will help elucidate the mechanisms of hearing loss and vertigo associated with AIED and facilitate the development of new therapeutic methods.

Scuba Diving-Induced Inner-Ear Pathology: Imaging Findings of Superior Semicircular Canal and Tegmen Tympani Dehiscence.

BACKGROUND Superior semicircular canal dehiscence is an inner-ear pathology which presents with vertigo, disequilibrium, and hearing loss. Although the exact etiology of superior semicircular canal dehiscence is unknown, it is thought that an increase in middle-ear pressure disrupts a thin overlying temporal bone. Superior semicircular canal dehiscence is frequently seen in association with dehiscence of the tegmen tympani, which overlies the middle ear. Here, we present a case report of a 52-year-old Puerto Rican man with vertigo, dizziness, vomiting, and mild hearing loss associated with superior semicircular canal and tegmen tympani dehiscence after performing improper scuba diving techniques. CASE REPORT A 52-year-old Puerto Rican man presented to the emergency department with vertigo, dizziness, vomiting, and mild hearing loss in the right ear. The symptoms began shortly after scuba diving with inadequate decompression techniques on ascent. He was treated with recompression therapy with mild but incomplete improvement in symptoms. Bilateral temporal magnetic resonance imaging was suggestive of segmental dehiscence of the right superior semicircular canal and tegmen tympani. High-resolution computed tomography of the temporal bone confirmed right superior semicircular canal and tegmen tympani dehiscence with an intact left inner ear. CONCLUSIONS The increased inner-ear pressure that occurs during scuba diving can lead to dehiscence of the superior semicircular canal and tegmen tympani, causing vertigo and hearing loss. Performance of improper diving techniques can further increase the risk of dehiscence. Therefore, appropriate radiologic evaluation of the inner ear should be performed in such patients.

Periodic vertigo and downbeat nystagmus while supine: Dysfunction of Purkinje cells coding gravity.

Cerebellar nodulus and uvula and their connections with the vestibular nuclei form the so-called velocity-storage circuit. Lesions involving the velocity-storage circuit give rise to positional vertigo and nystagmus. Herein, we present a 32-year-old man with cerebellar nodulus and uvular hemorrhage who showed periodic vertigo and downbeat nystagmus in the supine position. To explain this unusual pattern, we adopted velocity-storage model with a lesion on the neural connection between the gravity and inertia estimators, resulting in periodic neural impulses and a gravity bias in a specific position. This report expands the spectrum of central positional nystagmus due to dysfunction of the velocity-storage mechanism.

[A man in his fifties with near-syncope episodes and persistent dizziness]. / En mann i 50-årene med nærbesvimelser og vedvarende svimmelhet.

BACKGROUND: A previously healthy male patient in his fifties presented with subacute onset of severe, diffuse dysautonomia with orthostatic hypotension as the main symptom. A lengthy interdisciplinary workup revealed a rare condition. CASE PRESENTATION: Over the course of a year, the patient was twice admitted to the local department of internal medicine because of severe hypotension. Testing showed severe orthostatic hypotension with normal cardiac function tests and no apparent underlying cause. On referral to neurological examination, symptoms of a broader autonomic dysfunction were discovered, with symptoms of xerostomia, irregular bowel habits, anhidrosis and erectile dysfunction. The neurological examination was normal, except for bilateral mydriatic pupils. The patient was tested for ganglionic acetylcholine receptor (gAChR) antibodies. A strong positive result confirmed the diagnosis of autoimmune autonomic ganglionopathy. There were no signs of underlying malignancy. The patient received induction treatment with intravenous immunoglobulin and later maintenance treatment with rituximab, resulting in significant clinical improvement. INTERPRETATION: Autoimmune autonomic ganglionopathy is a rare but likely underdiagnosed condition, which may cause limited or widespread autonomic failure. Approximately half of the patients have ganglionic acetylcholine receptor antibodies in serum. It is important to diagnose the condition as it can cause high morbidity and mortality, but responds to immunotherapy.

[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.

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.

The Value of Subjective Visual Vertical in Diagnosis of Vestibular Migraine.

