In order to estimate the accuracy of diagnoses of Meniere's disease (M.D.) we designed a pilot study to invesigate the diagnosis and treatment by doctors in our university hospital by means of a questionnaire in November, 1993. The questionnaire included the following items: age, sex, symptoms, examination findings, severity of M.D., treatment and prognosis. Responses from 98 doctors were analyzed, and the attitudes of internists and otorhinolaryngologists were compared. M.D. diagnosis and treatment were found to vary considerably. It is important to standardize the criteria for the diagnosis of M.D. and the estimation of its prevalence, but also to investigate its cause and establish its treatment. In our next study, we will survey all the doctors in Tottori prefecture and discuss the results of a survey of patients.
We investigated the influence of a cold front (CF) on the onset of Meniere's disease (MD) and concluded that the onset of MD was influenced by the passing of a CF. But it was not clear whether patients with MD were stressed by the passing of a CF or the passing of a CF directly influenced the inner ears. Among the patients with MD who visited the Neuro-Otological clinic of the Toyama Medical and Pharmaceutical University Hospital from 1987 to 1992, 67 were sure of the date of the first attack and were chosen for the study. In 36 the first attack was on a day when a CF was passing or on the next day, so they were studied epidemiologically. 1) Age: more of these 36 patients were over 40 years of age than in the group of 31 patients with no definite relationship between CF and MD. 2) Hearing: in the 36 patients hearing was poorer than in the others.
Several investigators have recently reported that experimental conditions in a mouse model which affect the pressure/volume ratio in the endolymphatic space increase the amount of a stainable substance in the endolymphatic sac (ES) lumen. They suggest that this stainable substance may play an important role in the regulation of pressure/volume homeostasis. The guinea pig is often used as an animal model of experimentally induced endolymphatic hydrops. In this study we interrupted the endolymphatic duct selectively in guinea pigs. The histology of the ES was studied by light microscopy at various time intervals after the operation. The amount of the stainable substance in the ES lumen on the operated side was increased for a few weeks postoperatively. This finding suggests that in the guinea pig model also the stainable substance in the ES lumen is involved in the regulation of pressure/volume homeostasis in the endolymphatic space.
It is well known that some kinds of vertigo and some hearing problems are caused by impairment of the vertebro-basilar circulation. The influence of unilateral vertebral artery (VA) occlution on bilateral inner ear blood flow was studied in rats by the laser Doppler method. After tracheotomy, both cochleas were exposed through a ventral approach for the measurement of cochlear blood flow (CBF). One VA was occluded by photochemically induced thrombosis. The right femoral artery was cannulated for continuous measurement of systemic blood pressure (BP). BP and CBF showed little change after unilateral VA occlu-sion alone. However, subsequent hypotension induced by venesection not only reduced CBF, but also caused bilateral imbalance between the CBF reduction rates. CBF changed independently of BP, indicating the existence of a local CBF regulation system.
The effect of retinoic acid (RA) on the development of the inner ear was examined in mouse embryos. Embryos were injected with RA into the left inner ear on day 13 of gestation (E13), after which they continued to develop exo utero until E18. The inner ears were then examined histologically. One of the four embryos in the RA-injected group had a deformed saccule, whereas no abnormality was seen in the controls, but it is not clear that this deformity was specifically caused by RA. This experimental system with further modifications appears to be useful in the examination of the molecular aspects in the development of the inner ear and in the development of animal models for congenital defects of the inner ear.
Morphological and metabolic differences in the otoconia on vestibular dark cells of the ampullary area before and after streptomycin treatment were studied by scanning electron microscope and X-ray microanalyzer. Young adult pigmented guinea pigs were used in this study. In the control group, distribution of the otoconia showed a regular pattern. In the SM group, the otoconia were decreased and their distribution pattern was irregular. The calcium content of the otoconia was also decreased in the SM group. These findings indicate that SM might affect not only the sensory and supporting cells but also the vestibular dark cells.
