meniere's disease: overview, epidemiology, and natural history

Meniere’s disease: overview, epidemiology,and natural history

Sady Selaimen da Costa, MD, MSc, PhDa,b,*,Luiz Carlos Alves de Sousa, MDc,

Marcelo Ribeiro de Toledo Piza, MD, MScc

aDepartment of Otolaryngology Head & Neck Surgery, School of Medicine,

Universidade Federal do Rio Grande do Sul, BrazilbDivision of Otology, Universidade Luterana do Brasil, Cristovao Columbo 3084/1001,

CEP 90560-002 Porto Alegre/RS, BrazilcPaparella Association of Otolaryngology, Ribeirao Preto, Brazil

Doctor, this is like being completely drunk but sober!

from a patient

Meniere’s disease is a clinical disorder defined as the idiopathic syndromeof endolymphatic hydrops. The underlying pathophysiologic state in

Meniere’s disease is endolymphatic hydrops, which can be demonstrated

with certainty only after death by histopathologic study of the temporal

bones. For clinical purposes (treatment and reporting), the presence of

endolymphatic hydrops can be inferred during life by the presence of the

following signs and symptoms: recurrent spontaneous episodic vertigo, fluc-

tuating hearing loss, aural fullness or pressure, and tinnitus [1].

In 1861, Prospere Meniere first described this disease, which later wouldbe named after him, in a series of six articles in theMedical Journal of Paris

[2–4]. He challenged the general terminology used for vertigo at the time

(apoplectic cerebral congestion), which connoted a brain disorder. Meniere’s

articles [2–4] discussed the fact that pathologic conditions in the peripheral

end organs cause these episodes of vertigo and fluctuating hearing loss. A

little earlier, working as a professor of comparative anatomy, Flourens [5]

published a series of studies pertaining to the function of the inner ear of

pigeons. His experiments provided the first scientific clues that the semi-circular canals were intimately involved in the regulation of balance [5].

Otolaryngol Clin N Am

35 (2002) 455–495

* Corresponding author.

E-mail address: [email protected] (S.S. Costa).

0030-6665/02/$ - see front matter � 2002, Elsevier Science (USA). All rights reserved.

PII: S 0 0 3 0 - 6 6 6 5 ( 0 2 ) 0 0 0 2 8 - 2

In 1927, Guild [6] referred to the endolymphatic sac as the site of ‘‘out-

flow of endolymph’’ in his studies of guinea pigs, clearly demonstrating the

longitudinal flow of endolymph. Almost at the same time, Portmann [7,8]described endolymphatic sac surgery for Meniere’s disease and Dandy [9]

popularized the sectioning of the vestibular nerve as a treatment for vertigo

(a surgical operation first successfully employed by Parry [10] in 1904). The

next important date to remember is 1938, when Hallpike and Cairns [11]

described the pathologic conditions in this entity by studying two patients

who had cranial nerve VIII sectioned, and had succumbed in the postoper-

ative period. Subsequently, a number of excellent, well-documented articles

on Meniere’s disease appeared in the medical journals [12–14]. In 1967,Kimura [15], after a series of failures, induced experimental hydrops in the

laboratory after blocking the endolymphatic sac and duct of guinea pigs.

This piece of evidence finally proved that after being produced from various

sources within the inner ear, endolymph slowly moves toward the endolym-

phatic duct and sac and that an obstruction of this flow would cause endo-

lymph to build up and hydrops to develop [15].

Physiopathology of the vertiginous crisis

Vertigo, often described by the patient as ‘‘dizziness,’’ ‘‘giddiness,’’

‘‘light-headedness,’’ or ‘‘a turning sensation,’’ is a common complaint, but

the concept of vertigo to be considered from the otoneurologic point of view

needs precise definition. Indeed, clinical experience proves that many vari-

ous and divergent sensations are conceived as ‘‘dizziness’’ by the patient

[16]. When a patient complains of dizziness, the physician should first ascer-

tain whether the condition truly represents vertigo or not. True vertigo isdescribed as a sensation of twirling motion; whether the patient or the envi-

ronment moves, regardless of the direction of the rotation (clockwise or

counterclockwise, rocking, or up-and-down), any rotational hallucination

of motion is considered vertigo [17–19]. When the symptom presented by the

patient can be characterized as true vertigo, the cause is probably located in

the ear. According to Paparella and colleagues [19], 85% of these patients

will have a peripheral disorder in the vestibular system and only 15% will

have a central disorder.Our spatial orientation is smoothly maintained by the perfect interaction

among three systems: the static-kinetic system, the proprioceptive system,

and the visual system. The static-kinetic system is grossly composed of the

peripheral end organ (posterior labyrinth), the labyrinthine division of the

eighth cranial nerve, and the vestibular nuclei and its connections in and

through the brainstem. The proprioceptive system works both through

receptors located within the joints and muscles (the so-called ‘‘interocep-

tors’’) and through tactile receptors located in the soles of the feet and thepalms of the hand (exteroceptors). The visual system, in its turn, consists

of the eyes, the ocular musculature, and neural connections and nuclei of

456 S.S. Costa et al / Otolaryngol Clin N Am 35 (2002) 455–495

cranial nerves III, IV, and VI. This apparatus functions as a polyinput net-

work, operating below the level of consciousness that collects stimuli in the

periphery and addresses to the central nervous system (CNS) a constant

flow of information [20,21]. The CNS rapidly integrates this informationin a subcortical level, keeping the body subliminally informed of its precise

spatial orientation [20,21].

Physiologic or pathologic vertigo is thought to be generated by an acute

sensorimotor conflict (mismatch) between the converging sensory inputs and

the expected sensory patterns or a vestibular tone imbalance [22]. A physio-

logic mismatch arises, for example, when the multisensory consequences of

being a passenger in a moving vehicle or of moving actively do not match the

expected patterns that have been calibrated by prior experience of activelocomotion (reading during a car ride instead of watching its motion) [22].

Thus, it is the sensory mismatch (visual-vestibular or between right and left

vestibular input) rather than a sensory loss that causes vertigo in this case.

Depending on the situation, the absence of one channel of redundant sensory

input—important as it is for demanding balancing tasks in sports—rarely

manifests as vertigo [22]. On the other hand, inappropriate information from

one or multiple sensory systems produces an illusion of bodily motion and

causes vertigo [22].As McCabe [20,21] pointed out, for a conceptual understanding of the

physiopathology of the vertiginous crisis, it is not necessary to have an in-

depth knowledge of the highly complex ultrastructure of the labyrinth and

its connections. It is mandatory, however, that we recognize the peripheral

end organs (semicircular canals: crista ampullaris, utricle, and saccule) as

a paired (right and left) dynamic structure sensitive to linear and angular

accelerations that maintain a basal rhythm of discharge even in the resting

position. This rhythm is up-regulated or down-regulated in fine synchronywith the movement of the head. The canals are displayed in such a manner

that they form three synergistic pairs (lateral R/lateral L, posterior R/supe-

rior L, posterior L/superior R) representing, through this configuration, the

three spatial planes (axial, coronal, and sagittal). Therefore, a movement of

the head in any direction always implies concurrent stimulation of at least

one of these pairs [20,21].

Taking into consideration only the lateral semicircular canals, when the

head is standing perfectly still and facing forward, both cristae ampullariswill be found to be operative, discharging an identical baseline-firing rate.

The electric impulses thus generated in both labyrinths will travel through

the fibers of the eighth cranial nerve to reach the CNS with exactly the same

frequency and intensity but modulated in opposite phases. When analyzing

this sequence of impulses, the CNS concludes the equality and the polarity

of the information that is presented to it, resuming itself in symmetry. This

symmetry is expressed clinically as a feeling of balance [20,21].

When the head is rotated to the right, the inertia of the fluids filling thelabyrinth generates a flow of endolymph toward the ampulla and the crista

457S.S. Costa et al / Otolaryngol Clin N Am 35 (2002) 455–495

of the right lateral semicircular canal (ampullipetal flow), up-regulating its

firing rate. At the same time, an ampullifugal flow occurs in the left lateral

semicircular canal, down-regulating its firing rate. Again, both impulsestravel the fibers of the vestibular nerve, reaching the CNS, which now does

not perceive symmetry any more but rather asymmetry. As a result, the CNS

learns that this asymmetry signifies that the head is moving to the right

[20,21]. Rotation of the head triggers off at least three other vestibular re-

flexes in order to maintain visual orientation in the environment and to pre-

pare the body for a new position about to be assumed: the vestibulo-ocular

reflex proportionally moves the eyes in the opposite direction to that of the

head, and the vestibulocerebellar and vestibulospinal reflexes adjust theposition and the tone of the musculature of the trunk and members [20,21].

A labyrinthine crisis, in general, represents a unilateral labyrinthine

failure. During an attack of Meniere’s disease, for example, regardless of the

physiopathology of the symptoms (rupture of membranes, hyperdistention

of the membranous labyrinth altering the function of the crista ampullaris),

the affected labyrinth diminishes its activity, rendering it incapable of

maintaining even its basal rhythym of discharges [23]. The contralateral

labyrinth, however, continues discharging normally in the CNS. In thismanner again, the impulses reach the CNS in an asymmetric form, even

though at this moment, the head is maintained in the neutral position. The

CNS will interpret this asymmetry in the unique way that after years of

experience it has learned to do: as a rotating sensation of movement.

Obviously, information of this gross asymmetry also will be sent to the

ocular nuclei, with the consequent sway of the gaze in the direction of the

affected labyrinth. The eyes, still, cannot continue to track indefinitely in

a single direction, although by the moment at which the ocular sway equalsthe number of motor neurons available for this movement, inhibitory neu-

rons of the reticular formation are activated, cutting off the flow of impulses

provided by the vestibular nuclei. At the same time, excitatory reticular neu-

rons direct nuclei of the ocular muscle to bring the eyeballs rapidly back to

their initial position. The reticular excitatory neurons, having fired, undergo

an absolute refractory period, and the end-organ inflow from the vestibular

nuclei resumes its effect on the ocular muscle tract, reinitiating a new cycle of

sway in the gaze. This rhythmic and cyclic movement of the eyes with a slowphase of vestibular origin and a fast phase of reticular origin is known as

nystagmus [20,21].

