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48DOI: 10.24411/2181-0443/2021-10014
ЭПИДЕМИОЛОГИЯ, ПАТОФИЗИОЛОГИЯ, ДИАГНОСТИЧЕСКИЕ МЕТОДЫ И ВЕДЕНИЕ БОЛЕЗНИ МЕНЬЕРА
Эргашева Зумрад Абдукаюмовна
Андижанский государственный медицинский институт Андижан, Узбекистан
Болезнь Меньера - одно из заболеваний уха, вызывающее расстройство внутреннего уха, головокружение и потерю слуха. В большинстве случаев болезнь Меньера поражает только одно ухо. Это заболевание может возникнуть в любом возрасте, но обычно начинается у молодого и среднего возраста. Ежегодно во всем мире диагностируется 45 500 человек. В этой статье обсуждаются эпидемиология, патофизиология, диагностика и лечение болезни Меньера.
Ключевые слова: Меньер, внутреннее ухо, головокружение, патофизиология, эпидемиология, диагностика.
EPIDEMIOLOGY, PATHOPHYSIOLOGY, DIAGNOSTIC TECHNIQUES AND MANAGEMENT OF MENIERE'S DISEASE
Meniere's disease is a disorder of the inner ear that can lead to dizzy spells (vertigo) and hearing loss. In most cases, Meniere's disease affects only one ear. Meniere's disease can occur at any age, but it usually starts between young and middle-aged adulthood. It's considered a chronic condition, but various treatments can help relieve symptoms and minimize the long-term impact on your life. Around 45,500 people are diagnosed each year in the world. This article discusses the epidemiology, pathophysiology, diagnosis, and management of Meniere's disease.
Keywords: Meniere, inner ear, vertigo, pathophysiology, epidemiology, diagnosis.
МЕНЬЕР КАСАЛЛИГИНИНГ ЭПИДЕМИОЛОГИЯСИ, ПАТОФИЗИОЛОГИЯСИ, ДИАГНОСТИК УСУЛЛАРИ ВА ОЛИБ БОРИЛИШИ
Меньер касаллиги — бу ички ;уло;даги бузилишлар, бош айланишлар ва эшитиш ;обилиятининг йу;олишига олиб келадиган ;уло; касалликларидан биридир. Куп Х,олларда Меньер касаллиги фа;ат битта ;уло;к;а тах,сир курсатади. Ушбу касаллик х,ар ;андай ёшда учраши мумкин, аммо одатда ёш ва урта ёшли инсонлар орасида кузатилади. Х,ар йили дунё буйича 45500 кишига ушбу ташХ,ис ;уйилади. Ушбу ма;олада Меньер касаллигининг эпидемиологияси, патофизиологияси, диагностика ва даволаниши ёритилган.
Калит сузлар: Меньер, ички ;уло;, vertigo, патофизиология, эпидемиология, диагностика.
Introduction: Meniere's disease is a disorder of the inner ear that can lead to dizzy spells (vertigo) and hearing loss. In most cases, Meniere's disease affects only one ear. Meniere's disease can occur at any age, but it usually starts between young and middle-aged adulthood. It's considered a chronic condition, but various treatments can help relieve symptoms and minimize the long-term impact on your life.
