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Objective: In the present study, we examined the effects of high-dose betahistine on dizziness handicap inventory (DHI) scores in patients with unilateral vestibulopathy., Methods: An uncontrolled, open-label, multicenter clinical trial was conducted. Fifteen patients with unilateral vestibulopathy, such as vestibular neuritis, who complained of intractable dizziness for more than three months were enrolled. Initially, all patients were orally administered betahistine at a dose of 36 mg/day for four weeks, which is the standard dose and dosing period for the treatment of dizziness in Japan. The patients were then administered betahistine at a double dose of 72 mg/day for four weeks. Six patients who became aware of the benefits of high-dose betahistine were further administered betahistine at 72 mg/day for an additional 12 weeks (a total of 16 weeks). Perceived disability due to dizziness was assessed by DHI scores., Results: In all 15 patients, short-term administration with high-dose (72 mg/day) betahistine for four weeks, but not low-dose betahistine (36 mg/day) for four weeks significantly decreased DHI scores. In particular, in six responding patients with self-reported benefits after short-term administration with high-dose betahistine, long-term administration with high-dose betahistine for 16 weeks further significantly decreased DHI scores. However, DHI scores of the remaining nine non-responding patients were not changed after short-term administration with high-dose betahistine for four weeks., Conclusion: Short-term administration with the standard dose and dosing period of betahistine did not improve DHI scores in the enrolled patients, indicating that they were not compensated for unilateral vestibulopathy with intractable dizziness. The present findings suggest that long-term administration with high-dose betahistine facilitates vestibular compensation to improve intractable dizziness in some, but not all patients with uncompensated unilateral vestibulopathy., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest in this study., (Copyright © 2023. Published by Elsevier B.V.)

Objective: To provide diagnostic and therapeutic strategies for vestibular neuritis in accordance with the Japanese Clinical Practice Guidelines for Vestibular Neuritis 2021., Methods: The Committee for Clinical Practice Guidelines for Vestibular Neuritis was entrusted with a review of the relevant scientific literature on the above topic. Clinical Questions (CQs) concerning the treatment of vestibular neuritis were produced, and a search of the literature was conducted to identify studies related to the CQs. The recommendations were based on the literature review and the expert opinion of a subcommittee., Results: We proposed the diagnostic criteria for vestibular neuritis, as well as answers to CQs, recommendations, and evidence levels for the treatment of vestibular neuritis., Conclusion: The diagnostic criteria for vestibular neuritis were based on clinical history and examination findings after completing the differential diagnosis process. The treatment of vestibular neuritis was divided into acute, subacute, and chronic stages. The Japanese Clinical Practice Guidelines for Vestibular Neuritis 2021 should be used as a reference in the diagnosis and treatment of vestibular neuritis., Competing Interests: Declaration of Competing Interest None, (Copyright © 2022. Published by Elsevier B.V.)

Background: Delayed endolymphatic hydrops (DEH) is an inner ear disease that causes recurrent vertigo in the ipsilateral ear or fluctuating hearing in the contralateral ear due to endolymphatic hydrops secondary to preceding deafness. There are few reports of large, multicentre studies investigating the clinical-epidemiological characteristics of DEH., Objective: This study aimed to clarify the characteristics of DEH in Japan., Methods: Clinical data on 662 patients with DEH were analysed by nationwide, multicentre surveys conducted by the Peripheral Vestibular Disorders Research Group of Japan., Results: The proportion of ipsilateral DEH (IDEH) was slightly higher than that of contralateral DEH (CDEH) at 55.4%. The time delay between onset of precedent deafness and onset of DEH was significantly longer for CDEH than for IDEH. The most common cause of precedent deafness was a disease of unknown cause with onset in early childhood (33.1%). Epidemiological characteristics were not significantly different between CDEH with and without vertigo., Conclusion: DEH appearing to be caused by viral labyrinthitis has a high rate of onset within 40 years of precedent deafness. Clinical and epidemiological characteristics of IDEH, CDEH with vertigo, and CDEH without vertigo were very similar., Significance: The clinical-epidemiological characteristics of DEH in Japan were clarified.