This conflicting information is also sent to the spinal medulla and the

cerebellum. The position and the tone of the trunk and limbs are thus ad-

justed for a new position that the body probably would not otherwise

assume, causing disequilibrium and ataxia. A series of neurovegetative sig-

nals and symptoms add to the vertigo and the nystagmus to compose the

final clinical picture. All of them flow with multiple vestibular connectionsvia the reticular formation with the dorsal nucleus of the vagus (nausea and

vomiting), frenic (vomiting), salivary nuclei (sialorrhea), ambiguous nucleus


(regurgitation), and sympathetic ganglionar chain (pallor and cold sweating)

[20,21]. In short, vertigo itself results from a disturbance of cortical spatial

orientation; nystagmus is secondary to a direction-specific imbalance in the

vestibulo-ocular reflex that activates neuronal circuitry in the brainstem;vestibular ataxia and postural imbalance are caused by inappropriate acti-

vation of monosynaptic or polysynaptic vestibular pathways; and auto-

nomic responses travel along ascending and descending vestibuloautonomic

pathways to activate medullar centers [22].

A labyrinthine crisis should not last indefinitely or, in some way, the pa-

tient would confront serious systemic disturbances such as deep dehydration

and hydroelectric imbalance. So, as soon as the crisis begins, the nervous

system sets up a series of mechanisms aiming to minimize the severity of thesymptoms. These mechanisms will be operational on a short-term, medium-

term, or long-term basis; therefore, equilibrium can be re-established fun-

damentally in three ways: (1) central inhibition of the healthy contralateral

vestibular nuclei, (2) restoration of the end organ, and (3) electrical neorhy-

thym in the underdischarging ipsilateral vestibular nuclei [20,21].

Just a few minutes after the beginning of the crisis, the cerebellus imposes

a shutdown of electrical activity of the contralateral healthy medial vestib-

ular nucleus. This cerebellar clamp reconstitutes only grossly the symmetrybetween the sides. The symptoms, however, are partially alleviated because

not all of the fibers coming from the periphery have synapses in this nucleus;

some of them are diffusely distributed in the brainstem and the cerebellum

without passing through the vestibular nuclei. Therefore, control of symp-

toms by the cerebellar clamp is in the first moments, making the symptoms

only tolerable. In those cases where there is the possibility of healing—the

anatomy/physiology of the compromised end of the labyrinth returning

function to the end organ (as in Meniere’s disease)—the cerebellar clampover the healthy nuclear vestibule is alleviated and reflexes revert to normal

as equal and opposite reactions are signaled from the two end organs [20,21].

Epidemiology

Despite the large number of scientific contributions published annually on

Meniere’s disease, consistent epidemiologic information is sparse. To date,the true incidence and prevalence of Meniere’s disease is not known. The

actual spectrum of this inner ear disorder and its natural history is poorly

understood except for an indeterminate number of clinically moderate-to-

severe cases. Estimates of the incidence and prevalence of Meniere’s disease

have varied greatly for many reasons.

Inconsistency in establishing the diagnosis by primary physicians

It is still widespread among the general population and some primarycare physicians to have an almost dogmatic idea that any form of dizziness


is readily referred to as ‘‘labyrinthitis’’ and, obviously, ‘‘there is no cure

for labyrinthitis.’’ Within minutes and without a proper investigation, a

topodiagnosis is made, a specific diagnosis is established, a symptomatictreatment is initiated, and a bad prognosis (which sounds more like a

sentence) is given [17].

The natural history of the disease

Meniere’s disease frequently conspires against clinicians and researchersby waxing and waning and often coursing through atypical forms. One of

the greatest problems in this regard is that the initial presentation of the dis-

ease is often the cochlear form, which goes unrecognized, is again attributed

to another specific cause, or is presumed to be due simply to aging. Even

after the vestibular component becomes obvious, long periods of remission

may mask the final full-blown picture of episodic vertigo, fluctuant hearing

loss, tinnitus, and aural fullness. Therefore, only the clinically moderate-to-

severe cases have been tabulated in estimates to date [24].

Problems with methods of collection and analysis of data

Many of the epidemiologic studies have to rely on chart reviews or med-

ical databases, each having their own flaws. Data collected during routine

clinical care will vary in quality, and their interpretation is limited by theconsistency, accuracy, availability, and completeness of source records

[25]. Although more reflective of ‘‘real life’’ than a contrived experiment,

observational retrospective studies are susceptible to bias [25]. Although

studies of medical databases are relatively inexpensive and data often are

already organized and computerized, these studies do not eliminate possible

bias, often present high rates of missing data or errors, and have definitions

by which data are encoded that may change over time (absolutely true in

Meniere’s disease). There is also an intrinsic difficulty in identifying ‘‘timezero’’ [25].

Some of the epidemiologically oriented studies published to date have

had a tendency to mix different epidemiologic concepts. The direction of

these studies is mostly retrospective (the subjects are identified after an out-

come or disease), and they actually measure only prevalence (existing events

or the number of cases of a disease at a given time divided by the population

at risk). Incidence rate represents the number of new cases of a disease over

a specified period of time divided by the population at risk. Only prospectivestudies (subjects are identified prior to an outcome or disease; future events

are recorded) have the power to measure incidence [25].

Multiplicity of diagnostic criteria

In 1972, the Committee on Hearing and Equilibrium and Its Measure-

ment at the American Academy of Otolaryngology (AAO) proposed a


specific definition of Meniere’s disease and guidelines for evaluation of it

in reporting results of treatment [26,27]. The following are the 1972 criteria

for the diagnosis of Meniere’s disease:

Fluctuating, progressive, sensorineural deafness.

Episodic characteristic definitive spells of vertigo lasting 20 minutes to 24

hours. The patient remains fully conscious with no neurologic accom-paniments or sequelae; vestibular nystagmus is always present.

Usually tinnitus.

The attacks are characterized by periods of remission and exacerbation.

The committee recognized that ‘‘criteria for diagnosis vary greatly’’ and

that ‘‘a uniform set of criteria for diagnosis and judging and reporting the

results of treatment’’ was needed. There have been two updates from the

Committee on Hearing and Equilibrium since 1972. In 1985, it was felt that

the definition of Meniere’s disease needed restricting to those cases with a

full complement of classic symptoms and signs; there was then no evidence

that ‘‘cochlear’’ or ‘‘vestibular’’ Meniere’s disease was based on the same

pathologic process (see Display Box 1) [28,29].The 1995 criteria aimed to simplify the definition of Meniere’s disease and

allow more flexibility, making it more usable in a wide range of settings. A

minimum set of signs and symptoms must be fulfilled so that the degree of

certainty of the diagnosis can be established (see Display Box) [1].

Underlining these difficulties is the low number of published studies

on the epidemiology of Meniere’s disease. Cawthorne and Hewlet [30] in

Great Britain in 1954 reported 43 cases during 1 year in a population of

27,365 persons, or a rate of occurrence of 157 cases per 100,000. Althoughtheir study has the merit of being one of the early epidemiologic studies on

Meniere’s disease, many of the subjects included in the sample had their

Box 1 1985 criteria for the diagnosis of Meniere’s disease

1. A fluctuating, progressive, sensorineural hearing lossassociated with tinnitus—the deficit is characteristically oflow frequency or flat type

2. Vertigo—spontaneously occurring sensation of movementhat is accompanied by unsteadiness and lasts from minutesto hours. More than one attack is needed to establishdiagnosis.

Definitive spell—often prostrating, often accompanied bynausea and vomiting. Patient oriented and conscious, noneurologic sequelae. Horizontal or horizontal rotatory nystagmusis always present during the definitive spell.


diagnoses established by nonotologists, and it is unclear whether the study

included patients with onset in preceding years, raising again the question

of mixing prevalence and true incidence [31]. In another British study,Harrison and Naftalin [32] estimated a rate of 100 per 100,000 cases in

England but, again, the population and the time period under considera-

tion are unspecified, and the rate of incidence represents clinical estimates

rather than population-based findings [31].

A frequently quoted population-based study carried out by Stahle and

colleagues [33] in 1973 in Sweden found an incidence of 46 cases per

100,000 in the Uppsala and Skane regions. The group under study was

comprised of inpatients and outpatients in the Uppsala region and inpatientsin the Skane region. According to Wladislavosky-Waserman [31] and col-

leagues, though, the information was collected from a uniform, nationally

administered system for making and retrieving medical records, and the sta-

tistics are a combination of prevalence and incidence (the problem of mixing

apples and oranges again) and did not include data from private practices.

Extrapolating the numbers verified in the Swedish study to the United States

(on the basis of the American population in 1973), an incidence of 97,000

new American cases per year was calculated. Arenberg and colleagues [25]attempted to calculate the prevalence of Meniere’s disease in the United

Box 2 1995 criteria for the diagnosis of Meniere’s disease

1. Recurrent spontaneous episodic vertigo.Definitive spell—spontaneous rotational vertigo lasting atleast 20 minutes (commonly several hours), often prostrating,accompanied by disequilibrium that may last several days;usually nausea (commonly vomiting or retching); no loss ofconsciousness. Horizontal or horizontal rotatory nystagmusis always present.

2. Hearing loss (not necessarily fluctuating).3. Either aural fullness or tinnitus (or both).

Certain Meniere’s disease is ‘‘definite’’ disease withhistopathologic confirmation.

Definite Meniere’s disease requires two or more definitiveepisodes of vertigo with hearing loss plus tinnitus and/oraural fullness.

Probable Meniere’s disease needs only one definitiveepisode of vertigo and the other symptoms and signs.

Possible Meniere’s disease is defined as definitive vertigowith no associated hearing loss or hearing loss with nondefinitivedisequilibrium.


States by multiplying by 25 the extrapolated annual incidence of 97,000

(considering the estimated life expectancy of a patient with a nonlethal

chronic disease process with average onset at 30 years of age), giving a total

number of 2,425,000 American cases in 1973. Although these authors recog-nized that simple extrapolation lacked precision and was statistically highly

problematic (because it assumed that the demographic characteristics of the

Swedish and American populations were identical and directly comparable),

the Arenberg study served as a crude estimate of the potential number of

patients in the United States afflicted with Meniere’s disease [24].

