A bibliometric and visualization study of Meniere’s disease: Current status and global hotspots and emerging trends

Background:

Meniere’s disease (MD) is a clinical condition characterized by endolymphatic hydrops. Persistent symptoms negatively affect patients mood, and the underlying etiology remains unclear. It is necessary to comprehensively understand the relevant publications, review the history and current status of research, and analyze hotspots and frontiers of research on MD.

Methods:

We retrieved literature on Meniere’s disease from 2003 to 2022 from the Web of Science database and extracted the data. Data visualization and analysis was conducted using Cite Space, VOS viewer, an online web tool, and Microsoft Office Power Point 2019.

Results:

In total, 2847 publications were analyzed. The number of annual publications was relatively stable, with an accelerated upward trend over the past 5 years. The country with the most publications was USA (751, 26.38%), while the University of Munich contributed more publications than any other institution (117, 4.11%). The article titled “Diagnostic criteria for Meniere’s disease” by Lopez-Escamez J et al in 2015 was the most cited and co-cited publication, and also had the top co-cited references with the strongest citation bursts. Naganawa S was the author with the most publications (85, 2.99%). The top 3 journals and co-cited journals were Otology Neurotology, Acta Oto Laryngologica, and Laryngoscope. Recently, the key theme words were “sensorineural hearing loss,” “therapy,” “intratympanic injection method,” “vestibular-evoked myogenic potentials,” “vestibular migraine,” “magnetic resonance imaging,” and “meniere’s disease.”

Conclusions:

The US has the largest number of publications and research institutions, many European countries have high-quality journals, and Japan has the highest number of scholars. The international opinion on Meniere’s disease is relatively uniform. The stepped-therapy for MD is scientific and clear. Intratympanic injection of steroids and intratympanic injection of gentamicin are commonly used, but steroids are considered safer. Saccular dysfunction may be more common in patients with MD than in those with utricular dysfunctions. It is worth paying attention to study the relationship between MD and vestibular migraine through headache. Progress in magnetic resonance imaging technology is still required for the imaging diagnosis of MD.

1. Introduction

Meniere’s disease (MD) is an inner ear disorder with endolymphatic hydrops (EH) as its pathological feature. The main clinical manifestations are recurrent rotatory vertigo, fluctuating progressive hearing loss, tinnitus, and ear fullness.^[1] As the disorder progresses, hearing loss and tinnitus may gradually become permanent, which has a heavy psychological burden to patients. It will aggravate the disease and induce a vicious cycle.^[2] Beyond this, neuro-otological complications may develop, such as benign paroxysmal positional vertigo, vestibular drop attacks, and bilateral vestibulopathies. MD also causes frequent falls, greatly increasing the risk of disability in the elderly.^[3,4] Age, sex, sleep disorders, and genes are risk factors for MD.^[5] With multiple contributing factors, including genetic factors, viral infection, autoimmunity, and allergy, the etiology and pathogenesis of MD remains unclear.^[6–8]

The internationally accepted diagnostic criteria for MD were defined by the American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) in 1995 and the Barany Society in 2015.^[7–9] In 2020, clinical practice guidelines published in AAO-HNS were updated.^[1] Besides symptoms, functional inner ear tests include audiometry, cervical and ocular vestibular-evoked myogenic potential (cVEMP and oVEMP) testing, videonystagmography with caloric testing, electrocochleography, video head impulse testing, and rotary chair. Inner ear magnetic resonance imaging (MRI) was developed to visualize EH.^[1,10] To date, there are no specific diagnostic methods for MD. The main purpose of treatment is to alleviate EH and improve symptoms, such as vertigo crises, hearing loss, tinnitus, and ear fullness.^[11] A low sodium diet, restricting caffeine and alcohol intake, and vestibular rehabilitation exercises are indispensable.^[12,13] According to international consensus, diuretics and betahistine are the first choices for oral medication. Intratympanic corticosteroids, such as dexamethasone and methylprednisolone, are the most commonly used second-line medical treatments.^[14,15] The third step is endolymphatic sac surgery. As a last resort, intratympanic injection of gentamicin (ITG), and surgical destructive treatments, such as surgical labyrinthectomy, and vestibular neurectomy, are performed.^[16] Over the past 20 years, uncertain aspects have attracted scientific attention to explore the etiology and pathology mechanisms, diagnostic methods, and new clinical therapies. It is urgent to use bibliometric and visualization analysis methods to collect published literature, analyze the evolution of knowledge, the current status and hotspots, and emerging trends, and provide insights for future research.

Bibliometric and visualization analyses based on mathematical and statistical methods depict the knowledge structures and trends to identify the most prolific countries or regions, institutions, authors, journals, and references, determine rate of the international cooperation and geographic distributions,^[17,18] and estimate hotspots and emerging trends in research from references and keywords,^[19,20] providing valuable information and direction for further research.^[21] The most commonly used bibliometric and visualization statistical analysis software are Cite Space and VOS viewer.^[22,23]

2. Materials and methods

2.1. Data collection

Data were retrieved and extracted from the science citation index expanded of the web of science core collection database. The query formula was as follows: TS = (“Ménières disease” OR “Ménière disease” OR “Meniere’s Disease” OR “Menieres disease” OR “Meniere disease”). The retrieval time was from January 1, 2003, to October 1, 2022. Only articles and reviews written in English were considered. All searches were conducted on 1 day (October 20, 2022). Duplicates were removed; and ultimately, 2847 publications including 2500 articles and 347 reviews, were collected for further analysis. The retrieval and screening processes are illustrated in Figure 1.

Figure 1.

Flowchart of retrieval and screening data.

