Ballengers othorhinolaryology 18th edition

Dizziness and vertigo

● Key questions:
○ Does the patient have vertigo?
○ Are the patient’s symptoms continuous or episodic?
○ If the symptoms are episodic, what is their duration?
○ What can provoke them?
○ What are the associated symptoms?
● Symptoms: dizziness, lightheadedness, wooziness, fatigue, disconnectedness, disequilibrium, imbalance, and
vertigo
● Vertigo: sensation of motion when no motion is occurring relative to earth’s gravity.
○ Most commonly rotational or spinning in nature
○ Can also be a sensation of being pulled or pushed in one direction
○ Oscillopsia: a person’s visual field jumps during rapid head movements such as when riding in a car
over a rough road
○ Vertigo points toward a peripheral, otologic source of symptoms
○ More general feeling of being disoriented, disconnected, “drunk” or sensitive to motion are less
specific for an otologic cause
● Each of the vestibular-end organs is paired with a vestibular end-organ in the contralateral ear
● Normally, as the head is rotated, tilted, accelerated or decelerated, the firing rate on one side increases
while the firing rate on the opposite side decreases -> normally equal and opposite
● Vestibular asymmetry -> brain “sees” the diff. In firing rate and interprets this as continued movement ->
illusion of motion occurs
○ Rotational receptor asymmetry -> rotational vertigo
○ Gravitational receptor asymmetry -> tilting, being pushed, the floor falling out from under them, or
tilting type of perception
● Episodic dizziness is consistent with BPPV, vestibular migraine, superior semicircular canal dehiscence, or
meniere disease
● More constant symptoms are typical of a peripheral vestibular loss or increased motion sensitivity

Vestibular physiology

● The canals signal head rotations and the otolith organs signal linear accelerations
● Linear accelerations can be caused both byy tilting relative to gravity and linear movements
● Most afferent fibers leading from each vestibular end-organ maintain a baseline spontaneous firing rate of
between 10 - 100 spikes/sc
○ Rate depends on the direction of deflection of ciliary bundles of the HC connected to the nerve,
creating a “push-pull” system allowing each afferent to signal excitatory or inhibitory stimuli
● Due to inertia, endolymph in the canal stays in place as the head rotates -> pressure diff. Across the cupula
-> occludes the canal -> pressure diff. deflects the cupula and the angle of the cilia in the underlying crista
-> affecting firing rate of individual vestibular afferents
● The uniform direction of the HC causes each canal to have an excitatory and an inhibitory direction of
rotation
 ○ Afferents leading from the left HSCC fire faster when the head is rotated to the left; slower
when to the right
● The canals on each side are orthogonal to e/o
○ The parallel pairs consist of the two horizontal (lateral), the left superior (anterior) and right
posterior, the superior and left posterior canals
○ Any time a head motion increases one canal’s firing rate, the afferents in that canal’s parallel
partner on the opposite side fire more slowly
● The HC on the neuroepithelial surface (macula) are not parallel to e/o
○ Linear acc. Can excite and inhibit many HC at a time across various areas -> inc. by the presence of
striola (zone of reversal) -> HC on facing sides of the striola are stimulated by linear acc. In
approximately opposite direction

Meniere disease

● When no cause can be identified, the condition is called meniere disease

● Usually present unilaterally, with estimates of contralateral involvement ranging from 2 - 78%

Presentation

● Vertigo is rotational, recurrent, lasts 20 mins to 2

hours, is spontaneous rather than provoked by
particular event
● Vertigo occurs w/o other neurologic symptoms
● Hearing loss is sensorineural, predominantly at low
frequencies, and fluctuates in severity
● Hearing threshold may improve following attack of
vertigo
● Typically unilateral and worsen with time, with
progressively less likelihood of normal hearing loss
● Hearing loss may be due to eustachian tube
dysfunction or serous otitis media
● Aural fullness may be present at all the time
● Tinnitus is generally low pitched and is often
described as a rumble, machine sound, ocean/seashell,
hum, or low buzzing
● Tinnitus lateralized to the same side as the hearing
and vestibular loss

Evaluation and diagnostic testing

● Electrocochleography can be useful in the diagnosis of endolymphatic hydrops (EH)

