After the first and second nation-wide surveys of the Meniere's Disease Research Committee of Japan from 1974 to 1976, the third nation-wide survey was carried out in the 435 departments of otolaryngology, internal medicine and neurology of both general and university hospitals for one week in June 1977 (Watanabe, 1978). In this survey, 747 patients with definite Meniere's disease were collected from 214 departments, that is 0.76% of the total number of out- and in-patients and were statistically evaluated with respect to severely disabled patients.
Nakae and Komatsuzaki (1978) conducted an epidemiological analysis of 512 patients with Meniere's disease by means of questionaires comparing them with the 321 vertiginous patients and 512 ENT out-patients in whom Meniere's disease had been ruled out; the complications of hypotension, preceding presence of fatigue, insufficient sleep and mental stress were frequently observed in the group of Meniere's disease. Yasuda (1978) analysed a correlation between the vertiginous attack of Meniere's disease and the weather at four different districts in Japan.
Between December 1978 and October 1979, a follow-up of the second nation-wide survey of Meniere's disease was made. Among the 180 selected patients who were sick for a shorter period than one year at the second nationwide survey, 120 patients (66%) were collected by the seventeen members of this Committee in 1979, and were evaluated from the epidemiological and clinical points of view (Mizukoshi et al., 1980).
According to these epidemiological and clinical surveys of the period during 1977-1979, the characteristic features of Meniere's disease are as follows.
1) From the nation-wide one-day and one-week surveys, a total number of patients with Meniere's disease in Japan was calculated to be about 4, 000-80, 000, and a prevalence rate was also estimated to be 35-170 per million inhabitants (Nakae et al., 1978).
2) There was an increasing number of patients in the southern area of the Kanto district, compared with the northern area. (Naito, 1973; Watanabe, 1976 and 1979; and Nakae et al., 1978).
3) The rate of patients who were severely disabled to the point of their daily lives being handicapped was estimated to be 54.7% (in the 3rd survey) or 15.2% (in the 4th follow-up study). (Watanabe, 1979; and Mizukoshi et al., 1980).
4) In 67 (60.9%) of the 110 follow-up patients who were sick for 2-4 years, vertigo was of less intensity in the last year and the vertigo tended to change into dizziness as the duration of the illness became longer. (Mizukoshi et al. 1980).
5) The hearing level as expressed by the pure-tone audiogram deteriorated by an average of 10.5dB in the 4th follow-up survey. (Mizukoshi et al., 1980).
6) The incidence of bilateral Meniere's disease increased as the duration of illness became longer. (Mizukoshi et al., 1977 and 1980)

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厚生省特定疾患メニエール病調査研究班として集計されたメニエール病確実例520例中比較的初期例とみられた180例について, 個人追跡調査票による追跡調査を120例 (66%) に施行し, その疫学, 臨床的特徴をPDP 11/40にて集計分析した. 全体にメマイ発作は著しく改善していたが, 聴力障害は若干増悪した症例もみられ, とくに高令発症症例に増悪の傾向がみられ, 約2年間に両側化症例も2例から5例に増加していた. 初期症状やその発症条件から予後を判定することは極めて難しく, 今後よりきめの細かい追跡調査が必要であるとみられた.

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1. 北里大学病院のめまい平衡障害外来の7年間の患者総数は5,920名でそのうちメニエール病患者は180名3.0%であった.
2. 北里大学病院患者の36.8%が居住する人口約40万人の相模原市のメニエール病患者数を北里大学病院のメニエール病患者数から大学病院診療圏の調査に基いて推定した.
3. 相模原市のメニエール病患者数は年間平均10.11人, 7年間合計は70.74人と推定され, 年間メニエール病発生率は人口10万人対2.764, 有病率は人口10万人対16.763であった.
4. メニエール病の発生率, 有病率を算定する一方法を示し問題点についてのべた.