2.2. Bibliometric and visualization analysis

In this study, we used Cite Space 6.1 R3 (https://sourceforge.net/projects/citespace/files/), a Java-based software developed by Professor Chaomei Chen at Drexel University. It can generate visualization analysis and create various characteristic figures, such as presenting a co-occurrence cooperation network map of countries or regions and authors, the most prolific countries or regions, institutions, authors, journals, co-citation of journals and references, co-occurrence keyword clusters, and keywords with the strongest citation bursts.^[24,25]

The free computer program VOS viewer v1.6.18, developed by Nees Jan van Eck and Ludo Waltman from Leiden University in the Netherlands, was used to perform co-citation and co-occurrence analysis and construct and visualize bibliometric network graphs, such as network and chronological order of co-occurrence keywords with high frequencies.^[26]

In addition, the Web of Science Citation Report Analysis, the online web analysis platform (www.bioinformatics.com.cn), and Microsoft Office Power Point 2019 were used for auxiliary analysis data, creating a geographical distribution map, figure, and flowchart.

The articles from China mentioned in this article included Taiwan. Articles from the United Kingdom included England, Wales, Scotland, and Northern Ireland.

3. Results

A total of 2847 publications, including 2500 articles and 347 reviews, were retrieved from the web of science core collection database. The total number of citation records of the retrieved articles was 52,356, and the average number of citations per year and article was 2615 and 18.39, respectively. The H-index for all publications was 81.

3.1. Annual publications and citations status

According to the annual distribution of publications and citations (Fig. 2), the interest in MD has consistently increased over the past 2 decades. In the first 5 years there were fewer than 100 publications, and since then, the number has increased until it exceeded 200 in 2021. From 2003 to 2008, the annual number of cited records was <1000, whereas only 4 years later, the cited records exceeded 2000 and 2 years thereafter they exceeded 3000; indicating that the growth rate increased significantly. Furthermore, the cited records that experienced ladder-type growth from 2018 to 2021 were 3972, 5414, 6497, and 7072, respectively.

Figure 2.

The annual trends of global publications and citations.

3.2. Countries or regions and institutions analysis

A total of 70 countries or regions and 2126 relevant institutions participated in the MD studies. The geographical distribution of the total number of MD research publications in all countries and regions is shown in Figure 3A, darker colors represent a higher number of publications. The most prolific countries were the USA in North America, followed by Japan and China in Asia, and Germany and Italy in Europe. The top 5 countries contributed to more than 60% of the total number of publications (Table 1). The United States produced the most publications (751, 26.38%), followed by Japan (394, 13.84%), China (291, 10.22%), Germany (265, 9.31%), and Italy (192, 6.74%). The citations from USA were 183,318, higher than that in other countries. USA, Germany, Japan, Australia, and Italy ranked high on the H-index. Although the number of publications in China was large, it is slightly insufficient in terms of the number of citations and the H-index.

Figure 3.

Geographical distribution of publications and cooperation network map of countries/regions in Meniere’s disease. (A) Geographical distribution of the number of publications. (B) Cooperation network map of countries/regions.

Table 1.

The top 10 most prolific countries/regions and institutions involved in MD research.

Rank	Countries/regions	Count (% of 2847)	Times Cited	H-index	Rank	Institutions	Count (% of 2847)	Times Cited	H-index
1	USA	751 (26.379)	18,318	62	1	University of Munich	117 (4.110)	4245	38
2	Japan	394 (13.839)	8024	43	2	Nagoya University	97 (3.407)	3291	32
3	China	291 (10.221)	3024	27	3	University of California System	79 (2.775)	2148	26
					3	University of Sydney	79 (2.775)	2243	24
4	Germany	265 (9.308)	9164	51	4	Udice French Research Universities	78 (2.740)	1467	24
5	Italy	192 (6.744)	4205	31	5	Harvard University	68 (2.388)	1634	23
6	South Korea	167 (5.866)	3012	24	6	Johns Hopkins University	59 (2.072)	3856	29
7	The United Kingdom	149 (5.233)	3114	27	7	Harvard Medical School	57 (2.002)	1371	20
8	Spain	133 (4.672)	3112	29	8	Tampere University	53 (1.862)	1313	17
9	Australia	132 (4.636)	4062	32	9	University of Granada	51 (1.791)	1962	24
10	France	114 (4.004)	1826	24	10	Massachusetts Eye Ear Infirmary	49 (1.721)	1177	18

MD = Meniere’s disease.

In the collaboration network map of countries and regions, a node represents a country or a region (Fig. 3B). The larger the area of the node, the larger the number of publications. The thicker curved line connecting the nodes indicates the frequency with co-occurrence, as they indicate collaborative relationships. An isolated node without any connections is devoid of collaboration. Red tree rings manifest the so-called high scholarly activity, whereas purple rimmed nodes indicate a high degree of centrality. The United States, which possessed the broadest scientific collaboration, worked intensively with Japan, China, Germany, India, Sweden, Finland, France, Australia, the United Kingdom, South Korea, Italy, the Netherlands, Spain, Belgium, and New Zealand. China cooperated closely with the USA, Japan, Finland, India, Sweden, and Germany. The main collaborators in Germany were Italy, Spain, France, and Switzerland. High scholarly activity strong bursts were mainly detected in China, Japan, and India, followed by the Netherlands, USA, and Sweden. According to centrality, the countries closest to pivotal points in the evolution of an entire research field were the US, Australia, the United Kingdom, France, Canada, Sweden, and Switzerland.

As Table 1 indicates, the top 10 institutions have the most MD-related publications. The University of Munich in Germany accounted for 4.11% of all publications worldwide, and with 117 publications it had the most publications of any institution; moreover, it was cited the most often (4245) and had the highest H-index (38). Nagoya University in Japan produced the second most publications, with 97 (3.41%) publications, and the H-index was 32. The University of California in USA and the University of Sydney in Australia have the third most publications (79, 2.78%), with H-indexes of 26 and 24, respectively; the number of citations exceeded 2000. These institutions were followed by Udice French Research Universities (78, 2.74%) and Harvard University (68, 2.39%). Although the Johns Hopkins University ranks only 6th in terms of the number of publications, the number of citations was 3856.