○ Cochlea responds to repeated presentations of sound with a summating potential (SP) and an action
potential (AP)
○ SP has been reported to be larger and more negative -> reflect the distention of the basilar
membrane into the scala tympani -> increase in the normal asymmetry of its vibration
● Contrast-enhanced MRI can reveal the endolymphatic and perilymphatic compartments
Disease of ENT

Inner ear fluid

Membranous labyrinth

Cochlear duct
● The basilar membrane -> support organ of corti
● Reissner’s membrane -> separated it from scala vestibuli
● Stria vascularis -> vascular epithelium and secretion of
endolymph
● Connected to the saccule by ductus reuniens
● Length of basilar membrane increased (from basal coil ->
apical coil) -> higher frequencies are heard at the basal;
low frequencies at apical
Utricle and saccule
● Utricle lies in the posterior part of bony vestibule
● Five opening of the 3 SCD
● Connected to the saccule thru utriculosaccular duct
● Sensory epithelium of utricle & saccule -> macula -> linear
acc. And de-acc
● Saccule lies in the bony vestibule, anterior to the utricle
and opposite the stapes footplate
Semicircular ducts
● ampullated end of each duct contains neuroepithelium
(crista ampullaris)
Endolymphatic duct and sac
● ED is formed by the union of two ducts (1 saccule, 1
utricle). Terminal part of SD is dilated to perform ES. ES
lies between 2 layers of dura on the posterior surface of
the petrous bone

Inner fluid and their circulation

Perilymph
● Resembles ECF and is rich in Na+
● Fills the space between the bony and membranous labyrinth
● Communicates with CSF thru the aqueduct of cochlea which
opens into the scala tympani
● This duct contains connective tissue resembling arachnoid ->
perilymph percolates
● It is a filtrate of blood serum and is formed by capillaries of
the spiral ligament
● A direct continuation of CSF and reaches the labyrinth via
aqueduct of cochlea
 Endolymph
● Fills the entire membranous labyrinth
● Resembles ICF -> rich in K+
● Secreted by secretory cells of the stria vascularis & dark
cells (utricle and near the crista ampullaris)
● Longitudinal flow -> endolymph from the cochlea reaches
saccule, utricle, ED and gets absorbed thru ES which lies in
the subdural space
● Radial flow -> endolymph is secreted by stria vascularis and
gets absorbed by the stria vascularis -> presumes that ES is a
vestigial structure and plays no part in endolymph absorption

Meniere disease

● Disorder of the inner ear where the endolymphatic system is distended with endolymph

Pathology

● The main pathology is distention of the

endolymphatic system, mainly affecting the
cochlear duct (scala media) and the saccule, and to
a lesser extent the utricle and SCC
● The dilatation of cochlear duct is such that it may
completely fill the scala vestibuli
● There is marked bulging of Reissner’s membrane,
which may even herniate thru the helicotrema into
the apical part of scala tympani
● The distended saccule may come to lie against the
stapes footplate
● The utricle and saccule may show outpouching into
the SCC

Aetiology

● Increased production of endolymph / faulty absorption

-> Distension of endolymphatic system due to increased
volume of endolymph
● Defective absorption by endolymphatic sac
○ Endolymph is carried by the endolymphatic duct to the
sac where it is absorbed
○ Defective absorption by the sac may be responsible for
raised endolymph pressure
○ Experimental obstruction of ES and ED also produces EH
○ Poor vascularity -> defective absorption -> Ischemia of
sac
 ○ Distension of membranous labyrinth -> rupture of
reissner’s membrane -> mixing of perilymph with
endolymph -> vertigo

● Vasomotor disturbance
○ Sympathetic overactivity resulting in spasm of internal auditory artery and its branches ->
interfering with the function of cochlear / vestibular sensory neuroepithelium -> deafness and
vertigo
○ Anoxia of capillaries of stria vascularis -> increased permeability -> transudation of fluid ->
increased production of endolymph
● Allergy
○ Inner ear act as shock organ producing excess endolymph
● Sodium and water retention
○ Excessive amount of fluid are retained leading to EH

