Unbalanced New Spin on Ménière's Disease by Maia Szalavitz
Posted June 22, 2001 · Issue 105

Abstract

Researchers studying Ménière's disease, an inner ear disorder that causes severe attacks of dizziness as well as hearing loss, may hold the key to understanding what goes wrong when balance fails.

Many people don't think of dizziness as a serious problem - the word itself is part of a sexist stereotype of frivolity, the "dizzy blonde." But lasting dizziness can be a severe disability, and will drive 40 percent of Americans to seek treatment at some point in their lives.

Researchers studying Ménière's disease, a disorder of balance that causes severe attacks of dizziness as well as hearing loss, may hold the key to understanding what goes wrong when balance fails.

Ménière's disease is named for Prosper Ménière, the French doctor who first diagnosed the condition in 1861. It is a progressive disorder of the inner ear - marked by attacks of extreme vertigo, a ringing in the ears called tinnitus, and hearing loss. Some believe that artist Vincent van Gogh cut off his ear in an attempt to end a Ménière's attack (though this doesn't explain why he chose to send the severed organ to a prostitute of his acquaintance).

The exact prevalence of Ménière's disease is not known, but, according to Steven Rauch, assistant professor of otology and laryngology at Harvard University Medical School, "Whether Ménière's is very common or not, it's extremely important to study because it is an example of an inner ear disorder that is at least partially reversible, and offers a window into the physiology and pathophysiology of the inner ear."

Rauch uses the analogy of an auto mechanic. If he studied only totaled wrecks, he wouldn't learn much. But if he could examine cars that had periods of dysfunction and other periods when they behaved normally, he could learn what was different when things went wrong.

Balance is maintained by a complex system involving auditory, visual, postural, and vestibular signals that are processed mainly in the brain stem. Vestibular signals are generated in parts of the inner ear known as the utricle, the saccule, and the semicircular canals. The utricle and saccule of each ear send signals that record linear acceleration (movements up, down, forward, backward, etc., whether self-generated or otherwise), while the semicircular canals handle angular accelerations (turning of the head or body).

These signals are produced by movement of a fluid called endolymph against hair cells within these organs. A Ménière's attack occurs when the organs swell and endolymph leaks out. Because the fluid contains high levels of potassium, it can depolarize nerve cells in the surrounding area and make them more sensitive over time. This may contribute to the progression of the disease.

"When you were a toddler learning to walk," says Rauch, "your brain essentially had to learn a new language - when the left ear says this and the right ear says that, I'm still; when the left ear says that and the right ear says this, I'm moving right or left; and so on. Normally this is corroborated by what you see and feel, and the auditory, visual, and somatosensory systems are all singing the same song."

In Ménière's attacks, however, the signals don't match. As described by Timothy Hain, associate professor of neurology and otolaryngology at Northwestern University Medical School, "An imbalance between the two ears gives the sensation of spinning because when you turn your head, normally, the signal goes up for one ear and down for the other." When an ear having a Ménière's attack sends its erratic signal, though, it is out of synch with the other ear and the other senses. The brain interprets the experience as one of being spun.

The situation is further complicated by the fact that in order to keep a target fixed in sight while your head is moving (so that when you walk by a sign, you can keep reading it, for example), your brain conducts a series of adjustments known collectively as the vestibular ocular reflex. "If you are rotating," says Alec Salt, associate professor of otolaryngology at the Washington University School of Medicine, "your body doesn't want your visual field to blur. If you are just sitting and your ears are telling you that you are spinning, your eyes will try to do a slow phase to one side and then flip back to the other to [to try to keep the world in focus]."

This mangled set of inputs produces an intense feeling of seasickness - which can come on so suddenly that people may fall as an attack begins. Attacks last up to several hours, and the vertigo causes nausea, sweating, and vomiting. The experience is so exhausting that patients must sleep for hours - sometimes even days - afterward to recover.

"It has been theorized," says Rauch, explaining the connection between dizziness and nausea, "that one of the common indications of being poisoned by eating something bad is to fall over or feel dizzy, so evolution developed a means of evacuating the poison by nausea and vomiting. The balance organs are linked to the emesis centers in the brain stem."

The causes of Ménière's are unknown. Rauch says, "Ménière's is a syndrome, not a disease. The most up-to-date thinking is that any ear that gets sick can be susceptible. In the ear, there are very tightly controlled mechanisms for fluid recycling, ion [balance], neuronal conditions; in a sick ear, there may be dysfunction in any or all of these, and for someone with a fragile ear, there are a host of triggers for decompensation [i.e., a Ménière's attack]." Amongst the known triggers are stress, hormonal changes, high levels of dietary salt (which changes fluid balance), autoimmune problems, and infection.

Previously, researchers believed that the endolymph was generated in the cochlea and absorbed by the endolymphatic sac, and that Ménière's arose when the sac didn't drain properly.

But, says Salt, "We did a measure of flow, and [sometimes] there isn't any." What happens is that if endolymphatic volume increases, endolymph flows to the sac, but if it decreases, the sac itself can produce the fluid.