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.

Objective: To develop a diagnostic algorithm for chronic vestibular syndromes by determining significant items that differ among diagnoses. Methods: Two hundred thirty-one patients with chronic vestibular syndromes lasting for >3 months were included. Full vestibular tests and questionnaire surveys were performed: bithermal caloric test, cervical and ocular vestibular-evoked myogenic potential assessment, video head impulse test (vHIT), posturography, rotatory chair test, dizziness handicap inventory, hospital anxiety and depression scale (HADS), and Niigata persistent postural-perceptual dizziness (PPPD) questionnaire (NPQ). Differences in each item of the vestibular tests/questionnaires/demographic data were tested among the diagnoses. A receiver operating characteristic (ROC) curve was created for the significant items. The value that provided the best combination of sensitivity/specificity on the ROC curve was adopted as a threshold for diagnosing the targeted disease. Multiple diagnostic algorithms were proposed, and their diagnostic accuracy was calculated. Results: There were 92 patients with PPPD, 44 with chronic dizziness due to anxiety (CDA), 31 with unilateral vestibular hypofunction (UVH), 37 with undifferentiated dizziness (UD), and 27 with other conditions. The top four diagnoses accounted for 88% of all chronic vestibular syndromes. Five significant items that differed among the four diseases were identified. The visual stimulation and total NPQ scores were significantly higher in the patients with PPPD than in those with UVH and UD. The percentage of canal paresis (CP %) was significantly higher in the patients with UVH than in those with PPPD, CDA, and UD. The patients with CDA were significantly younger and had higher anxiety scores on the HADS (HADS-A) than those with UVH and UD. Moreover, catch-up saccades (CUSs) in the vHIT were more frequently seen in the patients with UVH than in those with PPPD. The most useful algorithm that tested the total and visual stimulation NPQ scores for PPPD followed by the CP%/CUSs for UVH and HADS-A score/age for CDA showed an overall diagnostic accuracy of 72.8%. Conclusions: Among the full vestibular tests and questionnaires, the items useful for differentiating chronic vestibular syndromes were identified. We proposed a diagnostic algorithm for chronic vestibular syndromes composed of these items, which could be useful in clinical settings., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Kitazawa, Morita, Yagi, Takahashi, Ohshima, Yamagishi, Izumi, Koizuka and Horii.)

Objective: To investigate the effect of systemic administration of salicylate as a tinnitus inducing drug in the auditory cortex of guinea pigs., Methods: Extracellular recording of spikes of the primary auditory cortex and dorsocaudal areas in healthy male albino Hartley guinea pigs was continuously performed (pre- and post-salicylate)., Results: We recorded 160 single units in the primary auditory cortex from five guinea pigs and 156 single units in the dorsocaudal area from another five guinea pigs. The threshold was significantly elevated after the administration of salicylate in both the primary auditory cortex and dorsocaudal areas. The Q10dB value was significantly increased in the primary auditory cortex, whereas it has significantly decreased in the dorsocaudal area. Spontaneous firing activity was significantly decreased in the primary auditory cortex, whereas it has significantly increased in the dorsocaudal area., Conclusion: Salicylate induces significant changes in single units of both stimulated and spontaneous activity in the auditory cortex of guinea pigs. The spontaneous activity changed differently depending on its cortical areas, which may be due to the neural elements that generate tinnitus., Competing Interests: The authors have declared that no competing interests exist.