Clinical features

● Disease is commonly seen in the age group of 35 - 60 years. Males are affected more than females
● Vertigo
○ Attacks come in clusters, with periods of spontaneous remission lasting for weeks, months, or years
○ Usually accompanied by nausea and vomiting with ataxia and nystagmus
○ Severe attacks -> vagal disturbances (abdominal cramps, diarrhea, cold sweaters, pallor, and
bradycardia)
○ Tullio phenomenon = loud sounds or noise produce vertigo -> distended saccule lying against the
stapes footplate
● Hearing loss
○ With recurrent attacks, improvement in hearing during remission may not be complete -> slow and
progressive deterioration of hearing
○ Distortion of sound -> a tone of particular frequency may appear normal in one ear and of higher
pitch in other -> diplacusis
○ Intolerance to loud sounds -> cant tolerate amplification of sounds -> recruitment phenomenon
● Other features = show signs of emotional upset -> apprehension of the repetition of attacks

Examination

● Otoscopy = no abnormality is seen in the TM

● Nystagmus = seen only during acute attach -> towards the unaffected ear
● Tuning fork tests = indicate SNHL; rinne test (+), absolute bone conduction is reduced in the affected ear,
weber lateralized to the better ear
Investigations

● Pure tone audiometry -> SNHL. lower frequencies are affected and the curve is of rising type
● Speech audiometry -> discrimination score is usually 55 - 85%, discrimination ability is much impaired during
and immediately following an attach
● Special audiometry test -> indicate cochlear nature of disease
○ Recruitment test (+)
○ SISI (short increment sensitivity index) is > 70%
○ Tone decay test -> decay of less than 20 dB
● Electrocochleography -> SP/AP ration > 30%
● Caloric test
○ Shows reduced response on the affected side
○ Reveals canal paresis on the affected site
● Glycerol test -> dehydrating agent. When given orally, reduces endolymph pressure -> improvement in
hearing

Variants of meniere disease

Cochlear hydrops
● Vertigo is absent
● There is block at the level of ductus reuniens -> confining the
increase endolymph in cochlea only
Vestibular hydrops
● Typical attacks of episodic vertigo while cochlear function remain
normal
● With time typical symptoms of meniere will appear
Drop attacks (Tumarkin’s otolithic crisis)
● Sudden drop attack without loss of consciousness
● No vertigo or fluctuation of hearing loss
● Feeling of having been pushed to the ground -> poleaxed
● Occurs in early or late course of disease
Lermoyez syndrome
● Symptoms are seen in reverse order
● Progressive deterioration of hearing -> attack of vertigo
Treatment

General measures

● Reassurance -> particularly impt. In acute attack

● Cessation of smoking -> nicotine causes vasospasm
● Low salt diet -> no extra salt should be permitted (not exceed 1.5 - 2.0 g/day)
● Avoid excessive intake of water
● Avoid overindulgence in coffee, tea, and alcohol
● Avoid stress
● Avoid activities requiring good body balance

Management of acute attack

● Severe vertigo with nausea and vomiting -> head movements provoke giddiness
● Reassurance
● Bed rest -> head supported on pillows to prevent excessive movements
● Vestibular sedatives to relieve vertigo (dimenhydrinate, promethazine theoclate, prochlorperazine)
○ Diazepam IV 5 - 10 mg -> tranquilizing effect -> suppresses the activity of medial vestibular nucleus
● Vasodilators
○ Inhalation of carbogen (5% CO2 and 95% O2) -> good cerebral vasodilator and improves
labyrinthine circulation
○ Histamine drip -> histamine diphosphate 2.75 mg fisdolive in 500 ml glucose -> IV drip at slow rate

Management of chronic phase

● Vasodilators
○ nicotinic acid 50 mg, taken about an hour before meals, 3x a day
○ Betahistine (vertin) 8 - 16 mg, 3x a day, PO -> increases labyrinthine blood flow -> releasing
histamine
● Vestibular sedatives -> prochlorperazine, 10 mg, 3x a day, PO for 2 months
● Diuretics -> diuretic furosemide, 40 mg tablet, taken on alternate days with potassium supplement -> helps
to control recurrent attacks
● Propantheline bromide (probantine) -> 15 mg, 3x a day, alone or in combination with vasodilator
● Intratympanic gentamicin
○ Gentamicin is mainly vestibulotoxic
○ Absorbed thru the round window -> destruction of the vestibular labyrinth
○ Hearing loss sometimes severe and profound occurs
● Microwick
○ Meant to deliver drugs from the external ear to the inner ear -> avoid repeated intratympanic
injection
○ Requires a tympanostomy tube -> inserted to TM -> wick is passed through it
○ Deliver steroids in sudden deafness and gentamicin

