Perilymphatic fistula with characteristic findings of the inner ear by contrast-enhanced magnetic resonance imaging: a case report.

A perilymphatic fistula (PLF) presents with abnormal traffic in the otic capsule, causing cochlear and vestibular symptoms. However, the mechanisms underlying symptom recurrence remain controversial. Herein, we report the case of a 27-year-old female who complained of hearing disturbance in her right ear and recurrent vertigo after sudden onset of hearing loss with vertigo. The caloric test revealed unilateral weakness in the right ear, and the video head impulse test (vHIT) showed decreased vestibulo-ocular reflex (VOR) gain. Contrast-enhanced magnetic resonance imaging (MRI) using hybrid of reversed image of positive endolymph signal and negative image of perilymph signal (HYDROPS) indicated a collapsed endolymphatic space. As the vestibular symptoms did not improve, an exploratory tympanotomy was performed on the right ear. Although perilymph leakage was not noted in the oval or round windows, both windows were sealed with connective tissue. The patient's vestibular symptoms rapidly improved after surgery, and postoperative contrast-enhanced MRI showed improvement in the collapsed endolymphatic space. Although the caloric test revealed unilateral weakness, the VOR gain on the vHIT improved to normal on the right side. Thus, these findings indicated that recurrent symptoms caused by PLF are associated with a collapsed endolymphatic space. We speculate that the collapsed endolymphatic space was due to a ruptured Reissner's membrane. We hypothesized that sealing the fistula would promote normalization of perilymph pressure. The ruptured Reissner's membrane may have been gradually repaired as vestibular symptoms improved. This case adds to the existing literature on the occurrence of the "double-membrane break syndrome". Collapse of the endolymph due to a ruptured Reissner's membrane may be the cause of PLF symptoms.

Case report: Perilymphatic fistula from a round window microfissure.

A microfissure near the round window niche is an anatomical structure that communicates between middle ear and the ampulla of the posterior semicircular canal. It has been suggested that the microfissure can cause inner ear symptoms; however, the etiology has not yet been confirmed clinically. We report, to our knowledge, the first case of microfissure with complaint of hearing loss and vertigo and improvement in hearing after surgical sealing of the microfissure. A 50-year-old man complained of hearing disturbance, tinnitus with flowing-water sound in the left ear, and a floating sensation upon pushing the left tragus. He had moderate sensorineural hearing loss (43.3 dB) in the left ear for 3 days. His hearing worsened and he complained of severe vertigo. An exploratory tympanotomy was performed 8 days after onset. A microfissure and accumulation of clear fluid in the floor of the round window niche were detected, and leakage point was packed with connective tissue. One month after surgery, his hearing (20.0 dB) and disequilibrium had improved. The inner ear symptoms improved after the surgery in this case, suggesting that the microfissure might have caused the symptoms.

Endolymphatic hydrops presumption tests for patients with vestibular migraine.

BACKGROUND: The aetiology of vestibular migraine (VM) has not yet been defined; endolymphatic hydrops (EH) has been suggested as a candidate. OBJECTIVES: This study aimed to clarify the relationship between VM and EH using neuro-otological tests, including the EH presumption test. MATERIALS AND METHODS: Fourteen patients with VM underwent caloric testing, video head impulse test (vHIT), cervical and ocular vestibular evoked myogenic potential (cVEMP and oVEMP), and EH presumption tests such as the Futaki's test and furosemide loading VEMP. RESULTS: Caloric testing was abnormal in two of the 14 cases (14.3%), and vHIT was abnormal in one of 12 cases (8.3%). Abnormal asymmetry ratios (ARs) of cVEMP and oVEMP were observed in two of 14 cases (14.3%) and six of 13 cases (46.2%), respectively. Futaki's test results were positive in five of 14 cases (35.7%). Furosemide loading VEMP was positive in seven of 14 cases (50.0%). Nine patients (64.3%) were positive for at least one EH presumption test. CONCLUSIONS AND SIGNIFICANCE: EH is not a rare finding in VM; however, the ratio is less than that in Meniere's disease.

Diagnostic and therapeutic strategies for Meniere's disease of the Japan Society for Equilibrium Research.

