Vestibular schwannoma (VS) is a benign tumor that originates from the vestibular nerve, extending to the cerebellopontine angle. It was first described in the latter part of the 1700s. The symptoms of VS include unilateral sensorineural hearing loss, tinnitus, dizziness, etc. In general, the hearing loss develops gradually, although some patients develop deafness of sudden onset. The audiogram in patients with VS who present with deafness of sudden onset shows trough-type hearing loss at mid-frequencies. Audiogram, caloric testing and ABR are useful tools for the diagnosis of VS, however, a definitive diagnosis can only be made by MRI with gadolinium enhancement.
Currently, there are tree treatment options for VS: “wait and scan,” surgical removal, and radiotherapy. Selection among these treatment options is mainly made based on the tumor size, preoperative hearing level and the patient's age. Herein, we present the key points for early diagnosis and appropriate management of VS.
Purpose: This present study was aimed at evaluating the effects of our original teaching method called “Bang Bang, Hu, Kacha” on the learning efficiency. Methods: We invented this method, which involves hand modulation and vocalization of words, for medical students to enable them to easily understand and memorize the anatomy of the inner ear and vestibular organs. We evaluated its effectiveness based on self-completed questionnaires by the students. Results: The results suggested that the comprehension level of the 30 medical students of the anatomy of the inner ear organs, especially the positional relationships of the semicircular canals and cochlea improved dramatically after they underwent training using this methodology. The medical students assigned high scores to this relational hand modulation method. Conclusion: This “Bang Bang, Hu, Kacha” method seemed to be a very useful for medical education, and allowed easy comprehension and memorization of the inner ear and vestibular anatomical structures.
A-31-year-old woman presented with a history of experiencing oscillopsia every time she looked at the clock on the night table from a lateral lying posture or at a red traffic light 2 blocks away from her car while driving at night. She had never experienced vertigo, dizziness or unsteadiness before in her life. She visited the outpatient clinic of our university hospital, worried about the nystagmus that she had already noticed. She exhibited lateral gaze nystagmus in both lateral gaze positions. No induced nystagmus was recognized in any specific position or in the positional change tests. Brain MRI revealed no remarkable findings. She was diagnosed as having congenital nystagmus (a manifest latent nystagmus; fusional maldevelopment nystagmus syndrome) based on the absence of any remarkable neurological or neuroradiological findings, with the following characteristic findings on electronystagmography (ENG): 1) In the light, lateral gaze nystagmus in both lateral gazes, and also leftward nystagmus at the primary position 2) In the dark also, lateral gaze nystagmus in both lateral gazes, with rightward nystagmus being predominant. The slow phase showed an approximately exponential decreasing velocity. 3) Rightward nystagmus was still recognized with both eyes closed, even though congenital nystagmus is usually suppressed by eye closing 4) Rightward nystagmus while her head was tilted leftward, while leftward nystagmus was scarcely induced when her head was tilted rightward 5) When her head was tilted rightward, leftward nystagmus was noticed when she closed her right eye and rightward nystagmus when she closed her left eye. However, when her head was tilted leftward, only rightward nystagmus was induced, regardless of whether she kept either eye closed or kept both eyes open. 6) On testing with one eye covered, latent nystagmus was recorded on both the side of the covered eye side and on the contralateral side. 7) Both horizontal and vertical ETTs were preserved 8) Caloric nystagmus was induced bilaterally. Visual suppression (VS) was also recognized bilaterally, with “augmentation” of caloric nystagmus during the VS test. 9) The peak slow phase velocities of optokinetic nystagmus (OKN) were remarkably reduced and gradually showed an “inversion pattern” as the OK-stimulation velocities increased, while no OKN responses were noticed intermingled with the square wave jerks (SWJs) as the OK-stimulation velocities decreased. 10) The optokinetic after-nystagmus (OKAN) on the left showed an “inversion pattern,” while OKAN was scarcely evoked on the right side. These findings are mainly discussed for comparison, from the pathophysiological point of view, with the usual findings of congenital nystagmus. In conclusion, it is speculated that such unique ENG findings are derived from asymmetry of the bilateral velocity storage mechanisms receiving asymmetrical visual inputs from the bilateral nuclei of the optic tracts (NOTs) since her birth.
