Meniere disease subtyping: the direction of diagnosis and treatment in the future

Figures & data

Table 1. A summary of Meniere’s disease subtypes

Study	Variables	Subtypes
Committee on Hearing and Equilibrium, 1972 [73]	The predominant symptom	Typical/ cochlear/ vestibular MD
Gürkov R, 2018 [76]	The predominant symptom	Cochlea/vestibular/cochleovestibular MD
Iwasaki S, 2021 [75]	The predominant symptom	Cochlear/vestibular/ Typical MD
Chaves AG, 2007 [77]	Disease laterality	UMD/BMD
Clemmens C, 2012 [78]	Disease laterality	UMD/BMD
Wang Y, 2018 [83]	Migraine diagnosis	MD with/without migraine
Rego ÂR [89]	Cardiovascular risk factors	MD with/without cardiovascular risk factors
Montes-Jovellar L, 2011 [90]	Audiometric test result vestibular test result posturographical finding disability severity	Mildly active elderly Mildly active young Active compensated Active uncompensated
Frejo L, 2016 [92]	Disease laterality (BMD) the types onset of hearing loss FMD migraine symptom AD	Type 1, metachronic hearing loss Type 2, synchronic hearing loss Type 3, FMD Type 4, MD with migraine Type 5, MD with AD
Frejo L, 2017 [93]	Disease laterality (UMD) DMD FMD migraine AD	Type 1, sporadic MD without migraine and AD Type 2, DMD Type 3, FMD Type 4, MD with migraine Type 5, MD with AD
Lee HJ, 2019 [99]	The interval for bilateral progression	The early/late bilateral involvement group
Frejo L, 2018 [101]	The basal levels of IL-1β	MD with low/high level IL-1β
Requena T, 2014 [19]	Familial/sporadic	FMD/SMD
Frejo L, 2016 [102]	Familial/sporadic	FMD/SMD
Eckhard AH, 2019 [103]	ES pathology	MD-hypoplasia/degenarative ES
Bächinger D, 2019 [104]	Imaging	The hypoplasia ES (αexit> 140°) The degenerative ES (αexit<120°)
Bächinger D, 2019 [105]	Imaging	UMD-unilateral/bilateral hypoplastic/degenerative BMD-bilateral degenerative/hypoplastic

Figure 1. The comparison of MD subtypes distribution between European and USA cohorts. Bar chart comparing percentages of Ménière’s disease (MD) subtypes reported by Crossley J et al [96] in US population and Frejo et al [92, 93] in a European population, respectively. a, unilateral Meniere’s disease subtypes distribution. Type 1, sporadic MD without migraine and autoimmune disease; type1 delayed MD; type 3, familial MD; type 4, MD with migraine; type 5, MD with autoimmune disease. b, bilateral Meniere’s disease subtypes distribution. Type 1, bilateral MD with metachronic hearing loss; type 2, bilateral MD with synchronic hearing loss; type 3, familial MD; type 4, MD with migraine; type 5, MD with autoimmune disease.

Table 2. Genes involved in familial Meniere’s disease

Genes involved in FMD	Description
DTNA [21]	Alpha-dystrobrevin, a membrane protein
FAM136A [21]	A mitochondrial protein of unknown function
PRKCB [110]	A serine and threonine-specific protein kinase, a proteinkinase C beta
DPT [22]	Dermatopontin, an extracellular matrix protein
SEMA3D [22]	A semaphoring protein, related to axonal guidance signaling and neuronal growth
OTOG [24]	Otogelin, the extracellular structures overlying the stereocilia of the hair cells
MYO7A [25]	A motor protein with a key role in the organization of stereocilia in auditory and vestibular hair cells
LSAMP [111]	A neuronal surface adhesion glycoprotein in cortical and subcortical regions located in the limbic system

Table 3. Genes involved in sporadic Meniere’s disease

Function	Gene
Deafness-related genes	ESRRB, GJB2, USH1G
Neurotrophic signaling molecule	NTN4, NOX3
Immune response gene	HLA II, MICA, TLR10, NFKB1, TWEAK, rs4947296, MIF, PTPN22, HCFC1
endolymph regulation	ADD1, AQP 1–5, KCNE1 and KCNE3, COCH, DFNA9, SLC8A1, SIK1

Figure 2. A pattern diagram of Meniere’s disease occurrence. ES, endolymphatic sac; EH, endolymphatic hydrops.

Horii A, Kitahara T, Uno A, et al. Vestibular function and vasopressin. Acta Otolaryngol Suppl. 2004;124:50–53.

 Google Scholar

Chung JW, Fayad J, Linthicum F, et al. Histopathology after endolymphatic sac surgery for Meniere’s syndrome. Otol Neurotol. 2011;32:1–7.

 PubMed Web of Science ®Google Scholar

Thomsen J, Per Bonding BB. The Non-specific effect of endolymphatic sac surgery in treatment of Meniere’s disease: a prospective, randomized controlled study comparing “classic” endolymphatic sac surgery with the insertion of a ventilating tube in the tympanic membrane. Acta Otolaryngol. 1998;118:769–773.