OBJECTIVE: We provided diagnostic and therapeutic strategies for Meniere's disease in accordance with Japanese Clinical Practice Guideline of Meniere's disease and delayed endolymphatic hydrops 2nd ed. Tokyo: Kanehara Shuppan; 2020 edited by the Japan Society for Equilibrium Research. METHODS: The Committee for Clinical Practice Guidelines was entrusted with a review of the scientific literature on the above topic. Clinical Questions (CQs) concerning the treatment for Meniere's disease were produced, and the literature according to each of them including CQ was searched. The recommendations are based on the literature review and the expert opinion of a subcommittee. RESULTS: Diagnosis criteria of Meniere's disease are classified into Meniere's disease with typical cochlear and vestibular symptoms, and atypical Meniere's disease with either cochlear symptoms or vestibular symptoms. Treatment of Meniere's disease was composed of lifestyle changes, medications such as anti-vertigo drugs and diuretics, middle ear positive pressure treatment, and selective destruction of the vestibule. CONCLUSION: Meniere's disease is diagnosed based on clinical histories and examination findings after processes of differential diagnosis. Treatment option of the disease should be selected in order of invasiveness, according to the severity of the disease and the response to each treatment.

Prevalence of potential candidates for electric-acoustic stimulation implant in a hearing-impaired population.

OBJECTIVE: To estimate the prevalence of potential electric-acoustic stimulation (EAS) implant candidates in a hearing-impaired population through a review of auditory examinations. METHODS: In total, 7356 patients underwent audiometric examination in our department between 2011 and 2014. The prevalence of patients meeting the audiometric criteria for EAS and standard cochlear implant (CI) was assessed. RESULTS: The percentage of EAS implant candidates meeting the pure-tone audiometric criteria was 0.71% (n=34) among the hearing-impaired individuals (n=4758) examined in our department, whereas 2.52% (n=120) met the criteria for standard CI. Among the 34 EAS implant candidates, 2 individuals (5.83%) received EAS implant surgery after approval of the EAS device in Japan. CONCLUSIONS: There was a lower prevalence of EAS implant candidates than standard CI candidates. Nevertheless, healthcare professionals should carefully examine the audiograms of patients with high frequency hearing loss with regard to meeting the indication criteria for EAS implant. This will enable patients to gain access to adequate information relating to further examinations and treatment options.

Primary Liposarcoma with Cholesteatoma in Mastoid.

Liposarcoma is a soft tissue neoplasm that commonly develops in the lower extremities and rarely in the head and neck region. Herein, we report the case of a patient with primary liposarcoma that was detected in the mastoid antrum during staged tympanoplasty for cholesteatoma. The tumor adjacent to the attic cholesteatoma was resected completely, and the pathological diagnosis was that of myxoid-type liposarcoma. Because positron emission tomography after the surgery showed no signs of tumor remnants or systemic metastasis, a second-stage surgery was performed 8 months after the first surgery. After confirming that there was no recurrence, tympanoplasty type III with interposition between the stapes and malleus and canal reconstruction was performed. No recurrence was observed for 5 years, and to date, good hearing has been maintained. This is the first report on long-term follow-up of a patient with liposarcoma in the mastoid antrum.

Vestibule-Middle Ear Dehiscence Tested With Perilymph-Specific Protein Cochlin-Tomoprotein (CTP) Detection Test.

An 8-year-old boy was referred to the ENT department for further evaluation of right-sided conductive hearing loss. A small cyst anterior to the oval window and fixation of the stapes footplate were observed during an exploratory tympanotomy. The concentration of a perilymph-specific protein, cochlin-tomoprotein (CTP), in the middle ear lavage fluid was measured with an ELISA-based CTP detection kit. The level of CTP in the middle ear lavage fluid before fenestration of the cyst was 0.26 ng/ml (negative), and its level after fenestration was 2.98 ng/ml (positive), confirming the presence of perilymph in the cyst. A small bone dehiscence, considered to be the fissula ante fenestram, was observed anterior to the stapes footplate after removal of the cyst. The CTP detection test results allowed us to confirm that the small bone dehiscence was connected to the inner ear.

The prevalence of vestibular schwannoma among patients treated as sudden sensorineural hearing loss.