OBJECTIVE: To study the value of the subjective visual vertical (SVV) in the diagnosis of vestibular migraine (VM). METHODS: This study recruited 128 VM patients and 64 age-matched normal subjects. We detected the SVV during the interval between attacks in both groups, in sitting upright, and the head tilted at 45° to the left or right. We then examined the correlation between the SVV results with the vestibular evoked myogenic potential (VEMP) and canal paresis (CP). RESULTS: It was found there was a significant difference in SVV at the upright position between VM patients and normal controls (P=0.006) and no significant difference was found at the tilts of 45° to the left or right between the two groups. The SVV results at the upright position were significantly correlated with cervical VEMP (P=0.042) whereas not significantly correlated with CP and VEMP. There existed no significant difference in the conformity to the Müller effect (M effect) between the two groups. ROC analysis exhibited that the sensitivity, specificity of SVVs at the upright were 67.200% and 62.500% respectively. The diagnostic value of SVV at the upright position was significantly higher than that at tilts of 45° to the left and right (P=0.006). Nonetheless the diagnostic accuracy was relatively low. CONCLUSION: Abnormality in SVV possibly stems from the lasting functional disorder of cerebellar or high-level cortical centers in VM patients or is linked to the vestibular compensation. The SVV is of low diagnostic value for VM and the value of SVV in VM warrants further study.

Vertigo: Streamlining the Evaluation through Symptom Localization.

Vertigo is defined as the illusion of internal or external motion. The evaluation of a patient with vertigo in the primary care setting should not necessarily focus on providing a specific diagnosis. Rather, the physician should aim to localize the lesion. This practice streamlines the workup of patients. This article provides detailed information regarding appropriate organ system-based clinical history and the clinical workup of vertigo. Additional signs and symptoms that can facilitate appropriate referral and treatment are highlighted. Although disorder-specific treatments exist the mainstay of therapy for vertigo-induced pathology is physical therapy.

Long-term efficacy of triple semicircular canal plugging in the treatment of patients with ipsilateral delayed endolymphatic hydrops.

This study aims to explore the long-term efficacy of triple semicircular canal plugging (TSCP) in the treatment of intractable ipsilateral delayed endolymphatic hydrops (DEH), so as to provide an alternative therapy for this disease. Forty-eight patients diagnosed with ipsilateral DEH referred to vertigo clinic of our hospital between Dec. 2010 and Dec. 2017, were included in this study for retrospective analysis. All patients were followed up for 2 years. Vertigo control and auditory functions were measured and analyzed. Pure tone audiometry, caloric test, and vestibular evoked myogenic potential (VEMP) were performed in two-year follow-up. Forty-five patients who accepted intratympanic gentamicin (26.7 mg/mL) twice given one week apart were selected as a control group. The total control rate of vertigo in TSCP group was 97.9% (47/48) in the two-year follow-up, with complete control rate of 83.3% (40/48) and substantial control rate of 14.6% (7/48). The rate of hearing loss was 22.9% (11/48). The total control rate of vertigo in intratympanic gentamicin group was 80.0% (36/45), with complete control rate of 57.8% (26/45) and substantial control rate of 22.2% (10/45), and the rate of hearing loss was 20.0% (9/45). The vertigo control rate of TSCP was significantly higher than that of intratympanic gentamicin (χ2 = 6.01, p < 0.05). There was no significant difference of hearing loss rate between two groups. (χ2 = 0.12, p > 0.05). TSCP, which can reduce vertiginous symptoms in patients with intractable ipsilateral DEH, represents an effective therapy for this disorder.

Global multisensory reorganization after vestibular brain stem stroke.

OBJECTIVE: Patients with acute central vestibular syndrome suffer from vertigo, spontaneous nystagmus, postural instability with lateral falls, and tilts of visual vertical. Usually, these symptoms compensate within months. The mechanisms of compensation in vestibular infarcts are yet unclear. This study focused on structural changes in gray and white matter volume that accompany clinical compensation. METHODS: We studied patients with acute unilateral brain stem infarcts prospectively over 6 months. Structural changes were compared between the acute phase and follow-up with a group of healthy controls using voxel-based morphometry. RESULTS: Restitution of vestibular function following brain stem infarcts was accompanied by downstream structural changes in multisensory cortical areas. The changes depended on the location of the infarct along the vestibular pathways in patients with pathological tilts of the SVV and on the quality of the vestibular percept (rotatory vs graviceptive) in patients with pontomedullary infarcts. Patients with pontomedullary infarcts with vertigo or spontaneous nystagmus showed volumetric increases in vestibular parietal opercular multisensory and (retro-) insular areas with right-sided preference. Compensation of graviceptive deficits was accompanied by adaptive changes in multiple multisensory vestibular areas in both hemispheres in lower brain stem infarcts and by additional changes in the motor system in upper brain stem infarcts. INTERPRETATION: This study demonstrates multisensory neuroplasticity in both hemispheres along with the clinical compensation of vestibular deficits following unilateral brain stem infarcts. The data further solidify the concept of a right-hemispheric specialization for core vestibular processing. The identification of cortical structures involved in central compensation could serve as a platform to launch novel rehabilitative treatments such as transcranial stimulations.

