Menieres Disease May 2012

TITLE: Menieres Disease SOURCE: Grand Rounds Presentation, Department of Otolaryngology The University of Texas Medical Branch (UTMB Health) DATE: May 29, 2012 RESIDENT PHYSICIAN: Samuel Ross Patton, MD FACULTY PHYSICIAN: Tomoko Makishima, MD, PhD, MD FACULTY PHYSICIAN: Dayton Young, MD DISCUSSANT: Dayton Young, MD SERIES EDITOR: Francis B. Quinn, Jr., MD ARCHIVIST: Melinda Stoner Quinn, MSICS
"This material was prepared by resident physicians in partial fulfillment of educational requirements established for the Postgraduate Training Program of the UTMB Department of Otolaryngology/Head and Neck Surgery and was not intended for clinical use in its present form. It was prepared for the purpose of stimulating group discussion in a conference setting. No warranties, either express or implied, are made with respect to its accuracy, completeness, or timeliness. The material does not necessarily reflect the current or past opinions of members of the UTMB faculty and should not be used for purposes of diagnosis or treatment without consulting appropriate literature sources and informed professional opinion."

Introduction Menieres disease --also known as idiopathic hydrops-- is a disease process characterized by vertigo, sensorineural hearing loss, tinnitus, and aural fullness. Most aspects of the disease including its pathophysiology, method of diagnosing, and treatment are controversial. As it is a diagnosis of exclusion, there are several other possible entities that must be ruled out prior to treatment (14). History Menieres Disease derives its name from Prosper Meniere, a French physician from the 19th Century. At the time, vertigo and several other neurological symptoms were believed to occur secondary to overfilling of blood vessels in the head. The role of the inner ear in balance was unknown. Seizures, headaches, and vertigo were considered part of apoplectiform cerebral congestion (1) which was treated with blood-letting and leeches. Meniere identified a subgroup of patients with vertigo and hearing loss who had a benign clinical course. Observing that many of these patients improved without aggressive treatment, he formulated the theory that their vertigo was caused by hemorrhage into the middle ear. He presented his findings to the Imperial Academy of Medicine in 1861 (1). Presentation Vertigo classically occurs in discrete attacks that last three hours, but may vary in duration from twenty minutes to twenty-four hours. Patients occasionally describe an aura-similar to migraine aura--which occurs before the onset of their vertigo. In contrast, other patients describe rapid and violent onset of their vertigo attacks which results in a fall. These drop attacks can cause traumatic injury (5). Hearing loss is sensorineural and usually unilateral. The side of the hearing loss is the same as the side as the vestibular weakness that causes the vertigo. Similar to the episodic nature of the vertigo attacks, patients often describe a fluctuating course of their hearing loss. The vertigo attacks and episodes of hearing loss often

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occur concurrently (5). Tinnitus is variable in pitch but is often described by patients as a buzzing sound. Patients also complain of a feeling of ear fullness which may feel like the ear is stopped up. Early in the disease process, patients do not complain of all symptoms simultaneously. Frequently, vertigo will occur first followed by hearing loss after several months. The course of the disease is highly variable. Patients may experience clusters of frequent vertigo attacks followed by long periods of remission (5). Pathophysiology of Hydrops Endolymph is produced in the stria vascularis by dark cells of the vestibular labyrinth. In endolymphatic hydrops, an overaccumulation of endolymph results in encroachment of the perilymphatic space. The mechanism is officially unknown but remains controversial. Hydrops could occur from inadequate absorption in the endolymphatic sac or by constriction of the endolymphatic duct (5). Nomenclature Terminology for Menieres and other related disorders is often confusing. Endolymphatic hydrops causing hearing loss, tinnitus, and vertigo is known as Menieres Syndrome. If the cause of the hydrops is unknown, the entity is further designated as Menieres Disease. If, however, there is a known cause of the hydrops (e.g. otosclerosis at a location that causes mechanical endolymphatic blockage), the condition is termed secondary endolymphatic hydrops (5). Possible Mechanisms for ELH Auto-immune disease via the production of antibodies is a possible by which endolymphatic hydrops occurs. It has been observed that patients with Menieres Disease tend to have certain types of HLAs. Unlike other auto-immune diseases of the ear, Menieres Disease patients show no white blood cell infiltration or evidence of cellular destruction (5). Viral causes are also possible. A sub-clinical viral infection could cause a delayed-onset hydrops. To date, no virus has been consistently isolated from Menieres patients. Finally, neuro-vascular mechanism similar to migraine could be responsible. Additionally, endolymphatic hydrops occurs from several known mechanisms such as trauma, acute otitis media, labyringthisis, and congenital inner ear deformity. It is not clear why only a small subset of these patients develop Menieres Disease (5). Schuknecht Theory Not only is the mechanism by which hydrops occurs idiopathic, the mechanism by which hydrops produces symptoms in Menieres Disease is also unknown. Rupture of the membranous labyrinth is thought to occur frequently in menieres because of the increased pressure within the scala media. Membranous ruptures have been found in all parts of the inner ear in patients suffereing from Menieres. Healed scars (presumly forming after rupture of the scala media) have been found throughout temporal bones of Menieres patients. The Schuknecht theory is a prominent theory that postulates that ruptures in the membranous labyrinth allow leakage of potassium-rich endolymph into the perilymph/ The potassium is then exposed to CNVIII and the surrounding hair cells. Depolarization of the nerve cells occurs resulting in their inactivation. The final result is decreased hearing and vestibular function: A menieres attack. When the membranous labyrinth heals symptoms subside (5).

