Causes of Meniere's disease

The term "idiopathic" takes first place in the definition of this disease, therefore, it can be said that the causes of Meniere's disease are unknown; the main cause (or causes) of this nosological entity depends on a number of factors that can lead to the development of endolymphatic dropsy. [ 1 ] Among them are viral infections, vascular disorders, autoimmune processes, [ 2 ] allergic reactions, injuries, endocrine diseases, etc.

Genetic and environmental factors play a role. [ 3 ]

Several recent studies have conducted genetic evaluation of families with Meniere's disease. Women are affected slightly more than men, accounting for 56% of cases. Genetic predisposition has been found in 2.6–12% of patients with Meniere's disease. Familial cases appear to be associated with autosomal dominant inheritance with incomplete penetrance (60%).[ 4 ]

Chromosomal studies involving a Swedish family with multiple cases of Ménière's disease demonstrated an association with several markers on chromosome 12; further studies narrowed the locus to 12p12.3. The only known gene in this region encodes gamma-phosphatidylinositol 3-kinase class 2 (PIK3C2G), the activation of which has been shown to promote utricular macula cell regeneration in rats.[ 5 ] Two other studies have shown an association between Ménière's disease and single nucleotide polymorphisms. One was an alteration in the heat shock protein HSP70-1, possibly involved in the cellular stress response;[ 6 ] the other was an alteration in adduction (Gly460Trp), which was associated with changes in sodium metabolism and Na +,K + -ATPase activity.[ 7 ]

Autoimmunity has also been implicated in the pathogenesis of Meniere's disease, largely due to the high frequency of autoimmune diseases associated with Meniere's disease. Gazquez et al. [ 8 ] found a higher prevalence (compared to that expected in the general population) of rheumatoid arthritis, systemic lupus erythematosus, and ankylosing spondylitis in patients with Meniere's disease.

Hornibrook et al. [ 9 ] hypothesized 3 possible mechanisms by which the autoimmune response may lead to changes in the absorptive capacity of the endolymph drainage system:

1. direct tissue cell damage caused by autoantibodies;
2. deposition of antigen-antibody complexes leading to activation of the complement cascade and tissue destruction; or
3. inflammatory response mediated by sensitized T lymphocytes.

Pathogenesis of Meniere's disease

The symptom complex, including attacks of dizziness and hearing impairment (hearing loss and tinnitus), was first described by Prosper Meniere in 1861, and it was he who suggested a connection between these symptoms and the condition of the human inner ear. Further studies confirmed the correctness of these assumptions, so the disease was named after the author, Prosper Meniere, who first described a typical symptom complex, which is a very complex clinical problem for doctors both in terms of diagnosis and in terms of the effectiveness of treatment of this disease.

There is now much evidence that hydrops in the inner ear occurs in the clinical disorders typical of Meniere's disease. According to morphological studies, this involves stretching of the vestibular membrane and a change in the volume of fluid in the endolymphatic space. The endolymph is completely isolated by the walls of the membranous labyrinth and surrounded by perilymph, which communicates with the cerebrospinal fluid through the vestibular aqueduct. Theoretically, the pressure of the cerebrospinal fluid can be transmitted to the endolymph through the vestibular aqueduct, although there is no free interaction. Intracranial vascular pressure can affect the fluids of the inner ear, since the vessels are in direct contact with these fluids. In this case, thin-walled venules have a more significant influence on pressure transmission compared to thick-walled, elastic arteries.

There is some disagreement about the source of endolymph production. The following mechanisms of its formation have been proposed:

• the seepage of fluid from the blood plasma through the capillaries of the vascular strip:
• seepage of fluid from the perilymph through the epithelium of the membranous labyrinth;
• maintaining the existence of endolymph to a greater extent than its secretion, that is, endolymph homeostasis,

Theories regarding endolymph flow include:

• longitudinal flow mechanism in which endolymph is produced in the cochlea, flows into the saccule of the membranous labyrinth, and is finally absorbed in the endolymphatic sac;
• radial flow mechanism in which endolymph is secreted and absorbed into the cochlear duct.