Wilmot [34] reported an average annual incidence of 10 to 20 per 100,000

in Northern Ireland. His findings were based on his own clinical records and

represented a clinical statement rather than population-based data [31]. InJapan, from 1975 to 1990, the Research Committee on Meniere’s Disease

and the Committee of Peripheral Vestibular Disorders performed three

nationwide surveys on Meniere’s disease. The results showed an almost con-

stant prevalence of 16 to 17 per 100,000 [35]. These results were identical to

those reported in 1976 by Nakae and Komatuzaki (17 per 100,000) [16] and

in 1983 by Tokumatsu and colleagues [36] (16.8 per 100,000). Okafor [37] in

1984 reported a relative frequency—defined as the relationship of the num-

ber of clinical cases of a given disease, hospital deaths, or autopsies (associ-ated with it) to the total number of admitted patients, deaths, or autopsies

performed in a population—of 400 per 100,000 black patients in Nigeria,

suggesting that improved diagnostic facilities in the future might show that

Meniere’s disease is as common in blacks as in any other ethnic group. Cor-

roborating this impression, Celestino and Ralli [38] found the number of

cases to be 3.4 times greater among hospital staff in Italy and concluded that

the magnitude of access to medical care largely influences the epidemiologic

profile of Meniere’s disease. Pointing in the same direction, Naito [39] dem-onstrated that cases of Meniere’s disease had increased rapidly in Japan

since the end of the second world war. He concluded that this interesting

phenomenon was related to the ‘‘westernization’’ of the Japanese way of life

and the improved availability of medical assistance [40].

Wladislavosky-Waserman [31] and colleagues designed a well-controlled

study to investigate the incidence of diagnosed Meniere’s disease in the

Rochester, Minnesota population from 1953 to 1980. Working with a well-

defined population and using rigid criteria and clinical guidelines, they wereable to confirm 180 cases of Meniere’s disease during the 30-year period [31].

The annual age-adjusted rate of incidence was 15.3 per 100,000 population.

There was no change in annual incidence from 1951 to 1970, and a slight

decrease in the period between 1971 and 1980. Interestingly, of 1164 his-

tories reviewed, 436 (37.4%) had been diagnosed as Meniere’s disease or

syndrome, but when the 1972 AAO guidelines were used, only 180 (41.3%

of the diagnosed) met the pre-established criteria for Meniere’s disease [31].

Kotimaki and colleagues [40] assessed the prevalence of Meniere’s diseasein the Finnish population (5 million people) according to the 1995 American


Academy of Otolaryngology–Head and Neck Surgery (AAOHNS) recom-

mendations. Their study was a retrospective investigation based on the

records of 306 patients treated for Meniere’s disease in seven Finnish hos-pitals between 1992 and 1996. After careful re-evaluation, a total of 131

(42.8% of those so treated) definite cases were identified according to the

1995 AAOHNS guidelines. A prevalence of at least 43 per 100,000 and an

average annual incidence of 4.3 per 100,000 were obtained [40].

Meniere’s disease is much more common in adults, with an average age

of onset in the forth decade, the symptoms beginning usually between ages

20 and 60 years [19,41,42]. In their series of 180 patients, Wladislavosky-

Waserman [31] and colleagues reported the age of onset as being between11 and 88 years old, with a mean of 50 years and a median of 51 years. Age

at diagnosis was also variable, ranging from 15 to 88 years old [31]. Watanabe

and colleagues [35] reported an average age of onset of 42.2 years for males

and a little earlier (41.4 years) for females. Despite its being much more com-

mon in adults, Meniere’s disease can be found in approximately 3% of all

patients in the pediatric age group, as was pointed out by Meyerhoff and

colleagues [43]; they reported on a case in which the age of onset was only

4 years old. In 1977, Bedoe [44] reviewed 22 cases coded as dizziness or ver-tigo in children and diagnosed two of them as suffering from Meniere’s

disease. According to Kacker [45], although Meniere’s disease is not very

common in children, it is twice as common after 10 years of age than below

10. A large proportion of these children may be labeled as suffering from

Meniere’s syndrome because frequently they will present a past history of

an otologic insult such as hearing loss secondary to mumps, meningitis,

or trauma to the temporal bone. Years after these insults, they will present

the typical full-blown Meniere’s syndrome [22].Depending on the series, the male/female ratio varies curiously. Some

reports point out that Meniere’s disease affects both sexes equally or there

is a slight female preponderance, up to 1.3:1 [19,41,42]. The study by

Wladislavosky-Waserman [31] and colleagues reported a slight (though not

statistically significant) preponderance of females. Following the 3 decades

covered by the study, there was a progressive decline over time in numbers

of women affected. In contrast, for men there was a slight (but not signifi-

cant) increase in rates for the same period [31]. According to Japanesereports, in that country since the second world war (for some inexplicable

reason), there has been a rapid increase in the total number of patients with

Meniere’s disease. Curiously, before the mid-1960s, there was a marked

male preponderance that has narrowed down consistently during recent

years [16,36,46]. Mizukoshi and colleagues [47] reviewed the epidemiologic

data from 520 patients with definite Meniere’s disease between 1975 and

1976. Their male/female ratio was close to unity and their age distribution

peaked in the age group 40 to 49 years for males and 30 to 39 years forfemales [47]. The same authors interestingly reported a significant prepon-

derance of females in those cases with bilateral disease and those with


vestibular Meniere’s disease [46,47]. According to Watanabe and colleagues

[35,46], apart from the epidemiologic survey, the influences of pregnancy

and parturition were observed in individual female patients with definite

Meniere’s disease. Marked improvement was the rule after parturition.Heermann [48] studied laterality in Meniere’s disease, sudden deafness,

tinnitus, and damage to the inner ear and found a predominance in the left

ear. The difference was statistically significant [48]. These findings were not

confirmed in several studies by Paparella and colleagues [19,42] who found

that the disease affects both ears equally [49,50]. A positive family history (or

at least of symptoms suggesting Meniere’s disease in blood relatives) is

found in one in five patients, suggesting a genetic predisposition in some

[19,41,42,49]. Regarding race, results are conflicting. Okafor [37] identified34 new cases of Meniere’s disease per 8550 black patients in Nigeria, giving

a relative frequency of 400 per 100,000. These results are in contradiction to

the results of others who reported a lower incidence in blacks compared with

other ethnic groups [51,52]. Although Watanabe and colleagues [35] found a

higher incidence in professional and managerial occupations when these

were compared to a control group, the difference was not statistically signif-

icant. These negative findings were supported by those in other studies [31].

Individual factors were analyzed by Watanabe and colleagues [35] whofound definite Meniere’s disease to be statistically more common in married

persons and in people with a nervous and precise character, and to have

lower incidence in obese people. The number of onsets was significantly low-

er where the family lived together and physical and mental fatigue induced

the onset of attacks [35]. The influence of the weather was addressed by

Wladislavosky-Waserman [31] and colleagues who found attacks to be evenly

distributed throughout the year, except for a slight increase at the end of

winter and beginning of spring. Similar findings were reported by Mizukoshiand colleagues [47], whereas in another Japanese study, Naito [16] reported

a higher number of cases of the disease to occur in autumn and winter.

The endolymphatic system: anatomy and physiology

The membranous labyrinth is a system of epithelium-lined spaces and

tubes containing endolymph. It is surrounded by the perilymph-filled peri-

otic labyrinth, which in turn is encased in the bony labyrinth of the otic cap-sule. The membranous labyrinth consists of the endolymphatic duct and sac,

the saccule, the utricle, the semicircular canals, and the cochlear duct. These

are interconnected by small canals: the utricular duct, the saccular duct, and

the ductus reuniens [53].

The utricle is an oblong, slightly flattened sac with a rounded end. It

occupies an elliptic recess in the posterosuperior portion of the vestibule.

The saccule is a spherical organ, smaller than the utricle, located in the

anteroinferior portion of the vestibule in the spherical recess. The utricleconnects posteriorly with the semicircular canals and anteriorly via the


utricular duct with the endolymphatic and saccular ducts. Communication

between the utricle and the utricular duct may be limited by the utricular

fold or valve. The saccule communicates inferiorly with the cochlear ductvia the ductus reuniens. It is at the junction of the utricular and saccular

ducts that the endolymphatic duct arises [53].

The endolymphatic sac lies partly within a bony niche on the posterior

surface of the petrous bone and partly between the layers of the dura mater

of the posterior cranial fossa. It is connected to the endolymphatic duct that

lies in a bony canal known as the vestibular aqueduct. Mainly squamous

and cuboidal cells line the duct, and its lumen at the isthmus (the narrowest

portion) measures 0.1 to 0.2 mm in diameter. The endolymphatic sac can bedivided into three parts: the proximal rugose portion, the intermediate por-

tion, and the distal smooth portion [54]. The proximal portion lies within a

bony niche and has epithelial cells that are slightly taller than those of the

duct. The intermediate portion lies partly within the bony niche and partly

between the layers of the dura mater and has an epithelial lining of tall cylin-

dric cells (of two types: light and dark) irregularly arranged in papillae and

crypts. The distal portion is located within layers of the dura mater over the

lateral sinus and has a cuboidal epithelium with both light and dark cells[54]. The amount of the endolymphatic sac that is intraosseous varies among

individuals but, typically, about one third of the sac is within the bone [55].

According to Gibson and Arenberg [56], about 10% of human endolym-

phatic sacs are completely extraosseous. The rugose portion of the sac is the

most functional and because it lies in an intraosseous position, some have

considered it part of the duct [56].

The sac appears to consist of a series of tubules that lie transversely to the

duct. Within these tubules, the cellular structure suggests both a secretoryand a resorptive role. The lumen of the sac contains cellular debris, free-

floating macrophages exhibiting marked pinocytotic activity, and blood cells

with a preponderance of leukocytes [57].

Gibson and Arenberg [56] precisely categorized the functions of the

human endolymphatic sac:

• Resorption of the water content of endolymph• Ability to participate in some ionic exchanges with endolymph• Removal of metabolic and cellular debris including otoconia• Immunodefense of the ear• Inactivation and removal of viruses• Secretion of glycoproteins to attract extra fluid• Secretion of saccin to increase production of endolymph

Of the above-mentioned functions, the resorption of endolymph and

maintenance of homeostasis in the inner ear are the best studied and well

established.Endolymph derives primarily from the stria vascularis. The planum semi-

lunatum and dark vestibular cells also contribute. Endolymph can also


derive from perilymph across labyrinthine membranes. Gradually, endo-

lymph is absorbed in the endolymphatic duct and sac, which (as pointed

out) is a highly biologically active structure where absorption primarily

occurs as well as, to a lesser degree, secretion [19,58]. The evidence stronglysuggests that both theories are operational: that of longitudinal (slow pro-

cess) and that of radial (rapid ongoing process) flow.

Portmann [7,8] pioneered research on the role of the endolymphatic duct

and sac in the physiology of the inner ear. Studying the endolymphatic

apparatus of the Leiobatis pastinacea (a fish of the Ragides family), he

noticed that an obstruction of a small canaliculum that communicates

between the endolymphatic sac and the surrounding medium (sea water)

caused a flagrant lack of balance in the animal in various swimming posi-tions. The observed phenomenon seemed to show that a lack of contact with

the surrounding medium had modified pressure in the fluids of the inner ear

[7,8]. According to the author, this experiment encouraged him to devise the

first operation on the endolymphatic sac, which he carried out in 1926

[7,8,59]. Shortly thereafter, in 1927, Guild [6] undertook a series of experi-

ments where he injected a solution of potassium ferrocyanide and iron

ammonium citrate into the scala media of several living guinea pigs. After

they were killed and the tissues prepared for histologic examination, acidin the fixing fluid precipitated Prussian blue granules along the scala media.