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Controversy/Problems with Theory Merchant et al. 2004 conducted a review of cadaveric temporal bone specimens. 100% (28/29) of patients diagnosed with Menieres Disease had histological evidence of endolymphatic hydrops. In contrast, not all temporal bones with findings of hydrops correlated with Menieres disease. 35% (28/79) patients with temporal bones found to have ELH did not have any symptoms of vertigo. Merchant concluded that endolymphatic hydrops may not be the final common pathway for Menieres Disease (7). Natural History Early in the disease, patients do not frequently describe the entire triad of vertigo, aural fullness, and hearing loss. Vertigo is a common initial complaint. The course of the disease is highly variable and symptoms can range from mild to incapacitating. Patients may experience attacks clustered in a short period of time with long periods of remission. Silverstein et. al. reported that vertigo spontaneously remitted in 57% of their patients after 2 years. After 8 years, they found that 71% of patients reported no vertigo. An additional 10% of these patients reported good control of their symptoms (16). Making the Diagnosis History, physical exam, and audiogram are standard in evaluating complaints involving vertigo and hearing loss. In addition to these basic tools, there are several other diagnostic modalities that may be used to aid in the diagnosis of Menieres Disease. ENG (electronystagmography) can localize the involved ear experiencing vestibular weakness. Significant reduction in caloric response is found in 48-73% of patients with Menieres patients (5). ECoG (electrocochleography)- measures evoked potentials that are created in the normal chain of events during hearing. Endolymphatic hydrops changes the ratio of these potentials in a characteristic way that can be measured to aid in the diagnosis VEMPs (vestibular evoked myogenic potential) is a measurement of a type of neural impulse created when a person hears a sound. This impulse is altered in patients with ELH. MRI is frequently ordered to rule out an accoustic schwanoma since many of these patients will have unilateral SNHL. Blood tests may be used to rule out auto-immune inner ear disease (RPR, sed rate, cmp, ana) (5). ECoG To understand ECoG, thehe normal physiology of hearing will be reviewed. Sound is collected by the auricle which then travels through the EAC to vibrate the TM. The TM moves the ossicular chain, causing the footplate of the stapes to vibrate on the oval window. A compression/rarefaction wave in the inner ear fluid is created which travels across the scala vestibuli, up to the helicotrema, and through the scala tympani toward the round window. While the compression wave travels on the scala vestibuli, there is a pressure differential between the scala vestibuli and the scala tympani. The pressure gradient results in vibration of the basilar membrane. The basilar membrane vibrates as a traveling compression wave which creates a shear force between the basilar membrane. The shear force deflects of the sterocillia of the hair cells which opens cationic channels resulting in hair cell depolarization (or hyperpolarization).

