Clinical and Health Affairs
Meniere’s Disease
New Concepts, New Treatments
By Norman T. Berlinger, M.D., Ph.D.
■ Our understanding of Meniere’s disease is being revamped. For decades, the condition was thought to be caused by excessive fluid retention (hydrops) in the endolymphatic spaces of the inner ear, which led to tears or ruptures of the membranous structures that affect hearing and balance. More recently, research has shown that hydrops is not always associated with Meniere’s and ought not to be considered the ultimate cause of its symptoms. New theories center on the fact that Meniere’s disease may not have a single cause but may well be a common endpoint of a variety of anatomic or physiologic variables, including ischemic or even autoimmune injuries. This article describes the new thinking about Meniere’s and explains why current treatment approaches, although they are based on outdated understanding, may still be valuable for alleviating symptoms in some patients.
Meniere’s disease is a disorder of the inner ear that manifests with spontaneous episodic attacks of vertigo, sensorineural hearing loss, and tinnitus. In addition, patients often complain of a sensation of aural fullness. The prevalence of Meniere’s disease varies around the world. The landmark study of prevalence in the United States, which originated from Mayo Clinic data from 1951 through 1980, showed a rate of 218.2 cases per 100,000 population.1 Meniere’s disease can present at any age, but most people are diagnosed in their 30s or 40s. Recently, more cases have been seen among people in their 50s and 60s. Bilateral disease may occur in up to 24% of cases and may be either synchronous or metachronous, and up to 20% of cases may be familial.
A Disease of Inference
Before the 1850s, balance and vertigo were attributed to the central nervous system, and disorders of balance were often considered psychiatric illnesses, sometimes called “apoplectic cerebral congestion.”2 While serving as the chief physician at the Imperial Institute for Deaf Mutes in Paris, Prosper Meniere in 1861 was the first to report that balance problems were related to the inner ear. Using autopsy studies, he asserted that the semicircular canals provided vestibular function and that vertigo resulted when they were diseased.
The histopathology associated with Meniere’s disease was first described nearly 75 years ago when Hallpike and Cairns detected dilation of the endolymphatic spaces of the inner ear with ballooning of Reissner’s membrane in temporal bones obtained from patients who died after eighth-nerve surgery to relieve their vertigo.2 (Figure 1 shows a photomicrograph of a normal human cochlea. Figure 2 shows a photomicrograph of the cochlea of a patient with a dilated endolymphatic space associated with Meniere’s disease.) Although their work located Meniere’s disease within the ear, it also led physicians and researchers to make a number of inferences that led to misconceptions. And so began the attempted scientific study of—and the misconceptions about—Meniere’s disease.
Misconceptions occurred because pathogenesis was inferred only from histopathology. In 1927, Guild inferred that the endolymphatic fluid flowed primarily longitudinally, down the length of the cochlea, and was drained at the endolymphatic sac.3 Guild’s and Hallpike and Cairns’s theories led to the conclusion that hydrops of the endolymphatic compartment occur as a result of obstruction of the endolymphatic sac, which serves as an overflow valve or absorptive structure for the endolymph system.
There was no explanation for how distension of the endolymphatic space produced the classic symptoms of Meniere’s—vertigo, tinnitus, and hearing loss—until Lawrence and McCabe in the 1950s inferred that the overdistension of the endolymphatic space caused rupturing of its membranes. They suggested the resulting spillage of the potassium-rich endolymph into the relatively postassium-poor perilymph caused acute labyrinthine dysfunction by potassium “intoxication.”4 Release of the built-up endolymphatic pressure allowed the ruptured membranes to heal.Continued cycles of membrane rupture and repair accounted for the episodic symptoms associated with Meniere’s disease.
This was our understanding for the next four decades. Although this model was neat and encompassing, it was also highly speculative and was never validated by animal research. Recent clinical and scientific data call into question many of the central assumptions about our classic understanding of this disorder.
Anatomical Studies
A number of anatomical studies have led us to question the assumption that endolymphatic hydrops is the cause of the vertigo, tinnitus, and hearing loss associated with Meniere’s disease. If that were the case, then it would be reasonable to presume that all cases of Meniere’s disease should show hydrops and that all cases of hydrops ought to manifest the classic symptoms. Indeed, an important temporal bone study by Rauch et al. showed evidence of hydrops in all patients who had been diagnosed with Meniere’s disease. However, hydrops was also found in a large number of patients who showed none of the symptoms.5 Thus, we know that endolymphatic hydrops and Meniere’s disease are not synonymous, and that endolymphatic hydrops almost certainly is not the cause of the specific symptom complex of vertigo, tinnitus, and fluctuating hearing loss associated with Meniere’s disease.