MicroRNA-219a-5p-mediated inhibition of CaMKIIγ facilitates vestibular compensation in acute vertigo by promoting protein kinase C expression.

Vestibular compensation (VC) refers to a behavioral recovery process in which firing rates of bilateral vestibular nuclei neurons are rebalanced. Our study aimed to investigate the underlying mechanism by which miR-219a-5p regulates Ca2+ /calmodulin-dependent protein kinase II γ isoform (CaMKIIγ) and protein kinase C (PKC) in VC. A unilateral vestibular deafferentation rat model was established by unilateral labyrinthectomy (UL), after which VC was evaluated in rats with UL-induced vertigo-like behavior by measuring vestibular defect behavior and performing rotarod tests, as well as by BrdU immunohistochemistry on medial vestibular nuclei. We found that miR-219a-5p was increased while CaMKIIγ was decreased during VC in the medial vestibular nucleus of rats that had undergone UL. Next, gain- and loss-of-function assays were conducted to evaluate the effects of miR-219a-5p and CaMKIIγ on the vestibular defect behaviors and VC, the results of which suggested that in rats after UL overexpression of CaMKIIγ inhibited VC, while overexpression of miR-219a-5p facilitated VC. A dual-luciferase reporter gene assay identified that miR-219a-5p targeted CaMKIIγ. This led to additional experiments showing that miR-219a-5p aptomir expression downregulated CaMKIIγ in cortical cells with a concomitant increase in PKC expression, which were verified further in vivo. In summary, in rats with acute vertigo, miR-219a-5p overexpression inhibits CaMKIIγ and elevates PKC, thereby facilitating VC. Our study offers possible targets for further evaluation as treatment of acute vertigo in humans.

Prevalence and Risk Factors of White Matter Lesions in Tibetan Patients Without Acute Stroke.

Background and Purpose- Studies on the prevalence and risk factors of white matter lesions (WMLs) in Tibetans living at high altitudes are scarce. We conducted this study to determine the prevalence and risks of WMLs in Tibetan patients without or with nonacute stroke. Methods- We undertook a retrospective analysis of medical records of patients treated at the People's Hospital of Tibetan Autonomous Region and identified a total of 301 Tibetan patients without acute stroke. WML severity was graded by the Fazekas Scale. We assessed the overall and age-specific prevalence of WMLs and analyzed associations between WMLs and related factors with univariate and multivariate methods. Results- Of the 301 patients, 87 (28.9%) had peripheral vertigo, 83 (27.3%) had primary headache, 52 (17.3%) had a history of stroke, 36 (12.0%) had an anxiety disorder, 29 (9.6%) had epilepsy, 12 (4.0%) had infections of the central nervous system, and 3 (1.0%) had undetermined diseases. WMLs were present in 245 (81.4%) patients, and 54 (17.9%) were younger than 40 years. Univariate analysis showed that age, history of cerebral infarction, hypertension, the thickness of the common carotid artery intima, and plaque within the intracarotid artery were related risks for WMLs. Ordered logistic analysis showed that age, history of cerebral ischemic stroke, hypertension, male sex, and atrial fibrillation were associated with WML severity. Conclusions- Risk factors for WMLs appear similar for Tibetans residing at high altitudes and individuals living in the plains. Further investigations are needed to determine whether Tibetans residing at high altitudes have a higher burden of WMLs than inhabitants of the plains.

Dissecting basilar artery aneurysm manifesting as sudden sensorineural hearing loss: a case report and literature review.

Highlights • Dissecting basilar artery aneurysm (DBAA) is relatively rare. • We report the first case of a DBAA manifesting as sudden sensorineural hearing loss. • This case report adds to the symptom spectrum of DBAA.

Neurovascular compression syndrome of the brain stem with opsoclonus-myoclonus syndrome combined with vestibular paroxysmia and autonomic symptoms.

We describe a rare case of neurovascular compression syndrome (NVCS) of the brain stem and opsoclonus-myoclonus syndrome (OMS) complicated with vestibular paroxysmia (VP) and autonomic symptoms. Moreover, we discuss the case with respect to the available information in medical literature. A 36-year-old man with vertigo and nausea had difficulty standing, and was transported by an ambulance to our hospital. He had VP, opsoclonus, cervical myoclonus, anxiety, and restless legs syndrome. Magnetic resonance imaging at hospitalization showed that the dolichoectatic vertebral artery was in contact with the postero-lateral side of the pontomedullary junction. He was diagnosed with NVCS of the brain stem (most likely of the input to the vestibular nucleus) associated with contact with the dolichoectatic vertebral artery. Combination therapy using multiple antiepileptic drugs, such as low-dose carbamazepine, clonazepam, and lacosamide, improved his clinical symptoms. He was finally able to walk and was discharged on day 42 after admission. He is being routinely followed-up since then. Further research is needed to confirm the validity of the combination therapy.