OBJECTIVE: To assess the prevalence of vestibular schwannoma (VS) in patients with sudden sensorineural hearing loss (SSNHL). METHODS: This is a retrospective chart review of 861 patients who were diagnosed with or treated for SSHNL between January 2008 and February 2017 at our department in a tertiary academic center. We retrospectively analyzed the medical charts and MRI findings of 499 patients who had undergone MRI. RESULTS: Fifteen (3.0%) of the 499 patients exhibited tumors at the cerebellopontine angle on the same side affected by SSNHL. In one patient, a tumor was incidentally detected in the contralateral ear. The 15 VS lesions were graded using the Koos acoustic neuroma grading system as follows: grade I (intracanalicular tumor), n=8; grade II (up to 2cm), n=6; and grade III (up to 3cm), n=1. Koos grade IV tumors, which are large tumors that displace the trunk or cranial nerves, were not found. CONCLUSION: The prevalence of VS in patients with SSNHL was 3.0% in the present study. Considering this high prevalence, clinicians should consider detailed examinations in addition to audiometry for patients with SSNHL.

Recent and Frequent Vertigo Attacks Produce Negative Findings on Furosemide-Loading Vestibular Evoked Myogenic Potential Testing in Meniere's Disease.

Objective: The peak-to-peak amplitude of the p13-n23 wave in cervical vestibular evoked myogenic potential can increase after furosemide administration in patients with Meniere's disease [furosemide-loading VEMP (FVEMP) testing]. The examination is used to test for the presence of endolymphatic hydrops; we investigated factors that may influence the results. Methods: Forty-two subjects (23 males and 19 females, aged 24-70 years) with unilateral definite Meniere's disease who underwent FVEMP testing were retrospectively studied. Possible factors associated with the results of FVEMP testing were studied using logistic regression analysis. Results: Ages, sex, affected side, stage, disease duration, and mean hearing level of pure tone audiometry did not influence the results of FVEMP testing in the univariate analysis (p > 0.05). Number of days since the last vertigo attack [odds ratio (OR): 1.07, p = 0.031] and frequency of vertigo attacks per month (OR: 0.42, p = 0.003) were significantly associated with the results of testing. Multivariate analysis showed that both days since the last vertigo attack < 7 (OR: 0.13, p = 0.04) and frequency of vertigo attacks per month ≥ 2 (OR: 0.06, p = 0.004) were risk factors for negative results on FVEMP testing. Conclusion: This study found that recent and frequent vertigo attacks produced negative findings on FVEMP testing in Meniere's disease. This apparently irrational finding can be explained by the consequences of membranous labyrinth rupture during vertigo attacks, where the altered saccular resonance due to EH cannot be recovered by furosemide administration because of the dissolving dehydration effect that occurs through communication between the endolymphatic and perilymphatic spaces. In addition, the impairment of sensory cells that is caused by endolymph and perilymph mixing upon rupture does not improve upon furosemide administration. FVEMP testing results may provide us with pathophysiological information regarding the membranous labyrinth.

Residual dizziness after successful treatment of idiopathic benign paroxysmal positional vertigo originates from persistent utricular dysfunction.

OBJECTIVE: We used ocular vestibular evoked myogenic potentials to investigate the relationship between residual dizziness and utricular function following the canalith repositioning procedure for benign paroxysmal positional vertigo. METHODS: Ocular vestibular evoked myogenic potentials were measured in 44 patients (40 included in analyses, four excluded) with successful results from the canalith repositioning procedure. The patients were examined before treatment and again one week after treatment. We analyzed how various general factors and ocular vestibular evoked myogenic potentials related to residual dizziness. RESULTS: Residual dizziness was not related to gender, affected side, age, duration of symptoms, recurrence, or the results of the initial ocular vestibular evoked myogenic potential test (p > .05). However, residual dizziness was significantly associated with the results of the second ocular vestibular evoked myogenic potential test (p = .007). CONCLUSIONS: Residual dizziness after a successful canalith repositioning procedure may be caused by persistent utricular dysfunction.

Revision of a furosemide-loading vestibular-evoked myogenic potential protocol for detecting endolymphatic hydrops.

