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Table of Contents
Vol. 70, No. 1, 2008
Issue release date: February 2008
Section title: Paper
Free Access
ORL 2008;70:52–62

Sudden Deafness: Is It Viral?

Merchant S.N.a, c · Durand M.L.b, d · Adams J.C.a, c
aDepartment of Otolaryngology, Massachusetts Eye and Ear Infirmary, bInfectious Disease Unit, Massachusetts Eye and Ear Infirmary and Massachusetts General Hospital, and Departments of cOtology and Laryngology and dMedicine, Harvard Medical School, Boston, Mass., USA
email Corresponding Author

Saumil N. Merchant, MD

Massachusetts Eye and Ear Infirmary

243 Charles Street

Boston, MA 02114 (USA)

Tel. +1 617 573 3503, Fax +1 617 573 3939, E-Mail saumil_merchant@meei.harvard.edu

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A number of theories have been proposed to explain the etiopathogenesis of idiopathic sudden sensorineural hearing loss (ISSHL), including viral infection, vascular occlusion, breaks of labyrinthine membranes, immune-mediated mechanisms and abnormal cellular stress responses within the cochlea. In the present paper, we provide a critical review of the viral hypothesis of ISSHL. The evidence reviewed includes published reports of epidemiological and serological studies, clinical observations and results of antiviral therapy, morphological and histopathological studies, as well as results of animal experiments. The published evidence does not satisfy the majority of the Henle-Koch postulates for viral causation of an infectious disease. Possible explanations as to why these postulates remain unfulfilled are reviewed, and future studies that may provide more insight are described. We also discuss other mechanisms that have been postulated to explain ISSHL. Our review indicates that vascular occlusion, labyrinthine membrane breaks and immune-mediated mechanisms are unlikely to be common causes of ISSHL. Finally, we review our recently proposed theory that abnormal cellular stress responses within the cochlea may be responsible for ISSHL.

© 2008 S. Karger AG, Basel



J.R. García-Berrocal: The critical review presented by the authors states the lack of evidence for any etiology for SSHL, including the viral infection. Although viral and vascular etiologies were classically suggested, inner ear membrane breaks and more recently immune-mediated mechanisms have been added. Efforts to assign either etiology may be conceptually wrong based on current knowledge since the implication of diverse etiopathogenetic factors in suddenly presenting cochleovestibular damage has been proven. Thus, an immune reaction could be triggered by a virus, leading to vasculitis and lymphocyte recruitment to the inner ear. However, until advances in technology allow us to identify viruses in vivo in inner ear fluids without causing irreparable damage, as well as to confirm the direct cytopathic effects of viral infection in the cochlea, the application of immunological and serological studies will continue to provide a presumptive diagnosis in some patients with sensorineural hearing loss. Otherwise, authors consider an attractive hypothesis that states that idiopathic sudden deafness (SD) may be induced by activation of cellular stress inside the cochlea. Triggering events such as a systemic viral illness, a systemic inflammatory disorder and physical, mental or metabolic stress have been previously involved as predisposing risk factors in the development of SD. Stressors modulate immune function; after initiation of a psychological or physical stressor, a transient increase in the number of CD8 and natural killer lymphocytes is observed [1]. Chronic stress decreases CD8 T cells, contributing to the increase in viral infectious diseases (increased susceptibility to infection or to activation of latent infection) because the CD8 population is a critical defense against viral infections [2]. During an immune response, the nervous and the immune system interact and this interaction is essential for maintaining homeostasis, even under stressful stimulation/challenge. Hence, stress has a significant impact upon the activity of the immune response. Cortisol, the end product of the hypothalamic-pituitary-adrenal (HPA) axis, is produced and secreted in stress and is capable of decreasing proinflammatory activities by inhibiting type 1 immunological pathways (thereby favoring type 2 activities). Further, under stimulation the catecholamine norepinephrine, an effector of the sympathetic nervous system (SNS), is released from the sympathetic nerve terminals in lymphoid organs and the target immune cells express adrenoreceptors. Through stimulation of these receptors, norepinephrine affects lymphocyte traffic, circulation and proliferation, and it modulates cytokine production and the functional activity of different lymphoid cells. Catecholamines also inhibit the production of type 1 proinflammatory cytokines, where they stimulate the production of type 2 – mainly anti-inflammatory cytokines – and various types of antibodies [3]. Therefore, the activation of stress response components – mainly the SNS – during an immune response may have proinflammatory consequences as well. Stress/stressors (bacterial and viral infections, free radicals, oxidative stress) and basic stress response functions (HPA axis and SNS activity) involve the stimulation of stress-sensitive heat shock protein production/gene expression and NFκB activation. The nuclear transcription factor NFκB triggers the activation of a large number of genes in response to inflammation, viral and bacterial infections and other stressful situations. Proinflammation involves complex pathways that include stress response, heat shock protein, NFκB, iNOS and free radical activation/induction and may represent an underlying concept that contributes to the onset and progression of various disease processes [3]. Thereby, the stress response theory could represent a common etiopathogenetic pathway for the main etiologies suggested for SD. Likewise, this hypothesis provides a main role to type II fibrocytes and supporting cells of the organ of Corti. In this respect, we fully agree with the authors since these cells should be a critical target of any treatment for inner ear disorders [4]. However, further research must be performed in order to clarify clinical situations in which patients with a stress-induced SD do not improve their hearing after corticosteroid therapy and situations in which the hearing loss is not reversed after such a treatment in patients with an autoinflammatory disease [unpubl., pers. obs.].

