**13. Physiology of hydrops and treatment**

Most treatment strategies are geared toward the hydrops theory of etiology [44, 45]. Irrespective of the treatment instituted, the success rate of controlling vertigo episodes hovers at 60–80%, strongly suggesting nonspecific therapeutic effect or placebo effect in play. While studies are not always optimally designed with adequate controls; subjective symptoms and the fluctuating nature of the disease itself may compound the results making it difficult to distinguish spontaneous remission versus drug effect versus placebo effects.

Most commonly employed treatments include diuretics and dietary salt restriction which are used based on the rationale of altering the fluid and electrolyte balance; thus decreasing the hydrops, which has shown conflicting results in studies from being effective [46] versus flawed [47].

Several surgical procedures have been devised, such as endolymphatic sac decompressions, shunts and vestibular ablation. The aim of a majority of sac procedures is to decompress the EH and provide a path for drainage. This is conceptually flawed as most shunts created undergo fibrosis and loss of patency and endolymph would not drain into a higher pressure area such as CSF. Ventilation tubes placed in the tympanic membrane were shown to reduce vertigo [48], suggesting that middle ear pressures are involved in the pathophysiology of vertigo. The vari‐ able results noted that post‐surgery gives credence to the nonspecific placebo effect theory [49].

An interesting result of endolymphatic sac surgery for patients with MD has been the knowl‐ edge contributed toward the pathophysiology during revision surgery due to recurrence of symptoms. Extensive granulation tissue and fibrosis found in the mastoid area, in the region of the sac, create a secondary compression coupled with color changes in the implants sug‐ gesting that transudative processes in play provide evidence toward endolymphatic malab‐ sorption as the basis of the secondary (induced) MD.

## **14. Future**

they have been attributed to postmortem‐processing artifacts, strengthening the theory that the pressure effects along with biochemical effects act in concert. With regard to the theory that ruptures are responsible for the acute attacks, studies have questioned the likelihood of a rupture in one anatomical area impacting the function of other areas, or the likelihood of simultaneous rupture of both the cochlear duct and saccule (not supported by histology find‐ ings) affecting cochlear and vestibular functions [36]. It is also logical extension of theory to expect relief of symptoms after rupture, as relief of the pressure should alleviate symptoms. Vestibular symptoms such as nystagmus were induced in animal models with an injection of artificial endolymph into the perilymphatic space, presumed to represent the actual events in

Imaging studies in vivo using gadolinium‐contrasted magnetic resonance imaging (MRI) demonstrated that in MD, different areas affected by the EH (vestibular vs. cochlear) were correlated to different symptoms experienced by patients as seen in the distinct cochlear or vestibular variants of Meniere's disease [38]. Such imaging studies also found a correla‐ tion between the progress of the EH imaged with the clinical deterioration of the inner ear functional measurements [39], strengthening the role of hydrops in the pathophysiology

Measuring the cross‐sectional area of the scala media in vivo overcomes the drawbacks of histological shrinking and other artifacts. It has been used in animal models of hydrops with an endolymphatic marker, to study the temporal relation in the development of hydrops, post duct ablation (occurs within days). Functional deficits, measured electrophysiologically (such as cochlear potentials), were surprisingly initially only small changes and most marked at the 8‐ to 16‐week time period when no further hydrops or endolymphatic expansion occurred. The logical extension, if it holds true in humans, would imply that factors apart from or in addition to the hydrops could be responsible for symptoms and relieving the hydrops may

Studies determined that the hydrops causes a displacement of the basilar membrane toward the scala tympani which due to anatomical considerations is predominantly at the apex of the cochlea affecting its mechanical‐electrical properties. This displacement results in sensorineu‐ ral hearing loss of frequency below 100 Hz (due to anatomical locations of receptors) which is unlikely to result in clinically appreciated hearing loss, usually tested at frequencies of 250 HZ and higher. Thus, this in endolymphatic hydrops, the pathological findings do not correlate to

Given the prevalence of EH in patients of MD, diagnostic tests developed to visualize the EH in vivo have been studied such as gadolinium‐based contrast media using heavily T(2)‐weighted 3D FLAIR [42]. The advent of such dynamic imaging technologies provides new insights into the pathophysiology of MD such as differential involvement of cochlear and vestibular com‐ partments and the fact that EH occurs in the asymptomatic or unaffected ear with a high (75%)

the low‐frequency hearing lost observed in Meniere's disease [41].

play during an attack of episodic vertigo [37].

not restore normal functioning [40].

**12. Hydrops and diagnosis**

of MD.

62 Up to Date on Meniere's Disease

Despite advances in technologies, the fundamentals of the pathophysiology in MD remain incomplete. The gaps in knowledge are wide ranging, from natural progression of the dis‐ ease to etiology, pathophysiology and treatment. To reconcile these controversies, research endeavors should adhere to standardized definitions of MD, selection criteria, control devel‐ opment and results reporting, which will allow comparable analysis across studies.

Animal models and experimental designs more closely reflecting the clinical entity of MD should be the pillar for future research. Overcoming the shortcoming of traditional animal models may allow breakthroughs in answering these questions. Newer models more closely resembling the pathophysiological process in play in MD include mice with vasopressin administration and exploring the role of Latanoprost in MD therapy [50]. Technological advancements in inner ear imaging, histology, immunohistochemistry, genetic testing and functional measurements will allow a more molecular and refined examination of the patho‐ physiological process.

## **15. Summary**

The pathophysiology of MD remains elusive despite intense research. It is likely that hydrops may not be the cause of MD symptoms, rather an epiphenomenon. Theories on the patho‐ physiology of MD thus leave several important gaps, mainly around the central theory of EH causing hydrops. They include the following:


However, given a 100% association of EH in at least one ear of patients with MD, it is likely that EH is more than just an epiphenomenon, rather it is a condition that is necessary but not sufficient for the clinical picture of MD.
