Image produced in collaboration with Dr Robert Kimura, Harvard University.
This figure shows a section through a cochlea with endolymphatic hydrops. Compared to the normal situation, the endolymphatic space is enlarged. Reissner's membrane can be seen bowed out into scala vestibuli.
Meniere's disease in humans is characterized as a disorder in which endolymphatic hydrops develops. The symptoms usually associated with Meniere's disease (low-frequency hearing loss, tinnitus (ringing in the ears), episodes of rotatory vertigo (dizziness), and a sensation of "fullness" or pressure in the ear) were believed to result from a malfunction of the endolymph volume regulation mechanisms. It was thought that endolymph volume increased slowly, disturbing the motion of the basilar membrane and thus giving rise to hearing loss. This explanation is now thought unlikely as in both animals an humans there can be cases where endolymphatic hydrops is present with little or no hearing loss. Our current thinking is that endolymphatic hydrops may initially not be pathologic, and the symptoms arising from hydrops may be mild or negligible, but that over time there are secondary changes in ion transport systems that result in hearing loss.
Similarly, the cause of the Meniere's attack remains equally uncertain. It had been thought that the vertigo attack was caused by hydrops developing to the point where a boundary membrane, such as in the saccule breaks, which results in a release of endolymph into the perilymphatic system of the vestibule (the “potassium intoxication hypothesis”). The leak may not necessarily be a complete rupture of a membrane but may be in the form of a more diffuse leak. The high-potassium endolymph is highly toxic to cells not specialized to deal with it. Cells become depolarized (activating transmitter release and afferent nerve fiber activity) and swell in a high-potassium environment, resulting in vestibular dysfunction. One major problem with this explanation is that hearing sensitivity is often unchanged during the Meniere's attack, when perilymph potassium level is supposedly raised. So by this hypothesis it is difficult to account for vestibular dysfunction with no change in hearing sensitivity.
Other investigators are now developing alternative explanations. One involves endolymph volume changes during the attack mechanically disturbing semi circular canal hair cells, causing an initial stimulation followed by inhibition. The underlying endolymph volume change may result from a change in transport (such as if the endolymphatic sac switches from secreting fluid to resorbing fluid) so that endolymph volume declines with time without a membrane rupture taking place.
At present, it is very difficult to establish exactly what is happening in the ear at the time of the attack. As our measurement capabilities become more sophisticated, and if Meniere's patients allow themselves to be monitored during attacks, we will eventually establish what is happening in the ear during these events.
In order to treat endolymphatic hydrops in humans, it is necessary to understand how endolymph volume is regulated in the normal ear. At present, the details of how endolymph volume is regulated are unknown. The primary goal of research in our laboratory is to develop such an understanding. One important aspect of our studies has been to develop methods to measure endolymph volume. Obviously, it is impossible to study how endolymph volume is regulated if endolymph volume cannot be measured. Hydrops can be clearly demonstrated histologically but is difficult to quantify by this technique. We have now developed methods which can measure endolymph volume with accuracy in vivo. In addition we have developed techniques to quantify endolymph volume more accurately using 3-D imaging techniques in conjunction with magnetic resonance microscopy.
One structure which appears essential for normal endolymph volume regulation is the endolymphatic sac. If the endolymphatic sac is ablated in some animals then endolymphatic hydrops develops, similar to that seen in patients with Meniere's disease. For years it was believed that endolymph was secreted in the cochlea and flowed out through the ductus reuniens, to be resorbed by the endolymphatic sac. Our research have shown that this is incorrect. In the normal cochlea the rate of longitudinal endolymph flow is extremely low, so that flow does not make a significant contribution to the homeostasis of ions in endolymph. However, recent studies in our lab suggest that when endolymph volume is disturbed, longitudinal flows may be induced which play a part in the recovery of normal volume. These flows may be directed toward the cochlear apex (when endolymph volume is reduced) or towards the cochlear base (when endolymph volume is increased). The conditions under which flows can be induced, and the role they play in volume regulation are presently being studied.
Page generated by: Alec N. Salt, Ph.D.,
Cochlear Fluids Research Laboratory,
Washington University, St. Louis