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The effect of streptomycin sulfate (SM) on the sensory epithelia of the inner ear of guinea pigs were studied histochemically. The guinea pigs, in which the right endolymphatic duct were obliterated surgically, were injected with SM 250mg/kg ten times in one month. Succinate dehydrogenase staining was used in the histochemical study. The enzymic activity of the sensory cells in the surface specimens from the cristae ampullares, maculae utriculi, maculae sacculi and the organ of Corti were investigated light microscopically.
The study revealed that SM caused more remarkable damage on the vestibular sensory cells of the operated side compared with that of the opposite. The organ of Corti remained intact on both sides.
To explain these findings, we considered that SM might be accumulated in large amounts in the endolymphatic space.

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メニエール病の場合の尿素の内耳に及ぼす影響を明らかにするために, 一側の内リンパ管に閉塞手術を施し, 1週および3週を経過したモルモットに, それぞれ尿素2g/Kgを経口投与し, 2時間後の内耳をベンチジン血管染色と Nitro-BT の超生体還元組織化学反応によって検索し, 次の点を明らかにした.
1. 術後1週目の術側の内耳には内リンパ腔に面している前庭器, 蝸牛, 血管条の毛細血管網に散発性に血管の狭窄あるいは乏血がみられた. これらの血管の変化は蝸牛では1回転下端部側につよく, 2回転後半部まで認められた.
2. 術後3週目の術側の内耳のラセン器の外有毛細胞にホルマザンの形成障害がみられた. これらの変化は4回転以上に強く, 頂回転では外有毛細胞の消失とともに内有毛細胞の消失をきたしていた.
3. 尿素投与後には, 内リンパ腔面の毛細血管の変化の改善がみられ, また外有毛細胞のホルマザン形成障害にも改善がみられた.
4. 尿素の内リンパ腫とその場合に起こる変化に対する影響の機序を考察した.

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Several experiments were reported with regard to the experimental endolymphatic hydrops of guinea pigs after obliteration of the endolymphatic sac.
1. Uno (1969) reported that the cochlear potentials of guinea pigs with endolymphatic hydrops were depressed to a maximum amplitude of CM and the N₁ amplitude of AP was decreased.
2. Tomiyama (1969) and the present authors reported the increase in the directional preponderance differences of C & E DPRT in the guinea pigs after obliteration of the endolymphatic sac.
3. The guinea pigs with experimental endolymphatic hydrops produced positive results to the experimental furosemide test by C & E DPRT, and the histology of the inner ears of guinea pigs with the positive furosemide test revealed either normalizing or collapsing of the endolymphatic hydrops which had once been produced in the affected ear, while the opposite ear was almost normal.

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Serum, cerebrospinal fluid (CSF), scala vestibuli perilymph and scala tympani perilymph were collected from 286 normal anesthetized guinea pigs (sodium pentobarbital 20-30mg/kg I. P.) both before and after intravenous administration of furosemide (15mg/kg) and normal saline (1.5ml/kg). One hundred and twelve guinea pigs receiving normal saline were used as a control group. Then, the sodium and potassium concentrations were assessed using a microflame photometer (I. L. 443 Instrumentation Lab.).
Measurement was made of 104 normal guinea pigs to obtain the preinjection values as standards for the subsequent experiments.
Marked increase in the sodium concentration was observed both in the scala vestibule and tympani perilymphs, and slight increase was found in CSF, while there was no significant change in the serum.
The potassium concentration was increased in both scala vestibuli and tympani perilymphs, but there was no significant change in CSF or serum.
The results of the present study revealed that the increase in sodium concentration was a result of dehydration in the above-mentioned fluid spaces.
Changes in potassium concentration was found in both perilymphs, and this may not be attributable to such a simple process as dehydration. The elevation of these potassium concentrations will be understood when concomitant changes in the electrolytes in the endolymph are clarified, or considered the specific effects of Furosemide to these fluid spaces in the point of transport system of electrolytes.
For the elucidation of the effect of furosemide, the above findings of electrolyte concentrations should be further evaluated with respect to their possible significance.