3.3. Analysis of highly cited publications

The publications are listed in descending order of total number of citations (Table 2). The top 12 most cited publications were published between 2005 and 2017. The main type of study was an article. Three publications were cited more than 480 times. The first was “Diagnostic criteria for Meniere’s disease” by Lopez-Escamez et al in 2015, followed by “Vestibular migraine: Diagnostic criteria and Disorders of Balance” by Lempert et al in 2012, both of which were published in the Journal of Vestibular Research. The third was “Vestibular Function in US Adults Data from the National Health and Nutrition Examination Survey, 2001-2004” published by Agrawal et al in Archives of Internal Medicine in 2009.

Table 2.

The top12 highest cited publications.

Rank	Year	Publication title (Author)	Journal	Total citation	Type of study
1	2015	Diagnostic criteria for Meniere’s disease (Lopez-Escamez J, et al)	Journal of Vestibular Research-Equilibrium & Orientation	613	Article
2	2012	Vestibular migraine: Diagnostic criteria (Lempert T, et al)	Journal of Vestibular Research-Equilibrium & Orientation	503	Article
3	2009	Disorders of Balance and Vestibular Function in US Adults Data from the National Health and Nutrition Examination Survey, 2001-2004 (Agrawal Y, et al)	Archives of Internal Medicine	489	Article
4	2010	Vestibular-evoked myogenic potentials: Past, present and future (Rosengren SM, et al)	Clinical Neurophysiology	339	Review
5	2005	Epidemiology of vestibular vertigo - A neurotologic survey of the general population (Neuhauser HK, et al)	Neurology	363	Article
6	2007	Visualization of endolymphatic hydrops in patients with Meniere’s disease (Nakashima T, et al)	Laryngoscope	356	Article
7	2005	Characteristics and clinical applications of vestibular-evoked myogenic potentials (Welgampola MS, Colebatch JG.)	Neurology	290	Review
8	2007	Aminoglycoside-induced ototoxicity (Selimoglu E)	Current Pharmaceutical Design	268	Review
9	2008	Meniere’s disease (Sajjadi H, Paparella MM.)	Lancet	257	Article
10	2007	Epidemiology of vertigo (Neuhauser HK)	Current Opinion in Neurology	244	Article
11	2009	Grading of endolymphatic hydrops using magnetic resonance imaging (Nakashima T, et al)	Acta Oto Laryngologica	222	Article
12	2017	Bilateral vestibulopathy: Diagnostic criteria Consensus document of the Classification Committee of the Barany Society (Strupp M, et al)	Journal of Vestibular Research-Equilibrium & Orientation	204	Article

3.4. Authors contributions to global publications

Overall, 740 authors contributed to the MD studies. As shown in Table 3, MD publications were mostly published by Naganawa S (85, 2.99%), Sone M (72, 2.53%), Nakashima T (64, 2.25%), Kitahara T (60, 2.11%), and Lopez-Escamez J (58, 2.04%); indicating that these authors are very familiar with this field and have conducted extensive research on MD. The authors with the highest centrality were Naganawa S (0.14), Lopez-Escalmez J (0.14), Strupp M (0.11), Pyykko I (0.08), and Kitahara T (0.07).

Table 3.

The top 10 authors of MD research.

Rank	Author	Count (% of 2847)	Centrality
1	Naganawa S	85 (2.99)	0.14
2	Sone M	72 (2.53)	0.01
3	Nakashima T	64 (2.25)	0.02
4	Kitahara T	60 (2.11)	0.07
5	Lopez-Escamez J	58 (2.04)	0.14
6	Strupp M	47 (1.65)	0.11
7	Pyykko I	46 (1.62)	0.08
8	Young Yh	43 (1.51)	0.01
9	Teranishi M	42 (1.48)	0.01
10	Yoshida T	39 (1.37)	0.01

MD = Meniere’s disease.

With regards to the author’s collaboration network, Naganawa S, and Lopez-Escamez J were located at a central position in the collaboration network (Fig. 4). Active collaborations were Naganawa S, Sone M, Nakashima T, as well as Lopez-Escamez J, Strupp M, Pyykko O I, and Young Y. The main collaborators with KitaharA T were Ito T, Inohara H, Inui H, Yamanaka T, and Horii A.

Figure 4.

Collaboration network of authors engaged in MD research. MD = Meniere’s disease.

3.5. Journals and co-cited academic journals

A total of 465 journals published relevant articles or reviews on MD. The top 10 journals are listed in Table 4. Three journals were from the USA; 2 from the United Kingdom, Switzerland, and the Netherlands; and 1 from Germany. In terms of quantity and proportion, Otology Neurotology had the maximum number of publications (316, 11.10%), with an impact factor (IF) of 2.619 and an H-index of 36. Next, Acta Oto Laryngologica was (263, 9.24%) with an IF of 1.698 and an H-index of 28, followed by Laryngoscope (122, 4.29%) with an IF of 2.97 and an H-index of 32. The top 4 journals have more than 100 publications, accounting for nearly 30% of the total. The IF of journals in this field are generally low. The highest-ranked journal had an IF of 5.591, an American journal called Otolaryngology-Head and Neck Surgery. The journal citation reports of the top 10 journals in terms of the number of publications, only 2 journals, Otolaryngology-Head and Neck Surgery, and Hearing Research belong to quartile 1 in the category, followed by 4 journals in quartile 2, 3 in quartile 3, and 1 in quartile 4.

Table 4.

Top 10 journals in MD research.