In 16 of the 20 animals, he could find blue granules in the walls of the endo-

lymphatic sac. From these findings, he concluded that the flow of endo-

lymph is from the stria vascularis through the scala media and the ductus

reuniens to the saccule and endolymphatic sac [6].

If the longitudinal flow was then elegantly demonstrated, then the exis-

tence of an operative fast radial flow was later theorized after Lindsay and

colleagues [60] (and others) obliterated the endolymphatic duct and sac inmonkeys and found no build-up of endolymph nor any functional changes

in the membranous labyrinth. Aware of such conflict, Lawrence [61] de-

signed another series of electrophysiologic experiments in guinea pigs, the

results of which suggested that the circulation of endolymph is also local

and radial. In other words, secretion and absorption of nutrients would

appear to take place continuously along the length of the scala media

[61]. It was then clear that endolymph is generated as an extracellular fluid

from various cellular elements within the membranous labyrinth and movesconstantly and slowly toward the sac (longitudinal flow) but, at the same

time, there is also a constant chemical exchange between the basic fluid and

specialized cellular structures—the stria vascularis, Reissner’s membrane,

the planum semilunatum—within the membranous labyrinth (radial flow)

[61]. In short, according to Lawrence [61], the exchange of chemical com-

ponents within the endolymph takes place all along its path as it slowly

drains toward the sac. The endolymphatic flow is longitudinal, but

the exchange and balance of chemicals is radial and continuous along theducts [61].


Clinical features and natural history

The major categoric triad of symptoms of Meniere’s disease includes ves-

tibular symptoms, auditory symptoms, and aural pressure. The vestibular

symptoms in Meniere’s disease include episodic paroxysmal vertigo associ-

ated with nausea, vomiting, or both, a feeling of imbalance or disequili-

brium that can last for a long period of time, and positional vertigo that

exacerbates an attack of vertigo or can occur between attacks. Rarely,patients also have attacks of such explosive onset that they fall violently

to the ground; these attacks have been termed ‘‘falling spells of Tumarkin’’

or drop attacks [19,42,58]. Classic cochlear symptoms consist of progressive

fluctuating sensorineural hearing loss, tinnitus, intolerance of loudness, and

diplacusis. Lermoyez syndrome is a condition in which a paradoxic im-

provement of hearing follows the acute attack [19,42,58]. Pressure is a

remarkable symptom and is almost always present in patients with

Meniere’s disease. Most times it is an aural pressure, but the patient may feelit in any part of the head or even the neck [19,42,58].

Usually this triad occurs together, whereas in many patients, auditory

symptoms alone (more frequently) or vestibular symptoms alone may pre-

cede the development of the full-blown syndrome for many months or years.

So, in the course of the disease, tinnitus and fluctuating hearing loss some-

times announce years in advance of the first attack of vertigo because the

hydrops normally begins in the pars inferior of the labyrinth and cochlear

duct [22]. Purely vestibular attacks without cochlear symptoms are compa-ratively rare but may be the initial manifestation at the beginning of the dis-

ease [22]. Still, because vertigo is often the most alarming symptom, its

appearance is frequently regarded as the onset of the disease [62]. According

to Paparella [19,42], episodic vertigo associated with vegetative symptoms is

the most disabling symptom (96.2%). This is in accordance with the findings

of Cohen and colleagues [63] who administered a questionnaire to determine

disability in Meniere’s disease that revealed the most incapacitating symp-

tom to be vertigo, followed by hearing loss.Haye and Quist-Hanssen [62] followed a group of 111 patients with

Meniere’s disease for 5 or more years and found that hearing symptoms pre-

ceded the first attack of vertigo in 40% (by less than 3 years in two thirds of

these patients). Schmidt and colleagues [64] studied a group of 53 carefully

selected patients with Meniere’s disease and showed that the sequence of

development of symptoms showed marked individual differences: in 16

patients, cochlear and vestibular symptoms started at the same time, where-

as in 26 patients, the cochlear symptoms started first, and in only 11 did thereverse occur. Inversely, in the series studied by Wladislavosky-Waserman

and colleagues [31], 42.3% of their cases started as cochlear, 50.5% as vestib-

ular, and only 7.2% as classic full-blown Meniere’s. On the other hand, 65%

of their patients ended with classic Meniere’s disease, 26.1% with vestibular,

and 8.8% with cochlear Meniere’s disease [31].


Regarding the duration and severity of the attacks of vertigo, Paparella

and colleagues [19,65] found that in 25% of patients, vertiginous attacks

lasted less than 1 hour; in 50%, 1 to 2 hours; and in 25%, more than 2 hours

to a day or so. In another series of patients, the duration of the first and thelongest attack were almost the same, and in about half of the patients, these

lasted less than 6 hours [62]. According to the same authors, when severely

decompensated, one third of these patients had more than 30 attacks of ver-

tigo per year, and their longest period without vertigo was (in 39%) 5 years

or more [62]. Friberg and colleagues [66] followed a group of 161 patients

for 9 or more years and found a marked variation in the annual mean num-

ber of attacks. Patients who were observed for more than 20 years had an

average of three to four attacks per year, and the range was much narrower.The same study showed that caloric responses in the affected ear decreased

markedly during the first decade of the disease and then stabilized at

approximately 50% of the normal functional level [66]. Katsarkas [67],

studying retrospectively the caloric responses of 475 patients, showed a large

variation in results but, overall, these deteriorated over time and did not

correlate with the level of hearing loss in most cases.

In analyzing the group with cochlear symptoms, Paparella and colleagues

[19] noted that hearing loss was reported in 87.7% of cases, tinnitus in 91.1%,loudness intolerance in 56%, and diplacusis in 43.6%. Aural pressure in one or

both sides is related in 74.1% of cases [19,42,58]. Traditionally during the early

stages of Meniere’s disease, the hearing loss involves mainly the lower fre-

quencies (‘‘rising audiogram’’); as the disease progresses, the higher frequen-

cies are affected and the patient will then present a nearly flat audiogram

[68,69]. The duration of the disease appears to have a discrete effect on the dis-

tribution of patients with different types of audiograms [68], except that an

increased number of patients with up-sloping curves may be seen duringinitial stages. The same holds true for the ‘‘peak audiogram’’ as reported by

Paparella and colleagues [70]. Comparing the audiometric patterns of 300

patients with Meniere’s disease and 400 controls, Paparella and colleagues

[70] described the presence of a peak audiogram (with the peak situated most

commonly at 2000 Hz) in the group withMeniere’s disease, with a prevalence

six times greater than in the control group. A peak audiometric configuration

was seen in half the patients, and a slight peak (incipient Meniere’s disease?)

was commonly seen in the ‘‘normal’’ ear of those with unilateral cases [70].Other common audiometric patterns include low-frequency losses in

early Meniere’s disease and flat losses in advanced Meniere’s disease [65].

A certain subset of patients will progress to complete deafness. Less com-

mon audiometric patterns include high-frequency losses and trough-shaped

losses. Hearing deteriorates essentially within the first years of the disease;

thereafter, there is a halt in the labyrinthine functional loss, and stabilization

occurs [68].

The course of the disease may be progressive or nonprogressive. In pro-gressive Meniere’s disease, the symptoms worsen despite medical treatment


and often become incapacitating and intractable. These patients (estimated

as one out of four) are candidates for surgery. The remaining three out of

four patients whose disease is nonprogressive (symptoms do not worsen) canbe successfully managed with medical treatment [19,42,71,72].

Filipo and Barbara [73] proposed a staging system that involved a pro-

dromic stage (stage 0) characterized by intermittent isolated symptoms of

variable duration. In disabling stage 1 the patient presents with the full-

blown syndrome. Within this stage, two sub-stages can be identified accord-

ing to whether spontaneous or test-induced hearing fluctuates (stage 1a) or

not (stage 1b). Patients may remain in this stage for a highly variable length

of time before entering the ‘‘stabilized’’ stage 2 (characterized by the absenceof vertigo). After a period without symptoms, some patients in stage 2 may

become symptomatic again either by returning to stage 1 or by progressing

to stage 3, when bilateral disease is the rule [73].

The incidence of bilateral Meniere’s disease raises questions not only of

pathogenesis but also of diagnosis and treatment. The incidence of bilateral

Meniere’s disease cited in published reports has been estimated at 2% to 78%

[74,75]. Thomas and Harrison [76], following a series of 610 patients for at

least 5 years, noted that 31.8% developed bilateral disease and over half ofthem did so within 5 years of the onset of the disease. Morrison [77], study-

ing another group of patients, showed that 42.5% developed bilateral disease

within 20 years of initial onset. Following these patients over the years, he

concluded that the rate of increase of bilateral involvement approximated

a linear function of time [77]. The incidence as well as the time interval

between onset of the disease and clinical manifestations of bilateral involve-

ment can vary significantly [74]. In Sweden, Stahle and Bergmann [78]

showed that after 3 years following onset of the disease, 8% of patients hadbilateral disease. This number increased threefold by 7 years later [78].

Paparella and Griebie [79], analyzing a series of 360 patients, showed that

bilateral disease was definitely seen in one in three patients, and 78% of all

patients with Meniere’s disease had a hearing loss in the contralateral ear.

In 1990, Yazawa and Kitahara [80] reviewed the literature on autopsies of

temporal bones in cases of Meniere’s disease from 1938 to 1988 and selected

72 well-documented cases for histopathologic examination. Sixty-seven

cases showed endolymphatic hydrops, and 20 (29.9%) displayed unequivo-cal bilateral involvement [80]. The wide range of bilateral disease reported

in the literature (2% to 78%) clearly demonstrates a need for stricter diag-

nostic criteria [74]. Greven and Oosterveldt [81] established a minimal coch-

lear criterion for bilateral involvement: a sensorineural hearing loss more

than 15 dB in the contralateral ear with concomitant tinnitus and recruit-

ment. If these criteria are broken down to individual symptoms and are

considered individually or in lesser combination, the prevalence rises dra-

matically [74].A very thought-provoking study conducted by Conlon and Gibson [82]

analyzed the incidence of endolymphatic hydrops in the asymptomatic


contralateral ear of 3000 patients with classic Meniere’s disease who under-

went electrocochleography. For such, the presence of hydrops was highly

suggested by a 1 Hz tone-burst summating potential response that exceeded

�6.0 lV. Results demonstrated that more than 10% of contralateral asymp-tomatic ears had an electrocochleography recording highly suggestive of

endolymphatic hydrops. Conlon and Gibson [82] concluded that a high

percentage of patients who had what appeared to be unilateral Meniere’s

disease had evidence of contralateral endolymphatic hydrops.

