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Meniere’s Disease May 2012
TITLE: Meniere’s 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
Meniere’s 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
occur concurrently (5). Tinnitus is variable in pitch but is often described by patients as a
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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 Meniere’s and other related disorders is often confusing.
Endolymphatic hydrops causing hearing loss, tinnitus, and vertigo is known as Meniere’s
Syndrome. If the cause of the hydrops is unknown, the entity is further designated as Meniere’s
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 Meniere’s Disease tend
to have certain types of HLA’s. Unlike other auto-immune diseases of the ear, Meniere’s
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 Meniere’s 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 Meniere’s Disease (5).
Schuknecht Theory
Not only is the mechanism by which hydrops occurs idiopathic, the mechanism by which
hydrops produces symptoms in Meniere’s 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 Meniere’s. Healed scars (presumly forming after rupture of the scala media)
have been found throughout temporal bones of Meniere’s 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 meniere’s 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 Meniere’s Disease had histological evidence of
endolymphatic hydrops. In contrast, not all temporal bones with findings of hydrops correlated
with Meniere’s 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 Meniere’s 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 Meniere’s Disease. ENG
(electronystagmography) can localize the involved ear experiencing vestibular weakness.
Significant reduction in caloric response is found in 48-73% of patients with Meniere’s
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).
Depolarization leads to neurotransmitter release across the synapse onto auditory nerve fibers.
The auditory nerve then depolarizes and sends signal to the brain (5).
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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 Meniere’s 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 Meniere’s 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.
Meniere’s ears have elevated VEMP thresholds with flattened tuning (5).
Classification
The AAO-HNS issued diagnositic criteria for Meniere’s Disease in 1995. Four
categories exist. Certain Meniere’s requires a histologic diagnosis which is impossible in a
living person. Definite Meniere’s 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 Meniere’s Disease is classified by one episode of
vertigo, an audiogram documenting hearing loss, tinnitus or aural fullness, and other possible
causes excluded. Possible Meniere’s 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 Meniere’s
Disease, therapy centers around controlling vertigo. Initial medical management includes low
salt diet, diuretics, avoidance of triggers (alcohol), and vasodilators. Symptomatic management
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 Meniere’s, neither treatment modality has been evaluated in a double-blind placebo
controlled study. The Cochrane Database Review conducted a search of all prospective
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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 Meniere’s patients had
at least good control of their vertigo after 8 years. They found no difference between ESS and
the natural history of Meniere’s disease in the long term (16). To reconcile these two findings.
Quaranta et al followed 38 patients with intractable Meniere’s 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 1990’s. 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 1930’s. 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).
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 Meniere’s patients. They had things like BPPV and things like that. They found
that the people who had things that weren’t Meniere’s had better responses than those with
Meniere’s.
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 don’t
understand the problem, and that’s really what the heart of the problem is here. Part of the
problem is that we don’t understand the definition of Meniere’s 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 don’t 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 we’ll call it Meniere’s; if it lasts longer than that we’ll call it labyrinthitis or
something like that. Some otologists think that if it happens once it’s Meniere’s and if it
happens more than once, it’s 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 isn’t good evidence for low salt diet,
but there is some evidence for diuretic medication and there’s some evidence for
betahistamine as well. It’s a vasodilator and why it works we just don’t know. It fits with the
vascular theory but it doesn’t work with the membrane rupture theory.
With regards to surgical treatment, there’s a lot of controversy surrounding
endolymphatic sac surgery, and you should know about this in preparing for your board
examinations. For years we’ve offered endolymphatic sac decompression, but around 1970 this
group in Denmark randomized a group of Meniere’s 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 Meniere’s disease. Otol Neurotol 2008;29:33
3. Burgess A, Kundu S. Diuretics for Ménière’s disease or syndrome. Cochrane Database of
Systematic Reviews. 2006;3:CD003599.
4. Chia SH. Gamst AC. Anderson JP. Harris JP. Intratympanic Gentamicin Therapy for
Meniere’s 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.
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Labyrinthectomy. Otology &
Neurotology. 2006;28:74-76
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Symptoms Caused by Endolymphatic Hydrops? Otology & Neurotology. 2005;26:74-81.
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Potentials Show Altered Tuning in Patient’s with Meniere’s Disease. Otology & Neurotology.
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Vestibular Neurectomy. Otolaryngology Head Neck Surg. 1996;114:32-7
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15. Semaan MT, Megerian CA. Meniere’s Disease: A Challenging and Relentless Disorder.
Otolaryngol Clin N Am 44 (2011) 383–403.
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Otolaryngol Head Neck Surg. 1989’100;6.
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in Meniere’s 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
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