Surgical treatment

● Conservative procedures -> vertigo is disabling but hearing is still useful and needs to be preserved
○ Decompression of endolymphatic sac
○ Endolymphatic sac operation -> tube is put, connecting ES with SAS
 ○ Sacculotomy (fick’s operation) -> puncturing of saccule with a needle thru stapes footplate
○ Cody’s tack operation -> placing a stainless steel tack thru stapes footplate
○ Cochleosacculotomy -> cochlear duct is punctured and drained into the perilymph
○ Section of vestibular nerve -> nerve is exposed by retrosigmoid or middle cranial fossa approach
and selectively sectioned
○ Ultrasonic destruction of vestibular labyrinth
● Destructive procedures -> totally destroy cochlear and vestibular function; only when cochlear function is
not serviceable
○ Labyrinthectomy -> membranous labyrinth is completely destroyed either by opening thru the LSCC
by transmastoid route / thru oval window by transcanal
● Intermittent low-pressure pulse therapy (meniette device therapy)

● Perform a myringotomy and insert ventilation tube so that the device when coupled to external ear canal
can deliver pressure waves to the round window membrane via the ventilation tube
● Pressure waves pass thru the perilymph -> redistributing endolymph thru ES or the BV -> reduction in
endolymph pressure

A Hypothetical Proposal for Association between Migraine and Meniere’s Disease (2020)

● Hypothesis -> MD a migraine related phenomenon, with both conditions united by a common unknown, though
potentially vasculogenic or related to spreading cortical depression, pathophysiology of risk factor that can
predispose to development of both diseases
● As part of migraine attack, spreading cortical depression -> release of neuropeptides and cytokines
(calcitonin gene-related peptide and substance P) from the trigeminal ganglion -> vasodilation, increased
vascular permeability, and extravasation of plasma -> neurogenic inflammation and pain in migraine
● Response of inner ears with EH to substance P differs from non-hydropic inner ears
● Chronically hydropic ears -> lose their ability to autoregulate their vasculature and blood flow -> existing
neuropeptide and vasomotor dysfunction in the trigeminal nerve (migraine) -> MD
● MD and migraine share common triggering factors: stress, weather change, and dietary intake
● Stress -> ability of steroids to increase the frequency of spreading cortical depression in the presence of
certain genetic mutations
● Fluctuations in estrogen -> spreading cortical depression -> can provoke migraine
● Tyramine and caffeine -> vasoconstrictors and hypertensive agents
● Caffeine promote vasoconstriction and decreased blood flow -> normally compensated by adenosine
receptors -> long term use ->> impaired autoregulation of blood flow in hydropic ears -> prevent adaptation
and allow for easier provocation -> migraine and MD
Maqbool Textbook of ENT 9th Edition

Differential diagnosis of meniere disease

Eight nerve tumour (acoustic neuroma)

● Difficult to differentiate esp. In early stages -> only
otological symptoms
● Progressive unilateral SNHL associated with tinnitus
and diminished caloric response
● Vertigo is neither marked nor paroxysmal
● Audiometry -> retrocochlear lesion
Vestibular neuronitis
● Vertigo of sudden onset
● Sometimes occurring in small epidemics
● Recent history of upper respiratory tract infection
● Usually unilateral
● Caloric response are diminished but hearing tests are
normal
BPPV
● Recurring attacks of vertigo -> induced by change in
position
● Neurological examination is normal
● Hearing is usually unaffected
● Caloric tests are usually normal
● Vertigo and nystagmus that develop when head is
placed in a particular position
Epileptic vertigo
● Cases of epilepsy may present with an attack of vertigo
● Loss of consciousness, fits, and normal hearing
Vertebrobasilar insufficiency
● Transient episodes of ischaemia occur in the
distribution of vertebrobasilar arterial system may
present with vertigo and tinnitus
● Diplopia, ipsilateral ataxia, facial paralysis and
homonymous hemianopia -> lesion in the vascular system
Clinical Hints and Precipitating Factors in Patients Suffering from Meniere’s Disease (2010)

Treatment

● Recommendation to restrict sodium intake was originally conceived as a way of reducing fluid retention in
the inner ear
● Perspiring and subsequent fluid replacement is another potential source of inner ear stress
● Caffeine and alcohol -> large fluid shifts the physiologic fluid compartments
● Diuretics affect ion pumps and ionic gradients in the ear as well as in the kidney