In short, bilateral disease is much more common than has been supposed.

This concept has tremendous clinical implications for counseling the patient

and for planning treatment. Destructive treatments should be reserved for

only very special and particular situations. Again, the estimated frequencyof bilaterality in Meniere’s disease dictates that, when considering therapy,

every attempt at conservation should be made [19,42,71,79,83].

Meniere’s disease can be divided further into two subsets: typical

Meniere’s disease, inwhich apatient develops the full-blown complex of symp-

toms; and atypical Meniere’s disease, in which either vestibular symptoms

(vertigo) or cochlear symptoms (hearing loss) appear first and full-blown

Meniere’s disease does not develop. Cochlear Meniere’s disease is recognized

as a fluctuating, progressive sensorineural hearing loss associated with auralpressure in the absence of vestibular symptoms or findings [42,84]. Vestibular

Meniere’s disease [85,86] is characterized as the occurrence of episodic vertigo

and disequilibrium associated with pressure in one or both ears. Hypofunc-

tion is often seen on electronystagmographic testing. There are patients who

have presented with incapacitating vestibularMeniere’s disease formore than

45 years and never developed the full-blown syndrome [87].

Pathology

After the original description of the disease by Prosper Meniere in 1861

[2–4], the first step toward an understanding of its pathology was the histo-

logic finding of endolymphatic hydrops by Hallpike and Cairns [11] in 1938.

Together, Charles Sinner Hallpike and Hugh Cairns reported on histo-

pathologic findings in two patients with Meniere’s disease who died shortly

after an attempted section of the eighth cranial nerve. Their article entitled

‘‘Observations on the Pathology of Meniere’s Syndrome,’’ published in theJournal of Laryngology and Otology, became a classic that provides histopa-

thologic description of the characteristic changes in the labyrinth associated

with this disease [11,88]. Both cases demonstrated dilatation of the saccule

and scala media, with obliteration of the perilymphatic spaces of the vestib-

ule and scala vestibuli. Actually, credit for the first description of the pathol-

ogy behind Meniere’s disease should be shared with Kyoshiro Yamakawa

who, at about the same time, presented at a medical congress in Kyoto

his own studies on the pathologic changes in a patient with Meniere’s dis-ease; these were later reported in German publications [88,89]. Since then,


detailed reports of histopathologic findings in cases of Meniere’s disease

have been published systematically. Schuknecht [57] separated these findings

into eight subgroups as follows.

Endolymphatic hydrops

In the early stages of the disease, hydrops involves mainly the pars infe-

rior and, in later stages, the whole endolymphatic system becomes involved.

Cochlear hydrops is omnipresent (Fig. 1), saccular hydrops is very common

(Fig. 2), and utricular hydrops is rarely seen. Frequently, the endolymphatic

system bulges into the helicotrema; often, the saccule bulges into a semicir-

cular canal (usually the horizontal) and the footplate of the stapes. Thehydrops may also obliterate and displace perilymphatic spaces in the scala

and cisterna vestibuli [57,90]. It should be emphasized that on the basis of

observations made in 1980 by Schuknecht and Richter [91], pure apical

endolymphatic hydrops should not be considered as pathologic because

15% of normal human cochleae display this finding.

Ruptures of the membranous labyrinth

Dilatations, outpouchings, ruptures, and collapse can occur in almostany part of the labyrinth. In a 1984 study of 16 temporal bones from the

collection at the University of Minnesota that had clinical histories of

Meniere’s disease, only in those with severe hydrops was rupture of the

membranes observed [90]. Antoni-Candela [92] reported 13 temporal bones

with membranous ruptures out of 19 bones from patients with Meniere’s

Fig. 1. Midmodiolar section of a temporal bone displaying severe endolymphatic hydrops in

the basal, middle, and apical turns of the cochlea, with a marked bulging of the Reissner

membrane (arrows). (Courtesy of the Otopathology Lab, University of Minnesota Collection.)


disease. Fraysse et al [93] published a study based on a series of 23 temporal

bones where cochleosaccular hydrops were found in most, but ruptures were

found in only three. Schuknecht [57] pointed out that ruptures are rarely

seen in the nonampullated parts of the semicircular ducts. It was not clear

whether a rupture of the inner layer caused the outpouchings observed in themembranous labyrinth, followed by distention of the outer layer or whether

they were products of a complete rupture, followed by healing through

fibrous proliferation aided by the perilymphatic trabeculae.

Fistulae of the membranous labyrinth

Fistulae are unhealed perforations of the membranous labyrinth.

Schuknecht and Ruther [94] found fistulae in 18 of 46 temporal bones with

hydrops. Nine of them were located between the saccule and the perilym-

phatic space of the vestibule, four between the saccule and the cochlear duct,

four between the saccule and utricule, and one between the cochlear duct

and the perilymphatic space of the vestibule [94].

Collapse of the membranous labyrinth

Collapse of the distended walls may occur in any part of the labyrinth

and probably represents perpetuation of a fistula between the endolym-

phatic and perilymphatic compartments. Okuno and Sando [95] described

22 temporal bones with hydrops mainly in the pars inferior rather than the

superior, many of which displayed collapsed membranes.

Fig. 2. Temporal bone section showing severe saccular hydrops. The membrane of the saccule

is attached to the footplate of the stapes and the utricule (vertical arrows) and also extends into

the semicircular canal (horizontal arrows). (Courtesy of the Otopathology Lab, University of

Minnesota Collection.)


Obstruction of longitudinal flow

Considering the theory that the etiopathogenesis of Meniere’s disease

somehow involves an obstruction to the flow of endolymph in the endolym-phatic duct or sac, such pathologic obstructive sites should be searched for.

Indeed, Schuknecht and Ruther [94] examined 46 temporal bones from

patients with Meniere’s disease and were able to find blockage of the endo-

lymphatic duct in 8 (17%), blockage of the endolymphatic sinuses in 9

(26%), blockage of the ductus reuniens in 27 (57%), and blockage of the sac-

cules in 7 (15%).

Vestibular fibrosis

Wide dilatations of the saccule, cochlear duct, and utricle may bring their

walls in close contact and, sometimes, bring proliferation of fibrous tissue

between them. Sometimes, the fibrosis may involve a dilated saccule (which

touches the footplate) extending to the utricular macula. This finding can be

responsible for a false-fistula test, present in about 35% of ears with

Meniere’s disease [96].

Sensory lesions

Loss of hair cells in the organ of Corti or vestibular sensory organs is

infrequent during the initial phases of Meniere’s disease. On the contrary,

in advanced disease, there are many pathologic changes that include loss

of hair cells, atrophy of supporting cells, collapse of Reissner’s membrane,

and atrophy and entrapment of the tectorial membrane. In the vestibular

system, there may be severe dilatation or collapse of the ampullary walls [57].

Neural lesions

Again, the cochlear and vestibular neuronal population is unaffected dur-

ing early stages of the disease. Later in the course of the disease, degenera-

tion of the sense organs may affect mainly cochlear neurons. In about 10%

of ears with Meniere’s disease, there is a focal loss of neurons in the apical

region of the cochlea. Vestibular neurons are rarely affected [57].

Pathophysiology

Any correlation of pathologic findings with the symptoms of Meniere’s

disease must account for both the fluctuations in hearing and the episodes

of vertigo commonly known as the ‘‘definitive symptoms,’’ as well as for the

persistent, nonepisodic, and often progressive hearing loss and disequili-

brium, the so-called ‘‘adjunctive symptoms’’ [57]. The literature containscontroversial mechanical, chemical, and vascular explanations for the chain

of signs and symptoms characteristic of Meniere’s disease. Despite the


number of publications addressing the pathophysiology of the attacks and

the progressive dysfunction in the inner ear typically seen in Meniere’s dis-

ease, a consensual theory has not yet emerged. The authors will present, in

the next paragraphs, three different theories that have been dominant in thisdebate: membranous ruptures and perfusion/intoxication of the neuroepi-

thelium by high concentrations of potassium [57], pressure and mechanical

displacement of the end organs [19,42], and obstruction followed by secre-

tion of saccin and abrupt clearance of the endolymphatic duct [56].

As pointed out by Brandt [22] in 1991, application of the mechanical

theory to explain the vestibular dysfunction as a simple consequence of

changes in pressure in the inner ear cannot explain the prolonged nystagmus

and vertigo typical of an attack of Meniere’s. Bekesy [97], using electrophy-siologic methods, determined that the sensory nerves and nerves of the coch-

lea and vestibular labyrinth are located in the perlymphatic compartment,

and Tasaki and Fernandez [98] found that bathing the scala tympani with

a solution of potassium blocked cochlear microphonic responses and action

potentials. Schuknecht [57] proposed that a malfunctioning endolymphatic

duct and sac causes endolymphatic pressure to build up, with consequent

distention of the endolymphatic system. Thinning and atrophy of the more

yielding parts of the membranous labyrinth (Reissner’s membrane and sac-cule) would follow and, eventually, there would be ruptures of these delicate

membranes with spillage of large amounts of endolymph (rich in potassium)

into the reduced perilymphatic space [57]. Consequently, the sensory and

neural structures exposed to the potassium-rich endolymph would be

paralyzed, resulting in sudden hearing loss and vertigo. As the biochemical

components of the perilymphatic compartment are restored to normal, the

symptoms subside. Aided by the collapse of the distended membrane, the

rupture heals and another cycle of increased pressure and rupture is readyto start. The adjunctive symptoms can be attributed to progressive disturb-

ance in motion mechanics caused by the distorted, dilated, and collapsed

membranes, as well as to a loss of specialized cell types and to alterations

in biochemistry and bioelectric potentials of the inner ear [57]. This concept

can be summarized in a logical five-step sequence: (1) decreased endolym-

phatic reabsorption, (2) progressive hydrops, (3) membranous ruptures and

spillage of large amounts of neurotoxic endolymph into the perilymphatic

compartment, (4) healing of the membranes, and (5) distortion and atrophyof sensory and neural structures [57].