OBJECTIVE: The presence of endolymphatic hydrops can be suggested by improving the amplitude of vestibular-evoked myogenic potential (VEMP) after furosemide administration (furosemide loading VEMP [FVEMP]). The authors aimed to determine a stimulation frequency and judgment criteria to ascertain whether a revised FVEMP protocol can be applied to clinical settings. METHODS: The study included 25 individuals with unilateral Meniere's disease (MD) and 11 normal healthy volunteers. Normalized amplitude of VEMP, using a tone burst sound at 250, 500, 700, 1000, 1500 and 2000 Hz, was measured before and after furosemide administration in the two groups. Improvement ratio (IR) of amplitude was calculated at each frequency. RESULTS: There were no significant differences in IR between the control group and the MD group at each frequency, except at 500 Hz. Receiver operating characteristic curve analysis revealed an IR cut-off value of 14.2% at 500 Hz, with a sensitivity of 0.706 and a specificity of 0.810. CONCLUSIONS: The revised FVEMP protocol using a 500 Hz tone burst stimulus and normalized amplitudes was defined as positive when IR exceeded 14.2% or when a biphasic wave could be detected after furosemide administration in cases without a detectable biphasic wave before administration.

Discovery of phenyl acetamides as potent and selective GPR119 agonists.

The paper describes the SAR/SPR studies that led to the discovery of phenoxy cyclopropyl phenyl acetamide derivatives as potent and selective GPR119 agonists. Based on a cis cyclopropane scaffold discovered previously, phenyl acetamides such as compound 17 were found to have excellent GPR119 potency and improved physicochemical properties. Pharmacokinetic data of compound 17 in rat, dog and rhesus will be described. Compound 17 was suitable for QD dosing based on its predicted human half-life, and its projected human dose was much lower than that of the recently reported structurally-related benzyloxy compound 2. Compound 17 was selected as a tool compound candidate for NHP (Non-Human Primate) efficacy studies.

Clinical course of persistent geotropic direction-changing positional nystagmus with neutral position-Light cupula.

CONCLUSION: A short clinical course and frequent recurrence are common features of persistent geotropic direction-changing positional nystagmus with neutral position (positional nystagmus of light cupula: PNLC) and cupulolithiasis of the lateral semicircular canal. It is suggested that PNLC is caused by light debris attached to the cupula of the lateral semicircular canal. OBJECTIVES: PNLC is a sub-type of direction-changing positional nystagmus. It is thought to be caused by anti-gravitational deviation of the cupula of the lateral semicircular canal (light cupula); however, the exact mechanism is yet to be elucidated. To this end, the clinical features of PNLC were studied. METHOD: Clinical charts of 27 patients (13 men and 14 women) with PNLC were reviewed. RESULTS: The nystagmus had resolved within a week in 70% and within 30 days in 89% of the patients. The recurrence rate was 33%. The subjects did not have a history of alcohol intake, head trauma, or vestibular neuritis.

Design of Potent and Orally Active GPR119 Agonists for the Treatment of Type II Diabetes.

We report herein the design and synthesis of a series of potent and selective GPR119 agonists. Our objective was to develop a GPR119 agonist with properties that were suitable for fixed-dose combination with a DPP4 inhibitor. Starting from a phenoxy analogue (1), medicinal chemistry efforts directed toward reducing half-life and increasing solubility led to the synthesis of a series of benzyloxy analogues. Compound 28 was chosen for further profiling because of its favorable physicochemical properties and excellent GPR119 potency across species. This compound exhibited a clean off-target profile in counterscreens and good in vivo efficacy in mouse oGTT.

Intractable persistent direction-changing geotropic nystagmus improved by lateral semicircular canal plugging.

Antigravitational deviation of the cupula of the lateral semicircular canal, which is also called light cupula, evokes persistent direction-changing geotropic nystagmus with a neutral point. No intractable cases of this condition have been reported. In our case, a 67-year-old man complained of positional vertigo 3 months after developing idiopathic sudden hearing loss in the right ear with vertigo. He showed a persistent direction-changing geotropic nystagmus with a leftward beating nystagmus in the supine position. The nystagmus resolved when his head was turned approximately 30° to the right. He was diagnosed with light cupula of the right lateral semicircular canal and was subsequently treated with an antivertiginous agent. However, his symptoms and positional nystagmus did not improve, so the right lateral semicircular canal was plugged by surgery. One month after surgery, his positional vertigo and nystagmus were completely resolved. We speculated that the cause of the patient's intractable light cupula was an enlarged cupula caused by his idiopathic sudden hearing loss.

LECT2 functions as a hepatokine that links obesity to skeletal muscle insulin resistance.