Cytokines and Inflammation in Meniere Disease (2021)

Theory of immune involvement in the inner ear

● Sudden bilateral hearing loss could be associated with the production of anti-cochlear antibodies
● The clinical presentation of SNHL can be quite variable, often overlapping with other disorders such a MD
or deafness autosomal dominant 9 (DFNA9)
● DFNA9 is caused by pathogenic variants in the COCH gene, which encode cochlin
● Cochlin -> major component of the ECM in both the cochlea and vestibule of the inner ear, is a potential
candidate antigen for autoimmune inner ear disease (AIED)
● DFNA9 with or without vestibular abnormalities related to inner ear immunity and stimulation of the
secretion on inflammatory cytokines

Autoimmune MD

● Hypothesis: bystander damage, cross-reactions, intolerance, genetic factors

● Antibodies or rogue T-cells may cause accidents inner ear damage -> shares common antigen with a
potentially harmful substances, virus, fungus, bacterium -> AIED
● The body may not recognize all inner ear antigens. The body may wrongly attack the “foreign” antigens
● Eh can be induced experimentally by injection of antigens or monoclonal antibodies
● The deposition of circulating immune complexes (CIC) could produce inflammation and interfere with the
capability of ES filtering
● Autoantibodies has been found in MD patients sera

Cytokines in the inner ear

● Immune responsiveness in the inner ear was initially associated with ES since it possesses immunological
capacities and is responsible for major party of the trans-epithelial ion transport occurring within the inner
ear
● Macrophage of the stria vascularis, spiral ligament, and SG expressed MHC II
● Co-expression of IBA1 and MHCII in epithelial cells and transepithelial migration -> Uptake and processing
of antigens from the ES lumen
● ES-> Cellular and humoral innate immune-system (TLR 4 and 7, beta-defensin, lactoferrin)
● Autoinflammatory diseases are triggered by an overactive inflammatory response -> immune dysregulation
fundamentally mediated by IL-1 beta, IFN-1, and NF-kB
 TNF-alpha
● Mainly secreted by macrophages
● Induces the infiltration of immunocompetent cells into
the tissues and amplifies the immune response
● Potent pyrogen by direct stimulation of IL-1 secretion,
and under certain conditions it can stimulate cell
proliferation and induce cell differentiation
● Upregulates the expression of protein phosphatase 1 ->
dephosphorylates the key Ser418 residue of FOXP3 ->
inactivating FOXP3band rendering Treg cells
functionally defective
● TNF-alpha and IL-6 significantly elevated with sudden
SNHL and progressive SNHL
IL-1 Beta
● Produced by monocytes as an inactive 31kDa precursor
-> pro-IL-1 beta, in response to molecular motifs
carried by pathogens referred to as PAMPs
● pro-IL-1 Beta is cleaved by the protease caspase-1
● Activation of caspase -1 -> recruitment of
inflammasome -> active 17kDa form of IL-1 Beta
● Early immune response to PAMPs may drive many of
the later adaptive T cell responses that maintain the
disease
● IL-1 beta -> key proinflammatory cytokine
● The absence of expression of IL-1 receptor antagonist
(IL-1Ra) could promote development of AD
● SNHL has been observed as a component of clinical
diseases involving IL-1 beta dysregulation

Cytokines and MD

● Basal levels of the proinflammatory cytokines TNF-alpha, IL1- beta, and IL-6 could be increased in some
MD patients

Endolymphatic Hydrops: Mechanical Causes of Hearing Loss (1976)