Rank	Journal	Count (% of 2847)	Country/region	IF (2021)	JCR	H-index
1	Otology Neurotology	316 (11.10)	USA	2.619	Q2	36
2	Acta Oto Laryngologica	263 (9.24)	The United Kingdom	1.698	Q4	28
3	Laryngoscope	122 (4.29)	USA	2.97	Q2	32
4	European Archives of Oto-Rhino Laryngology	120 (4.22)	Germany	3.236	Q2	22
5	Frontiers in Neurology	85 (2.99)	Switzerland	4.086	Q2	15
6	Otolaryngology-Head and Neck Surgery	79 (2.78)	USA	5.591	Q1	22
7	Journal of Laryngology and Otology	77 (2.71)	The United Kingdom	2.187	Q3	15
8	Auris Nasus Larynx	71 (2.49)	Netherlands	2.119	Q3	13
9	Audiology and Neuro Otology	64 (2.25)	Switzerland	2.213	Q3	19
10	Hearing Research	60 (2.11)	Netherlands	3.672	Q1	21

IF = impact factor, JCR = journal citation reports, MD = Meniere’s disease.

Journal co-citation refers to the frequency with which 2 or more journals are cited simultaneously in a third paper. This analysis found that research publications in MD were co-cited by 952 scholarly journals. Acta Oto-Laryngol had the highest number of co-citations (2210), followed by Laryngoscope (2104) and Otol Neurotol (1971). Ann Oto Rhinol Laryn had a high centrality value (0.36) (Table 5).

Table 5.

Top 10 co-cited journals in MD research.

Rank	Journal	Count	Centrality
1	Acta Oto-Laryngol	2210	0.29
2	Laryngoscope	2104	0.29
3	Otol Neurotol	1971	0.19
4	Otolaryng Head Neck	1872	0.04
5	Ann Oto Rhinol Laryn	1411	0.36
6	Arch Oto-Laryngol	1150	0.03
7	Eur Arch Oto-Rhino-L	993	0.05
8	Am J Otol	853	0.04
9	J Laryngol Otol	661	0.00
10	J Vestibul Res-Equil	569	0.03

MD = Meniere’s disease.

3.6. Co-cited references and references with strong citation bursts

Of the 2847 MD publications, 1202 references were co-cited. Table 6 lists the top 10 co-cited publications published between 2005 and 2020. Among them, 2 were published in Jvestibul Res-Equil, 2 were published in Lancet, followed by Nat Rev Dis Primers, Laryngoscope, J Neurol, Acta Oto-Laryngol, Otolaryng Head Neck, Otol Neurotol, BMJ Open, and Eur Radiol. Lopez-escamez et al published an article entitled “Diagnostic criteria for Menière’s disease” in J Vestibul Res-Equil, which ranked first with 241 citations. “Meniere’s disease” and “Visualization of EH in Patients with Meniere’s Disease” both authored by Nakashima et al in Nat Rev Dis Primers and Laryngoscope had 77 and 73 citations, respectively. The article, “Vestibular migraine: Diagnostic criteria” by Lempert et al had 56 citations. “What is Meniere disease? A contemporary reevaluation of endolymphatic hydrops” by Basura et al had 53 citations. Of the 11 co-cited references sorted by centrality, 2 were published in Otol Neurotol and J Vestibul Res-Equil, whereas other journals published only 1 paper (Table 7). The highest centrality reference was titled “Imaging of Meniere’s disease after intravenous administration of single-dose gadodiamide: utility of subtraction images with different inversion times.”

Table 6.

Top 10 co-cited references in MD research.

Rank	Reference	Citation	Journals	Year
1	Diagnostic criteria for Menière’s disease	241	J Vestibul Res-Equil	2015
2	Meniere’s disease	77	Nat Rev Dis Primers	2016
3	Visualization of Endolymphatic Hydrops in Patients with Meniere’s Disease	73	Laryngoscope	2007
4	Vestibular migraine: Diagnostic criteria	56	J Vestibul Res-Equil	2012
5	What is Ménière’s disease? A contemporary reevaluation of endolymphatic hydrops	53	J Neurol	2016
6	Grading of endolymphatic hydrops using magnetic resonance imaging	47	Acta Oto-Laryngol	2009
6	Clinical Practice Guideline: Ménière’s Disease	47	Otolaryng Head Neck	2020
7	Pathophysiology of Meniere’s syndrome: are symptoms caused by endolymphatic hydrops?	46	Otol Neurotol	2005
8	Meniere’s disease	42	Lancet	2008
9	Ménière’s disease: a reappraisal supported by a variable latency of symptoms and the MRI visualization of endolymphatic hydrops	41	Bmj Open	2013
9	MRI of endolymphatic hydrops in patients with Meniere’s disease: a case-controlled study with a simplified classification based on saccular morphology	41	Eur Radiol	2017
10	Intratympanic methylprednisolone versus gentamicin in patients with unilateral Ménière’s disease: a randomized, double-blind, comparative effectiveness trial	40	Lancet	2016

MD = Meniere’s disease, MRI = magnetic resonance imaging.

Table 7.

Top 10 co-cited references with the highest centrality.