Recent articles have reported an association between fatty liver disease and systemic insulin resistance in humans, but the causal relationship remains unclear. The liver may contribute to muscle insulin resistance by releasing secretory proteins called hepatokines. Here we demonstrate that leukocyte cell-derived chemotaxin 2 (LECT2), an energy-sensing hepatokine, is a link between obesity and skeletal muscle insulin resistance. Circulating LECT2 positively correlated with the severity of both obesity and insulin resistance in humans. LECT2 expression was negatively regulated by starvation-sensing kinase adenosine monophosphate-activated protein kinase in H4IIEC hepatocytes. Genetic deletion of LECT2 in mice increased insulin sensitivity in the skeletal muscle. Treatment with recombinant LECT2 protein impaired insulin signaling via phosphorylation of Jun NH2-terminal kinase in C2C12 myocytes. These results demonstrate the involvement of LECT2 in glucose metabolism and suggest that LECT2 may be a therapeutic target for obesity-associated insulin resistance.

Is a pulling sensation in the anteroposterior direction associated with otolith dysfunction?

CONCLUSION: A pulling sensation in the anteroposterior direction is suggested to originate from a dysfunction of the otolith organs. OBJECTIVES: Previous study with vestibular evoked myogenic potential (VEMP) confirmed that a falling sensation (in an up or down direction) and a lateral tilt sensation (in a right or left direction) were caused by otolith lesions. The purpose of this study was to clarify whether a pulling sensation in the anteroposterior (forward or backward) direction originates from otolith dysfunction. METHODS: The otolith function was assessed by cervical and ocular VEMPs (cVEMPs and oVEMPs) in 12 patients who complained of a forward or backward pulling sensation. cVEMPs were evaluated by the asymmetry ratio (AR) of the amplitude of the p13-n23 wave and the peak latencies of the p13 and n23 waves. oVEMPs were evaluated by the AR of the amplitude of the n1-p1 wave and the peak latency of the n1 and p1 waves. RESULTS: Abnormal ARs on cVEMP were observed in 7 of 12 patients. Nine of 12 patients had abnormal oVEMP results including 3 bilateral absent responses. Most (10 of 12) patients had abnormal cVEMP and/or oVEMP results. The latency of each detected wave was within the normal ranges.

Detection of utricular dysfunction using ocular vestibular evoked myogenic potential in patients with benign paroxysmal positional vertigo.

BACKGROUND: The ocular vestibular evoked myogenic potential (oVEMP) is thought to originate from the contralateral utricular organ. However, the clinical use of oVEMP has not yet been established. This study aimed to clarify whether oVEMP could be used to detect utricular dysfunction in patients with benign paroxysmal positional vertigo (BPPV). MATERIALS AND METHODS: Sixteen patients with BPPV underwent oVEMP measurements. Recordings were made on 2 separate occasions: when typical nystagmus was confirmed (pretreatment oVEMP) and 1 week after performing Epley's maneuver (posttreatment oVEMP). Results were evaluated using the asymmetry ratio (AR) of n1-p1 wave peak-to-peak amplitude and defined as reduced oVEMP when AR was >31.6%, or augmented oVEMP when AR was <-31.6%. RESULTS: Bilateral responses were recorded in 13 patients on the pretreatment oVEMP. Abnormal results were found in 11 patients (84.5%). These included 5 patients with reduced response and 6 with augmented response. On the posttreatment oVEMP, abnormal results were found in 5 patients (38.5%). All indicated reduced oVEMP. Abnormal results on the pretreatment oVEMP were not related to any persistent positional vertigo (p>0.05, Fisher's exact test). Three out of 4 patients (75.0%) with continuing unsteadiness had abnormal results (reduced response) on the posttreatment oVEMP. DISCUSSION: The oVEMP measurements indicated abnormal function of the utricle in patients with BPPV. Reduced oVEMP is thought to originate from the partial degeneration of utricular hair cells. Conversely, augmented oVEMP in the affected ear is thought to originate from a hypermobility of the stereocilia due to the detachment of otoconia within the utricle. The above-mentioned utricular dysfunction should be independent of the existence of otoconia in the semicircular canal; thus, the results of oVEMP were not related to the recovery of symptoms. CONCLUSION: oVEMP can be reliably used to detect utricular lesions in patients with BPPV.