Calcium distribution was measured in cultured utricular supporting cells following streptomycin sulfate (SM) intoxication. An organ culture system and potassium pyroantimonate (PA) precipitation method were used. Calcium ions were demonstrated in the otoconia and in the secretory granules of the supporting cells. When the supporting cells were exposed to SM lysosomes were increased and secretory granules were decreased in the cytoplasm. These lysosomes had many granules which contained calcium ion. It appeared that calcium secretion from the secretory granules was inhibited by SM and that this might lead to the reduction of otoconia.
The bustling mouse (BUS/Idr: bus) is a mutant mouse strain which displays several behavioral abnormalities: hyperkinesia, circling, head tilting, and head bobbing. This phenotype develops in homozygous (bus/bus) mice progressively after birth and has been shown from cross experiments to be inherited by a single autosomal recessive gene. The effect of deuterium oxide, which has been shown to influence vestibular function, on abnormal behavior was examined in homozygous mice of different ages. Using light and electron microscopy, we also examined the development of pathological changes in the inner ears of homozygous mice. The pathological changes seen in the inner ears were: impairment and/or loss of auditory hair cells, deformity and/or loss of the inner and outer tunnels of the organ of Corti, hypoplasia of otoliths, and decreased numbers of neurons in the spiral ganglion. These abnormalities were present in homozygous mice before weaning and progressed thereafter, but were not seen in heterozygous (bus/+) mice. Although histological changes were also noted in the crista ampullaris and maculae, they were less prominent than in the cochlea, at least until six weeks of age. The oral administration of deuterated physiological saline (8-16 mg/kg) tended to reduce the abnormal behavior of homozygous mice, including rapid circling. These morphological and functional findings suggest that BUS mice may be a useful model for the analysis of the pathogenesis and treatment of vestibulocochlear disorders.
To clarify the non-specific defense mechanism (first defense mechanism) of the inner ear against pathogens, we injected K562 myelogenous leukemia cells into guinea pigs' perilymphatic space through the round window membrane and observed the reaction in the inner ear on day 1 to day 9. K562 cells injected into the perilymphatic space could survive and multiply for a couple of days. At 67 hours, however, some macrophages entered the perilymphatic space, and at 86 hours some K562 cells had degenerated a little, but most of them seemed to be intact. NK (natural killer) cells which were positive for anti-asialo GM1 appeared in the perilymphatic space on day 7 when most K562 cells were still intact. On day 9 there were many K562 cells with adherent phlogocytes in the perilymphatic space, and most of them had degenerated. K562 cells were attacked by NK cells coming from the surrounding venules. The source of NK cells in the perilymphatic space may be vessels around the modiolus and the cochlear bony wall. Also, NK cells derived from white blood cells of guinea pig whole blood could attach to, recognize, and attack K562 cells, and their attack showed an ordinary pattern of NK cell-induced cytolysis. The emergence of NK cells was much later in the perilymphatic space than in the skin after the injection of K562 cells. It is possible that this delay can lead to an irreversible change in the cochlea due to pathogens before the mobilization of NK cells. In addition, humoral factors in the inner ear fluid are not so powerful in suppressing viral infection, and the endolymphatic sac does not seem to play an important role to rescue the cochlea from viral infection. Thus the inner ear seems to be an environment in which it is relatively difficult for immunocompetent cells to function.
Head and body movements during walking on a treadmill were analyzed with a 3-D motion assessment system (ELITE system), which enabled real time analysis of target movement in each subject. Head roll in counter action to body motion in the coronal plane and pitch rotation in the sagittal plane were noted in the control data. Head movement became small due to compensatory counter motion, though lateral sway became larger in the upper part of the body than in the lower. After the recording of control data, ice water was irrigated into the ear canal for vestibular stimulation in six healthy subjects. Walking immediately after caloric stimulation showed that step length and gait cycle time became shorter than before caloric stimulation. Lateral sway and vertical translation of the head also increased. Head counter roll in the coronal plane and pitch rotation in the sagittal plane became indistinct after caloric stimulation. Behavioral changes in human locomotion after vestibular stimulation are described in this report.