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Depolarization leads to neurotransmitter release across the synapse onto auditory nerve fibers. The auditory nerve then depolarizes and sends signal to the brain (5). ECoG measures evoked potentials generated in the cochlea and auditory nerve as part of normal hearing physiology. SP (summative potential) occurs during depolarization of the hair cells. AP (action potential) is generated by the summed response of numerous auditory nerve fibers firing simultaneously. Both potentials are measured within 3-4 milliseconds after presentation of a stimulus to the ear. The SP/AP ratio in normal hearing patients has a characteristic ratio. The SP/AP ratio becomes elevated in hydrops (greater than 0.4). The mechanism for this increased ratio has been been fully explained but may occur from mechanical biasing of vibration of the organ of corti from the endolymphatic hydrops. The sensitivity and specificity reported for ECoG varies widely. It has been reported as high as 90% and as low as 20%. The episodic and fluctuating nature of endolymphatic hydrops during the course of Menieres may explain this discrepancy. Feraro et al found that normal patients have SP/AP ratio of 0.16-0.31 while patients with menieres typically had ratios of 0.4-0.5. 90% of Menieres patients in that series with active symptoms of aural fullness and hearing loss had increased SP/AP (9). Pou found that changes in SP/AP relationship varied proportionately to the degree of hearing loss. As a result, testing patients while they are acutely symptomatic is more likely to lead to the diagnosis (11). The limited hours available for obtaining these tests may make this impractical. Additionally, many patients will not be able to tolerate extensive vestibular vesting while suffering from an acute vertigo attack. VEMPS When a loud sound (such as a click) is placed in the ear, the stapes footplate is moved which stimulates the saccule. This causes a reflex arc which results in a stimulus to relax the SCM on the ipsilateral-lateral side of the body. This normal reflex is known as VEMPs (vestibular evoked myogenic potential). In a normal ear, the best response is obtained at 500Hz. Menieres ears have elevated VEMP thresholds with flattened tuning (5). Classification The AAO-HNS issued diagnositic criteria for Menieres Disease in 1995. Four categories exist. Certain Menieres requires a histologic diagnosis which is impossible in a living person. Definite Menieres disease requires two episodes of vertigo (lasting at least twenty minuntes), an audiogram confirming decreased hearing, tinnitus or aural fullness, and all other possible causes excluded. Probable Menieres Disease is classified by one episode of vertigo, an audiogram documenting hearing loss, tinnitus or aural fullness, and other possible causes excluded. Possible Menieres Disease only requires vertigo without documented hearing loss OR SNHL with disequilibrium. Treatment Since no therapy has been identified to treat the hearing loss associated with Menieres Disease, therapy centers around controlling vertigo. Initial medical management includes low salt diet, diuretics, avoidance of triggers (alcohol), and vasodilators. Symptomatic management

