Cause of idiopathic sudden sensorineural hearing loss: The stress response theory

Table 1 Proposed causes of idiopathic sudden sensorineural hearing loss during this decade

Main category	Subcategory	Significantly associated factors	NOT significantly associated factor	Ref.
Vascular impairment		MTHFR poly., homocysteine	FV poly., PT poly., AT, LAC, protein S, protein C	[1,2]
	Medical history	MTHFR poly., FV Leiden poly., folate, cardioV risk factors		[3]
	Medical history	Platelet GlyIa poly.	Platelet GlyIIIa poly., Framingham cardioV risk factors, FV Leiden poly., PT poly., history of cardioV events, brain stroke, antiphospholipid syndrome	[4,5]
		PAI-1 poly.		[6]
	Medical history	CFH poly. with DM	HT, lipid	[7]
	Medical history	Low FMD of the brachial artery	Low C-IMTl, LDL, cardioV risk factors	[8]
		Vertebrobasilar junction angulation		[9]
		High global oxidative stress index		[10]
			FV Leiden poly., PT poly.	[11]
	Medical history	SBP, personal/family history cardioV events	FV poly., PT poly., HT, DM, lipid, smoking, personal/family history or in the presence of thrombotic factors	[12]
		PKCH poly., MTHFR poly.		[13,14]
		Cho, LDL		[15]
		Cho, LDL, unsaturated fatty acid, coenzyme Q10, folate, homocysteine	MTHFR poly., FV poly., PT poly., antithrombin III, protein C and S, D-dimer, FG, activated protein C resistance	[16-18]
		MTHFR poly., FV Leiden poly., PT poly., platelet GlyIIIaA1/A2 poly., homocysteine, Cho, FG, folate		[19,20]
		MTHFR poly.	FV, PT, EPCR, PAI-1	[21]
	Medical history	ICAM-1, VCAM-1	Cho, triglyceride, FG, ESR, smoking, DM	[22]
		MTHFR poly. with MTR poly., MTR poly.	MTHFR poly. alone	[23]
		FV Leiden poly.	PT poly.	[24]
	Auto-immunity	Cho, homocysteine, PAI-1, anticardiolipin antibodies	FV Leiden poly., FII poly., antithrombin, protein C and S, lupus anticoagulant, lipoprotein(a)	[25]
		eNOS poly.		[26]
		FMD		[27]
		Whole blood viscosity, erythrocyte deformability index, activated clotting time, clot rate, PAI-1 antigen, factor VIII:C	Plasma viscosity, FG	[28]
	Auto-immunity	Antiendothelial cell antibody		[29,30]
Cytokine		IL-1B poly., TNF-β poly.		[31,32]
		TNF-α	IL-10, IL-12	[33]
		IL-6 poly.	IL-4R poly., IL-10 poly., TNF-α poly., TNFRSF1B poly., VEGF poly.	[34]
		IL-1A poly.	IL-1B poly.	[35]
	Vascular impairment		IL-6, IL-8, ICAM-1, VCAM-1, E-selectin, MCP-1, lipid, FG	[36]
		TNF-α, sCD40, sCD40L, T lymphocyte, CD40, cyclooxygenase 2, CD38 positive T or B lymphocyte	Monocyte, macrophage	[37]
Cellular stress		HSP70 poly.		[38]
			GPX1 poli., PON1 poli., PON2 poli., SOD2 poli.	[39]
			GST poly., CYP poly.	[40]
	Auto-immunity		Anti-HSP70 antibody, TNF-α, ESR, ANA, antiphospholipid antibody	[41]
	Auto-immunity	Anti-HSP70 antibody, anti-phospholipids antibody		[42]
		HSP70		[43]
			GST poly.	[44]
Infection		IgA to HSV1	IgG and IgM to CMV, VZV, HSV1, and HSV2. IgA to CMV, VZV, and HSV2	[45]
			Borrelia	[46]
			Herpes zoster	[47]
		Recent subclinical viral infection (cytomegalovirus, herpes simplex, Epstein-Barr virus), toxoplasmosis infections		[48]
			Enterovirus, cytomegalovirus, Epstein-Barr virus	[49]
Auto-immunity			Anti-double stranded DNA, RF, antiphospholipid IgG and M, antinuclear antibody, complements C3 and C4	[50]
		T cell responding to cochlin		[51]
Stress response theory		Neutrophil, NKCA, IL-6	TNF, hCRP	[52]
		Histological evidence of severe osmotic stress of the organ of Corti		[53]
Medical history		HIV		[54]
	Vascular impairment	SLE		[55]
	Vascular impairment	AMI		[56]
		Migrane with HT		[57]
	Vascular impairment	ED		[58]
	Vascular impairment	DM		[59]
		Chronic kidney disease with and without DM		[60]
		Allergy		[61]
		Male with OSA	Female with OSA	[62]
	Vascular impairment	CardioV risk factors, DM, Cho		[63]
		Family history of ISHL		[64]
	Vascular impairment	CerebroV stroke		[65]
Other aetiologies			Aquaporin 4 and 5 poly., estrogen receptor α poly.	[66]
		Round window membrane rupture		[67]
		Endolymphatic hydrops		[68]
			Eustachian tube dysfunction	[69]
		General anaesthesia		[70]
			Month, weather	[71]
		HLA-DQB1 and -DRB1		[72]
			Season, weather	[73]