Objective: Adults over the age of 65 years with balance disorders are at about twice the risk of falls, compared with those without balance disorders. Falls contribute to about 74% of the proximal femoral fractures commonly seen in the elderly. Since balance disorders are more prevalent in older adults than in younger adults, it is important to deal with balance disorders in older adults to prevent falls and the resulting deterioration in their ADL (activity of daily living). In this study, we investigated the effects of vestibular rehabilitation (VR) and cane use on improving gait and balance in patients aged over 65 years with balance disorder., Methods: Patients aged over 65 years presenting to the Department of Otolaryngology at St. Marianna University School of Medicine between July 1 and November 1, 2018, with symptoms of dizziness for ≥ 3 months and a Japanese translation of the Dizziness Handicap Inventory score of ≥ 26 were included in the study. We quantitatively analyzed their gait before and after VR, and with and without the use of a cane., Results: A total of 21 patients participated in the study (14 women; mean age 73.9 ± 6.9 years). Before VR, using a cane made no difference to step length or walking speed. After VR, using a cane increased step length from 50.5 cm (95% confidence interval [CI], 47.4-53.7 cm) to 52.0 cm (95% CI, 48.9-55.1 cm) (p = 0.039). There was no change in walking speed. A comparison of walking assessment results while using a cane before and after VR showed that step length increased from 49.9 cm (95% CI, 46.6-53.2 cm) to 52.0 cm (95% CI, 48.9-55.1 cm) (p = 0.005), and walking speed increased from 90.5 cm/s (95% CI, 82.7-98.4 cm/s) to 96.1 cm/s (95% CI, 88.3-103.9 cm/s) (p = 0.005)., Conclusions: Walking speed and step length with the use of a cane significantly improved following VR. VR and cane use may act synergistically to improve walking., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest with respect to this article., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: The aim of this study was to determine whether the extent and intensity of pain caused by wearing goggles during the video head impulse test (vHIT) could be reduced by adjusting the direction in which the band pulls the goggles, without increasing the number of artifacts recorded during vHIT., Methods: vHIT tests were performed in 65 healthy adult subjects, and the Visual Analog Scale (VAS) and Numerical Rating Scale (NRS) were used to evaluate pain intensity. Temporal adjusters were used to adjust the direction in which the band pulls the goggles, without decreasing the tightness of the temple straps. Artifacts were compared by calculating the instantaneous gains at 40 ms, 60 ms, and 80 ms of head movement., Results: Maximum VAS and NRS of pain were significantly reduced from 22.0 ± 2.3 to 13.0 ± 1.7 and from 3.0 ± 0.2 to 2.0 ± 0.2 (both P < .0001). The VAS score without adjusters was significantly correlated with the improvement of the VAS score with temporal adjusters (P < .0001, r = 0.61). The higher the VAS score without adjusters, the greater the improvement in the VAS score with temporal adjusters. The instantaneous gains were close to 1.0 under both conditions., Conclusion: The pain induced by the goggle was significantly mitigated with temporal adjusters in the bilateral temple strap. Using temporal adjusters is a useful and easy solution to reduce discomfort during vHIT, while maintaining the tightness of the strap to decrease the slippageinduced artifacts.

Acquired external auditory canal atresia is characterized by fibrous tissue formation in the ear canal, hearing loss and chronic otorrhea. Although the disease can be treated surgically, the recurrence rate is high. This study explored whether autologous oral mucosal epithelial cell sheets could be used as a novel therapy for ear canal atresia. We succeeded in generating a rabbit model of acquired external auditory canal atresia by dissecting the skin of the ear canal. Endoscopic and histological findings in this model indicated that atresia developed over a 4-week period and was not inhibited by the placement of polyglycolic acid sheets immediately after skin dissection. By contrast, transplantation of autologous oral mucosal epithelial cell sheets, which had been fabricated by culture on temperature-responsive inserts without a feeder layer, prevented the development of atresia during the 4-week period after skin dissection. Transplantation of autologous epithelial cell sheets after surgical treatment of acquired external auditory canal atresia could be a promising new method to reduce the risk of disease recurrence. STATEMENT OF SIGNIFICANCE: Acquired external auditory canal atresia is characterized by fibrous tissue formation in the ear canal, which leads to hearing loss and chronic otorrhea. Although surgical treatments are available, the recurrence rate is high. In this study, we successfully generated a rabbit model of acquired external auditory canal atresia by dissecting the skin of the ear canal. Furthermore, we utilized this new animal model to investigate whether the transplantation of autologous oral mucosal epithelial cell sheets could be used as a novel therapy for ear canal atresia. Our results raise the possibility that the transplantation of autologous epithelial cell sheets after surgical treatment of ear canal atresia could be a promising new method to reduce the risk of disease recurrence., Competing Interests: Declaration of Competing Interest Yamato Masayuki is a stakeholder of CellSeed Inc., and Tokyo Women's Medical University is currently receiving research funding from CellSeed Inc. Yamato Masayuki is also an advisor to Helios and Nippi., (Copyright © 2020. Published by Elsevier Ltd.)