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The reality of allergic endolymphatic hydrops as a cause of recurrent episodes of Meniere's disease was suggested from the results of the following studies: 1) Clinical studies
a) The skin test using 34 sorts of food antigen extracts and the glycerol test were performed on 23 patients with Meniere's disease. The rate of positive glycerol test was higher in the group with the positive skin reaction than in the negative group (p=0.05).
b) In some patients, whose episodes were provoked by the challenge-feeding test, improvement in hearing was produced after Portmann's endolymphatic operation. 2) Experimental studies
a) Labyrinthine reactions were produced when challenged with the antigen through the left foramen stylomastoideum in 4 groups of rabbits as follows: (A) rabbits sensitized by hen's serum, (B) control rabbits, (C) rabbits inoculated with BCG vaccine and (D) control rabbits. Among these 4 groups, the positional nystagmus observed in group A bore a striking resemblance to that of Meniere's attack. The electrocochleograph of group A showed a pattern of cochlear impairment and a histological study revealed endolymphatic hydrops in the ear on the challenged side. This endolymphatic hydrops was not found in the other groups. From these findings, endolymphatic hydrops does not appear to be induced by cell-mediated immunity, but by humoral immunity.
b) To determine the place of antigen-antibody reaction, the labyrinths of guinea pigs sensitized by horseradish peroxidase (HRP) were investigated by electronmicroscopy after challenge with this antigen through the perilymphatic space. Particles of HRP could pass through the Reissner's membrane by intracellular transportation and clung to the surface of dark cells in the stria vascularis. These findings were not observed in the control study and suggest that hyper-permeability of the Reissner's membrane and hypersecretion of the stria vascularis induced by the antigen-antibody reaction are probable causes of endolymphatic hydrops.

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Both of the temporal bones of a 52-year-old man who died of a metastatic cancer of the stomach were histologically studied. One year prior to death, he had stayed in bed for 3 days suffering from a severe vertiginous attack. His left temporal bone showed collapse of the cochlear duct and rupture of the saccular wall. The deficit of the saccular membrane affected almost half of the entire membrane. The distension of the Reissner membrane indicated the presence of endolymphatic hydrops before the occurrence of its collapse. The rupture of the saccular membrane was considered to be caused by rapid increase in endolymph within the saccule, resulting in collapse of the cochlear duct. Though these pathological findings resemble those of Meniere's disease, this patient failed to be so diagnosed because of the lack of repetition of vertigo, which may have been due to a persistent endolymphatic fistula in the saccule. The right ear of this patient had a normal cochlear duct and saccule.

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Three cases of Meniere's disease are reported. Case 1, a 39-year-old man suffered from vertigo with right fluctuant hearing loss and tinnitus. After an interval of about 5 years, he experienced left fluctuant hearing loss and tinnitus with a vertigo attack. Case 2, a 51-year-old woman suffered from left Meniere's disease, and 5 years there-after was troubled with right fluctuant hearing loss and tinnitus with vertigo attack. Case 3, a 22-year-old woman developed sudden deafness on the right side without vertigo in the course of left Meniere's disease. Cases 1 and 2 were diagnosed as bilateral Meniere's disease.
Generally the criteria for Meniere's disease are well-known, but those for bilateral Meniere's disease are not yet clear. We propose the following criteria of bilateral Meniere's disease.
1) Unilateral Meniere's disease with contralateral fluctuant sensorineural hearing loss and tinnitus accompanied by vertigo is definite bilateral Meniere's disease.
2) Unilateral Meniere's disease with contralateral fluctuant sensorineural hearing loss and tinnitus regardless of vertigo is suspected bilateral Meniere's disease.