Signs and symptoms of Meniere's disease include: Recurring episodes of vertigo. You
have a spinning sensation that starts and stops spontaneously. Episodes of vertigo occur without warning and usually last 20 minutes to several hours, but not more than 24 hours. Severe vertigo can cause nausea; Hearing loss. Hearing loss in Meniere's disease may come and go, particularly early on. Eventually, most people
have some permanent hearing loss; Ringing in the ear (tinnitus). Tinnitus is the perception of a ringing, buzzing, roaring, whistling or hissing sound in your ear; Feeling of fullness in the ear. People with Meniere's disease often feel pressure in an affected ear (aural fullness). After an episode, signs and symptoms improve and might disappear entirely for a while. Over time, the frequency of episodes may lessen. The cause of Meniere's disease is unknown. Symptoms of Meniere's disease appear to be the result of an abnormal amount of fluid (endolymph) in the inner ear, but it isn't clear what causes that to happen. Factors that affect the fluid, which might contribute to Meniere's disease, include: Improper fluid drainage, perhaps because of a blockage or anatomic abnormality; Abnormal immune response; Viral infection; Genetic predisposition. Because no single cause has been identified, it's likely that Meniere's disease results from a combination of factors. The unpredictable episodes of vertigo and the prospect of permanent hearing loss can be the most difficult problems of Meniere's disease. The disease can unexpectedly interrupt your life, causing fatigue and stress. Vertigo can cause you to lose balance, increasing your risk of falls and accidents. In Asian countries, there is one previous epidemiologic study that used a retrospective survey of a specific district. Previous studies have demonstrated that weather variables are strongly associated with symptom aggravation in MD. However, no study has reported on seasonal variation of MD.
Epidemiology. Kim and Cheon made the following comments in an article they wrote about this disease, the current study has indicated the following: [1] the incidence rate of MD in Korea showed a rapid yearly increase from 2013 to 2017; [2] MD is most common in older adults and females; and [3] there is no seasonal variation in incidence rate of MD. The rapid increase in the incidence rate may be due to the following reasons: first, possibly the rapid progression to an aging society of the Korean population. MD shows the highest incidence rate in the 70, 60, and 50 year olds (in descending order) in many studies. The proportion of the population aged over 50 years increased from 32.1 to 36.3% (from 2013 to 2017) showing the most rapid progress of an aging society in the
world [4]. Second, there has been an increase in medical accessibility in the Korean population. With rapid economic growth, health expenditure in Korea increased from 94,030 billion won in 2013 to 130,974 billion won in 2017, a 39% growth rate. An increase in health expenditure suggests that medical use and the possibility of receiving a diagnosis have also increased. Another ear disease, sudden sensorineural hearing loss, also showed a rapid increase of 208% from 2011 to 2015 in another Korean population-based study [5]. Third, there may have been a true substantial increase in MD incidence. There have been many reports regarding the prevalence and incidence of MD (Table 1). The only epidemiological study of MD in Asian countries, which was published in 2005, reported that the prevalence of definite MD was 34.5 per 100,000 persons in Japan [6]. In the current study, the prevalence of MD in Korea in 2017 is approaching the prevalence in Western countries [7]. Dietary components (e.g., salt, caffeine, aspartame, and alcohol) and mental stress have been suggested as potential triggers for MD, and westernization of the Asian diet and industrialization could influence the increase in the inci dence of MD. Furthermore, with the rapid emergence of lifestyle changes, the prevalence of metabolic diseases has greatly increased in the Korean population. From 2012 to 2016, the prevalence of diabetes in the Korean population increased from 9.9 to 13.0%. In addition, from 1998 to 2012, the prevalence of asthma, atopic dermatitis, and allergic rhinitis in the Korean adult population also increased from
1.2 to 3.1%, from 1.2 to 17.9%, and from 2.7 to 3.8%, respectively [8]. These allergic diseases and diabetes have been demonstrated to be more frequent in patients with MD than in the general population [9]. Further studies of the relationship between dietary and lifestyle changes and MD symptoms and its mechanisms would be needed to manage the symptoms of MD and control the incidence in Asian countries. MD is more common in women than in men, with a female-to-male ratio ranging from
1.3 to 4.3 [10]. In our study, this ratio was 2.17. A hormonal influence [11] and health-seeking behavior of women might account for the sex differences. In this study, the seasonal incidence of MD was higher in summer and autumn and
lower in winter and spring. However, due to the rapid yearly increase in incidence rate, the standard deviation increased, and there were no significant differences. Due to its medium latitude location, Korea's four seasons are truly distinctive, with each lasting approximately three months [12]. In summer, the weather is very hot and humid, and the atmospheric pressure is relatively low. In winter, the weather is very cold and dry, and the atmospheric pressure is relatively high (Fig. 1). The humidity is the highest and the atmospheric pressure is the lowest in summer; this decreases and increases, respectively, in the order of autumn, spring, and
winter. A previous study reported that high humidity and lower atmospheric pressure are associated with higher odds of an attack and higher levels of vertigo, tinnitus, and aural fullness in patients with MD [13] A characteristic feature often observed in MD is endolymphatic hydrops, which is a condition of excessive accumulation of endolymph in the cochlea [14] The change in atmospheric pressure may influence endolymphatic hydrops via the middle ear. It is known that if the air is more humid, the speed of sound increases, and the effect of humidity on the speed of sound is slightly greater at lower air pressures.