Patients with peripheral disorders may experience abnormal vertical sensations while standing, which cause disorientation in their environment. A disturbance of vestibular function in the light is reflected by postural instability in space. The present study investigates the relationship between subjective vertical displacement and vestibular lesions. The subjects were patients with a unilateral vestibular lesion; control subjects had no past or present history of a vestibular lesion. A straight line consisting of 5 spotlights projected on a dome-shaped screen was concentrically moved like a stylus when a button was pressed. We examined the subjective vertical of the subjects standing in a dark room when the 5-spotlights-straight-line (the spotlight-line) was projected on the dome-shaped screen. Patients with a unilateral peripheral disorder showed a significantly greater deviation to the impaired ear side, especially when the spotlight-line was moved from the impaired side, while the deviation of the normal subjects was less than 1 deg.
We examined gait in relation to aging in normal adults and the characteristics of walking in patients with equilibrium disorders. Thirty-five normal adults and 14 patients with equilibrium disorders were examined with eyes open. The measurement was performed mainly in the first three steps. Force plates were used to measure the centers of pressure. Step length, step width, cadence, walking speed, step length/body height, step width/step length, and LG/LS were analyzed. In the aged there was a marked shortness of step length, broadness of step width, slight decrease in cadence, marked slowing of walking, and increase in body sway as shown by LG/LS. There were no statistically significant differences between normal young and normal middle aged adults or between normal subjects and patients with equilibrium disorders except for those with active peripheral vestibular disorders. Key words: gait analysis, force plate, center of pressure
To evaluate upright balance function, we examined 50 normal subjects and 11 patients with vestibular disorders using computerized dynamic posturography (EquiTest System). The normal range was determined from the results of tests of normal subjects. Under sway-referenced support conditions (conditions 4, 5, 6) nine patients (81.8%) showed abnormal test results. However only two patients (18.2%) with vestibular neuronitis revealed abnormal equilibrium scores under fixed support conditions (conditions 1, 2, 3). Somatosensory input appears to be very important in the maintenance of upright balance.
The acute effect of a moderate quantity of alcohol on balance was examined by the pendular optokinetic nystagmus test (P-OKN test), pendular rotation test (VOR test), caloric test and dynamic posturography (EquiTest). Ten healthy male volunteers aged 19-27 (avg. 22.8) years were given 1.5 ml whiskey (alcohol content 43%) per kilogram of body weight within 5 minutes. Their blood alcohol level (BAL) was measured before administration and 30, 90, and 150 minutes later. Equilibrium examinations were performed immediately after each blood sample was taken. At the highest alcohol level, in P-OKN gain, VOR gain, maximum slow phase velocity of the caloric test and equilibrium score of the sensory organization test in conditions 4 and 5 were significantly lower than before drinking. In some typical cases, the subjects' responses to all tests were most disturbed at the time of the highest alcohol level. Our results indicate that a moderate quantity of alcohol affects not only the oculomotor system but also the vestibular system. Furthermore, it may be that one of the reasons for postural instability after drinking alcohol is reduced vestibular function.
A method was developed to analyze fine nystagmus, such as spontaneous and positional nystagmus recorded by electro-nystagmography (ENG) in routine equilibrium examinations. Nystagmus waves in recorded eye movements were identified automatically by the computer program and the amplitude, duration and velocity of slow and fast phases in each nystagmus were analyzed. Such artifact as blinking, eye movements other than nystagmus and noise other than eye movements were automatically sorted out from the identification of nystagmus. In patients with inner ear disorders, slow phase velocity of spontaneous nystagmus increased and decreased depending on the interval from the onset of the vertigo attack. In patients with cerebellar disorders, the slow phase amplitudes were smaller than in patients with inner ear disorders, and slow phase duration was shorter. The method might be useful for both the observation of the clinical stage of vertigo patients and the differential diagnosis between inner ear disorders and central nervous system disorders.