Although membranous ruptures have been described as a cause of all

attacks of Meniere’s disease, some reports of hydropic human temporal

bones have failed to demonstrate such ruptures [90]. Even when present,

these ruptures were not necessarily seen in both the scala media and the sac-

cule or utricle simultaneously [90]. Considering that both radial and longi-

tudinal dispersal of fluid are operational, ruptures occurring in Reissner’s

membrane in the middle turn of a highly hydropic ear would be difficultto reconcile with the passage of endolymph. It is hard to explain how


endolymph (rich in potassium, which is neurotoxic) could bypass the sac-

cule (which when distended, practically fills the vestibule) to reach the crista

ampullaris of the semicircular canal and cause vertigo instantaneously [19].Typical attacks of Meniere’s disease would need simultaneous ruptures in

both the cochlear duct and saccule for cochlear deafness and vertigo to occur

together each time. Again, histopathologic reports do not corroborate this.

Vosteen and Morgensteen [99] explain the generation of hydrops and its

symptoms by giving a primary role to the disturbed ionic balance between

produced and reabsorbed endolymph. Patients report relief from an attack

when the pressure subsides and vertigo and cochlear dysfunction improve.

This suggests that ruptures usually alleviate, rather than precipitate, vertigi-nous episodes [99]. There is one more question waiting to be answered con-

clusively in this regard: when a break occurs in Reissner’s membrane, does

perilymph enter the scala media or does endolymph escape? To date, animal

experiments have shown that after a rupture of Reissner’s membrane has

occurred, perilymph enters the scala media and not the opposite. Still, these

findings must be approached with care because most of these experiments

were carried out in animals with nonhydropic inner ears [61].

Endolymphatic hydrops is characteristically seen in advanced Meniere’sdisease in the pars inferior (the scala media and saccule), which in many

cases, fill the vestibule and scala vestibuli. Sometimes, an extended utricule

or cochlear duct occupies the vestibule completely. In such decompensated

cases, displacement of perilymph causes diminished radial flow, and longitu-

dinal flow becomes dominant. In this situation, the saccule appears to func-

tion as a reservoir for endolymph prevented from flowing out toward the

duct and the sac. The stagnant endolymph can cause distention that can

mechanically interfere with traveling waves and interfere with cochlear func-tion. Severe saccular hydrops can also extend into the semicircular canal,

physically altering function of the crista ampullaris and causing instantane-

ous vertigo [19,42,90].

Gibson and Arenberg [56], in 1997, proposed another theory to explain

the constellation of signs and symptoms of Meniere’s disease. According

to these authors, after an abnormally narrow endolymphatic duct becomes

obstructed by cellular debris, the deprived sac acts in two ways to clear the

debris and re-establish the patency of the duct: by secreting glycoproteinsthat attract endolymph into its tubular structure and by secreting a natri-

uretic hormone called saccin (first isolated by Qvortrup and colleagues [100])

that increases production of endolymph [56]. With the additional produc-

tion of endolymph, the pressure mounts even more behind the obstructive

site and, eventually, the debris is cleared abruptly. The consequent sudden

movement of endolymph toward the endolymphatic sac causes an acute

attack of vertigo. In later stages of Meniere’s disease, the functions of the

sac decrease and finally cease, and the endolymphatic duct becomes blocked.At this late stage, the ear is affected by endolymphatic hydrops but the

attacks of vertigo disappear [56]. According to these authors, in those ears


displaying larger vestibular aqueducts, cochlear function may improve even

during the initial clearance of endolymph (Lermoyez’s syndrome). The

Tumarkin episodes could be explained through sudden ruptures of a highly

distended membranous labyrinth [56].

Etiopathogenesis

Since 1927, when Guild [6] introduced the concept of longitudinal flow,

pointing to the endolymphatic sac as the site where absorption of endo-

lymph occurs, investigators have attempted to produce endolymphatic

hydrops in the laboratory. In fact, working with guinea pigs, Kimura [15]

was the first to succeed in producing endolymphatic hydrops by the obliter-ation of the endolymphatic sac in a series of animals. Subsequently, exper-

imental obstruction of the endolymphatic duct and sac has been shown to

produce hydrops consistently in the guinea pig [61]. Concurrently, Hallpike

and Cairns [11] and Yamakawa [89] in 1938 unveiled the histopathologic

correlate of Meniere’s disease, clearly showing overdistention of the mem-

branous labyrinth (hydrops) in postmortem specimens. Again, after these

pioneering studies, histopathologic studies of temporal bones from patients

with Meniere’s disease showing similar findings have been systematicallyreported in the literature [12,13,60,90].

Transposing the results of years of basic scientific research to clinical use

was just a small step after such a long way, and important (but not all)

pieces of the puzzle finally could be put together: the normal physiology

(how the endolymph flows), the pathogenesis (how the system is disturbed),

and the pathologic correlate (endolymphatic hydrops). As a result, the most

popular theory of etiology reaffirms that Meniere’s disease is caused by

overdistention of the membranous labyrinth due to excessive endolymphaticfluid [101]. To simplify and popularize this theory, Paparella and colleagues

[19,42] explored the analogy between this hypothesis and a sequence of illus-

trative events, or what they used to call the concept of the ‘‘lake, river, and

pond.’’ In other words, normally, nothing disturbs the smoothness of the

rate of endolymphatic flow, but a physical or chemical obstruction (dam)

near the river or pond can cause hydrops to develop. When explaining

Meniere’s disease to our patients, the authors prefer to use another analogy:

the ‘‘faucet, sink, and drain.’’ It is almost self-explanatory. The pillars thatsupport this theory were built along the years: (1) histopathologic evidence

of hydrops in patients diagnosed as having, in life, Meniere’s disease; (2)

reported evidence of reduced vascularization and fibrosis in the perisaccular

tissue, with consequent reduction in the resorptive capacity of the sac; and

(3) experimental obliteration of the endolymphatic duct and sac followed by

hydrops [101].

When the malabsorption of endolymph was well established conceptually

as the origin of endolymphatic hydrops, the next question that needed to beanswered was what would be the specific etiologic bases behind this whole


process? Much research has been done on this topic during recent years and,

unfortunately, new questions have outnumbered answers. The lack of knowl-

edge has laid the field open to hypotheses based on new research and also onassumptions and beliefs. From these studies, endolymphatic hydrops can

now be classified as embryopathic, acquired, or idiopathic, depending on

its etiologic basis [102]. The embryopathic type is rare; as an example, it may

be secondary to Mondini’s dysplasia [57]. The acquired types were

further explored and redefined by Jongkees (see Paparella [58]) into two cate-

gories: Meniere’s syndrome, with a known and well-established cause, and

Meniere’s disease, in which the cause seems to be idiopathic. The authors

agree with Paparella [19,42] when he states that the concept of ‘‘idiopathicMeniere’s disease’’ seems defeatist. Clearly, as clinicians understand more

and more about the several different etiologic factors in the generation of

endolymphatic hydrops and its clinical symptoms, the less often the term

idiopathic will be used, and it is hoped that as understanding grows, the

term will definitely be discarded.

Since Shambaugh [103] reported the association of Meniere’s disease and

decreased perisaccular vascularity in temporal bones from the collection

at Northwestern University, histopathologic and radiologic studies pointingin the same direction have flooded the pertinent literature [104–108].

These studies have confirmed perisaccular fibrosis, loss of epithelial integrity

and atrophy of the sac, hypoplasia of the vestibular aqueduct, and narrow-

ing of the lumen of the endolymphatic duct. Stahle and Wilbrand [108]

described characteristic features in patients with Meniere’s disease as a lack

of periaqueductal pneumatization, a lack of pneumatization medial to the

arcuate eminence, a short vestibular aqueduct, and a reduction in size of the

mastoid air-cell system. Kodama and Sando [105], in a statistical analysis of79 normal temporal bones, observed a paucity of loose subepithelial connec-

tive tissue and of folds of the rugose portion of the sac associated with tem-

poral bones with hypoplastic vestibular aqueducts. Another study by Sando

and Ikeda [107] showed that vestibular aqueducts in temporal bones from

patients with Meniere’s disease were statistically smaller than in temporal

bones from controls. Paparella and Sajjadi [106] described the characteristic

finding of an anteriorly and medially displaced lateral sinus and the conse-

quent tightening of Trautmann’s triangle in patients with Meniere’s disease.On the other hand, Ikeda and Sando [104] compared degrees of perisac-

cular fibrosis in the rugose portion of the endolymphatic sac from patients

with Meniere’s disease and from controls and found the difference to be stat-

istically significant, although these authors recognized that their study could

have been biased. Wackym and colleagues [109] carried out a systematic

blind controlled study of the degree of density of subepithelial connective

tissue in the human endolymphatic duct and sac. They included in the study

18 temporal bones from patients with a known premortem clinical diagnosisof Meniere’s disease and 19 temporal bones from normal control subjects.

Three blinded observers (all experienced histopathologists of the temporal


bone) independently rated the density of fibrous connective tissue surround-

ing the endolymphatic duct and sac in a series of randomized photographs.

The results obtained from this blind controlled analysis tailed to demon-

strate statistically significant differences between the groups studied [109].Quijano and colleagues [110] corroborated this finding and failed to demon-

strate differences in the prevalence of fibrosis in the vestibular ganglia in

patients with Meniere’s disease.

Still, there is a consensus that a normal endolymphatic sac and a patent

endolymphatic duct are considered essential to normal labyrinthine func-

tion, and other possible mechanisms of dysfunction on the endolymphatic

sac may exist [111]. Among them, immune-mediated mechanisms or a dis-

turbed metabolism of glycoproteins should be considered [101]. Experimen-tal studies have indicated that the endolymphatic sac can produce and

secrete glycoprotein conjugates and proteoglycans into its lumen [101]. This

secretion seems to be related to changes in volume or pressure of endo-

lymph. It is possible that the endolymphatic sac could sense the lack of

endolymph in its tubules and respond to it by secreting saccin, which in turn

would increase the amount of endolymph and glycoproteins to attract endo-

lymph osmotically [56]. Ikeda and Sando [104] found a statistically signifi-

cant increase of an intraluminal eosinophilic precipitate (morphologicallyidentical to glycoproteins secreted by the sac) in endolymphatic sacs of

patients with Meniere’s disease. Hebbar and colleagues [112] reported that

the volume of the endolymphatic sac filled with the eosinophilic precipitate

was statistically larger in ears with moderate hydrops than in ears with mild

or severe hydrops. These studies suggest that an alteration in glycoprotein

metabolism in the endolymphatic sac could have a role in Meniere’s disease

in some cases [56,104,112].