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I. Introduction
The present paper was designed to study the presence of vestibular Meniere's disease (VMD) and the possibility of VMD transforming into Meniere's Disease (MD).
II. Examinees and Methods
1) According to the diagnosis criteria set by the Department of the Otorhinolaryngology, Gifu University School of Medicine, a comparative study was made of the clinical features of 40 patients diagnosed as VMD and 80 diagnosed as MD.
2) Using the same criteria, a study was made of 50 patients diagnosed as MD, regarding the delay in the appearance of cochlear symptoms against the first attack of vertigo.
III. Results and Consideration
1) Of those diagnosed as VMD, females were predominant and a few had spontaneous nystagmus, CP and CP+DP, compared with those diagnosed as MD. These findings indicate the presence of VMD which differs from MD in the pathological change.
2) In MD, there existed cochlear symptoms developing after vertigo, the delay ranging from 2 months to 6 years. During that period, repeated attacks of vertigo occurred unaccompanied by cochlear symptoms. This shows the presence of VMD which shifts to MD.
3) In other words, it seemed that among patients of VMD there were one type which was similar to MD and another type differing from MD in pathology.

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1. Purpose
From the pattern of the change of patient's hearing in the course of Meniere's disease, the course of Menierés diseae was classified from the pattern of the change of patient's hearing and that of vertigo.
2. Examinees
Examined were 53 proven patients of Meniere's disease according to the diagnostic criteria set by Gifu University. They were 19 males and 32 females, ranging in age from 15 to 71.
The classification of the patterns of the manifestations of vertigo was as follows.
Type 1: Recurrence of definitive spells at long intervals changes to repeated slight spells at short intervals…5 cases
Type 2: A definitive spell appears repeatedly in the same season once or twice every year…16 cases
Type 3: Recurrence of spells gradually decreases with time…7 cases
Type 4: A burst of spells occurs continuously from the onset of the disease…11 cases
Type 5: Repetition of single definitive spells and burst of spells appears with irregular alternation…14 cases
3. Results
(1) According to the change in hearing, 6 types were classifiable.
Type A: Hearing was not aggravated…13 cases
Type B: Hearing was gradually aggravated…14 cases
B1: Difficulty in hearing occurred simultaneously with the fit of the initial spell…9 cases
B2: Difficulty in hearing occurred subsequent the initial spell…5 cases
Type C: Difficulty in hearing appeared suddenly and did not worsen…10 cases
C1: Sudden hearing loss occurred simultaneously with the fit of the initial spell…6 cases
C2: Sudden hearing loss followed the onset of the initial spell…4 cases
Type D: Difficulty in hearing appeared suddenly and then was gradually aggravated with the course of the disease…3 cases
Type E: Difficulty in hearing had existed before the initial spell and was not aggravated…8 cases
Type F: Difficulty in hearing had existed before and was gradually aggravated…5 cases
(2) In the study of association with the classification of course of vertigo, Type A was found to be predominant in Type 2, Type B in Types 2 and 5, Type C in Type 4, Type E in Type 5, and Type F in Type 2.

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The pathogenesis of Lermoyez's syndrome was discussed on the basis of a patient, who was treated by perivascular sympathectomy at the proximal part of the vertebral artery. After this operation “episodic vertigo” disappeared completely, although cyclic fluctuating hearing loss continued as before. The glycerol test performed preand postoperatively was always negative.
Therefore, the mechanism of cochlear dysfunction was inexplicable in terms of the blood circulatory disturbance theory or the intralabyrinthine hyper-pressure theory.

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Extratympanic electrocochleographic findings were compared with the results of the glycerol test and the furosemide test in Meniere's disease. Increased negative summating potentials (SP) were recorded in 25 of the 35 ears (71%), while the glycerol test was positive in 14 of the 25 ears (56%) and the furosemide test was positive in 6 of the 22 ears (27%).
The relationship between the average hearing level at 2 to 8kHz and the increase of negative SP was examined in 35 ears with Meniere's disease. Increased negative SP's were recorded in many patients with mild to moderate deafness. In many of the patients with almost normal hearing and low tone loss with normal hearing above 2kHz, normal SP's were recorded, but no SP appeared in patients with severe deafness.
In the conditions other than Meniere's disease, increased negative SP's were recorded. In some of these, the glycerol test or the furosemide test revealed the existence of endolymphatic hydrops.
The relationship of increased negative SP to endolymphatic hydrops is discussed and the suitability of electrocochleography in the diagnosis of endolymphatic hydrops, compared with the glycerol test and the furosemide test is stressed.