Rank	Reference	Centrality	Journals	Year
1	Imaging of Ménière’s Disease after Intravenous Administration of Single-dose Gadodiamide: Utility of Subtraction Images with Different Inversion Time	1.01	Magn Reson Med Sci	2012
2	Grading of endolymphatic hydrops using magnetic resonance imaging	0.98	Acta Oto-Laryngol	2009
3	Vestibular-Evoked Myogenic Potentials (VEMP) Can Detect Asymptomatic Saccular Hydrops	0.94	Laryngoscope	2006
4	Ménière’s disease: a reappraisal supported by a variable latency of symptoms and the MRI visualization of endolymphatic hydrops	0.93	Bmj Open	2013
5	Etiology, pathophysiology of symptoms, and pathogenesis of Meniere’s disease	0.63	Otolaryng Clin N Am	2002
6	Endolymphatic hydrops in patients with vestibular migraine and auditory symptoms	0.59	Eur Arch Oto-Rhino-L	2014
6	Vestibular migraine: Long term follow up of clinical symptoms and vestibulo-cochlear findings	0.59	Neurology	2012
7	Long-Term Follow-Up of Transtympanic Gentamicin for Méniére’s Syndrome	0.49	Otol Neurotol	2001
8	Auditory and Vestibular Symptoms and Chronic Subjective Dizziness in Patients with Ménière’s Disease, Vestibular Migraine, and Ménière’s Disease with Concomitant Vestibular Migraine	0.48	Otol Neurotol	2012
9	Vestibular migraine: Diagnostic criteria	0.45	J Vestibul Res-Equil	2012
10	What is Menière’s disease? A contemporary reevaluation of endolymphatic hydrops	0.36	J Vestibul Res-Equil	2015

MRI = magnetic resonance imaging.

The top 10 levels of most cited or occurred items from each year were selected using Cite Space. To identify literature that received considerable attention from peers, the burst detection strategy was applied to publications cited at an increasingly fast rate. Strong citation bursts for the 25 references are shown in Figure 5. The year denotes when the article was published. Strength refers to citation strength. The length of the line corresponds to the period from 2003 to 2022, where the red segment indicates the time interval of citation bursts. The strongest citation burst was the article entitled “Diagnostic criteria for Meniere’s disease” by Lopez-escamez et al published in J Vestibul Res-Equil, with a citation burst lasting from 2017 to 2020 (97.81). Next, “Visualization of Endolymphatic Hydrops in Patients with Meniere’s Disease” and “Meniere’s disease” by Nakashima et al^[10], had citation bursts from 2008 to 2012 (35.41) and 2018 to 2022 (32.27), respectively. This was followed by “Vestibular migraine: Diagnostic criteria” by Lempert et al published in the J Vestibul Res-Equil, which had a citation burst from 2014 to 2017 (28.31). When focusing on citation bursts in recent years, the topics of the 7 references deserve special consideration.^{[11,14,27–30]}

Figure 5.

The top 25 co-cited references with the strongest citation bursts in MD research. MD = Meniere’s disease.

3.7. Keyword analysis

3.7.1. Co-occurrence network of keywords.

Figure 6A shows a map of keywords with high co-occurrence frequencies analyzed using VOS viewer, including network visualization and chronological order. With the minimum of 20 occurrences, 209 of 7067 keywords met the threshold. Keywords were stratified into 6 clusters: The most central and significant were “menieres disease” (red cluster) and “meniere’s disease” (yellow cluster), followed by “vertigo” (dark blue cluster), “endolymphatic hydrops” (baby blue cluster), “inner-ear” (green cluster), and “sensorineural hearing loss” (purple cluster). As shown in Figure 6B, different colors indicate the year of publication. Therefore, the keywords in yellow suggest that they were published later than the keywords in blue-green. The figure indicated that the terms “magnetic resonance imaging,” “visualization,” “evoked myogenic potential,” “gadolinium,” “vestibular migraine,” and “intratympanic injection” were the most recently trending keywords in MD research.

Figure 6.

The visualization map of keywords with highly co-occurrence frequencies in MD research. (A) Network of keywords. (B) Chronological order of keywords. MD = Meniere’s disease.

3.7.2. The keyword clustering knowledge map of MD research.

As shown in Figure 7, closely related keywords were grouped into different clusters. A cluster is assigned a tag number, and the smaller the number, the more keywords that comprise the cluster. A total of 20 clusters were formed; the top 15 blocks were as follows: Cochlear function; Shock protein; Public health insurance system; Functional change; Physiological role; Vestibular-evoked myogenic potential; Sudden sensorineural hearing loss; Single-dose gadodiamide; Acoustic trauma; Effective treatment; Vestibular migraine; Single intratympanic gentamicin injection; Endolymphatic sac decompression surgery; Obstructive sleep apnea, and; Acute dizziness.

Figure 7.

The keyword clustering knowledge map of MD research. MD = Meniere’s disease.

3.7.3. keywords with the strongest citation bursts.

The top 10 most cited or occurred items from each year were selected in Cite Space. Keywords with strong citation bursts were considered indicators of research frontiers and are highlighted within a particular period of time since the number of citations and occurrences of those terms have surged. According to strength, the top 16 keywords with the strongest citation bursts were identified in Cite Space (Fig. 8A). The keywords with the strongest citation bursts were “Sensorineural hearing loss” with a citation burst lasting from 2003 to 2012 (24.7), “therapy” from 2003 to 2009 (23.53), and “hearing” from 2018 to 2022 (21.68). Other keywords included “prevalence,” “magnetic resonance imaging,” “evoked myogenic potential,” “vestibular migraine,” “Meniere’s disease,” “guinea pig,” “intratympanic gentamicin,” “quality of life,” “endolymphatic sac,” “double-blind,” “vestibular-evoked myogenic potential,” “dizziness,” and “visualization.” As shown in Figure 8B, keywords were sorted by the beginning year and the frontier and hot key words of MD research during the previous 5 years were “hearing,” “prevalence,” “evoked myogenic potential,” “magnetic resonance imaging” and “dizziness.”

Figure 8.

The top 16 keywords with the strongest citation bursts. (A) Sorted by strengths of burst. (B) Sorted by the beginning year.

4. Discussion

4.1. General information

In terms of the annual number of global publications (Fig. 2), in 2003 to 2007, little attention was paid to Meniere’s disease. Research in this field has only recently gained momentum. There were only 9 citations in 2003, and the number continued to increase thereafter. This shows that scholarly communication and mutual knowledge references were more frequent. In the past 4 years, cited records have increased from 3972 times in 2018 to 7072 in 2021, and research in this field has been extensive and in-depth.