The old belief that the endolymphatic sac represented merely a vestigialorgan or a useless appendix of the inner ear in embryogenesis has dramat-

ically changed since recent researchers have gathered cumulative evidences

of its highly complex and active ultrastructure [111]. Furthermore, the outer

hair cells of the organ of Corti are now known to have motor functions with

high energy demands [56]. To meet these demands, the endolymph must

have a high turnover rate to remove metabolites and debris from the cochlea

[56]. The idea that the inner ear was also devoid of immune-response mech-

anisms has been completely reviewed. On the contrary, the inner ear dem-onstrates a vivid immunocompetence, with both cellular and humoral

immunity, and the endolymphatic sac has been shown conclusively to be the

site of generation of this immune response [113]. Immunoglobulins G, M,

and A and a secretory component are all found in the endolymphatic sac,

and numerous plasma cells and macrophages are found in the perisaccular

connective tissue [114,115]. The sac has been shown to be capable not only

of processing antigens but also of mounting its own local antibody response.

Additionally, two properties of the endolymphatic sac make it a potentialsite of immune injury: (1) its capillaries are fenestrated (unlike those of the


cochlea), a feature displayed in organs involved with fluid absorption and

subject to deposition of immune complexes, and (2) it has been shown to

be relatively hyperosmotic compared with serum, which could also incite thedeposition of immune complexes [113].

With a better understanding of the immunology of the inner ear and the

role played by the endolymphatic sac, new studies trying to relate endolym-

phatic hydrops and autoimmunity were a natural consequence. According

to Ruckenstein [113], it has long been speculated that Meniere’s disease

might be an immune-mediated or even an autoimmune condition. Many

of the clinical characteristics of Meniere’s disease suggest an underlying

autoimmune etiology. The tendency of the disease to wax and wane—becoming active after long remissions—suggests an inflammatory compo-

nent. It is bilateral in a significant number of cases, ultimately resulting in

a slow, progressive deterioration of the affected organ, similar to what is

seen in a variety of systemic autoimmune conditions. Autoimmune condi-

tions are exacerbated during periods of physical or psychologic stress, which

also holds true for patients with Meniere’s disease. Finally, an increased level

of circulating immune complexes has been noted in several studies [113].

Tomiyama [116] generated experimental hydrops (with auditory andvestibular dysfunction) in guinea pigs using a protocol of systemic immuni-

zation and secondary antigenic challenge through the endolymphatic sac

with keyhole limpet hemocyanin. Other studies searching for the presence

of specific human leukocytic antigens—typically associated with autoim-

mune diseases—noted an increase in the level of human leukocytic antigens

in patients with classic symptoms of Meniere’s disease [113,117]. According

to Ruckenstein [113], ‘‘despite these observations, the available histopatho-

logical data do not support the hypothesis that idiopathic Meniere’s diseaseresults from traditional immune-mediated destruction of the inner ear.’’ The

histopathologic picture of idiopathic Meniere’s disease is much more subtle

than catastrophic findings typical of an immune-mediated inflammatory

aggression [113].

Some investigators have reported allergy as an etiologic factor in

Meniere’s disease. Duke [23], in 1923, was the first to investigate such asso-

ciation. Derebery [114,115], in an excellent article, pointed out at least two

possible roles for allergy in the production of fluid in the endolymphatic sac:(1) the sac itself might be a targeted organ for mediators released from sys-

temic reaction to inhalants or foods (the anatomy of its walls would render

it vulnerable), or (2) the mechanism involves the production of a circulating

immune complex that is then deposited through fenestrated blood vessels

into the endolymphatic sac, producing inflammation and interference in the

filtering capacity of the sac. Many contemporary studies suggest a possible

link between Meniere’s disease and allergies to inhalants or foods. Although

good results are reported in the control or symptoms after medical therapyor immunotherapy, this relevant issue still needs further investigation

through more controlled clinical trials.


Unfortunately, in only a few cases can the Meniere’s symptom-complex

be consistently associated with a well-determined cause. Meniere’s syn-

drome has been described in patients with otitis media [11,118,119], viral

infections [22], metabolic diseases [120], otosclerosis [65,121] (Fig. 3), Paget’sdisease [57], congenital malformations (eg, Mondini) [57], syphilis [122],

Cogan’s syndrome [122], leukemia [123,124], acoustic or physical trauma

[125–127], tumors of the temporal bone [17] (10% of vestibular Schwan-

nomas may initially mimic Meniere’s disease), vascular anomalies (high jug-

ular bulb [128], anomalous vein of the vestibular aqueduct [129]), allergy

[114,115], and autoimmune disease [113]. It is interesting that regardless of

the nature of the initial insult (inflammatory, traumatic, congenital, or such),

the symptom-complex that follows is similar and quite characteristic. It isevenmore interesting that only aminority of patients with one of these poten-

tial triggering ‘‘risk factors’’ eventually develops the symptom-complex.

Fig. 3. Meniere’s syndrome and otosclerosis. (A) Normal proximal rugose portion (bony) of a

human endolymphatic sac. (B) Proximal portion of an endolimphatic sac invaded by a small

focus of otosclerotic bone. (Courtesy of the Otopathology Lab, University of Minnesota

Collection.)


It is clear that in addition to an extrinsic cause, patients with Meniere’s

disease must somehow be genetically predisposed to develop this condition.

As emphasized by Paparella [41], this multifactorial heritable predisposi-tion may include anatomic (eg, a small endolymphatic sac) or physiologic

(eg, chemical) abnormalities. Under normal conditions, such predisposed

patients would be completely free of symptoms, but when they are exposed

to major physical or biologic stress, the full-blown syndrome may ensue [41].

In other words, a subject would have a genetic predisposition or an inborn

potential to present the disease. Aggressive extrinsic factors acting during a

lifetime would down-modulate a delicate biologic equilibrium, sparking

(eventually) the development of the syndrome. As pointed out by Rucken-stein [113], ‘‘the concept of a triggering event is important from a clinical

perspective. Once [we have] recognized a risk-factor, early intervention may

prevent the development of the full-blown syndrome that, once fully estab-

lished, has proven to be both progressive and only marginally responsive to

current therapeutic regimens.’’

One last question is that of the so-called ‘‘central dogma for Meniere’s

syndrome,’’ which states that many possible factors can lead to endolym-

phatic hydrops, which in turn generates the clinical symptoms. A systematicdouble-blind assessment of case histories and histopathologic findings in

temporal bones was performed to test the hypothesis that clinical Meniere’s

syndrome is associated with endolymphatic hydrops [130]. All 13 cases with

clinical Meniere’s syndrome were found to present endolymphatic hydrops

not attributable to other causes, but 6 cases with idiopathic (histologic)

endolymphatic hydrops did not exhibit Meniere’s syndrome in their medical

records. These results challenge the dogma that endolymphatic hydrops per

se generates the symptoms of Meniere’s syndrome [130]. These authors offertwo possible explanations for these findings: (1) either a loss of peripheral

neurosensory elements occurred or there was some disorder of the CNS

affecting the auditory/vestibular pathways that could [mimic?] the appear-

ance of clinical symptoms; or (2) a number of mechanisms might affect fluid

management within the inner ear, finally producing both the clinical symp-

toms of Meniere’s syndrome and endolymphatic hydrops, in which case this

would be an epiphenomenon [130].

Investigation and differential diagnosis

Many structural or neurophysiologic abnormalities can compromise the

highly complex vestibular system. Lesions arising from the peripheral end

organs to central vestibular pathways can disturb the smoothness by which

the system operates, generating disabling symptoms. Clinical expressions of

these abnormalities may be quite similar (at least in early phases), regardless

of their location. Therefore, the clinician must pursue the evaluation of adizzy patient as extensively and reasonably as possible, so that a patient with

a life-threatening lesion can be differentiated from another patient with a


less morbid condition (but not necessarily less incapacitating) [17]. In the

assessment of a dizzy patient, it is extremely important to find out whether

one is dealing with a peripheral or a central syndrome. A peripheral syn-

drome would encompass lesions forming within the labyrinth and aroundthe eighth cranial nerve to the point of its entrance into the brainstem. A

central syndrome includes the auditory and/or vestibular pathways from the

brainstem, the vestibular nuclei and pathways, and several connections with

other structures in the nervous system [17].

It should be stressed that regarding the audiovestibular system, retroco-

chlear conditions are not synonymous with central conditions. The term ret-

rocochlear should be understood as an audiovestibular pathologic condition

beyond the inner ear, including the eighth cranial nerve in its entire course.In other words, all central lesions are by definition retrocochlear, but the

opposite is not true [17].

Given the symptom of vertigo or dizziness, the diagnosis should be made

at two levels: the identification of the specific vestibular syndrome or syn-

dromes involved and the underlying medical disease [17]. It is a major con-

cern to develop a logical workup oriented toward the distinction between

peripheral (labyrinthine) abnormalities and those involving central vestibu-

lar connections. The otolaryngologist has an extremely important role in theearly detection of central disorders, which could jeopardize the patient’s life

if diagnosis and treatment are delayed or not done [17]. Key to this distinc-

tion is the neurologic evidence for or against involvement of neighboring

structures in the brainstem. The diagnosis and proper management of

central and mixed lesions generally requires use of more sophisticated diag-

nostic tools and last-generation imaging techniques and others. To aid in

selecting the appropriate studies, the arts of a good history taking and a

complete and meticulous physical examination are fundamental [17].The diagnosis ofMeniere’s disease is one of exclusion, and a careful history

is the most important guide to a correct diagnosis. Indeed, in 90% of cases, a

good history may almost seal the diagnosis [19,42]. An audiogram followed

by vestibular studies is helpful. Common audiometric patterns include a peak

audiometric configuration, low-frequency losses in early stages, and a flat

pattern in advancedMeniere’s disease. Auditory brainstem response is some-

times used to distinguish a cochlear lesion from a central lesion. Hypoactivity

of the involved labyrinth as recorded by electronystagmography is the mostcommon finding of all vestibular tests [19,42]. A computed tomographic scan

and magnetic resonance imaging should be ordered only when intracranial

pathologic conditions have not been completely ruled out.

As pointed out by Weber and Adkins [131], other disease entities may

mimicMeniere’s disease, especially when patients present with atypical forms

such as vestibular or cochlear Meniere’s disease. These other conditions may

be central or peripheral in origin (see Display Box 3 and Table 1). Therefore,

before a diagnosis ofMeniere’s disease (typical or atypical) can bemade, theseother diseases must be ruled out [131].