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control during acute attacks may be improved with antivert, anti-emetics, sedatives, and antidepressants (15). Despite widespread use of salt restriction and diuretics as the first-line treatment for Menieres, neither treatment modality has been evaluated in a double-blind placebo controlled study. The Cochrane Database Review conducted a search of all prospective randomized controlled trials between 1966-2005 comparing diuretics with placebo. It failed to show a single trial that was high enough quality to be reviewed (3). Intra-tympanic steroid injections are a frequently used if conservative treatment fails. This is a reasonable option since steroids are unlikely to result in further hearing loss. BoleasAguirre reported control of vertigo symptoms in 91% of Menieres patients using dexamethasone (12mg/dL) intratympanic injections (2). The mechanism of action in ELH unknown and repeat injections may be required every three months (2). Endolymphatic sac surgery (ESS) was described first in 1926 by Portmann, but its efficacy remains controversial today. Telischi et al conducted a study of 234 patients who underwent ESS and were followed for 10 years. They reported an 80% success rate in avoid labyrinthectomy (17). Silverstein, however found that 81% of untreated Menieres patients had at least good control of their vertigo after 8 years. They found no difference between ESS and the natural history of Menieres disease in the long term (16). To reconcile these two findings. Quaranta et al followed 38 patients with intractable Menieres for minimum 7 years. Twenty patients underwent ESS and 18 declined. 85% of ESS group had vertigo control and 74% of natural history group had good control. They found that in the longterm, ESS may not affect natural history, but in the short term it may improve course of the disease by shortening the time until the disease process burns out and the patient is symptom-free (12). Intra-tympanic gentimicin (aka chemical labyrinthectomy) was first tried in 1970s, but came into wide-use in the 1990s. Gentimicin is a selectively vestibulotoxic aminoglycoside which induces apoptosis in vestibular dark cells. This reduces or eliminates peripheral vestibular function. The cochleotoxic effects are variable and hearing deterioration occurs in 13-35% of patients. Some patients are predisposed to gent toxicity which may occur through increased round window permeability, diffusion along the scala tympani or a genetic susceptibility to aminoglycosides. Dosing and technique of administration may also effect chochleotoxicity (5). Benefits of the procedure include reduction in vertigo without the substantial risks of inner ear surgery such as meningitis, CSF leak, facial nerve damage. General anesthesia is also unnecessary. The main disadvantage is the risk of hearing loss. Chia et al conducted a metaanalysis by reviewing twenty-seven papers from 1978-2002. Five administration methods on intra-tympanic gentimicin were examined. The titration method lead to the highest complete and effective vertigo control rate (81.7% vs 96.3%). The incidence of hearing loss was lowest in the low dose method and highest in the multiple daily dose method. Interestingly, the icidence of profound hearing loss was dose independent (4). Vestibular nerve section (VNS) via a retrosigmoid approach was first described by Dandy in 1930s. Today multiple possible approaches include translabyrinthine, retrolabyrinthing, retrosigmoid, middle fossa, and combined (5). Rosenberg studied undergoing 47 patients undergoing VNS. Vertigo was controlled in 90-95% of patients. Hearing improved in 1/3rd, stayed the same in 1/3rd, and worsened in 1/3rd (14).

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Nguyen found that 92% of patients undergoing retrolabyrinthine VNS achieved vertigo control with 2/3rds of those patients maintaining their hearing (10). VNS is preferable when the patient has serviceable heainrg. If hearing is poor, however, labyrinthectomy may be selected. Both transcanal and transmastoid approaches have been described. Diaz found that 98% of patients undergoing transmastoid labyrinthectomy reported improvement in QOL (6).

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Faculty comments by Dr. Dayton Young May 29, 2012 There was also another randomized controlled study that compared diazide versus a placebo and it was a crossover study and they also found that they had people in the study that were not just Menieres patients. They had things like BPPV and things like that. They found that the people who had things that werent Menieres had better responses than those with Menieres. There is evidence, a lot of it not great evidence, in fact when you find in the medical literature from twenty to fifty different treatments for a condition, it means that we really dont understand the problem, and thats really what the heart of the problem is here. Part of the problem is that we dont understand the definition of Menieres disease. According to the AAO definition you have to have histologic confirmation showing hydrops, and that they have to have this syndrome of episodic vertigo lasting twenty minutes or longer, etc. etc. I dont think that one has a lot to do with the other. There are a lot of theories out there and it was Schuckneckt, one of the fathers of Otology, who popularized the theory of membrane rupture. One of the currently popular theories is clinically based and arbitrary is that if it lasts less than twenty four hours well call it Menieres; if it lasts longer than that well call it labyrinthitis or something like that. Some otologists think that if it happens once its Menieres and if it happens more than once, its labyrinthitis. What we do know is if the ear is causing the problem and we cut the ear out, the problem goes away. There just isnt good evidence for low salt diet, but there is some evidence for diuretic medication and theres some evidence for betahistamine as well. Its a vasodilator and why it works we just dont know. It fits with the vascular theory but it doesnt work with the membrane rupture theory. With regards to surgical treatment, theres a lot of controversy surrounding endolymphatic sac surgery, and you should know about this in preparing for your board examinations. For years weve offered endolymphatic sac decompression, but around 1970 this group in Denmark randomized a group of Menieres patients and randomly assigned them to two groups, one got an endolymphatic sac decompression and the other group underwent only a cortical mastoidectomy and they found no difference in the results between the two groups. This raised a huge controversy in the United States and the rest of the world because you had a lot of surgeons for whom this operation formed a large part of their practice, with some of whom it formed the main focus of their practice. The Danish group responded several years later by repeating the study, replacing the cortical mastoidectomy with a simple tympanostomy and again they found no difference. About the same time, Silverstein offered patients a choice between endolymphatic sac decompression versus vestibular nerve section. He found that while the vestibular nerve section patients got better and the endolymphatic sac patients showed no improvement at all. Following this a lot of the otologists in this country stopped performing endolymphatic sac surgery. There still remains considerable controversy about this procedure because its alternative, vestibular nerve section is a big operation involving a craniotomy with attendant risks, while endolymphatic sac surgery is much easier, and entails much less risk.