Objective: We investigated whether adaptive plasticity of the vestibulo-ocular reflex in humans occurs in response to visual-vestibular conflict stimulation during rotation about a 30° incline (off-vertical earth axis rotation, OVAR)., Methods: Subjects were 26 healthy adults (17 males and 9 females), ranging in age from 22 to 33 years (mean: 24.4) with no history of neurotological symptoms. Each testing session consisted of a pre-test, an adaptation period, and a post-test. The pre-test and the post-test were performed in complete darkness with the subjects' eyes opened. Subjects were rotated sinusoidally at 0.16Hz under OVAR, with a maximum angular velocity of 60°/s for 30s. Subjects were divided into two groups depending on the kind of visual stimulation. One group of subjects was rotated sinusoidally at 0.16Hz and 60°/s peak velocity under OVAR for 20min while viewing optokinetic stripes, which moved at the same frequency and peak velocity as the rotational chair but in the opposite direction (X2 adaptation paradigm). The other group of subjects was rotated sinusoidally at 0.16Hz and 60°/s peak velocity under OVAR for 20min while viewing optokinetic stripes, which moved at the same frequency and peak velocity as the rotatory chair but in the same direction (X0 adaptation paradigm)., Results: There was no significant difference in gain before or after adaptation using the X2 adaptation paradigm. VOR gain decreased significantly after adaptation using the X0 adaptation paradigm., Conclusion: We hypothesize that attenuation of VOR gain increase after the X2 adaptation paradigm is caused by tilt suppression. In the X0 adaptation paradigm, the decrease in VOR gain was facilitated by tilt suppression in addition to the plastic change of the VOR gain caused by visual-vestibular conflict stimulation. Consequently, the VOR gain change ratio in the X0 adaptation paradigm increased significantly compared to that in the X2 adaptation paradigm., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Other iatrogenic immunodeficiency-associated lymphoproliferative disorders (OIIA-LPD) comprise lymphoid proliferations or lymphomas that arise in patients treated with immunosuppressive drugs for autoimmune diseases, especially rheumatoid arthritis (RA) treated with methotrexate (MTX). MTX has been increasingly administered to patients with RA, resulting in methotrexate-associated lymphoproliferative disorder (MTX-LPD) in patients. We report herein on four cases of patients with RA, who diagnosed with head and neck region. In two cases (one case MTX and another case tacrolimus) drug therapy was discontinued, when the patients were diagnosed as having OIIA-LPD in only a few local findings. These patients have followed good clinical courses for 24 months. In the other two cases, consultations were performed for cervical lymphadenopathy by the Division of Rheumatology. In one case drug therapy was discontinued and a good clinical course was followed. In case of the other patient, however, who had undergone tacrolimus therapy after MTX therapy was discontinued, she relapsed and died. In the case of patients with an autoimmune disease such as RA who are taking MTX, tacrolimus, or anti TNF-α therapy, when cervical lymphadenopathy and extranodal disease are detected, OIIA-LPD should be suspected. We should cooperate with a hematologist-oncologist, a rheumatologist, and pathologist in such a case.