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It is widely held that the electrocochleogram of the patient with Meniere's disease is characterized by increased -SP. The view that the increased -SP reflects the existence of endolymphatic hydrops is considered vital today. However, there are some typical cases of Meniere's disease in which increased -SP is not noted. We studied 44 patients of Meniere's disease and conducted electrocochleographic examination in order to determine whether there are any differences between those who had increased -SP and those who did not.
The following results were obtained.
1. No difference was noted in the nature of dizziness or in the length of the period from the vertigenous attack to the day of the examination.
2. Many of those whose course of the disease is longer than one year and shorter than five years, had positive -SP.
3. No difference was found in the degree of hearing loss.
4. Both positive and negative -SP's were observed in all types of hearing loss.
5. The equilibrium examination revealed no definite difference between these two groups.
From the above, we concluded that clinically there was no definite difference between the positive and negative -SP cases. This proves that electrocochleographic examination, which is considered to be vitally conductive to the diagnosis of the condition of Meniere's disease, fails to provide definite clue to the diagnosis of Meniere's disease. In our view it is appropriate to diagnose Meniere's disease on the bases of anamnesis, hearing and equilibrium examinations and electrocochleographic examination should be made to evaluate the existence of the endolymphatic hydrops.

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従来 Glycerol test は聴力を指標とし, Furosemide test は温度眼振を指標とすることが疑いもなしに行われていたが, 同一患者に両検査を負荷することにより Glycerol test で聴力, 温度眼振の両者を指標とすることが可能であることが証明された. 一方 Furosemide 使用量を20mgから30mgに増量すれば, 同様に聴力, 温度眼振を指標として内リンパ水腫を証明することができると推測される.

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メニエール病患者20名を対象として, 等速視運動刺激の頭部動揺におよぼす影響について, 小型コンピュータを使用して分析し, 次の成績を得た.
1. 頭部動揺軌跡
メニエール病患者の視運動刺激による軌跡型として3型が得られた. すなわち求心型, 左右動揺型および前後動揺型である.
2. 頭部動揺軌跡距離
起立時頭部動揺は視運動刺激の負荷により増大するが, その最大値は30°～90°/secにあった. 左右動揺型は右線条回転速度90°/sec以上で有意に大きな軌跡距離を示した.
3. 頭部動揺のY軸・X軸成分比
60°～90°/secの線条回転速度において, 水平方向刺激ぴ減少, 垂直方向刺激に対して増大を示した. 型別の特徴として, 左右動揺型は右線条回転刺激において120°/secに到るまで減少傾向を示した.
4. 頭部動揺中心の位置移動
頭部動揺中心の視運動性位置移動は軌跡型と刺激方向によって多彩な様相を呈した.
5. 頭部動揺周波数
視運動刺激によって, 頭部動揺は1Hz以下で主要な変動を示した. この変動は周波数スペクトルに加えて平均周波数算出により, 定量的にも表現することができた.
X軸成分では, 水平方向刺激に対し求心型の平均帯域周波数は増大, 左右型の平均帯域周波数は減少を示したが, 前後動揺型では無変動であった. 垂直方向刺激に対しX軸成分はどの型でも変動が少なかった. これに対しY軸成分では, 求心型と前後動揺型は減少続いて増大を示し, 左右動揺型は左線条回軽刺激に対して減少傾向を示した.