"If regulation of the sac goes awry," says Salt, "and it produces endolymph when it shouldn't, it can cause [swelling]." He compares the situation to a lake surrounded by factories that influence its water level. Each factory can change its outflow without effect so long as dams that regulate input and outflow are operating properly. But if the regulatory system malfunctions, any increase from any factory - such as an increase in stress or a change in hormones - can cause flooding.

Salt's current research is devoted to finding the chemical signal that turns the fluid-producing system on and off. A drug that affects this could potentially prevent or mitigate Ménière's attacks.

Some researchers theorize that Ménière's may, at least in some cases, be an autoimmune problem in which antibodies attack the inner ear. Says Hain, "The sac has been found to be the immune organ of the inner ear, with a role similar to that of the thymus."

He continues, "I think there is a huge amount of evidence that the immune system participates in at least 50 percent of Ménière's cases." He points to research showing that although only one-third of Ménière's patients have problems at diagnosis with both ears (which would suggest a systemic problem), that number increases over time. Half of those who have had Ménière's for over 15 years have it in both ears.

Hain believes that Enbrel (etanercept), a new drug that blocks the inflammatory immune modulator tumor necrosis factor and is currently used to treat rheumatoid arthritis, may potentially be useful against Ménière's.

Rauch and Salt, however, think that immune problems affect only a smaller subset of Ménière's patients. Rauch's group did find that people with Ménière's had a higher level of antibodies against a protein called heat-shock protein 70 - which would indicate autoimmune problems - but the difference didn't predict who would respond clinically to immune-related treatments. "My research now is about trying to take the undifferentiated population of Ménière's patients and parse them into subgroups," says Rauch.

Treatments for Ménière's range from a low-salt diet to a variety of drugs to surgery. About 80 percent of patients can manage the condition with drugs and/or diet - but 20 percent require surgery, which often involves destroying parts of the balance organs or even cutting the nerves in one ear. Losing balance organs in one ear doesn't lead to total loss of function, however; the brain is able to cope with a lack of signal much better than it can with a fluctuating one.

Hearing loss is also a significant problem for patients with Ménière's - and can result both from the disease and from some of the destructive surgeries used to treat it. "By 10 years [after its onset], about 50 percent of people with Ménière's have a 50-decibel loss in hearing - which is very significant hearing loss. They wouldn't be able to carry on a conversation without a hearing aid," says Hain.

Benzodiazepine antianxiety medications such as Valium frequently help alleviate the balance problems of Ménière's. There is a pattern of symptoms shared by patients with chronic pain, depression, and dizziness, including - not surprisingly - high levels of anxiety and obsessive worry. Intriguingly, one study found that patients with anxiety who did not report dizziness often had the same vestibular pathology as those who did. This could mean that some brains interpret "dizzy" signals as anxiety - and vice versa - and could explain how anxiety and dizziness can create a feedback loop that reinforces itself and exacerbates attacks.

Benzodiazepines are believed to ameliorate Ménière's symptoms by turning down the volume of vestibular signaling, but it's also possible that they help because anxiety can interfere with the vestibular ocular reflex. The brain area that processes arousal and anxiety (the locus coeruleus, from which norepinephrine neurons project) is also linked to the nuclei that handle balance signals.

With treatment and assessment of balance problems costing an estimated $4 billion annually in the U.S. alone - and with falls a factor in 50 percent of deaths among the elderly - a better understanding of Ménière's could lead to significant health improvements and cost reductions. Elucidating the connections between dizziness and anxiety might also help bridge the gap between neurology and psychology by allowing us to understand how the brain interprets its own signals.

Maia Szalavitz is a health/science journalist who has written for the New York Times, the Washington Post, Newsday, New York Magazine, Salon, and other major publications.

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Endlinks

Ménière's Disease: A Genetic Imbalance? - a review of studies suggesting a genetic basis for the disease. From Molecular Medicine Today, 1999, 5:11:464. Full text available from BioMedNet.

Acute Vestibulopathy - focuses on new aspects of the etiology, pathophysiology, epidemiology, and treatment of acute peripheral disorders such as Menière's Disease. Current Opinion in Neurobiology, 2001 Feb. 14:1 11-20. Full text available from BioMedNet.

Ménière's Page - Alec Salt, Washington University School of Medicine, offers a comprehensive site on Ménière's disease.

Ménière's Support Group - includes an index of over 500 articles available free through mail-order, online newsletters, and extensive links to related sites.

Vestibular Disorders Association - provides information and support to people suffering from inner-ear balance disorders.

Ear Surgery Information Center - describes the surgical and non-surgical treatment options for Ménière's Disease.

Medical and Surgical Treatment of Vertigo - a comprehensive medical article on Vertigo, including Ménière's disease. From the Michigan Ear Institute.

Related HMS Beagle article:

• Learning from Songbirds: Growing New Hair Cells May Overcome Deafness - a profile of Edwin Rubel and his research on the molecular underpinnings of hearing.

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