In the early 1990s, Schuknecht discovered that fibrosis could occur at many sites within the endolymphatic duct system, not just the terminal sac, and inferred that there was a resulting obstruction of endolymph flow at various points within the system with the development of hydrops.6 However, Wackym et al. showed in an excellent temporal bone study that there was no difference with regard to fibrosis in the endolymphatic systems of patients with and without Meniere’s disease.7
Physiological studies likewise have called the classic model into question. Guild’s inference about the longitudinal flow of endolymph was challenged in the 1980s when Salt et al. showed in experiments with guinea pigs that the longitudinal flow of endolymph is negligible.8,9 Furthermore, Salt demonstrated that the regulation of endocochlear fluid volume is achieved locally by the radial flow of endolymph through the perilymph. In addition, Takeuchi et al. showed in another guinea pig model that there is no difference in the hydrostatic pressures recorded in the perilymph and endolymph despite the presence of significant hydrops.10 Thus, the notion that increases in endolymphatic pressure lead to periodic rupture of the endolymphatic membranes with resulting potassium intoxication and Meniere’s symptoms has not been validated in animal studies.
Currently, some investigators claim that hydrops can exist in certain patients with Meniere’s disease and cause some of the symptoms or exacerbations of those symptoms. But others consider hydrops to be merely an epiphenomenon. Clearly needed is a new understanding of the pathogenesis of Meniere’s disease—one that does not rely solely on the notion of an anatomical abnormality, namely, hydrops.
New Thinking about Meniere’s Disease
Many researchers now believe that the abnormality related to Meniere’s symptoms may be more physiological than anatomical. That is, that Meniere’s disease is the outcome of a complex cascade of pathophysiologic processes that ultimately dysregulate the ionic composition of the endolymph rather than the outcome of a simple obstructive anatomical abnormality.
Investigation into reversible hearing loss may eventually shed light on the mechanisms behind Meniere’s in the coming years. For instance, we know that acoustic trauma can cause a temporary threshold shift, and even when this shift is dramatic, no morphologic abnormalities are demonstrable.11 Similarly, we’ve learned that salicylates can cause marked reversible cochlear dysfunction in the absence of morphologic abnormalities in the cochlea. It has been suggested that inner-ear neuropathology canresult from dysfunction of cellular channels and conductances. Gates has hypothesized that Meniere’s disease may result from such a channelopathy.12
This is not to say that the answers will be found in this work, only that scientific study is reorienting our thinking. We are now considering Meniere’s disease in physiologic terms and thinking of the histological changes as only one part of a very big picture. In 2010, Rauch went so far as to suggest discarding the term Meniere’s disease and redefining the symptom complex as a “degenerating inner ear” or an “unstable inner ear” that has dysfunction of one or more homeostatic systems resulting in dizziness and hearing fluctuation.13
So if the science surrounding Meniere’s disease is not quite on the mark, and our thinking about its pathophysiology is not quite correct, how does a physician treat the problem?
Interestingly enough, old treatments, even though they are based on misconceptions, do indeed have therapeutic value. Diet and lifestyle changes, which are often the first-line recommendation, can control vertigo in up to 60% of patients. Sodium restriction is one way of reducing fluid in the inner ear. Although with our current understanding it seems highly unlikely that sodium restriction alone could significantly reduce fluid within the endolymphatic compartment, many patients have benefited significantly from a low-sodium diet. Similarly, diuretics can reduce endolymph volume, and many patients benefit from this approach as well. But if hydrops can be asymptomatic or is a mere epiphenomenon, why do patients have success with these approaches?
Recently, Rauch offered an explanation for why they may work. He postulated that the unstable or degenerating Meniere’s ear has lost its ability to tightly control fluid and electrolyte balance. What the unstable ear may not tolerate, he theorized, is variations in sodium levels. If that is indeed the case, a constant sodium level, rather than a low sodium level, may be crucial to controlling the vertigo associated with Meniere’s disease, and the goal of sodium restriction therapy should be to even out the peaks and valleys of sodium intake.13 According to this line of thinking, patients find relief of their symptoms not because they are consuming less salt but because they are consuming consistent amounts of salt. For that reason, Rauch advocates an even intake of salt throughout the day. The idea is to avoid the spikes that may trigger symptoms. This can be achieved with a diet that includes 3,000 mg of sodium per day, with a target consumption of about 1,000 mg per meal, as opposed to a low-sodium diet, which restricts intake to 1,500 or 2,000 mg per day and can be difficult for patients to comply with. Moreover, if at some point during the day the patient on a 3,000 mg per day diet decides to consume a high sodium load, the temporary indiscretion will not have as much effect because his or her baseline salt level was not extremely low.
