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|Year : 2003 | Volume
| Issue : 20 | Page : 29--34
Stress in hearing and balance in Meniere's disease
KC Horner, Y Cazals
Equipe Inserm EPI 9902, Laboratoire Otologie NeuroOtologie, Univ. Méditerranée Aix-Marseille II, Faculté de Médecine Nord, Marseille, France
K C Horner
Equipe Inserm EPI 9902, Laboratoire Otologie NeuroOtologie, Univ. Méditerranée Aix- Marseille II, Faculté de Médecine Nord, Boulevard Pierre Dramard, 13916 Marseille Cedex 20
Stress is an unavoidable every-day phenomenon. Physiological coping with stress depends on the appropriate release of stress hormones as well as their alleviation at the termination of the stress. Despite quite a body of research indicating that stress affects inner ear function, this concept has found little application in otolaryngology. Today's evidence clearly indicates that the inner ear is equipped to detect stress hormones and some of these hormones have been shown to affect the inner ear function.
Major stress control pathways shown to affect the inner ear include several third order axes, the hypothalamus-pituitary-adrenal axis, the hypothalamus-pituitary-thyroid axis and the hypothalamus-pituitary-gonadal axis whose functioning are interactive and inter-dependent. Less well-studied are the second order hypothalamus-pituitary control axis and its interaction with other hormones. To explore these we carried out a retrospective study on a series of Meniere's patients who had undergone a neurotomy of the vestibular nerve in the dept of ORL at the Hopital Nord, Marseille. Meniere's patients were particularly appropriate for this study since stress has long been recognised as a factor associated with the triggering of the symptoms of this pathology. Patients with acoustic neuroma and facial spasm were taken as a control population.
We investigated the level of a battery of stress hormones including prolactin (3-endorphin and growth hormone. The blood sample was taken on the morning before surgery. The most striking observation was the presence of hyperprolactinemia in 30% of the Meniere patients (more than 20 µµg/l) with confirmation of prolactinoma in 6 patients. The level of O-endorphin could also be elevated. Horner, K.C., Guieu, R., Magnan, J., Chays, A. and Cazal, Y. Neuropysychopharmacology, (2001) 26:135-138.
These observations suggest that neuroendocrinological feedback pathways controlling stress can be disturbed in Meniere's patients and depression of hypothalamic dopaminergic inhibition of prolactin secretion might be implicated. A further study on non-operated Meniere's patients presenting hyperprolactinemia and on dopamine agonist treatment, is needed in order to assess the role of stress in Meniere's patients. Progress in this domain could open the door towards integration of the stress concept into clinical management of various inner ear disorders.
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Horner K C, Cazals Y. Stress in hearing and balance in Meniere's disease.Noise Health 2003;5:29-34
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Horner K C, Cazals Y. Stress in hearing and balance in Meniere's disease. Noise Health [serial online] 2003 [cited 2021 Nov 28 ];5:29-34
Available from: https://www.noiseandhealth.org/text.asp?2003/5/20/29/31691
The first documentation of Meniere's disease can be dated back to 1861 when the French clinician Prosper Meniere described a form of inner ear pathology associated with progressive and severe fluctuant deafness, vertigo and tinnitus.
One of the principle land-marks in the history of Meniere's disease can be associated with yet another French clinician - George Portmann. Indeed Portmann, who after extensive anatomical studies on the endolymphatic sac in fish, birds and mammals (see Portmann, 1978), hypothetised that the sac controlled inner ear fluid pressure and went on to try this operation on a patient for whom the operation resulted in a success (Portmann, 1927). The association of endolymphatic hydrops with this pathology was demonstrated only twelve years later (Hallpike and Cairns, 1938 Yamakawa, 1938) and has led to various experimental and clinical approaches aimed at reducing the inner ear endolymph volume in this pathology. Since the presence of endolymphatic hydrops can be confirmed only at post-mortem, the Committee on Hearing and Equilibrium of the American Academy of Otolaryngology- Head and Neck Surgery (AAOHNS, 1995) has adopted strict guidelines concerning the diagnosis and evaluation of Meniere's disease. There is a vast range of medical treatments including diuretics, vasoactive drugs, steroids, sedatives and all are reported to provide some short-term benefit but there is no cure for this disease. The progressive nature of the disease often leads to incapacitating vertigo when surgery is often proposed (reviews: Merchant et al. 1995; Claes and Van de Heyning, 1997). The publications by Torok (1977) and Jonkees (1980) provide indispensable and daring critical reviews on the treatment of Menieres disease. To cite Torok (1977) "Basically no one knows what one is treating and tries only to control the symptoms". Unfortunately this same commentary still applies today.