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References 1. Baloh RW. Prosper Meniere and His Disease. Arch Neurol. 2001;58:1151-1156 2. Boleas-Aguirre MS, Lin FR, Della Santina CC, et al. Longitudinal results with intratympanic dexamethasone in the treatment of Menieres disease. Otol Neurotol 2008;29:33 3. Burgess A, Kundu S. Diuretics for Mnires disease or syndrome. Cochrane Database of Systematic Reviews. 2006;3:CD003599. 4. Chia SH. Gamst AC. Anderson JP. Harris JP. Intratympanic Gentamicin Therapy for Menieres Disease: A Meta-analysis. Otology & Neurotology. 2004;25:544-552. 5. Crane BT. Schessel DA. Nedzelski J. Minor LB. Peripheral Vestibular Disorders. Otolaryngology Head & Neck Surgery. 5th Edition. 2328-2345. 6. Diaz RC. LaRouere MJ. Bojrab DI. Zappia JJ. Sargent EW. Shaia WT. Quality-of-Life Assessment of Menieres Disease Patients After Surgical Labyrinthectomy. Otology & Neurotology. 2006;28:74-76 7. Merchant SN. Adams JC. Nadol JB. Pathophysiology of Menieres Syndrome: Are Symptoms Caused by Endolymphatic Hydrops? Otology & Neurotology. 2005;26:74-81. 8. Ferraro JA. Arenberg IK. Hassanein RS. Electrocochleography and Symptoms of Inner Ear Dysfunction. Arch Otolaryngology. 1985;111:71-74. 9. Ferraro JA. Durrant JD. Electrocochleography in the Evaluation of Patients with Menieres Disease/Endolymphatic Hydrops. J Am Acad Audiol 17:4568 (2006). 10. Nguyen CD. Brackmann DE. Crane RT. Linthicum FH. Hitselberger WE. Retrolabyrinthine Vestibular Nerve Section: Evaluation of Technical Modification in 143 Cases. American Journal of Otology: 1992;13;4:328-332 11. Pou AM. Hirsch BE, Durrant JD, Gold SR, Kamerer DB. The Efficacy of Tympanic Electrocochleography in the Diagnosis of Endolymphatic Hydrops. The American Journal of Otology. 1996;16:607-611 12. Quaranta A. Marini F. Sallustio V. Long-term Outcome of Menieres Disease: Endolymphatic Mastoid Shunt vs Natural History. Audiol Neurootol. 1998;3:54-60. 13. Rauch SD. Zhou G. Kujawa SG. Guinan JJ. Herrmann BS. Vestibular Evoked Myogenic Potentials Show Altered Tuning in Patients with Menieres Disease. Otology & Neurotology. 2004;25:333-338. 14. Rosenberg SI. Silverstein H. Hoffer ME. Thaler E. Hearing Results After Posterior Fossa Vestibular Neurectomy. Otolaryngology Head Neck Surg. 1996;114:32-7

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15. Semaan MT, Megerian CA. Menieres Disease: A Challenging and Relentless Disorder. Otolaryngol Clin N Am 44 (2011) 383403. 16. Silverstein, H. Smouha E. Jones R. Natural History vs Surgery for Menieres Disease. Otolaryngol Head Neck Surg. 1989100;6. 17. Telischi FF. Luxford WM. Long-Term efficacy of Endolymphatic Sac Surgery for Vertigo in Menieres Disease. Otolaryngology- Head and Neck Surgery. 1993:109;1:83-7. 18. Timmer FCA. Zhou G. Guinan JJ. Kujawa SG. Herrmann BS. Rauch SD. Vestibular Evoked Myogenic Potential in Patients with Menieres Disease with Drop Attacks. The Laryngoscope. 2006;116;776-779.