Papers on human studies are categorized by the proposed etiologies. Papers that deduce possible etiologies from the effect of a treatment are excluded. For example, Kang et al[174] stated that the cause might be reactive oxygen metabolites produced by inner ear ischemia or inflammation, because high dose vitamin C was effective. Such papers are excluded from this table in order to save space, although they are noteworthy. AMI: Acute myocardial infarction; AT: Antithrombin; C-IMT: Carotid intima-media thickness; CardioV: Cardio vascular; CDL: CD ligand; CerebroV: Cerebrovascular; CFH: Complement factor H; Cho: Cholesterol; CMV: Cytomegalovirus; CYP: Cytochrome P450; DM: Diabetes mellitus; E-selectin: Endothelial selectin; ED: Erectile dysfunction; eNOS: Endothelial nitric oxide synthase; EPCR: Endothelial cell protein C receptor; ESR: Erythrocyte sedimentation rate; FG: Fibrinogen; FMD: Flow-mediated dilatation; FII: Factor II; FV: Factor V; Gly: Glycoprotein; GPX: Glutathione peroxidase; GST: Glutathione S-transferases; hCRP: High sensitivity C-reactive protein; HIV: Human immunodeficiency virus; HLA: Human leukocyte antigen; HSP: Heat shock protein; HSV: Herpes simplex virus; HT: Hypertension; ICAM-1: Intercellular adhesion molecule 1; IL: Interleukin; ISHL: Idiopathic sudden sensorineural hearing loss; LAC: Lupus anticoagulant; LDL: Low density lipoprotein; MCP-1: Monocyte chemoattractant protein 1; MTHFR: Methylene tetrahydrofolate reductase; MTR: Methionine synthase; NKCA: Natural killer cell activity; OSA: Obstructive sleep apnea; PAI-1: Plasminogen activator inhibitor-1; PKCH: Protein kinase C-Eta; poly.: Polymorphism; PON: Paraoxonase; PT: Prothrombin; RF: Rheumatoid factor; SBP: Systolic blood pressure; SLE: Systemic lupus erythematosus; sCD: Soluble cluster of differentiation; SOD: Superoxide dismutase; TNF: Tumor necrosis factor; TNFRSF1B: Tumor necrosis factor receptor superfamily 1b; VCAM-1: Vascular cell adhesion molecule 1; VEGF: Vascular endothelial growth factor; VZV: Varicella-zoster virus.