Location Study Study design Criteria Population size Prevalence/ Sex ratio
period incidence1 (M/F)
Bruderer el aL, 2017 UK 1993 -2014 Population-based MD diagnosis ■f audiometry -t- betahistine 10,000,000 -/13. L 1.7
Guerra- Jiménez et al.t 2017 Spain 2015 Medical health records MD diagnosis 459.872 -/5.2 -
Tyrrell et al., 2014 UK 2006 -2010 Questionnaire Self-reported MD 500.000 270/- 1.4
Harris and Alexander. 2010 USA 2005 -2007 Medical health records MD diagnosis &0,000,000 records 190/- 1.3
Radtke et al., 2008 Germany 2003 Cross-sectional population - based survey MD diagnosis 8,318 120/- -
Havia et aL, 2005 Finland - Questionnaire Self-reported symptoms 5,000 participants 513/- 4.3
Shojaku et al.. 2005 Japan 1980- -2004 Medical health records Definite MD diagnosis 1,100,000-1,120,000 per 5 years 34.5/5.0 1.3
1 Per 100,000 persons
Table 1. Reported Meniere's disease (MD) incidence in studies conducted in the past two
decades.
Aggravation of MD in high humidity and low atmospheric pressure conditions may be due to these reasons; however, more research is needed to investigate the mechanisms linking weather and MD. Furthermore, to accurately identify the seasonality of MD, long-term analysis over more than 10 years may be needed. There are some limitations of this study. The main limitation of all population-based studies is the difficulty of controlling confounders. In this study, there was potential enrollment of other inner-ear diseases. To lower this possibility, we counted only the cases diagnosed with the disease code for MD, diagnosed correctly using audiometry, and having been prescribed betahistine. Moreover, in reference to the
National Health Insurance statistics, the total health examination participation rates become higher as people age, after the age of 20 years. This is mainly due to a substantial increase in disease as people age; however, it could also be due to an increase in health-seeking behaviors in the older population. The age-related incidence of MD in this study may also be influenced by this factor. In terms of seasonal variation, the total number of insurance claims from 2016 to 2018 was the highest in winter; this was followed by spring, summer, and autumn [15]. Unlike those references, in this study, the incidence of MD was higher in summer and autumn. This may suggest that there is a true substantial association between MD and seasonal factors.
Fig. 1. Seasonal incidence of Meniere's disease, average relative humidity, and average
atmospheric pressure from 2013 to 2017.
Another limitation is the accuracy of the incidence of MD as MD is an episodic disease and that the data source is the insurance claim data. It is important to set the washout period appropriately to estimate the incidence of an episodic disease. However, due to the lack of prior studies, it is difficult to set a definite washout period; we had to follow the experts' opinions. The accuracy of diagnoses from claim data is still controversial. However, it is unlikely that betahistine, a medicinal criterion of this study, was prescribed for another disease; further, the diagnostic code was recorded as MD. In conclusion, this study is the first to analyze the incidence of MD in an Asian country in the last decade and the first to analyze seasonal variation of MD in the world. As the HIRA data include nearly the entire population, it was appropriate to use them to represent the South Korean population, and there was enough strength to reduce any sampling bias caused by random selection. Further studies about the relationship between diet and MD, seasonality of MD with long-term analysis, and investigating
the underlying mechanisms connecting weather and MD are needed [16].