Herein, we present a patient with superior semicircular canal dehiscence syndrome (SCDS) manifesting as convergence spasms, which were alleviated by canal plugging surgery. SCDS is described in the literature by Minor as “a condition characterized by vertigo and oscillopsia induced by loud sounds or changes in the pressure of the external auditory canal or middle ear due to the dehiscence of the bone overlying the superior semicircular canal.” Convergence spasms are characterized by intermittent sustained convergence, accommodative spasms and miosis, and are likely to be caused by a functional disease, although in some cases, it is a manifestation of an organic disease.
A 49-year-old male patient visited our department with a 2-year history of intermittent sudden vertigo and cloudy vision. The vertigo attacks had gradually increased in frequency and could last all day. Pure-tone audiometry showed bilateral conductive hearing impairment with air-bone gap at low frequencies from 125Hz to 500Hz. A head CT showed bone dehiscence above the bilateral superior semicircular canals and tegmen of the epitympani.
Initial equilibrium testing did not reveal any abnormal findings. Initial sono-ocular testing of the right ear indicated upbeat nystagmus. However, after multiple outpatient visits, the upbeat nystagmus disappeared during the sono-ocular test and was replaced by paradoxical convergence. The eye tracking test also revealed paradoxical convergence, which became frequent and was accompanied by pupillary miosis. This paradoxical convergence was ultimately diagnosed as convergence spasms.
No improvement of symptoms was achieved through non-surgical treatments over an extended period of time, therefore, canal plugging surgery was recommended. The surgery was performed through a middle fossa approach, and it completely eliminated the cochlear and vestibular symptoms associated with SCDS and the convergence spasms. Finally, we suspected that the convergence spasms were caused by ocular dysfunction as well as neurological factors related to the SCDS.
Syphilis is a sexually transmitted infection caused by the bacterium Treponema pallidum. Otosyphilis is a type of neurosyphilis; in otosyphilis, cochleovestibular dysfunction could be due to a lesion of the inner ear itself or of the eighth cranial nerve. In most cases, otosyphilis manifests as sensorineural hearing loss. We report a rare case of a 56-year-old male patient who developed vestibular symptoms, including dizziness and vertigo, caused by otosyphilis. The patient was admitted to our hospital with a 3-week history of dizziness and vertigo. He did not have deafness or tinnitus. All the serological tests for syphilis, including the T. pallidum hemagglutination assay (TPHA), the rapid plasma reagin test, and the fluorescent treponemal antibody absorption (FTA-ABS) test, were positive. Tests for HIV antibody were negative. The TPHA and FTA-ABS tests on the cerebrospinal fluid were also positive. On clinical neurological examination, the Romberg test was positive, and he had spontaneous nystagmus toward the left side and direction-changing positional nystagmus. Caloric tests revealed no response on the right side, indicating canal paresis. No cervical vestibular evoked myogenic potential (c-VEMP) response was observed on the right side. Based on the findings, the patient was diagnosed as having otosyphilis, and treated with penicillin G (24 million units/day) for 14 days. Two months after the treatment, the vestibular symptoms resolved and the abnormal nystagmus disappeared completely.
Chronic vertiginous conditions worsen the subjects' QOL over the long term. The problem has been brought into acute focus with the recent rapid aging of the society. To quantify this chronic vertiginous status, we have proposed the use of a 3-dimensional eye movement analysis, and also a description of the Listing's plane. In this manuscript, we provide an outline of our previous study and our future view.
We use infrared video-oculographic images and extract numerical data on eye movements along the horizontal, vertical, and torsional components. Then, we obtain rotational vector description, through Euler's angle. Assembly of this rotational vector description allows the Listing's plane to be described. Our previous study about this Listing's plane demonstrated the possibility of quantitative evaluation of the otolith vestibulo-ocular reflex, and also gravitational recognition. Not only some kinds of peripheral vestibular dysfunction and cerebellar ataxia, but also pseudo-inclination of one's head (so-called “vection,” caused by optokinetic stimulation), could thicken the Listing's plane, which implies decrease of the precision of the otolith vestibulo-ocular reflex or gravity recognition.
In the future, we propose to estimate the characteristics changes of the Listing's plane caused by spinocerebellar degeneration, which is a representative disease causing cerebellar ataxia. In addition, to improve the precision of measurement of the rotational eye movements, we are exploring the development of an algorithm, which can detect false measurement of rotational eye movements. On the other hand, we constructed a measurement system for the eye movements of mice, which enables us to study mouse models and also perform fracture experiments, to gain further knowledge on pathophysiological mechanisms. Our goal is to establish a clinical instrument and algorithm to measure the otolith functions and gravitational recognition in order to manage patients with chronic vertiginous conditions.