The longitudinal endolymph flow theory is supported mainly by data obtained using dyes or markers that, after introduction into the cochlear endolymph, were quickly detected in the endolymphatic sac. Evidence in favor of the radial theory is provided by data according to which damage to the cochlea leads to disturbances only in the area of damage, with preservation of the intracochlear potential and endolymph in areas proximal and distal to the site of damage. It is quite likely that both mechanisms are present, but with different representation and significance in different people.

Endolymphatic hydrops may result from a number of mechanisms. Based on the longitudinal gig theory, endolymphatic hydrops may result from a production-absorption discoordination in which endolymph absorption does not match production. This idea is oversimplified, since such a discoordination should also result in a change in endolymph composition, which is not observed in patients with Meniere's disease or in animals with experimental endolymphatic hydrops. Another mechanism for the development of hydrops involves an excessive accumulation of certain ions or substances with a high molecular weight, which leads to an osmotic gradient, an increase in endolymph volume with a corresponding increase in pressure, and, as a result, to hydrops. A diametrically opposed concept is the assumption of an insufficient perilymph volume, which could lead to endolymphatic hydrops.

Based on the associated changes in the temporal bone in endolymphatic hydrops, a mechanism of venous insufficiency of the endolymphatic passage and sac, as well as insufficiency or absence of the vein of the peri-vestibular canaliculus, has been proposed.

The supposed mechanisms of Meniere's disease may also be accompanied by an increase in venous pressure, which, in turn, will disrupt the outflow of venous blood from the endolymphatic sac. The study of the ultrastructure of the inner ear and the features of fluid exchange in it continues. In particular, observations of scientists on patients with Meniere's disease with hydrops of the labyrinthine showed that dissection of the endolymphatic duct in the area of its exit to the posterior surface of the pyramid of the temporal bone (before entering the endolymphatic sac) consistently eliminates the factors leading to attacks of dizziness and sensorineural hearing loss. Dissection of the endolymphatic duct was done in 152 patients. The attacks of dizziness ceased in all patients, 26% experienced an improvement in hearing by 10-20 dB, and the noise in the ear ceased. There were no repeat visits over a 20-year period. It is important to note that 94 patients were re-interviewed 20 years later - attacks of Meniere's disease did not recur in any of them. These data allow us to conclude that it is not the endolymphatic sac that eliminates endolymphatic hydrops and thereby normalizes intralabyrinthine functions, but that there is a free discharge of endolymph through the endolymphatic duct under the dura mater. These facts indicated that the cause of hydrops may be stenosis of the endolymphatic duct in the area located distal to its exit from the pyramidal bone, or deterioration in the absorption of endolymph by the epithelium of the endolymphatic sac.

The endolymphatic sinus is also involved in the regulation of endolymph. Given the distensible nature of its walls, associated with its position at the entrance to the endolymphatic duct, the sinus may act as a reservoir; [ 10 ] Another hypothesis is that a dilated sinus may block the entrance to the endolymphatic duct by compressing the valve of Bast.

The valve of Bast appears to function as a physiological mechanism to prevent collapse of the superior portion in the event of a sudden decrease in its volume.[ 11 ] However, both animal models and temporal bone studies have also demonstrated that the valve can open in response to increased pressure in the endolymphatic sac and duct, allowing excess endolymph to flow backwards.[ 12 ] If the valve opens in this way, progression of Ménière's disease and further impairment of the sac's absorptive mechanisms may prevent its closure; the sensory epithelium may be more vulnerable to pressure changes, leading to vestibular symptoms. These symptoms may affect patients with hydrocele even in the absence of overt hearing loss, a condition Paparella described as vestibular Ménière's disease. [ 13 ], [ 14 ] Greatly enlarged saccules can also displace the utricular walls toward the valve of Bast, causing it to appear blocked when examining the temporal bones.