Histopathology and
pathophysiology. EH has been considered the hallmark of MD since the histopathological investigation was first reported. Displacement of Reissner's membrane and dilation of the scala media of the cochlea are histological marker of EH. In the early study of MD, it is generally considered that all patients with MD should exhibit EH, and all patients with EH should also exhibit MD symptoms. However, study on human temporal bone histopathology indicates that EH should be considered as a histologic marker for MD, but not a true pathological mechanism. Other histological features have also been observed by temporal bone studies of MD patients. These studies include findings of ischemia of the stria vascularis, fibrous tissue proliferation in saccular, atrophy of the sac and loss of epithelial integrity, hypoplasia of the vestibular aqueduct, and spiral ganglion degeneration at the apex of the cochlea [17]. Recently, histopathological examination of
vestibular nerve (VN) in MD patients revealed evidence of various types of chronic VN impairment, including the formation of corpora amylacea, axon atrophy, and severe damage to the myelin sheath. Density of corpora amylacea is positively correlated with the duration of disease, as well as the degree of hearing impairment [18]. MD is considered a result of multiple genes interacting with environmental factors. Familial MD has been observed in 5— 15% patients and shows a feature of autosomal dominant inheritance. Martin-Sierra found two rare missense mutations on DPT and SEMA3D genes by Whole Genome Sequencing in two Spanish MD families. Extracellular signal encoded by the genes is associated with the formation and maintenance of inner ear structures. They concluded that DPT and SEMA3D gene mutations might be associated with the pathogenesis of familial MD [19]. Animal studies and human studies had provided evidences that endolymphatic sac has an immune function and the presence of autoantigens can damage inner ear by autoimmune reactions. Recently, an immune genotyping array study in bilateral MD identified the first locus, at 6p21.33. Signaling analysis predicted the pathway of TWEAK/Fn14, which is involved in the modulation of inflammation in several human autoimmune diseases, can induce an inflammatory response mediated by nuclear factor-jb in MD[20].
Diagnosis. The diagnosis of Meniere's disease still relies mainly on detailed medical history and clinical symptoms, supplemented by auditory and vestibular function examinations. The earliest diagnostic criterion was proposed by AAO-HNS in 1995 in which the diagnosis of MD is divided into four grades: namely certain MD, definite MD, probable MD, possible MD. More recently, the diagnostic criterion proposed by the Barany Association in 2015 only divided MD into two types: definite MD and probable MD. The pathological biopsy of the inner ear that could not be performed was excluded as definite diagnosis criterion. In the 1995 AAOHNS guidelines, MD was divided into four stages based on patient's pure tone hearing threshold. While the guideline proposed by Barany Society in 2015 did not adopt the classification of hearing threshold. Hearing
threshold is an important reference factor in the selection of treatment strategies and in the evaluation of treatment efficacy in MD. Because of the inability to perform inner ear biopsy on MD patients, direct visualization of EH has been an important goal for clinicians. In 2007, Nakashima first observed EH in patients by 3D fluid-attenuated inversion recovery (3DFLAIR) MRI after intratympanic injection of gadoliniumbased contrast agent. With recent technical developments in MRI, 3D real inversion recovery (3D-real IR), Rapid acquisition with relaxation enhancement (RARE), has made the visualization of EH more clearly. A subtraction of a positive endolymph image from a positive perilymph image which was termed a HYDROPS image (hybrid of the reversed image of the positive endolymphatic signal and native image of the positive perilymph signal) could demonstrate anatomic information of the various inner ear compartments in one image series. Different grading scale for evaluating the degree of EH has been proposed. A widely used three-stage grading system for hydrops in vestibule and the cochlea was proposed in 2009. In a more recent study, the authors proposed the inversion of the saccule to utricle ratio (SURI) on an oblique sagittal section as a marker of EH. They considered SURI a more reliable