In addition, we now suspect that the reason diuretics work for certain patients might also be different from what we once believed. Diuretics have a profound effect on ion pumps and ionic gradients in the kidneys. They also have a profound effect on the same pumps and gradients in the inner ear. Thus, it is more likely that diuretics work not by dehydrating the inner ear of endolymph, as we once thought, but rather by positively influencing inner ear fluid and electrolyte processing in an as-yet-unknown manner.
We also are thinking differently about the effects of consuming alcohol and caffeine. Our concern now is that large changes in alcohol and caffeine consumption could disturb the fragile or failing homeostatic mechanisms of the unstable inner ear. Likewise, we are thinking about how stress, allergy attacks, hormonal changes, and sleep deprivation can challenge homeostasis in the unstable Meniere’s ear. Thus, the basic principle underlying treating Meniere’s with lifestyle changes and diuretics is to disrupt the fluid- and electrolyte-regulating processes as little as possible.
These treatments are quite effective for managing the vertigo associated with Meniere’s disease. But if they fail, there is a new and powerful nonsurgical method for addressing it: intratympanic perfusions of dexamethasone. This recently developed treatment has achieved significant control of vertigo in up to 91% of patients who do not respond to sodium restriction and diuretics.14 The procedure is quite simple: A myringotomy is performed in the office with topical phenol anesthesia. High-concentration dexamethasone is then perfused through this tiny slit into the middle ear space. The patient lies still for 15 minutes and is told not to swallow, in order to avoid opening the Eustachian tube, which may cause the steroid to drain out of the middle ear. The patient can return to normal activity after the perfusion. This treatment is repeated two more times over a two-week period. Researchers from Cleveland Clinic recently reported that 88% of patients who had failed dietary and diuretic therapy achieved significant control of their vertigo with intratympanic dexamethasone.15 The reason why intratympanic steroid perfusions appear to control vertigo is unknown. Clearly, some Meniere’s disease is autoimmune in nature, and dexamethasone is a powerful immune modulator. Studies also have suggested that steroid perfusions influence sodium and fluid dynamics in the inner ear because of their mineralocorticoid properties.16,17
When disabling vertigo continues despite all medical treatment, surgery is indicated. Endolymphatic sac surgery has stood the test of time—nearly 45 years—and is the procedure of choice because it is nondestructive, preserves hearing, and has a long-term success rate of about 90%.18 During this procedure, a complete mastoidectomy is performed, and the endolymphatic sac adjacent to the sigmoid sinus is decompressed. House was responsible for this surgery gaining popularity in the early 1960s,19 and Paparella made a number of important refinements in the technique, including precise surgical localization of the sac and creative ways of decompressing it.20 In light of our new understanding of Meniere’s disease, however, further research is necessary to elucidate the mechanism of improvement. Currently, the theories about why this surgery is successful are based on our old understanding of Meniere’s disease: the simple release of external compression on the sac; promotion of neovascularization of tissue surrounding the sac to encourage the passive diffusion of endolymph; and creation of an osmotic gradient out of the sac. When we more fully understand the pathophysiology of Meniere’s disease, we will better understand why this surgical procedure works so well.
Looking Ahead
Our understanding of Meniere’s disease is changing as research is shedding new light on the interplay between the body’s chemical, neurologic, and physiologic processes. Although light microscopic study of human temporal bones will always be valuable, researchers now believe that improved understanding of the pathophysiology of Meniere’s disease will come from molecular biology experiments involving patients with the disease. In this regard, attention is being focused on possible etiologies involving autoimmune processes, recrudescent viral infections, or cellular channelopathies. This may be the only way of finding the crucial clues we need to develop an animal model that can lead to more targeted therapies instead of the nonspecific ones we currently use for helping patients alleviate symptoms of Meniere’s disease. MM
Norman Berlinger is director of the Tinnitus Clinic at the Paparella Ear, Head and Neck Institute in Minneapolis.
Refrences
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