References1Herbert TB, Cohen S, Marsland AL, Bachen EA, Rabin BS, Muldoon MF, Manuck SB: Cardiovascular reactivity and the course of immune response to an acute psychological stressor. Psychosom Med 1994;56:337–344.2Rabin BS: Effect of stress on immune function, allergy and health. Curr Opin Otolaryngol Head Neck Surg 2000;8:234–238.3Esch T, Stefano GB: Proinflammation: a common denominator or initiator of different pathophysiological disease processes. Med Sci Monit 2002;8:HY1–HY9.4Ramírez-Camacho R, García-Berrocal JR, Trinidad A, González-García JA, Verdaguer JM, Ibáñez A, Rodríguez A, Sanz R: Central role of supporting cells in cochlear homeostasis and pathology. Med Hypotheses 2006;67:550–555.

T. Linder: Saumil Merchant and his colleagues very elegantly listed the pros and cons of a viral etiopathogenesis for sudden sensorineural hearing loss (SNHL). Except for mumps virus, there are few other viral pathogens known which could consistently induce a unilateral SNHL [see the article by Oliveira et al., this issue, pp. 42–51]. Their arguments clearly illustrate the fact, that viral inflammation of the inner ear or cochlear nerve is very unlikely in SNHL. Even 1.5- and 3-tesla MRI scans performed within days of the acute onset could not verify signs of inflammation, ischemia or bleeding as a possible incident. Therefore, it is mandatory to look for other etiologies and they have come up with an interesting theory of ‘stress’-induced activation of NFκB within the cochlea. However, in their membrane-rupture section they state that ‘Indeed, many patients report experiencing deafness upon awakening or while being sedentary’ with no consistent relation to known stress factors within the body. Also the unilaterality of SNHL needs to be further addressed in their theory. In summary, there is great need for new ideas on a possible etiopathogenesis of SNHL and the NFκB theory is tempting to follow.

R. Maire: The authors made an excellent and exhaustive critical review of the different hypotheses proposed to explain the etiology and pathogenesis of idiopathic SSHL. Especially, they focused on the viral hypothesis which is severely questioned. As a new postulate, they proposed and discussed the pathophysiological concept of abnormal cellular stress response, which may be a promising alternative to explain SD.

C.A. Oliveira: This is a very thorough review of the current knowledge about the etiology of SSHL. At least two etiologies seem to be the cause of some but not all SSHL cases: viral and vascular etiologies. Other possible etiologies have less reliable evidence to support them. It seems to me that at least one statement could have been made from this review: SSHL seems to have multiple causes. Two are reasonably acceptable at least in some cases: viral and vascular causes.

I. Pyykkö: The paper describes an interesting mechanism producing apoptosis in the inner ear by activating the NFκB pathway, but the actual mechanism was not explained. No evidence for activation of this mechanism was demonstrated either. Therefore, no argument for or against it can be presented. An argument against viral infection presented in this paper was that Pitkäranta and Julkunen did not find cytokine activation that commonly occurs in general viral infection. Therefore, the ‘viral theory’ would be unlikely. The clinical evidence shows that it is very unlikely that in a local activation of viral replication the body cytokine responses would be significantly affected.

Article / Publication Details

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Published online: February 01, 2008
Issue release date: February 2008

Number of Print Pages: 11
Number of Figures: 0
Number of Tables: 0

ISSN: 0301-1569 (Print)
eISSN: 1423-0275 (Online)

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