Juvenile-onset laryngeal papillomatosis has a serious tendency for rapid growth and repeated recurrence. Thus, patience and prudence are required for the successful management of this pathology. We report herein on 2-year and 4-month-old boy with juvenile-onset laryngeal papillomatosis, which caused remarkable airway constriction that required urgent airway management. He was delivered vaginally by a mother with condyloma acuminatum. Hoarseness appeared at 1 year of age, and retractive breathing was observed at 1 year and 6 months of age. He finally presented with severe wheezing and was admitted to the emergency room of our hospital with a laryngeal tumor strongly resembling a papilloma. Emergency endotracheal intubation was possible by means of a fine endotracheal tube with an internal diameter of 2.5 mm. His supraglottic space was filled with the tumor; thus, making the visibility of the vocal folds difficult. The tumor was surgically removed using a microdebrider under general anesthesia. The histopathological diagnosis was benign papilloma and HPV11 virus was detected. The rapidly growing papilloma showed a strong tendency for recurrence, and four additional surgical procedures had to be performed within 6 months after the first operation. This patient will therefore require cautious medical care in the future.

Conclusions: An abnormally slower action potential (AP) recovery from adaptation (decreased recovery, dR) was characteristically detected in many ears with sensorineural hearing loss (SNHL) but not Meniere's disease and idiopathic sudden SNHL. We assumed that this abnormal AP recovery from adaptation was attributed to an imbalance in the distributions of auditory neurons with high and low spontaneous firing rates. The significant difference of initial hearing level between dR and normal AP recovery groups (nR) was assumed to partially result from AP recovery being determined by the inner hair cell synapse, and not from outer hair cells., Objective: This study aimed to detect the AP recovery pattern in SNHL., Methods: Electrocochleography (ECochG) was performed transtympanically in 30 patients with SNHL. AP recovery was measured by a paired click stimulation paradigm as a function of inter-click intervals from 5 to 100 ms., Results: The high prevalence of dR (9 of 30 ears) appears to be a characteristic ECochG finding in SNHL. Initial hearing level differed significantly between dR and nR groups.

Objective: The vestibulo-ocular reflex (VOR) was studied to determine the utility of off-vertical axis rotation (OVAR) in evaluating vestibular function in patients with canal paresis (CP). Our goal was to determine whether there is any correlation between caloric responses and sinusoidal rotatory responses., Methods: Subjects were rotated in a sinusoidal pattern with eyes open in complete darkness. Frequencies of 0.4 and 0.8Hz with a maximum angular velocity of 60°/s at either earth-vertical axis rotation (EVAR) or OVAR were used., Results: Twenty-three control subjects and 21 patients with CP were investigated. Results showed that (1) the VOR gain difference between EVAR and OVAR in the CP patients was not significant at 0.4Hz and at 0.8Hz; (2) the gain during 0.4Hz EVAR was less in the bilateral CP patients compared to controls; and (3) the VOR gain of the affected side at 0.8Hz was significantly less during OVAR than during EVAR., Conclusion: We concluded that the absence or reduction of caloric responses does not indicate the absence of vestibular function. In addition, separation analysis of the VOR gain of affected and intact sides is useful for evaluating laterality of otolith function in patients with CP., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Conclusions: High prevalence rate of an enhanced summating potential (SP)/action potential (AP) ratio (≥0.35) is considered to result largely from the imbalances of Ca(2+) homeostasis in the endolymphatic space. An increase in Ca(2+) is thought to augment the SP. Furthermore, a greater inflow of Ca(2+) into inner hair cells is supposed to influence the disturbed release of neurotransmitter, which may induce pathological functioning of inner hair cell synapses. We speculate that such abnormal synaptic functioning is responsible for the development of abnormally increased AP recovery from adaptation (iR)., Objectives: This study aimed to record the AP recovery from adaptation (AP recovery) and to investigate its clinical significance in association with other electrocochleography (ECochG) findings in Meniere's disease., Methods: ECochG was performed transtympanically in 27 patients with Meniere's disease. AP recovery was measured by a paired-click stimulation paradigm as a function of interclick intervals from 5 to 100 ms., Results: High prevalence of SP/AP ratio was observed in 27 patients. iR, suggesting abnormal functioning of inner hair cell synapse, was in many cases combined with an enhanced SP/AP ratio.