 PubMed Web of Science ®Google Scholar

Committee on Hearing and Equilibrium. Report of Subcommittee on Equilibrium and its Measurement. Meniere’s disease: criteria for diagnosis and evaluation of therapy for reporting. Trans - Am Acad Ophthalmol Otolaryngol. 1972;76:1462–1464.

 PubMedGoogle Scholar

Kato M, Sugiura M, Shimono M, et al. Endolymphatic hydrops revealed by magnetic resonance imaging in patients with atypical Meniere’s disease. Acta Otolaryngol. 2013;133:123–129.

 PubMed Web of Science ®Google Scholar

Orchik DJ, Shea JJ Jr, and Ge NN. Summating potential and action potential ratio in Meniere’s disease before and after treatment. Am J Otol. 1998;19(4):478–482.

 PubMedGoogle Scholar

Unlu M, Sevim DG, Gultekin M, et al. Changes in retinal vessel diameters in migraine patients during attack-free period. Int J Ophthalmol. 2017;10:439–444.

 PubMed Web of Science ®Google Scholar

Sarna B, Abouzari M, Lin HW, et al. A hypothetical proposal for association between migraine and Meniere’s disease. Med Hypotheses. 2020;134:1–5.

 Web of Science ®Google Scholar

Abouzari M, Abiri A, Djalilian HR, et al. Successful treatment of a child with definite Meniere’s disease with the migraine regimen. Am J Otolaryngol. 2019;40:440–442.

 PubMed Web of Science ®Google Scholar

Rego ÂR, Dias D, Pinto A, et al. The cardiovascular aspects of a Ménière’s disease population - A pilot study. J Otol. 2019;14:51–56.

 PubMedGoogle Scholar

Vergara-Jimenez M, Missimer A, DiMarco DM, et al. Higher prevalence of autoimmune diseases and longer spells of vertigo in patients affected with familial Ménière’s disease: a clinical comparison of familial and sporadic Ménière’s disease. EC Nutr. 2014;1:164–173.

 Google Scholar

Kim H-J, Lee H-J, An S-Y, et al. Analysis of the prevalence and associated risk factors of tinnitus in adults. Chen L, editor. PLoS One. 2015;10:e0127578.

 PubMed Web of Science ®Google Scholar

Requena T, Espinosa‐Sanchez JM, Cabrera S, et al. Familial clustering and genetic heterogeneity in Meniere’s disease. Clin Genet. 2014;85:245–252.

 PubMed Web of Science ®Google Scholar

Bruderer SG, Bodmer D, Stohler NA, et al. Population-based study on the epidemiology of Ménière’s disease. Audiol Neurotol. 2017;22:74–82.

 PubMed Web of Science ®Google Scholar

Lee HJ, Lee JM, Shim DB, et al. Is early progression to bilateral involvement in Menière’s disease a poor prognostic indicator?. Otol Neurotol. 2019;40:1333–1338.

 PubMed Web of Science ®Google Scholar

Enander A, Stahle J. Hearing in Menière’s disease: a study of pure-tone audiograms in 334 patients. Acta Otolaryngol. 1967;64:543–556.

 PubMedGoogle Scholar

Frejo L, Gallego-Martinez A, Requena T, et al. Proinflammatory cytokines and response to molds in mononuclear cells of patients with Meniere disease. Sci Rep. 2018;8:5974.

 PubMed Web of Science ®Google Scholar

Frejo L, Soto-Varela A, Santos-Perez S, et al. Clinical subgroups in bilateral Meniere disease. Front Neurol. 2016;7:1–10.

 PubMed Web of Science ®Google Scholar

Requena T, Cabrera S, Martin-Sierra C, et al. Identification of two novel mutations in FAM136A and DTNA genes in autosomal-dominant familial Meniere’s disease. Hum Mol Genet. 2015;24:1119–1126.

 PubMed Web of Science ®Google Scholar

Martín-Sierra C, Requena T, Frejo L, et al. A novel missense variant in PRKCB segregates low-frequency hearing loss in an autosomal dominant family with Meniere’s disease. Hum Mol Genet. 2016;25:3407–3415.

 PubMed Web of Science ®Google Scholar

Martín-Sierra C, Gallego-Martinez A, Requena T, et al. Variable expressivity and genetic heterogeneity involving DPT and SEMA3D genes in autosomal dominant familial Meniere’s disease. Eur J Hum Genet. 2017;25:200–207.

 PubMed Web of Science ®Google Scholar

Roman-Naranjo P, Gallego-Martinez A, Soto-Varela A, et al. Burden of rare variants in the OTOG gene in familial Meniere’s disease. Ear Hear. 2020;41:1598–1605.

 PubMed Web of Science ®Google Scholar

Roman-Naranjo P, Moleon MDC, Aran I, et al. Rare coding variants involving MYO7A and other genes encoding stereocilia link proteins in familial meniere disease. Hear Res. 2021;409:108329.

 PubMed Web of Science ®Google Scholar

Mehrjoo Z, Kahrizi K, Mohseni M, et al. Limbic system associated membrane protein mutation in an Iranian family diagnosed with ménière’s disease. Arch Iran Med. 2020;23:319–325.

 PubMed Web of Science ®Google Scholar