The mouse is the most commonly used animal in biomedical research, because of recent advances in molecular genetic techniques. Studies related to eye movements in mice are common in the fields of ophthalmology, neuro-otology, and psychology. We developed a new system for analyzing the three-dimensional rotation vector of eye movements in mice using high-speed video-oculography. Using the eye movement analysis system, we were able to analyze the eye movements associated with the vestibulo-ocular reflex (VOR) and optokinetic stimulation in mice. In this review, we introduce studies that we performed using this system and have already been published and also introduce our future plan for studies to be performed using this system and are expected to contribute to the treatment of patients complaining of vertigo.
Unilateral vestibular dysfunction mice were characterized by spontaneous nystagmus in the direction of the healthy ear. In mice with bilateral vestibular dysfunction, VOR was not induced during rotation.
We investigated cisplatin-induced vestibulotoxicity in C57BL/6J mice. Cisplatin decreased the VOR gain at 2.5Hz as compared to that in the vehicle control. This mouse model may be useful for studying cisplatin-induced vestibulotoxicity and its treatment.
We assessed the physiological function of the P2X2 receptor in vivo using P2X2 receptor-knockout mice. We showed that the P2X2 receptors are mainly localized in the supporting cells of the vestibular inner ear, and that the loss of P2X2 receptors causes mild vestibular dysfunction, i.e., a significant decrease of the VOR gain. Taken together, our findings suggest that the P2X2 receptor plays a modulatory role in vestibular function.
In the future, we expect that a rationale for vestibular rehabilitation of patients with vertigo will be established by clarifying the mechanism of interaction between VOR and the optokinetic response.
Due to the small size and optically clear body of larval fish, the zebrafish lateral line is a powerful system for identifying and evaluating drugs that damage or protect hair cells. The zebrafish lateral line is morphologically and physiologically similar to the inner ear hair cells. Owing to their location on the body surface, damage to hair cells can be rapidly assessed. In addition, because of the rapidity with which the experiments can be performed using zebrafish and the large population available, zebrafish are particularly valuable for thoroughly testing and modulating dose-response relationships.
In one example, libraries of 88 anti-cancer drugs were screened to evaluate the damage of hair cells on the zebrafish lateral line. The screen identified 13 drugs that caused hair cell damage. We further evaluated the effects of common combinations of anti-cancer drugs and identified evidence of synergistic hair cell toxicity.
Conversely, 18 supplement drugs and 80-kinase inhibitors were screened to evaluate their protective effects on the hair cells of the zebrafish lateral line; this allowed identification of three supplements and some kinase inhibitors with protective activity.
The results of our study indicate that screening drugs using zebrafish potentially allows determination of drugs with ototoxic effects/protective effects for the inner ear.
In our aging society, it is important to maintain a healthy balance. However, the risk of falling gradually increases with age because of various hypofunctions such as vestibular disorders. In birds, hair cells regenerate after damage caused by ototoxic drugs; however, their regeneration in mammals is poor. To date, no curative therapy for vestibular disorders has been established. Therefore, the development of new treatments is an important theme in our aging society. In the mammalian vestibule, spontaneous regeneration has been reported morphologically. However, it is not clear whether regenerated hair cells possess their correct function. We investigated the mechano-electrical transduction (MET) function of hair cells by measuring Ca2+ responses. We found an intact MET function in stimulated regenerated hair bundles. However, the self-repair of hair cells was only partial and insufficient to recover vestibular function. Therefore, additional treatments such as with anti-oxidant drugs, growth factors are needed. We also demonstrated that espin gene therapy restored stereocilia on regenerated hair cells after damage. Therefore, cell transplantation therapy might be promising for severe damage of the inner ear. We previously reported that induced pluripotent stem cells and human neural stem cells (hNSCs) differentiated into hair cells and vestibular ganglion cell-like cells, respectively. Therefore, these cells might be potential donor cells for the transplantation therapy of vestibular disorders. Currently, we are investigating the effectiveness of cell transplantation in vivo using an animal model. Morphologically, we confirmed the survival of transplanted cells in normal mice but without their differentiation into the desired cells. To evaluate vestibular function, we also examined the vestibulo-ocular reflex (VOR) and observed a decrease in VOR gain after the application of ototoxic drugs. We confirmed the functional effectiveness of cell transplantation in an animal model of vestibular disorders. Future studies should determine the optimal conditions for donors and recipients. Before new regenerative therapy can be established, further investigations are required.