Meniere's disease and stress
The pessimistic therapeutic picture of Meniere's disease today is almost certainly related to the fact that the cause of this inner ear disease is still unknown. About the same time that G. Portmann was investigating the endolymphatic sac function, the biology underlying stress was in its embryonic state and was about to undergo a parallel development. The sympathoadrenal medullary axis with the release of hormone under stress (Cannon 1929), different stages in the development of the stress syndrome (Seyle, 1936) and the hypothalamic control of pituitary hormones (Harris, 1948) were described. The possible contribution of stress to Meniere's disease was first proposed to be related to sympathetic hypertonus in this pathology at that time (Seymour and Tappin, 1953) and psychophysiological factors in Meniere's disease patients described (Fowler and Zeckel, 1952). This was followed by a period of twenty years during which various forms of sympathectomy were carried out on Meniere's patients with some beneficial results (Golding-Wood, 1973; Torok, 1977; Adams and Wilmot, 1982). More recently surgical or chemical ablation of the vestibular sense organs has become the most employed technique for the relieve of vertigo (see Merchant et al. 1995). In the last twenty years selective vestibular nerve section has increasingly been employed since it is reported to have highest success rate for controlling vertigo and in addition hearing is conserved (Silverstein et al., 1987).
Meniere's disease is an excellent patient population for assessment of the effect of psychological stress on inner function since the patients themselves often cite stress as a trigger for onset of their symptoms (Hinchcliffe, 1967). Compulsive-obsessional perfectionist individual appears particularly at risk (Stephens, 1975). Vertigo attacks can be correlated with psychological state and the integration of this kind of information into the assessment of such patients could lead to improved therapy (Hagnebo et al. 1998). The association between psychological state and dizziness is not limited to Meniere's disease but includes patients with panic disorders and anxiety (Yardley, 2000; Yardley et al., 2001)
Several physiological mechanisms exist which can account for the association between psychological stress and vertigo. The central vestibular pathways may be modulated by steroids (Seemungal et al., 2001). At the periphery, the inner ear is supplied with substantial sympathetic innervation and receptors for a series of stress hormones have been localised.
Inner ear and the sympathetic system
The sympathetic innervation of the inner ear has been described as being substantial with an ipsilateral innervation arising from the superior cervical ganglion and a bilateral innervation from the stellate ganglion. The sympathetic innervation is described as being associated with blood vessels or independent of the vasculature. (Spoendlin and Lichtensteiger, 1966). Electrical stimulation of different cochlear turns as well as local application of adrenergic agonists/antagonists to the cochlea has indicated that cochlear blood flow increase is mediated via adrenergic α2 - receptors (Ohlsen et al., 1991; Laurikainen et al., 1994). Surgical ablation of the superior cervical ganglion results in cochlear protection from temporary threshold shifts (Borg, 1982; Horner et al. 2001) as well as permanent threshold shifts (Hildesheimer et al., 2002).
The endolymphatic sac also is endowed with a sympathetic innervation (Birgersson et al, 1992; Hozawa and Takasaka, 1993). This is particularly interesting since it is within the sac where the immunocompetent cells of the inner ear are also specifically localised (RaskAndersen and Stahle, 1980). Stress, via the sympathetic system and stress hormones, is known to have a major influence on the immune system (Madden et al., 1995; Elenkov et al., 2000; Dorshkind and Horseman, 2001; Webster et al. 2002). A possible immune-related cause has recently been proposed in Meniere's disease (Veldman, 1998; Ryan et al., 2002).
Sympathetic innervation of human middle ear mucus-membrane has also recently been described (Nagaraj and Linthicum, 1998). Since sympathetic activity appears to contribute to complex regional pain syndromes (Baron et al., 2002) it might also be hypothesised that the middle ear pain experienced by some Meniere's patients might be associated with the hyperactivation of the sympathetic activity.
Part of the sympathetic cochlear innervation has been described as originating in the brainstem. These centrifugal sympathetic fibres follow the vestibular nerve, as does the cochlear efferent fibres, to reach the inner ear (Spoendlin and Lichtensteiger, 1966; Ross, 1969; Laurikainen et al., 1994). As pointed out earlier, selective vestibular nerve section is often employed today to control episodic vertigo. In addition this surgical intervention might interfere with the sympathetic efferent limb and so might induce other effects apart from suppression of vestibular afferent activity. Interestingly there is some indication that vestibular neurotomy might stabilise hearing in the operated ear and reduce the probability of developing the pathology in other ear (Magnan et al., 1999).