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A 53-year-old woman noted hearing difficulty on telephoning, and her mean pure tone average scores for 2, 000, 4, 000 and 8, 000Hz were 65dB in the left ear. There was no balance disturbance, and the caloric reaction remained within normal ranges. In impedance measurement, the normal uncrossed and crossed reflex thresholds on both ears (Jerger, S. et al., 1977) were observed, and only the reflex decay on left contralateral stimulation was abnormal.
A tumor with a diameter of 2cm was visible to the naked eye away from the internal acoustic meatus in the left-sided cerebellar-pontine angle. From the neurootological signs, the tumor seemed to have originated in the inferior vestibular nerve (Ylikoski, J. et al., 1978)

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メニエール病患者にメコリール点眼試験を行い, 瞳孔面積の測定によって検査結果を判定した. その成績を健康者における検査成績ならびに瞳孔径の測定によるメニエール病患者の検査成績と比較検討した.
1. 瞳孔面積の測定によるメコリール点眼試験成績では, メニエール病の患側眼のみならず健側眼においても, 間歇期, 準発作期, 発作期の三つの病期すべてで病的縮瞳の出現率が高かった.
2. 同一症例における検査結果を検討するとメニエール病患者の健側眼では縮瞳率の病期による変動は少ないが, 患側眼では病期が進むにつれ縮瞳率は著しく増加した.
以上の結果より, メニエール病患者においては患側, 健側ともに自律神経異常が存在するが, 発作の原因としては患側の自律神経異常の増悪が関与していると推論される.

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Ifenprodil, cinnarizine, and low molecular weight dextran (250ml) were administered to patients with Meniere's disease (typical and atypical types), and their effectiveness and side effects were evaluated. Ifenprodil was administered to 50 patients, 32 of whom had had diphenidol previously. In all of the 50 patients, who were observed on an average of 161 days, the rate of most effective was 40%.
The antivertiginous effect of cinnarizine was evaluated in a single administration to 38 patients with Meniere's diseas (typical and atypical types), who were observed at a mean of 105 days, the rate of most effective was 42%.
In 30 admitted or readmitted patients with Meniere's disease (typical and atypical types), the effect of low molecular weight dextran (250ml) was evaluated.
The rate of most effective was 40%, which was mainly observed in improvement in hearing difficulty in sudden sensoneural hearing loss or Meniere's disease.
Good effects were seen from all three drugs in patients with vestibular disorder with an apparent dysfunction of the central nervous system as reflected in the eye-tracking test and examination for optokinetic nystagmus.

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1959年より1980年の21年間の阪大および1967年より1979年までの13年間の国内の抗めまい剤の治験報告による有効率の文献的考察から次の結論を得た.
A 抗めまい剤の種類とめまい疾患に対する薬剤有効性には一定の関係はなかった.
B 抗めまい剤全体のめまい疾患に対する有効性をみると, 有効以上を含めた有効率は30～50%でやゝ一定の傾向がみられたが, やゝ有効以上を含めた有効率は, 45～85%と若干有効率はよくなるが, ばらついていた.
C メニエール病と他のめまい疾患との間に抗めまい剤の有効性には有意差はなかった. わずかに double blind studies で, isoproterenol がメニエール病でやゝ有効率が高く, diphenidol, ifenprodil は, 大体同等の有効率である傾向がみられた.

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Significant somatic conditions under which Ménierè's disease develops were discussed based on clinical observation of seven vertiginous patients (orthostatic disregulation, 4; cervical vertigo, 2; and combination of both, 1) whose onset of Ménière's disease was late in their life, and measures to prevent idiopathic onset or periodic attacks were considered.
It was demonstrated statistically that any of the following conditions have a sure prospect of Ménière's disease: one was the ipsidirectional appearance of both vestibular asymmetry (expressed as direction of the induced horizontal nystagmus on ENG) and vegetative asymmetry (expressed as direction to the side with wider responded amplitude on bi-auricular plethysmography) iduced by keeping the patient erect after resting in the supine position for 20 minutes as in Schellong's test, and the other was the labyrinthine type of the cervical threshold shift appearing on pure tone audiometry by keeping the same head position as in the cervical nystagmus.
The improvement in the above-mentioned significant conditions, the refore, may prevent the onset or expected next attack of Ménierè's disease and appropriate treatment for them may correct orthostatic disregulation and cervical vertigo.

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