approach than conventional semiquantitative methods for diagnosing MD [21]. The correlation between MRI image and audio-vestibular function test is still inconsistent. Quatre reported that the correlation between MRI and electrocochleography (EcochG), MRI and shift of distortion product otoacoustic emissions (DPOAEs) were not significant. While, EH was correlated with hearing loss [22]. EH observation in vivo patients also confirmed the theory that EH should be considered as a histologic marker for MD, but not a true pathological mechanism. EH is closely related to hearing loss but does not necessarily result in Meniere's symptoms. Appearance of EH could be observed in MD patients both in symptomatic and asymptomatic ears [23]. Clicks EcochG had been used for the diagnosis of EH since 1970s. EcochG shows a high average summating potential (SP) to action potential ( AP) ratio in patients with EH. The click
SP/AP ratio has been world-widely used as a diagnostic tool for MD and also become the basis of numerous publications. A new technique that can help to understand the low-frequency hearing loss in early stage of MD is called Auditory Nerve Overlapped Waveform (ANOW) [24]. ANOW originates in the apical half of the cochlear turn. Researchers believed that ANOW changes were more sensitive than traditional CAP thresholds in detecting apical turn hydrops. Vestibular-evoked myogenic potentials (VEMP) testing is a neurophysiological technique that can assess saccule and utricle function. Cervical VEMP (cVEMP) is believed to assess saccular vestibular signals carried via the vestibulospinal tract. Furosemide-loading VEMP (FVEMP), that is a cVEMP rises 60 min after furosemide administration in patients with MD, can also be a useful tool in assessing saccule function. Seo found that recent and frequent vertigo attacks were closely related with the results of FVEMP, which indicated a consequence of membranous labyrinth rupture during vertigo attacks [25]. Ocular VEMP (oVEMP) can be used in utricle function assessment. Caloric test and video-head impulse test (vHIT) can be used to examine the function of semicircular canals. Caloric test mainly assess the horizontal semicircular canal function while vHIT enables instrumental assessment of the vestibulo-ocular reflex in each of the 6 semicircular canals at high frequencies. It has been revealed that vHIT was almost normal in advanced MD patients while only 8% of caloric reflex test results were normal [26]. The contradiction between caloric test and vHIT could be explained as when the head turns in the plane of a semicircular canal, the ampulla
neurons are stimulated and neurons in the contralateral canal are inhibited by reverse endolymphatic flow. This mechanism operates in vHIT, but not during caloric reflex testing. Management. Management of MD should be a combination of lifestyle and dietary changes, medical therapy, and psychological counseling. The first goal of the management of MD is to reduce the attack frequency. Secondarily, vestibular function and auditory function preservation should also be considered. The modification of the lifestyle is important for MD Patients. High quality of sleep, decreasing stress, avoiding caffeine, alcohol and tobacco and adopting a low salt diet are recommended. Conservative treatment must first be considered and destructive treatment is preferred for patients with irreversible hearing loss [27] (Fig. 2). Treatment of bilateral MD is difficult and the choice of treatment strategy should be extremely cautious. The possibility of developing into bilateral MD should be taken into consideration by clinical physicians at the beginning of unilateral involvement of the disease. Betahistine Betahistine, a strong H3 antagonist that can increase cochlear blood flow, increases histamine turnover in the central nervous and vestibular system, and decreases vestibular input in the peripheral vestibular system. The minimum dose of 48 mg/d is effective. In patients with severe MD that low dose is ineffective, the dose of betahistine can be increased to 288 480mg/d. Betahistine is also effective to improve the recovery of static symptoms in MD patients with unilateral vestibular loss after unilateral vestibular neurectomy.
Figure 2. Treatment of MD should be a combination of lifestyle and dietary changes, medical therapy, and invasive therapy. Conservative treatment must first be considered and destructive treatment is preferred for patients with irreversible hearing loss.