According to the geographical distribution of the number of publications by country and region (Fig. 3A and B) and the ranking of the number of countries and regions (Table 1). The US has the highest number of citations and the highest H-index, and publications accounted for 26.38% of the total number globally. This indicates an outstanding research level and ability, higher academic achievements, and influence. The US plays a significant role in this field. Asian countries including Japan, China, South Korea, and Turkey also ranked high, with their publications exceeding 1-third of the total number. Among them, Japan and China ranked second and third, respectively, and have paid much attention to MD research and provided in-depth and extensive studies. However, low citations and the H-index indicate that Chinese scientists are still required to improve the quality of their work and gain international acceptance. Germany was ranked 4th. The citations and the H-index were very high for Italy, Spain, and Australia, indicating a high degree of international participation and recognition. From the national distribution of publishing institutions (Table 1), 5 of the top 10 institutions are American, which has an absolute advantage. These institutions have many ongoing research projects, capable scientists, sufficient funds, and high research levels. The contribution of the USA to this field is indispensable. The University of Munich in Germany, Nagoya University in Japan, University of California in the US, and the University of Sydney in Australia were the top 4 institutions. These institutions have a multitude of achievements, strong academic research ability, technical methods, and professional expert teams in the field of MD research and exercise great influence in the world. Among the top 12 most cited publications (Table 2), 4 are about the diagnostic criteria and consensus, which shows that international opinions on the diagnosis of the disease are relatively centralized, unified, and widely approved of. Three of them are epidemiological investigations. The epidemiological characteristics of MD vary according to the geographical and demographic factors of the patients studied; therefore, it is still a global problem. Two studies related to vestibular-evoked myogenic potentials and 2 on visualization imaging of EH illustrated that research on the examination method is a priority area in this field. Regarding citation rankings, both the first and second are from the same journal, namely the Journal of Vestibular Research-Equilibrium & Orientation, as one of the authoritative journals in the field of otorhinolaryngology and head and neck surgery, which has a high academic influence and global attention. The article titled “Diagnostic criteria for Meniere’s disease” published by Lopez-Escamez et al in 2015, was ranked first in terms of citations (613) and was jointly formulated by numerous internationally renowned national professional committees. As the most authoritative international diagnostic standard of MD in recent years, this article has been accepted and recognized by the academic community and has been widely used in various studies related to MD.^[8] The second most cited article was published in 2012 entitled “Vestibular migraine: Diagnostic criteria” by Lempert et al^[31] At present, the identification of the 2 diseases is still very challenging.^[32] Therefore, the reason for ranking second is probably that many scholars pay close attention to the relationship between them and use it for comparison. In Table 3 and Figure 4, the author’s country attribution was highly concentrated. Six of the top 10 productive authors were from Japan and stand at the forefront of MD research, wield major academic influence, and have displayed outstanding performance. The other authors in the top 10 were European authors from countries such as Spain, Finland, and Germany. Contrarily, the individual academic impact of American scholars was relatively minor. According to the cooperation networks of co-cited authors, Naganawa S, Nakashima T, Monsell EM, Lopez-Escamez J, Gurkov R, Murofushi T, Salt AN, Silverstein H, and Strupp M have close cooperative relations, comprising international cross regional academic cooperation. There was strong domestic cooperation between Naganawa S, Nakashima T, and Pyykko I with extensive scholarly communication and research results. Many senior scholars have deeply explored and studied this field for decades, leaving their mark in the research and development history of MD. This extensive cooperation and exchange are of great significance. The 2 most prolific journals are the American Journal of Otology Neurotology and the British Journal Acta Oto Laryngologica. These journals are highly professional and have higher academic status in this field (Table 4). The top 10 journals mainly belong to the United States and some European countries, some of which are backed by a long history and profound academic deposits. As the specialty of otorhinolaryngology, head and neck surgery is relatively strong, the development of journals in this field in other countries is relatively weak and should be vigorously developed. Researchers can gain insights into mainstream journals and their impact through journal co-citations (Table 5). By comparing the number of publications published and the co-cited journals, although the order differs, the top 3 journals are Acta Oto-Laryngol, Laryngoscope, and Otol Neurotol, with high centrality. Not only do they have the largest number of publications and profound academic influence but are also highly supported by international scholars.

4.2. Knowledge base

Co-cited references are publications that have been cited together by other publications, and are viewed as a knowledge base for a particular field of study. As shown in Table 6, the reference titled “Diagnostic criteria for Meniere’s disease” ranked first and was co-cited 241 times, far ahead of the other references. Amendments to the 2015 standard: Exclusion of certain MD and possible MD; Tightening the criteria for definite MD level to specify the presence of audiometrically documented low-to mid-frequency sensorineural hearing loss on at least 1 occasion before, during, or after one of the episodes of vertigo; and Attempt to distinguish vertigo related to vestibular migraine from MD through a method that stresses the interaction of the cochlear and vestibular symptoms.^[8,9,33,34] The top 10 co-cited references with the highest centrality were considered key to further understanding MD (Table 7). The references mainly focus on imaging studies of MD the relationship between MD and vestibular migraine, and the study of EH. The first study titled “Imaging of Meniere’s Disease after Intravenous Administration of Single-dose Gadodiamide: Utility of Subtraction Images with Different Inversion Time” by Naganawa S demonstrated that through intravenous injection of single-dose gadodiamide, they subtracted positive endolymph image (PEI) from positive perilymph image to visualization of endolymph, perilymph, and bone.^[35]

