Invited lecture to the Victorian Meniere’s Support Group
East Melbourne, 7 March 1999

Insights into Ménière’s disorder from the perspective of a cochlear mechanic

Eric L. LePage, Ph.D.
Hearing Conservation Research Unit
National Acoustic Laboratories
126 Greville Street, Chatswood, N.S.W. 2067

INTRODUCTION

This talk presents insights into the problem of Ménière’s disease and fluctuant hearing loss gained over a 25-year period. Part of the problem with Ménière’s syndrome is that anything to do with the inner ear is complex because normally we can only obtain a “keyhole” view of the mechanisms in the cochlear and vestibular apparatus. It is totally encased in bone and as a consequence any attempts to make invasive measurements on the ear tend to destroy the normal function of the ear, such is the delicate nature of the structures. One of the salient characteristics of the ear is that it is fluid filled and, for its size, uses a lot of biological energy for detecting sound and processing it. In that process, energy is expended to drive the mechanical structures in the cochlea, and it turns out that their movements are not just vibrations due to the sound coming in. The three rows of outer hair cells that response and interact with sound also regulate the sensitivity of the cochlea by controlling the angles of the arch of Corti and operating point of the inner hair cells (how far the hairs are deflected). The way this is achieved is by controlling the up-and-down position of the cochlear partition (LePage, 1987). Normally there are continual variations in cochlear pressure, due for example to variations in blood and CSF pressure. The normal ear does not suffer a hearing loss just because we have changed our posture, or engaged in strong exercise. The outer hair cells maintain hearing stability. We can loosely regard the cochlear partition containing these motor cells like a trampoline which is flexible in the middle position, but because stretched and stiff if pushed too far down or up. In the middle position sensitivity is greatest, but if deflected too far down sensitivity is reduced. In the past we have not thought too much about whether the pressures in the chambers are normally regulated, but clearly, in the case of hydropic ears the regulation set point has drifted. If scala media is tending to balloon (See Figure 1) this is because the pressures in it are rising so that in fluctuant pressure conditions outer hair cells have to work against a non-steady pressure.

 

Figure 1. Panel A shows the effect of endolymphatic pressure variation upon the position of the basilar membrane and hearing sensitivity. Normally the outer hair cell length change controls the deflection of the inner hair cell hairs via the position of the tectorial membrane (panel B). The sensitivity is thus controlled by setting the set point of the inner hair cells. However, when the the pressure rises abnormally the angle of the arch (the phalangial processes of the organ of Corti) is overridden by the pressure shutting down the inner hair cell.

INVOLVEMENT IN OUTER HAIR CELL ACTIVITY IN COCHLEAR HOMEOSTASIS

 

The outer hair cells have some ability to cope with some pressure fluctuation, but perhaps not under the extremely hydropic state in which Reissner’s membrane is greatly distended toward scala vestibuli. Small pressure variations will cause a few microns movement of the cochlear partition, and this is within the range of control of the outer hair cells. They can change their length (of say 70 microns) by easily 3% (i.e. 2 microns) so the sensitivity of the ear remains regulated by ensuring that the inner hair cells remain in their narrow working range (see Figure 2).

Figure 2. The outer hair cells change length as part of their normal operation of regulating hearing sensitivity. Here an outer hair cell is doing its pushups under electrical stimulation. In vivo, the length change is transmitted to the inner hair cells via the angle of the tectorial membrane. It is clear, however, that part of this set point setting process they must stablise hearing sensitivity for normal fluctuations in hydrostatic pressure, e.g. due the variations in the pressure of the cerebrospinal fluid.

Once the pressure in scala media rises beyond the limits of outer hair cell regulation, the basilar membrane is pushed too far in the direction of scala tympani, or the outer hair cells are reduced in numbers, the regulation can fail, reducing the sensitivity of the ear. Once can therefore begin to appreciate a major function of the outer hair cells, being the only active mechanical devices, must either be pressure regulation, or local compensation for externally imposed pressure variations. The reticular membrane normally constitutes a tight seal between the high potassium endolymph in scala media and the cortilymph (perilymph). If the reticular membrane is distended too far it can leak and the basal part of the outer hair cell becomes bathed in high potassium fluid instead of high sodium fluid, and this causes them to become depolarised (Zenner et al., 1994), further destroying their ability to regulate the membrane position. Indeed this can result in conditions hazardous to the cells; they can swell and even explode under osmotic force which can amount to the order of atmospheres of steady pressure. This leakage can be caused by many factors such as the effects of high level vibrations due to loud noise weakening the seal, but also steady pressure, such as experienced by scuba divers, could have the same effect. I hypothesise that a mild level of distension, over a long period can in some cases lead to a run-away situation in which fluid flows into scala medial under osmotic pressure. All one needs to have such pressures is some biological membrane across which some large molecule cannot pass. When this happens, water will readily flow across the mambrane to the compartment (e.g. scala media) containing the non-permeable particle such as a cell membrane and can do so with force.

CHICKEN AND EGG PROBLEM IN DRIFT IN SET POINT

 

The outer hair cells are nevertheless not the only structures involved in the cochlear homeostasis. The fluid channels are continuous between the cochlea and vestibular apparatus. This means that the pressure head between the cochlea and the vestibular apparatus can be high while fluid flow would normally be very low. ince pressure in a compartment is evenly distributed it follows that any part of the compartment which is free to balloon will do it in preference to other parts. In the cochlea the stiffness wil be least at the apical end so this is consistent with a low-frequency hearing loss and the tinnitus of Meniere’s being a low frequency “roaring” type of tinnitus (LePage, 1995) We have known for years that hydrops tends to occur in people who have a blocked endocochlear duct which leads to the endocochlear sac, long regarded as funtioning something like a pressure release valve and maybe as a toxic waste dump (see Fig. 3). Which comes first — the rise in pressure or the blocked duct — is still the subject of uncertainty, but one can imagine the products of cellular breakdown in the cochlea due to noise damage ending up in the duct. If the blockage is suddenly removed, or if any of the membranes in the making up the compartment rupture there will be rapid flow in all segments and this can create an acute vestibular disturbance.