Hydrochlorothiazide, acetazolamide and chlorthalidone are most commonly used diuretics as treatments of MD. But a systematic review including 19 studies overall, of which 4 were randomized trials, revealed that the certainty of the evidence that whether diuretics could lead to a relief of symptoms is still very low [28]. It is commonly believed that diuretics are supposed to relieve vertigo and hearing loss by decreasing volume and pressure in endolymph. But Rosenbaum outlined the possibility that an abrupt lowering of blood pressure by diuretics can trigger an adverse sympathetic reaction and transmit misleading information to the cochlear vasopressin receptors. This eventually would
lead to a permanent damage in inner ear [29]. When conservative and medical treatment failed in vertigo control, intratympanic corticosteroids are recommended as the second line treatment [27]. The rate of persistent tympanic membrane perforation following intratympanic steroid injection is low. Patients with a history of radiation to the head and neck may be at increased risk for persistent tympanic membrane perforation. The possible mechanisms of corticosteroids in treating MD could be the effect of changes of fluid regulation, and ion regulation [30]. Both dexamethasone and methylprednisolone are acceptable by intratympanic injection. Either daily injection for
consecutive days or weekly injection for consecutive weeks is proved to be effective. Several randomized, double-blind, placebo-controlled studies and systemic reviews have confirmed the significant improvements in vertigo control with intratympanic corticosteroids injection [31]. However there still lacks an international consensus on ideal frequency and dose of intratympanic corticosteroids injection. Also, controversy still exists regarding the efficiacy between intratympanic corticosteroids injection and oral medical therapy. Paragache compared application of intratympanic dexamethasone and conventional medical therapy with dietary control and oral betahistine. The result showed no difference in vertigo control and tinnitus. Intratympanic gentamicin (ITG), a chemical labyrinthine resection treatment, is recommended as a fourth line treatment in refractory MD [27]. The risk of hearing loss should not be ignored for its otoxic effects. Mitochondrial mutation of the gene MTRNR1 is not screened in most of the countries. This mutation exposes to a complete and definitive deafness after a single injection of gentamicin. Patients receiving ITG should be well informed before treatment. A double-blinded, randomized, placebo-controlled trial revealed that ITG can be an effective treatment for vertigo in MD. The potential risk of hearing loss exists, but the trials showed no difference in hearing level between pre-treatment and post-treatment [32]. Patel et al. [33] compared the effectiveness between ITG and intratympanic methylprednisolone in a randomized, doubleblind trail. The result showed an 87% reduction in vertigo frequency in ITG group and 90% reduction in vertigo frequency in intratympanic methylprednisolone group. There is no significant statistical difference in vertigo control and hearing levels. Both intratympanic methylprednisolone and gentamicin are safe and effective therapeutic options for refractory MD. Endolymphatic sac surgery (ELSS) is a preferred
treatment for refractory MD patients in the early stage. Both vestibular function and hearing function can be well preserved. Endolymphatic sac decompression (ESD) surgery is widely accepted for its easy manipulation and less postoperative complications. Literatures have shown efficacy of ESD for the control of vertigo and hearing loss in 64.5-90% of patients [34]. The controversy on the effectiveness of ESD still exists because it is difficult to conduct a singleblind or double-blind trail in surgical treatment of MD. Some clinicians question its long-term efficacy and consider that vertigo control is achieved more due to a placebo effect than because of the procedure itself. Recently, Saliba et al. [35] proposed endolymphatic duct blockage (EDB) surgery as a new surgical procedure for treating MD. They reported a 96.5% complete control of vertigo in EDB group and 37.5% in ESD group after 24 months follow-up. Hearing level was well preserved in both groups. The assessment of quality of life also showed a significant improvement. Labyrinthectomy and vestibular neurectomy (VN) are considered to have the highest possibility of vertigo control in intractable MD patients. VN could be considered when patients have poor but serviceable hearing. Labyrinthectomy is suitable for patients with severe to profound senserineural hearing loss. Meningitis, cerebrospinal fluid leak and epidural hematoma are possible post-operative complications following VN. Yu [36] reported a 100% vertigo control both in labyrinthectomy group and VN group. The quality of life also improved in both groups. Generally, destructive surgery is less and less performed.
Conclusion: In summary, Meniere's disease is one of the epidemiologically growing and widespread diseases. Through this article, we have discussed a number of data on the epidemiology, pathophysiology, diagnosis and treatment of this disease. We hope, this article will be at least a little motivation for further research.
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