4.3. Hot topics and frontiers

Of the 7 references in recent years, 3 papers scientifically analyzed and systematically summarized the knowledge and theory of MD, and were co-created by the world’s most influential scholars belonging to the field.^[10,11,29] Firstly, the article “2015 Equilibrium Committee Amendment to the 1995 AAO-HNS Guidelines for the Definition of Meniere’s Disease.” introduced an update and amendment to the 1995 standard at an annual meeting in 2015. Correspondingly, “Meniere’s disease” discusses the epidemiological characteristics, mechanisms and pathophysiology, clinical symptoms, diagnosis, screening and prevention, management, and quality of life, and the content is concise, accurate, and full. Next, “International consensus on treatment of Meniere’s disease” provided a detailed description of the tiered treatment plan of Meniere’s disease, which was divided into 5 steps and provided doctors a more standardized and scientific treatment plan. Two articles related to MRI MD are “What is Meniere’s disease? Contemporary reevaluation of endolymphatic hydrops” and “MRI of endolymphatic hydrops in patients with Meniere’s disease: a case-controlled study with a simplified classification based on saccular morphology.”^[27,28] The imaging postulated that EH are responsible not only for attacks of auditory and vestibular dysfunction, but also for other clinical presentations, and stated symptomatic and imaging characteristics could simplify diagnostic classification. Another study found that the saccule to utricle area ratio is currently the most specific criterion for the imaging diagnosis of MD, an attempt to make the non-symptom diagnosis of this disease. A high-quality clinical trial titled “Intratympanic methylprednisolone versus gentamicin in patients with unilateral Ménière’s disease: a randomized, double-blind, comparative effectiveness trial” confirmed that methylprednisolone injections are a non-ablative, effective treatment for refractory MD and provided suggestions on the choice between them.^[14] The last 1 is “Extended phenotype and clinical subgroups in unilateral Meniere disease: A cross-sectional study with cluster analysis” which used cluster analysis to compare unilateral and bilateral clinical subgroups and extended the phenotype, which would help to improve phenotyping in MD and facilitate the selection of patients for randomized clinical trials.^[30] In Figures 6, 7, and 8, the top priority in the study of MD is always inner ear, endolymphatic hydrops, vertigo, sensorineural hearing loss, and therapy. Many research keywords are mainly related to “magnetic resonance imaging,” “visualization,” “gadolinium,” “evoked myogenic potential,” “vestibular migraine,” “intratympanic injection,” and “prevalence.” The most important hotspots and emerging trends are as follows.

4.3.1. Intratympanic injection method.

Intratympanic injection has long been one of the standard treatment methods for MD, and has been recognized and applied by most international scholars.^[36] According to the 2018 international consensus^[11] and European Position Statement on Diagnosis and Treatment,^[37] intratympanic injection of steroids, such as dexamethasone and methylprednisolone, is proposed as the second-step treatment method, considering that they are not ototoxic. As the 4th step, ITG is likely the most effective nonsurgical treatment to eradicate vertigo in MD but is associated with the risk of hearing loss; there is a consensus that dexamethasone is more appropriate to use than methylprednisolone. Steroids are believed to be safer than gentamicin.^[38] There is no universal standard or instruction for specific drug dosage, possible adverse effects, and ultimate effects. From a clinical point of view, dexamethasone (3–4 mg/mL) administered daily for 5 consecutive days or once a week for 1 to 4 weeks is effective in many refractory cases.^[39,40] An authoritative report that 2 injections of methylprednisolone (62.5 mg/mL) given 2 weeks apart is as effective as gentamicin (40 mg/mL) for the treatment of refractory MD.^[14] But the choice between methylprednisolone and gentamicin should be made based on clinical knowledge and patient circumstances. A new report showed that intractable vertigo of MD can be effectively controlled by ITG injection and could improve the low- and medium-frequency hearing levels in the contralateral ear, suggesting that it may help prevent contralateral MD occurrence.^[41]

4.3.2. Vestibular-evoked myogenic potentials (VEMPs).

The significance of evoked potentials for MD has been extensively studied. VEMPs are reflexes that arise as a response obtained through the sternocleidomastoid and orbital muscles due to high-intensity acoustic stimuli. The cVEMP provides information from the saccule and inferior vestibular nerves, whereas the oVEMP provides information from the utricle and superior vestibular nerve. The clinical applications of VEMP are summarized as follows: The ear with the smaller cVEMP is not necessarily the affected 1: the cVEMP can be augmented in early MD, perhaps because the hydropic sacculus presses against the stapes footplate, enhancing saccular sensitivity to loud sounds.^[42] The sensitivity and specificity of the cVEMP were 50.0% and 48.9%, respectively.^[43] One of the distinct features of cVEMP in MD patients was a shift of a preferred frequency (tuning) to 1000 Hz.^[44,45] The oVEMPs were abnormal in 50% of patients with MD.^[46] These abnormal responses were not MD-specific and there is insufficient evidence to determine whether VEMP is useful for diagnosing MD by reviewing the studies.^[47,48] The 2018 European Position Statement on Diagnosis and Treatment of MD considers that VEMPs help evaluate the function of the utricle and saccule, as well as the superior and inferior vestibular nerves.^[37] All these results indicate that VEMP is insufficient to support a specific diagnosis of the disease. In addition, VEMP testing may be beneficial in differentiating between the initial stage of MD and sudden deafness.^[42] The cVEMPs were more often abnormal in MD patients than in oVEMPs, suggesting that saccular dysfunction may be more common than utricular dysfunction.^[49,50] Moreover, a previous study showed that in the early disease stage, abnormal saccule function occurred earlier than in the utricle, and the saccule remained more involved than the utricle in the late disease stage.^[51]