Although it has been speculated that BPPN is due to an abnormality of the utricle or posterior semicircular canal, the origin of BPPN is still controversial. In order to clarify the origin of BPPN, we carried out a three-component analysis of nystagmus, focusing on horizontal, vertical and torsional motion, using a computerized eye movement analysis system. Applying pendular rotation stimuli, we also measured three components of eye movements evoked from the vertical semicircular canals. The eye movements observed as rotatory nystagmus under Frenzel glasses, which are characteristic of BPPN, in most of the subjects had not only torsional, but also vertical and horizontal components. The vertical component dominant over the horizontal component. We compared two components (vertical and torsional) of BPPN with eye movements evoked from the vertical semicircular canals. In BPPN, the torsional component of the eye movement was larger than that of the vertical component. On the other hand, the vertical component of the eye movement from vertical semicircular canals was larger than that of the torsional component. These results suggest that the pathology of BPPN is not located only in the posterior semicircular canal.
Equilibrium and audiological examinations were conducted in 73 patients with a diagnosis of vestibular neuronitis during 1972 and 1993. In 23 patients central nervous system disorders were suspected from the results of tests of positional and positioning nystagmus, smooth pursuit, optokinetic nystagmus or auditory brainstem response. In this group of patients the mean age and the frequency of associated disorders and vertigo (dizziness) were significantly higher than in other patients, and the time intervals between the onset and improvement or disappearance of vertigo, nystagmus and canal paresis were longer. These findings suggest that aging and associated disorders of the central nervous system increase susceptibility to vestibular neuronitis.
To identify inner ear autoantibodies, we examined the sera of patients with sensorineural hearing loss and/or vertigo using the western blotting technique. SDS soluble extracts were examined as the inner ear antigen from bovine inner ear tissues. About 70% of patients showed inner ear specific autoantibodies which reacted with 32 kD (8.1%), 33-35 kD (14.9%), 42 kD (14.9%) and 68 kD (9.4%) determinants. We attempted to examine the relationship between the positive rate of inner ear autoantibodies and clinical symptoms, course and diagnosis. We could not find any inner ear specific autoantibody related to autoimmune inner ear disease. The positive rate of autoantibodies to the 68 kD antigen determinant, however, tend to increase with the elevation of the hearing threshold. A positive reaction of autoantibodies to the 42 kD antigen determinant also tended to have a high incidence in patients with a fluctuating hearing threshold. These results suggest that an autoimmunological mechanism may be of the causes of sensorineural hearing loss.
Correlations were investigated between plasma levels of antidiuretic hormone (ADH) and the frequency of vertigo attacks, and between hearing and serum Na levels in patients with Meniere's disease. Plasma ADH levels were measured every 3 months for 1 year in 48 patients. Those with persistently high plasma ADH levels tended to have frequent vertigo attacks (Fischer's exact probability test; P<.05). However, serum Na levels and pure tone average (PTA) levels showed no correlation with plasma ADH levels. These results, together with those of the previous study by the present authors, which showed a close correlation between plasma ADH levels and a positive glycerol test and ECoG, suggest that high plasma ADH levels in patients with Meniere's disease have a pathologic mechanism different from that of SIADH.
Plasma antidiuretic hormone (ADH) levels were studied in 105 patients with unilateral profound deafness, including 31 with delayed endolymphatic hydrops, 53 with sudden deafness, 6 with temporal bone fracture and/or perilymphatic fistula, and 15 with juvenile unilateral profound deafness. As previously reported, high plasma ADH levels were noted in patients with delayed endolymphatic hydrops. ADH levels were also elevated in juvenile unilateral profound deafness. No marked rise in plasma ADH level was observed in the other disease groups. In the present study, high plasma ADH levels were frequently observed in those with a long duration of disease. Delayed endolymphatic hydrops is known to develop years to decades after the onset of profound deafness. Although the pathogenesis of this process remains unclear, an increase in the plasma ADH level might be one of the underlying mechanisms of delayed endolymphatic hydrops.