Grey matter changes in patients with vestibular migraine.

AIM: To identify structural changes in the brain regions of patients with vestibular migraine (VM) so as to better understand its pathophysiology. MATERIAL AND METHODS: The differences in grey matter (GM) in patients with VM, patients with migraine without aura (MWoA), and healthy controls (HC) were investigated. Using a GE Signa 3 T magnetic resonance imaging (MRI) system, 3D structural images were acquired from 18 VM, 21 MWoA, and 21 age-, gender-, and education level-matched HC using a T1-weighted magnetization-prepared rapid acquisition gradient-echo (MPRAGE) sequence. The volumetric abnormalities of GM were estimated by voxel-based morphometry. Analysis of variance and Bonferroni multiple comparisons were applied. RESULTS: Compared with HC, patients with VM had significantly increased GM volume of the right medial superior frontal gyrus (p=0.008) and the right angular gyrus (p=0.009). Compared to patients with MWoA, patients with VM also had significantly increased volume of the right medial superior frontal gyrus (p=0.001), the right angular gyrus (p=0.008), and the left middle frontal gyrus (p=0.001). CONCLUSIONS: The GM volume of some brain regions of patients with VM is significantly larger than the other two groups. The increased GM volume in these brain regions in patients with VM may be related to self-adaptation of the nervous system, leading to an abnormal brain sensitization. Some of the brain regions with increased GM volume identified in this study were involved in assessment, integration, and expectations of pain and were strongly related to mood and anxiety.

Central positional vertigo: A clinical-imaging study.

The diagnosis of central positional vertigo (CPV) is challenging, mainly because symptoms overlap with the common variants of benign paroxysmal positional vertigo (BPPV). Recent correlations of imaging with neurotologic exams have improved our understanding of CPV and ability differentiate it from BPPV. Yet, there is still a need to develop better diagnostic algorithms to improve timely diagnosis and early intervention. Here we present a retrospective review of the clinical characteristics, neurotologic evaluation and imaging of CPV in a cohort of 27 patients and propose a diagnostic algorithm to be tested in future prospective fashion. Most patients had positional nystagmus (downbeat and apogeotropic horizontal), cerebellar ocular motor abnormalities and truncal ataxia indicative of a central lesion. 61.5% of our cohort had paroxysmal CPV, 30.5% had a non-paroxysmal CPV and 8% paroxysmal-evolving-to-non-paroxysmal CPV. The most common pattern of positional nystagmus evoked with maneuvers was positional downbeat nystagmus (pDBN, 69.2%), apogeotropic horizontal nystagmus (42.3%), geotropic (7.69%) and multiplanar (23.0%). Notably, 13 (50%) of patients had cerebral imaging prior to CPV being on the differential diagnosis, whereas another 50% of patients had CPV diagnosis preceding their work-up. Unilateral lesions on imaging were 4× less likely to exhibit nausea and vomiting, nearly 2× less likely to exhibit paroxysmal nystagmus, and 2× less likely to exhibit nystagmus with habituality. Findings of pDBN or apogeotropic nystagmus alone were enough to diagnose CPV in 50% of our patient cohort, underscoring the importance of clinical evaluation in a time when an "imaging-first" philosophy is gaining popularity in Neurology.

Proteome of normal human perilymph and perilymph from people with disabling vertigo.

The vast majority of hearing loss, the most common sensory impairment, and vertigo, which commonly causes falls, both reflect underlying dysfunction of inner ear cells. Perilymph sampling can thus provide molecular cues to hearing and balance disorders. While such "liquid biopsy" of the inner ear is not yet in routine clinical practice, previous studies have uncovered alterations in perilymph in patients with certain types of hearing loss. However, the proteome of perilymph from patients with intact hearing has been unknown. Furthermore, no complete characterization of perilymph from patients with vestibular dysfunction has been reported. Here, using liquid-chromatography with tandem mass spectrometry, we analyzed samples of normal perilymph collected from three patients with skull base meningiomas and intact hearing. We identified 228 proteins that were common across the samples, establishing a greatly expanded proteome of the previously inferred normal human perilymph. Further comparison to perilymph obtained from three patients with vestibular dysfunction with drop attacks due to Meniere's disease showed 38 proteins with significantly differential abundance. The abundance of four protein candidates with previously unknown roles in inner ear biology was validated in murine cochleae by immunohistochemistry and in situ hybridization: AACT, HGFAC, EFEMP1, and TGFBI. Together, these results motivate future work in characterizing the normal human perilymph and identifying biomarkers of inner ear disease.