Figure 3. Schematic describing the fluid connection between the cochlea (the endolymph in scala media) and the balanced organ, plus the tiny endocochlear duct which tends to block so that any normal pressure rises cannot be released by the sac.

The third structures involved in cochlear homeostasis is the stria vascularis, long thought to have its primary function as a ‘battery’, the source of the endocochlear potential. If the endocochlear potential is disabled e.g. with diuretics such as furosemide (Lasix) which in high concentrations can have a draumatic effects on outer hair cell motility (Hubbard et al, 1986). More modern study of the stria reveals that it has many cells which are individually specialised for regulating all the important ions. Calcium concentration in endolymph is normally extremely low, but if it cannot be maintained low, may lead to a pressure rise due to a change in the standing current through the hair cells. In summary, the reason progress is slow in Ménière’s disease is that we are dealing with highly complex, three strongly interactive systems, and invasive animal experiments designed to study them invariably interfere with their operation. Fortunately this does not mean that significant progress cannot be made.

OTOACOUSTIC EMISSIONS AS A POWERFUL MONITOR OF EARLY CHANGES

 

In the past, behavioural testing of hearing sensitivity and speech discrimination has been the mainstay of our diagnostic practice, but from our current perspective this is slow and imprecise. Faster, more precise determinations of cochlear homeostasis and sensitivity have been carreid out by otologists by measuring cochlear potentials. However, this is invasive and involves placing an electrode through the tympanum onto the round window. Generally, diagnostic of hydrops is evidence of a “downward” displacement basilar membrane leading to an increase in the postive summating potential in response to tone pips. if due to hydrops it can be reduced with glycerol administration via its osmotic effect. At Australian Hearing we are interested in doing something about early warning of hearing disability. The approach which holds much promise in many facets of diagnostic audiology, is the use of otoacoustic emissions (LePage et al, 1993) and we have gone some small distance in showing that groups of people with differing noise-exposure profiles have differing levels of accumulated latent ear damage (LePage and Murray, 1998). The jump in progress is because the technique is not only non-invasive, but is objective and fast, and can herefore track fast changes. It follows that ear emissions may also be useful in characterising the cochlear behaviour in hydrops and Ménière’s patients. The technique involves putting sounds into the ear and recording the active response of the outer hair cells with a microphone in the ear canal (see Fig. 4). We know that outer hair cell activity is modified by displacement of the basilar membrane, and we can oberve fluctuations in the emission levels. In one case of fluctuant hearing loss we have studied, rapid variations over a half-hour period were found to be greatest at low frequencies.

Figure 4. The otoacoustic emission probe sealed in the ear canal contains one or two speakers and a microphone which registes the sounds transmitted to the ear and sounds re-emitted as the result of outer hair cell activity evoked by the stimulus. Being a non-invasive, objective mesurement of dynamic cochlear behaviour it lends itself to monitoring of intracochlear mechanical changes oer months, days and even seconds.

STRONG CASE FOR AUSTRALIAN OAE RESEARCH FOR INDICATORS

There is much research to be done because there are many sources of pressure fluctuations, including CSF variations and fistulas. It is important at the outset, to characterise the type and level of fluctuation of eissions in normal hearing people and also in Ménière’s patients. There are ways of estimating the susceptibility of any individual to developing hydrops such as by monitoring otoacoustic emissions before and after administration effect of diuretics and new drugs such as the calcium channel blocker cinnarizine. Never before has it been possible to do non-invasive long-term monitoring of Ménière’s patients to determine if there are specific physiological triggers for a Ménière’s attack, but ear emissions offers an avenue to do so. Such a study should reveal much more precisely which pharmacological agents may impede the course of the disorder and limit the severity of attacks.

REFERENCES

Hubbard, A. E., Mountain, D. C., & LePage, E. L. (1986). Furosemide affects ear-canal emissions produced by the injection of AC currents into scala media. In: Lecture Notes in Biomathematics: Vol. 64. Peripheral Auditory Mechanisms (pp. 361-368). New York: Springer-Verlag.
LePage, E. L. (1987). Frequency-dependent self-induced bias of the basilar membrane and its potential for controlling sensitivity and tuning in the mammalian cochlea. J.Acoust.Soc.Am. 82, 139-154.
LePage, E. L., Murray, N. M., Tran, K., & Harrap, M. J. (1993). The ear as an acoustical generator: otoacoustic emissions and their diagnostic potential. Acoustics Australia, 21(3), 86-90.
Zenner, H. P., Reuter, G., Zimmermann, U., Gitter, A. H., Fermin, C., & LePage, E. L. (1994). Transitory endolymph leakage induced hearing loss and tinnitus: depolarization, biphasic shortening and loss of electromotility of outer hair cells. Eur Arch Otorhinolaryngol 251(3), 143-53.
LePage, E. L. (1995). A model for cochlear origin of subjective tinnitus: excitatory drift in the operating point of inner hair cells. In Jack A. Vernon and Aage R. Moller Mechanisms of Tinnitus (Vol. Chapter 11pp. 115-148). Boston: Allyn and Bacon.
LePage, E. L., & Murray, N. M. (1998). Latent cochlear damage in personal stereo users: a study based on click- evoked otoacoustic emissions. Med J Aust 169(11-12), 588-92.