The sensation of vertigo or dizziness shows individual differences in patients with inner ear or vestibular nerve damage. This study was designed to correlate the sensation of vertigo or dizziness with the severity of inner ear or vestibular nerve lesions. 1. Unilateral inner ear lesions Three months after the initial medical examination, patients no longer complained of vertigo or dizziness, and in 86%, the inner ear had recovered normal function. When the caloric response on the side of the lesion had recovered over 50% of normal function, 90% of the patients no longer complained of vertigo or dizziness. 2. Unilateral vestibular nerve lesions Three months after the initial medical examination, 90% of the patients no longer complained of vertigo or dizziness. When the caloric response on the side of the lesion had recovered over 30% of normal function, none of the patients complained of vertigo or dizziness.
A classification of Harada's disease presenting with aural symptoms and/or sings, was devised on the basis of otoneurological findings. Peripheral vestibular dysfunction, such as staggering on the stepping test, rotatory horizontal or horizontal nystagmus, and CP on the caloric nystagmus test, were observed in the vast majority of these patients. Harada's disease with such features was designated "peripheral type", and was further divided into vestibular, cochleovestibular, and cochlear subtypes. Patients only rarely presented with symptoms or signs of central nervous system involvement, and Harada's disease with such features was designated "central type". Patients with both peripheral and central involvement were called "mixed type".
Retrosigmoid vestibular neurectomy was performed on 12 patients being suffered form intractable vertigo during past 4 years. These included 11 Meniere and 1 delayed endolympahtic hydrops patients. Control for vertigo was satisfactory in all subjects. Long term follow up of their hearing revealed that it was preserved in 90.9% of patients. Their auditory function was also examined by the electro-cochleo graphy (ECoG). There was no change in -SP/AP ratio before and after the surgery. -SP/AP ratio measure on the affected side decreased when white noise was applied on the contralateral intact ear before RSVN. However, the reduction was no more found after the surgery. It was concluded that the crossed olivo cochlear bundle was also severed by RSVN.
The incidence of Meniere's disease was investigated in patients with vertigo or dizziness who visited Kitasato University Hospital from 1985 to 1991. Of a total of 3, 222, Meniere's disease was diagnosed in 251 patients (7.8%). The male female ration was 1 : 1.73. Seventy patients with Meniere's disease were classified into 5 groups, depending on the duration of the disease. Both ears were affected in 12 (17.1 %) of the 70, but in 4 (33.3%) of the 12 patients with more than 15 years of disease. Of the 70 patients 67 were treated conservatively, and 3 surgically. The frequency of vertigo attacks and the degree of hearing impairment during the past year in each group were compared. No vertigo attack was experienced in 13 (24.1 %) of the 70. In 49 patients the average number of vertigo attack was 4.5 in the past year. Adequate therapy is most desirable within one year after the onset of Meniere's disease, because the frequency of vertigo attacks and the hearing level can be best controlled when therapy is started less than one year after the onset.
In order to draft guidelines for reporting treatment results in Japan, the 17 Committee Members elected from the Japan Society for Equilibrium Research have held discussion for about two years. Preliminary guidelines are summarized here. 1) Evaluation of Symptoms: Only definite vertiginous spells with spontaneous nystagmus should be considered for evaluation (AAOO 1972). Hearing levels assessed from the four-frequencies pure-tone average (PTA) at 250 Hz, 500 Hz, 1 KHz, 2 KHz in Meniere's disease. 2) Evaluation Period: Valid results of the evaluation should be based on evaluation for over six months in pre-treatment and for more than twelve months in post-treatment after initiation of the therapy. 3) Evaluation Criteria: The formula expressing the effects of treatment on vertiginous spells should be the same as the AAOHNS (1985) criteria. If the duration of pre-treatment is less than six months, the divisor is the average number of definite spells per month during the period of observation. 4) Global Judgment: Patients and doctors should evaluate on their treatment results from the standpoints of their subjective symptoms and objective signs, respectively.