Inner ear and stress hormones
The pituitary controls the release of a battery of hormones and this process is radically modified under stress conditions. Since the functioning of each hormone involves control of release at the target, as well as at the pituitary (second-order) and at the pituitary and the hypothalamus (thirdorder), the release of each of the hormones is to some extent dependent on the activity of the others. The hypothalamic hormone vasopressin, anti-diuretic hormone, (first-order feed-back) has often been cited as possibly being implicated in Meniere's disease (Naftalin, 1994). Plasma vasopressin has been reported to be elevated in Meniere's patients (Takeda et al., 1995) and chronic administration of vasopressin induces experimental endolymphatic hydrops in the guinea pig (Takeda et al., 2000). The hypothalamus-pituitary-adrenal (third-order) stress control axis is particularly well addressed in the literature. Glucocorticoids not only play a specific essential role in the stress response but in addition they highly influence the other adaptive mechanisms and in particular the immune system (Webster et al., 2002). The homeostatic control of glucocorticoids in the stress responses is essential since they provide protection in an early phase of stress but longterm exposure to glucocorticoid can lead to neurodegenerative disease. Protein receptor complexes for mineralocorticoid and glucocorticoids in cochlear and vestibular tissues were first identified by Rarey and Luttge (1989). This has led on to a number of studies, for the most part carried out by the same group, which clearly demonstrate that in stress conditions glucocorticoids are functionally active within the inner ear. Recent data show that glucocorticoids probably contribute to cochlear protection in short-term stress conditions (Wang and Liberman, 2002). The hypothalamus-pituitarythyroid axis has also a major impact on inner ear function. Thyroid deficiency during development results in deafness (Uziel, 1985a,b) and raised thyroid levels in thyroid-receptor mutants have also profound deafness (Abel et al., 1999). Thyroid hormone has recently been shown to be implicated in regulation of the cochlear motor protein prestin (Weber et al. 2002). The hypothalamus-pituitary-gonadal axis is likely to have a direct impact on inner ear function since oestrogen receptors have been described (Stenberg et al., 1999; 2001) and oestrogen has been shown to inhibit K+ secretion in the stria vascularis in-vitro (Lee and Marcus, 2001).
The hypothalamus-pituitary hormones (second-order) have been less well investigated regarding their effect on the inner ear. Prolactin is of particular interest in the study of Meniere's disease since prolactin is synthetised in stress and is implicated in the homeostasis of osmotic balance (Freeman et al. 2000; Bole-Feysot et al. 1998). In addition prolactin receptors have been detected in tissues concerned with the immune system including the thymus, spleen, lymph nodes, bone marrow. Prolactin receptors have also been detected in lymphocytes. Since lymphocyte-macrophage complexes have been observed within the endolymphatic sac it seems likely that the sac acts as a site for the immunodefence of the inner ear (Rask-Anderson and Stahle, 1980) where prolactin might play a role. Interestingly we have recently reported hyperprolactinemia in some Meniere's patients which was associated with a prolactinoma in a few cases (Horner et al. 2002). A publication in Russian has pointed out that otoneurological disorders are systematically observed in cases of pituitary tumours with marked extrasellar growth (Blagoveshchenskaia and Leushkina, 1988). This is in flagrant contrast with the occidental publications where otoneurological symptoms have not been reported in association with pituitary tumours. It is interesting to note on the other hand, that serum prolactin levels are reported to be elevated in hypothyroidism and significant hypothyroidism has been reported in 17% of Meniere's patients (Rybak, 1995). Since prolactin production is under tonic inhibition from hypothalamic dopamine, dopamine deficiency might be involved. Indeed vestibular compensation observed after hemilabyrinthectomy in the guinea pig is improved after dopamine treatment (Petrosini and dell'Anna, 1993; Drago et al., 1996). These observations suggest that neuroendocrinological feedback pathways controlling stress might be disturbed in some Meniere's patients and depression of hypothalamic dopaminergic inhibition of prolactin secretion might be implicated. A further study on non-operated Meniere's patients presenting hyperprolactinemia and on dopamine agonist treatment, is needed in order to better understand the cause of the symptoms in Meniere's disease.
Fifty years have gone by since the effect of stress on the inner ear was first reported. A body of literature available today clearly indicates that this is not a psychological by-product and that stress might very well cause inner ear pathology. Despite this, a patient with vertigo consults either in otolaryngology or neurology or psychiatry while an integrated management scheme might be more appropriate. Pin-pointing stress-induced inner ear pathology is likely to be complex since each patient is likely to react differently to stress, stress hormone release is stress-type specific, different stress pathways interact and short/long-term effects are different.
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