**7. Pressure changes and hydrops**

such trauma, however, do not provide adequate backing to this theory [15]. The bilaterality of

Otosclerosis: Patients with otosclerosis have been found to have symptoms of MD due to the otosclerosis enveloping the aqueduct or invading the endosteum, resulting in changes in the

Low cerebrospinal fluid pressures: Connections between the inner ear and CSF allow pres‐ sure changes to be transmitted, notably, a drop in CSF pressures such as postoperatively, leading to decreased perilymphatic pressures and a corresponding relative endolymphatic

Other mediators: nitric oxide and vasopressin: Overexpression of the inducible nitric oxide synthase enzyme results in morphological (hair cell loss) and functional changes (endoco‐ chlear threshold and potential shifts) and stria vascularis toxicity, implicated in the devel‐ opment of MD, along with other free radicals [18]. Vasopressin levels have been shown to increase before and after a vertigo attack in MD patients, in humans and experimental models

The pathophysiology of Meniere's disease is tied to the physiology of the hydrops, which can be induced in experimental models by obliteration or blockage of the duct and/or sac in animals at a success rate approaching 100% in guinea pigs but with more variability in other species. The experimental animal models remain deficient, with no acute attacks of MD and lack of reported vestibular dysfunction despite severe hydrops, cautioning against direct equivalence from animal to human theories. This induced hydrops, despite being an incom‐ plete model, is used to study the effects on the labyrinthine and cochlear physiology such as

Despite logistical and technical difficulties in obtaining tissues and fluid (as composition is usually disturbed during surgical procedures), some human and animal studies show a change in the sodium‐potassium levels of the cochlear and vestibular endolymphatic fluids in MD and experimental hydrops, respectively [20]. In addition to the theory of ruptures caus‐ ing spillage of potassium ions into the perilymph, another possible explanation for the ionic and fluid imbalances in hydrops was postulated to be the Na, K‐ATPase enzymes found in the cochlear lateral wall. However immunohistochemical studies of human temporal bones did not show statistically significant differences in hydropic ears consistent with the normal func‐ tioning of the stria vascularis in patients with MD [21]. Possible theories diverging from the traditional disruption of Guild's principle of longitudinal endolymphatic flow include ionic disequilibrium being responsible for the hydrops. Cellular changes in Reissner's membrane

electrolyte homeostasis in the fluids and membranes, pressures and potentials.

MD cannot be explained in cases of unilateral trauma.

possibly contributing to the development of hydrops [19].

**5. Physiology in Meniere's disease**

**6. Ionic homeostasis and hydrops**

hydrops [17].

58 Up to Date on Meniere's Disease

flow and chemical composition of endolymph and perilymph [16].

Experimental models studying the effect of postural changes on endo‐ and perilymphatic space fluid pressures show a marked change in the hydropic versus control animals [23]. There is possibly an adaptation of the vestibular system to the increased endolymphatic pressures, given that the time period for the development of hydrops is over months. This adaptation is unlikely to remain in effect with changes in posture. This uncompensated disequilibrium of fluid pressures may be responsible for the vestibular dysfunction.

A second mechanism to consider is that an increase in pressures produced in the hydropic ear during postural changes compresses the microvasculature on the wall of the labyrinth, result‐ ing in ischemia of the inner ear [24].

The cerebrospinal fluid pressure dictates the inner ear hydrostatic pressure through the cochlear aqueduct. Studies measuring the positional changes of intracranial CSF pressure and its corresponding effects on the perilymphatic pressures showed insignificant differences between MD affected and control ears [25]. Animal models measuring endo‐ and perilym‐ phatic space fluid pressures before and after induced hydrops show no significance in pres‐ sure between the scala media and the scala tympani in either control or hydropic ears [26], with similar findings in humans, thus precluding the use of MMS‐10 tympanic displacement analyzer (Marchbanks' test) in a diagnostic capacity [27].

## **8. Endocochlear potential and hydrops**

Experimental models report a decrease in the endocochlear potential (EP) developing after inducing hydrops [26]. Measurements of the evoked responses of the cochlea such as cochlear microphonic potential (CM) show decreased maximum output and threshold levels. Auditory brainstem responses also show progressive deficits. Electrophysiological tests such as electro‐ cochleography (ECoG) are commonly used in the diagnosis of MD which includes both the compound action potential (CAP) and the summating potential (SP). The CAP is the summa‐ tion of responses from the auditory nerve which would be reduced in patients with hearing loss. The SP is the summation of responses from the hair cells. Since hydrops would push the basilar membrane closer toward the scala tympani, in the absence of hair cell damage or loss (seen in the early stages of the disease), this effect of hydrops would increase the SP. While the absolute values of these two components may differ, they do covary and hence the ratio between the two is often used in MD diagnosis.

Studies show that while rupture of the membranous labyrinth in hydrops was believed to be responsible for the inner ear dysfunction (through large volume injections into the endolym‐ phatic sac), the pattern of pressure changes in conjunction with techniques examining temporal bones via a micro‐CT and functional electrographic recordings shows that they are not solely responsible for the acute ear dysfunction, rather the hydrops is a continuing, prolonged process with Non‐rupture mechanisms in play, which can be correlated clinically with MD too [28].