4.3.3. Meniere’s disease and vestibular migraine.

Currently, it is generally accepted internationally that MD and vestibular migraine (VM) are independent diseases. MD is a disorder of the peripheral vestibular end-organs, while VM comprises central and vestibular dysfunctions originating from a central occurrence. However, comorbidity is common, with similar symptoms, particularly headache;^[32] therefore, they are difficult to differentiate clinically. A previous study reported that low cVEMP amplitudes on the affected side were the main feature in MD, differentiating it from VM.^[52] Flook et al^[53] found that a cytokine panel including interleukin 1, beta, Chemokine (C-C motif) ligand 3, Chemokine (C-C motif) ligand 22, and Chemokine (C-X-C motif) ligand 1, could be used as biological markers for the differential diagnosis of VM and MD, suggesting a high diagnostic value in patients with symptom overlap. Moreover, the team attempted to use prestin and otolin-1 as biomarkers to differentiate between MD and VM.^[54] Some scientists believe that there may be some connections between the 2 diseases. Pyykko et al^[55] found that patients classified as VM with frequent vertigo spells associated with migraine had more complaints of severe MD symptoms, experienced a reduced health-related quality of life, suffered more from anxiety, and found that migraine provokes the severity of MD. A new case-control study of 142,262 Korean adults from a nationally representative cohort suggested that patients with MD had a greater risk of migraine occurrence; subsequently, patients with migraine had a higher risk of MD.^[56] Some studies believe that migraine is the cause of vestibular migraine through effects on the inner ear from the trigeminal nerves and vessels system and through direct central activation of vestibular centers. In MD, the neurovascular regional pathology is limited to the neurovascular region of the inner ear, involving the vestibular and hearing organs in the membranous labyrinth-containing endolymph. Spreading cortical depression causes the release of neuropeptides and cytokines from the trigeminal ganglion, leading to vasodilation increased vascular permeability, and extravasation of plasma, which contribute to neurogenic inflammation and pain in migraine attacks. Therefore, as part of a migraine attack, the hydrops could be the epiphenomenon of a vascular pathogenetic mechanism that affects the neurovascular region of the inner ear.^[57,58] Research on the relationship between MD and vestibular migraine is still insufficient and requires further studies that focus on the etiology and pathological mechanism MD and vestibular migraine to fundamentally and objectively distinguish them.

4.3.4. Magnetic resonance imaging.

At present, the diagnosis of MD is mainly based on clinical symptoms as EH, the most characteristic pathological feature, can only be confirmed by postmortem examination of temporal bone specimens.^[59] Many scholars have attempted to diagnose MD by visualizing the inner ear fluid compartments using gadolinium-enhanced MRI.^[60] The currently used radiological hydrops grading systems include qualitative, semiquantitative, and volumetric scales.^[61] Nakashima et al^[62] performed a semiquantitative grading score based on a single-slice analysis within the cochlea, divided into no cochlear duct enlargement, moderate-grade, and significant-grade EH based on the extent of cochlear duct enlargement. The vestibule is divided into normal, moderate, and advanced EH by the endolymphatic space to vestibular fluid space area ratio.^[61,63] Attyé et al^[28] proposed a parameter, referred to as saccule to utricle area ratio, using a single reference sagittal cross-section. While, some considered that the inner ear structural assignment method is a more sensitive and specific diagnostic scoring method for diagnosis.^[64] Barath et al^[65] (2014) evaluated the enlargement of endolymphatic spaces separately within the cochlea and vestibule from grade 0, I, and II on a 3-grade scale. Bernaerts et al^[66] modified the scale and took a saccule larger than the utricle; the boundary between the 2 was maintained as grade I in 2019. Additionally, volumetric measurements may be more accurate.^[67,68] Kahn et al^[69] (2019) separately assessed endolymphatic spaces of the saccule, utricle, and ampullae of semicircular canals based on the anatomical division and confirmed that hydrops initially develop within the cochlear duct and extend sequentially into the saccule, utricle, and semicircular canals. By comparing the volume of the endolymphatic space between healthy volunteers and patients with MD, the importance of observing the semicircular canals for diagnosis was revealed and showed high diagnostic accuracy.^[70] At present, research on imaging diagnosis still focuses on qualitative and semiquantitative methods, which are not sufficiently accurate. The volume measurement method still needs requires scientific and technological progress. Although a newly published systematic review found that compared with audiovestibular function tests, including electrocochleography, cVEMP, and caloric tests, hydrops MRI in the vestibule has the highest diagnostic value for definite MD.^[71] Inner ear MRI techniques still have many pitfalls, and we look forward to a breakthrough in the future.

5. Conclusion and limitations

We are aware of the current status, global hotspots, and emerging trends. The United States has the highest number of publications and citations, and many institutions with strong scientific research capabilities play a decisive role in this field. European countries have many high-quality journals with long histories and profound academic publications. Japan has top scholars who work in close cooperation with each other, which is inspiring. International opinions on MD are relatively uniform, and correlative research is also continuously profound. The stepped-therapy of MD is clearly stratified, scientific and objective, widely recognized, and internationally supported. Intratympanic injection of steroids and ITG are the most popular therapeutic agents, and steroids are safer than gentamicin. There is no universal standard or instruction for specific drug dosages, possible adverse effects, or ultimate effects. The occurrence of abnormal cVEMPs was higher in MD patients than in oVEMPs, suggesting that saccular dysfunction may be more common than utricular dysfunction. With headache as the medium, the relationship between MD and VM is worth noting. With the continuous development of MRI technology, the imaging diagnosis of MD may lead to greater breakthroughs in the future. Finally, we quote a paragraph from Nature: “Bibliometrics and visual analysis are the only tools and methods available for studying existing publications, and no single evaluation model is applicable to all situations. Evaluators must not give up their final say only on numbers.”^[72] Academic research needs both objective science and human curiosity.

Author contributions

Conceptualization: Boshen Wang.

Data curation: Yuan Li, Qi Zhang.

Formal analysis: Jiawei Sun, Yu Tian.

Methodology: Boshen Wang, Dan Ma.

Project administration: Hui Leng.

Validation: Dan Ma.

Writing – original draft: Boshen Wang.

Writing – review & editing: Boshen Wang, Hui Leng.