Treatment

The management of Meniere’s disease has four aims [22]:

• To treat the acute attacks• To prevent further attacks• To improve and/or preserve hearing and vestibular function• To prevent the development of bilateral Meniere’s disease

Attacks

Patients should be given instructions on how to manage the acute attack

and, most important, they must be informed about the overall relatively

Box 3 Central lesions causing vertigo

Inflammatory

MeningitisBrain abscessEncephalitis

Space Occupying

Neoplasms of the CNSArachnoid cysts

Vascular

Internal auditory artery lesionInferior posterior cerebellar artery lesionVertebral basilar insufficiency

Systemic

ToxinsGeneticMultiple sclerosis

Traumatic

Brain concussion

Autonomic Nervous

Neonatal

Development anomaliesAnoxia, neonatal jaundice, prematurity


benign course of the disease and, in most cases, the spontaneous remission

or abatement of the attacks within a few years. The acute attack is self-

limiting and subsides within a few hours (rarely less than 1 hour or more

than a day) in a slow decrescendo. The following recommendations can

be made for management of the acute attack:

• With severe vertigo and postural imbalance, patients should lie or sitdown in order to prevent falls.

• Movement of the head or rapid changes in position of the head should berestricted because of cross-coupled accelerations and positional vertigo.

• Objectives of pharmacologic treatment during the acute attack arepurely symptomatic. Treatment aims to control the most disabling symp-

toms of vertigo, nausea, and vomiting. For such, a group of drugs used

in isolation or in different associations depending on the magnitude of

Table 1

Peripheral lesions causing vertigo

Middle ear

Inflammatory

Otitis media

Atmospheric

Tubal obstruction

Aerotitis

Labyrinth

Inflammatory

Labyrinthitis

Vestibular neuronitis

Vascular

Hemorrhage

Ischemia

Vasomotor

Allergy

Multifactorial

Hydrops

Otosclerosis

Systemic diseases

Bacterial or viral

Metabolic

Hematogenic

Drugs

Neoplastic lesions

Malignant tumors

Benign tumors

Glomus

Acoustic tumors

Trauma

Fracture temporal bone

Labyrinthine concussion

Acoustic trauma


the crises and the hierarchy of symptoms have been employed. These

drugs and their corresponding actions are summarized in Table 2 [22].

Attack-free interval

Establishing a good doctor-patient relationship is crucial in the care of

patients with Meniere’s disease. After an initial attack, a patient is extremelyapprehensive, requiring much support and reassurance. The most important

medical management of Meniere’s disease is perhaps this psychologic sup-

port for the patient, which should include a description of the disease that

emphasizes that the condition is not life threatening and explains various

expectations of its natural history and therapy. It is important to stress that

there is no cure for Meniere’s disease [19,42].

A number of different drugs have been used to treat Meniere’s disease,

including diuretics, vestibular sedatives, vascular agents, and vestibulotoxicdrugs. Because most drugs act on an empiric basis, policy is not to discour-

age use of any of them if they minimize symptoms, encourage nonprogressive

Table 2

Medical treatment of the acute attack of Meniere’s disease

Drug Dosage Action

Anticholinergics Muscarine antagonist

Scopolamine 0.6 mg po q 4–6 h or

Transdermal patch: 1 q 3 d

Antihistamines

Dimenhydrinate 50 mg po q 4–6 h or Histamine (H1) antagonist

IM q 4–6 h or Muscarine antagonist

100 mg suppository q 8–10 h

Meclizine 25 mg po q 4–6 h Histamine (H1) antagonist

Muscarine antagonist

Promethazine 15 or 50 mg po q 4–6 h or Histamine (H1) antagonist

IM q 4–6 h Muscarine antagonist

Suppository q 4–6 h Dopamine (D2) antagonist

Phenothiazine

Prochlorperazine 5 or 10 mg po q 4–6 h or Muscarine antagonist

IM q 6 h or Dopamine (D2) antagonist

25 mg suppository q 12 h

Butyrophenone

Droperidola 2.5 or 5 mg IM q 12 h Muscarine antagonist

Dopamine (D2) antagonist

Benzodiazepines

Diazepam 5 or 10 mg po bid–qid or GABA A agonist

IM q 4–6 h or

IV q 4–6 h

Clonazepam 0.5 mg po tid GABA A agonist

a Only used under strict anesthetic supervision.

Abbreviations: GABA, c-aminobutyric acid; IM, intramuscularly; IV, intravenously.Data from Brant T. Management of the dizzy patient. In: Brandt T, editor. Vertigo: its

multisensory syndrome. 2nd edition. London: Springer-Verlag, 1999.


Meniere’s disease, or help prevent progressive Meniere’s disease. Dietetic

therapies including restriction of salt, water, alcohol, nicotine, and caffeine

have also been recommended. In 1977, Torok [132] surveyed 834 articles

on the treatment of Meniere’s disease published over a 25-year period andconcluded that all of them claimed successes within the range of 60% to 80%.

In 1991, this study was revisited and updated by Ruckenstein and colleagues

[133] who came to the same conclusion, suggesting that patients with

Meniere’s disease could benefit from a placebo effect. Claes and Van de

Heyning [134] carried out another review of the pertinent literature and

found that only diuretics and the histamine-derived betahistine have a pro-

ven effect on the long-term control of vertigo. On the other hand, none of

the researched medical therapies appeared to halt the progression of thehearing loss or long-term evolution of the disease [134].

The effect of diuretics (acetazolamide) on experimental hydrops in guinea

pigs was confined to the period of administration, and administration

or nonadministration of the drugs did not have any effect on the extent of

cochlear sensory and neural atrophy in animals [135]. Urea, thiazide

diuretics, and acetazolamide have been recommended for chronic treatment

of Meniere’s disease [136]. In a double-blind placebo-controlled crossover

study, a combination of triamterene and hydrochlorothiazide effectivelycontrolled vertigo [136]. This combination, however, had no positive long-

term effect on hearing, which confirms an earlier report by Klockhoff and

co-workers [137] on long-term results with chlorthalidone. It should be

stressed that adequate search for and control of underlying etiologic and

contributory factors (such as hormonal and/or metabolic disturbances,

allergy, stress, and so on) is very important to long-term management.

Surgical treatment of Meniere’s disease

It is the authors’ policy that conservative treatment should always come

first. Medical treatment and psychologic support must precede any consid-

eration of surgery. Surgery can be considered when, in spite of a trial ofmedical therapy, the disease progresses and the symptoms become intract-

able [138,139]. Again, several principles must be fully addressed before con-

sidering a surgical procedure to treat Meniere’s disease:

• An accurate diagnosis and a search for predisposing or contributoryfactors

• A previous trial of medical therapy• The risks of the chosen surgical procedure should be weighed againstthe benefits and the natural history of the disease

• Bilaterality must be fully addressed before choosing a destructive orpartially destructive procedure

• The general health status of the patient must be considered and surgicalrisks stipulated to them


Surgery on the labyrinth may be either conservative (preserving the hear-

ing) or ablative (destructive of hearing). Preservation or even improvement

of function is the aim of conservative procedures, including endolymphaticsac enhancements. The authors agree with those who consider sac surgery to

be an extension of conservative treatment because it has minimal risks and is

possibly the only surgical treatment that might reverse the pathogenesis of

Meniere’s disease. More aggressive and destructive procedures such as

labyrinthectomy are generally avoided to enhance the chance of a future

cochlear implant in those unfortunate patients who develop complete bi-

lateral hearing loss.

It is beyond the scope of this article to discuss in depth the surgical treat-ment of Meniere’s disease. Surgical procedures currently available to treat

Meniere’s disease are summarized in Display Box 4. For more details, the

reader is referred to other articles in this issue.

Summary

Meniere’s disease is a disease of the inner ear characterized by a triadof symptoms: vestibular symptoms, auditory symptoms, and pressure. The

pathologic correlate of Meniere’s disease is endolymphatic hydrops and

the etiopathogenesis involves a deficiency in the absorption of endolymph.

The pathophysiology of the symptoms is still disputed:membranous ruptures,

pressure and mechanical displacement of the end organs, or obstruction fol-

lowed by an abrupt clearance of the endolymphatic duct. The course of the

disease may be progressive or nonprogressive and, in addition to the typical

presentation of Meniere’s disease, two variations of the disorder have beenidentified: cochlear Meniere’s disease, and vestibular Meniere’s disease. It

can be further broken into two subsets: Meniere’s syndrome, with a known

and well-established cause, and Meniere’s disease, in which the cause seems

to be idiopathic. It is likely that there are racial (genetic) as well as environ-

mental factors that influence differences in incidence among countries and

among various sections of countries. The disease is much more common

in adults, with an average age of onset in the fourth decade, the symptoms

beginning usually between ages 20 and 60 years. Meniere’s disease is(grossly) equally common in each sex, and right and left ears are affected

with fairly equal frequency.

The diagnosis of Meniere’s disease is by exclusion, and a careful history is

the most important guide to a correct diagnosis. Its medical treatment is

largely empiric. Surgery can be considered when, even after medical therapy,

the disease progresses and the symptoms become intractable. Surgery may

be either conservative or destructive. Bilaterality must be considered when

deciding the best surgical option for a patient with Meniere’s disease. It isthe authors’ opinion that endolymphatic sac surgery is an extension of con-

servative treatment.


Acknowledgments

The authors are grateful to Dr.MarianaMagnus Smith and to Dr. Cristia-no Ruschel for their help in the elaboration of this manuscript, to Mrs. Cris-

tina Dornelles for her assistance with the references, and to Dr. Michael M.

Paparella who dedicated a whole life to otology, education, and assistance.

Box 4 Surgical procedures to treat Meniere’s disease

1. Conservative procedures (hearing preserved)

A. Extralabyrinthine1. Endolymphatic sac enhancement2. Endolymphatic sac revision3. Sympathectomy

B. Invasive of the labyrinth1. Sacculotomy2. Cochleosacculotomy3. Stapedectomy-sacculotomy

2. Partially destructive procedures (hearing preserved)

A. Vestibular nerve section1. Through the middle fossa2. Retrolabyrinthine approach3. Retrosigmoidal approach4. Combined retrolabyrinthine-retrosigmoid vestibular

neurectomy

B. Singular neurectomyC. Ultrasonic irradiation of the labyrinthD. CryosurgeryE. Medical ablation with/without exploratory tympanotomy

3. Destructive labyrinthectomies (hearing destroyed)

A. Transtympanic1. Labyrinthectomy extended to the oval window2. Transcanal labyrinthectomy3. Transmeatal labyrinthectomy

B. Transmastoid1. Transmastoid labyrinthectomy2. Translabyrinthine section of the vestibular nerve3. Labyrinthotomy through the horizontal canal4. Labyrinthectomy through the middle fossa


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