Conclusion: The main differences in electrocochleography (ECochG) between recurrent and nonrecurrent idiopathic sudden sensorineural hearing loss (iSSNHL) were the high prevalence of an abnormally increased action potential (AP) recovery (iR) in nonrecurrent iSSNHL and the very low prevalence of iR in recurrent iSSNHL. An enhanced SP/AP ratio, low AP threshold, low initial hearing level, and up-sloping type of audiogram appear to be favorable prognostic factors in recurrent iSSNHL., Objectives: This study aimed to characterize differences in ECochG findings and other confounding prognostic factors between recurrent and nonrecurrent iSSNHL and to estimate how these findings are related to hearing outcome in recurrent iSSNHL., Methods: ECochG was performed transtympanically in 23 and 42 ears with recurrent and nonrecurrent iSSNHL, respectively. AP recovery was measured using a paired-click stimulation paradigm. Differences in ECochG findings associated with confounding prognostic factors between recurrent and nonrecurrent iSSNHL, and between three outcome groups were assessed., Results: iR was significantly more common in nonrecurrent iSSNHL (16 ears) than in recurrent iSSNHL (1 ear). In the outcome of recurrent iSSNHL, the prevalence rates of an enhanced summating potential (SP)/AP ratio, lower AP threshold, lower initial hearing level, and up-sloping type of audiogram were significantly higher in the cure group than in the improvement and no-recovery outcome groups.

Conclusion: Abnormal action potential (AP) recovery from adaptation was manifested as increased recovery (iR) or decreased recovery (dR) relative to the normal recovery range. dR was not analyzed statistically due to the very small number of cases. iR is considered an unfavorable prognostic indicator, whereas a normal AP recovery (nR), enhanced SP/AP ratio (≥0.35), and lower AP threshold are favorable prognostic indicators for idiopathic sudden sensorineural hearing loss (iSSNHL)., Objectives: This study aimed to determine the prognostic efficacy of AP recovery examinations associated with other electrocochleography (ECochG) findings in iSSNHL., Methods: ECochG was performed transtympanically in 58 iSSNHL ears. AP recovery was measured by a paired-click stimulation paradigm, and hearing outcome was classified into three groups. Additionally, the relationships of other confounding prognostic factors to hearing outcomes were assessed., Results: iR was significantly more common in the no-recovery group, while nR and an enhanced SP/AP ratio were significantly more common in the cure and improvement groups. The AP threshold was significantly lower in the cure group than in the other two groups. The other confounding prognostic factors generally showed similar trends to those reported previously.

On Earth, humans are constantly exposed to the gravity. During head and body tilts, the otolith organs sense changes in head orientation with respect to the gravitational vertical. These graviceptors also transduce transient linear acceleration generated by translational head motion and centripetal acceleration during rotation about a distant axis. When individuals are rotated at a constant velocity in a centrifuge, they sense the direction of the summed gravitational and centripetal acceleration as the vertical in the steady state. Consequently they experience a roll-tilt of the body when upright and oriented either left-ear-out or right-ear-out. This perception of tilt has been called the somatogravic illusion. Under the microgravity, the graviceptors no longer respond during static tilt of the head or head and body, but they are still activated by linear acceleration. Adaptation to weightlessness early in space flight has been proposed to entail a reinterpretation of the signals from the graviceptors (primarily the otolith organs), so that on return to Earth pitch or roll of the head with respect to the vertical is sensed as fore-aft or left-right translation. In this article, formulation of the spatial orientation on the earth and under microgravity was described.