● EH in the early stages of the disease is of the low-frequency, fluctuating type -> hearing loss might vary in
some proportion to the endolymphatic/perilymphatic pressure diff. Or to the volume of the cochlear duct
● Biochemical standpoint the separation is give by Reissner’s membrane on the side and the reticular
membrane on the other
● Structural standpoint, the restoring force of the partition between scala media and scala tympani is basilar
membrane
● Basilar membrane is an elastic structure and its compliance varies systematically from base to apex
● The stiffness gradient of the BM that is the basic structural property required for the generation the
traveling waves of the Bekesy type
● Reissner’s membrane is elastic only as long as its distention doesn’t last for too long
 ● Most connective tissue membranes possess visco-elastic properties -> on short lasting distension, they
react manly in an elastic manner, but with increasing time duration the viscous component come more and
more to the fore
● As soon as the less resistant of the two membrane become over extended (RM) -> endolymphatic system as
a whole can no longer be elastically biased
● Acute hydrops -> endolymphatic/perilymphatic pressure difference with volume increment of the cochlear
duct playing a lesser role
● Chronic hydrops -> the volume increment of the cochlear duct is the sole governing factor
● RM was made uniformly compliant, but less stiff than the BM
● Acute episodes -> the pitch in involved ear first becomes higher than that in the other one (elastic bias);
later on, when the attack subsides, the pitch becomes lower (mass bias)
● As soon as the mass bias become the sole governing factor -> flat sensitivity loss; diplacusis is also present,
with the shifts taking place in the direction of cochlear apex toward lower frequencies; distortion does not
occur anymore because the membranes are no longer elastically biased
● Increased noise level at the HC input, an increment of 55 dB -> partial decoup;in of the stereocilia from the
TM -> tinnitus
● The static displacement of BM that is brought about during acute episodes of EH (elastic bias) produces a
sharing displacement between the TM and the organ of corti -> should over-extend the tenuous junctions
between the stereocilia and the TM -> partial decoupling of these junctions
● Decoupling will increase the degree of the sensitivity loss
● Tinnitus -> the brownian motion in front of the tympanic membrane produces a broad-band noise -> noise
enters the cochlea -> frequency components are distributed along the partition in accordance with the
place principle -> decoupling is maximal in the region where the BM displacement is largest (apical region) ->
noise perceived as band-limited, low frequency noise

The Basic Science of Meniere’s Disease and Endolymphatic Hydrops (2005)

The role of intralabyrinthine fluid dynamics

● Longitudinal flow theory = endolymph is produced in the cochlear duct and flows in an unidirectional pattern
towards the ES -> resorption occurs
● Interruption of this flow results in accumulation of endolymph in the upstream compartment and
development of hydrops
● Longitudinal endolymph flow in the normal cochlea was in the range of 0.004 - 0.007 mm/min, which is
insignificant for the purpose of ionic homeostasis
● Control of endolymph homeostasis is distributed throughout the endolymphatic space -> favoring radial
theory
● Radial flow theory = endolymph is produced and absorbed throughout the endolymphatic space
● Radial flow is regulated by local factors, implicating the role of various molecules and ion channels in
endolymph homeostasis
● Endolymphatic compartment is regulated by unidirectional membranous valve -> endolymphatic sinus
● Anatomically explained by the collapse and obliteration of endolymphatic sinus blocking access of the ES.
● Withdrawal of fluid -> expansion of the sinus -> access of ions to the ES
● Changes in auditory threshold and endolymphatic potassium concentration were minimal and that alteration
in the AP threshold occurred at exposure levels below those inducing endolymph volume disturbances
 ● These findings suggest that volume change (hydrops) is the results and not the cause of the alteration seen
in the cochlear transducer
● The potassium cycle necessitates a recirculation pathway that involves multiple ionic channels, gap junction,
and tight junctions
● In the cochlea, K+ flows into HC via apical transduction channels -> transported back to the stria vascularis
by type I and type II fibrocytes located in the spiral ligament, a transport facilitated by intercellular gap
junctions (comprised of connexin proteins)
● K+ is released from the intermediate cells of the stria vascularis into the industrial space via KCNJ10
channels -> taken up by the basolateral membrane of marginal cells via ion channels NKCCL and Na+/K+
ATPase -> secrete K+ into the endolymph -> endocohlear potential -> cycle completed

Histopathology of Meniere’s Disease (2016)

Anatomical considerations

● In the cochlea, the scala media is filled with endolymph, whereas the scala tympani and the scala vestibuli
contain perilymph
● Two other tubular structures - saccular duct and utricular duct - joins in a single fusiform membranous
structure (the endolymphatic sinus) that lies in a groove on the posteromedial surface of the vestibuli
● In the proximal opening of the utricular duct, the sli-shaped utriculo-endolymphatic valve (Bast valve)
seems to control the inflow of ED and ES.
○ Bast valve seems to be passively activated in response to sudden decreases in the pressure
structures of the pars superior -> preventing those structures from working properly
● The inferior portion of the endolymphatic sinus connects to the ED -> membranous structure that runs
inside of the petrous bone thru a bony canal, the vestibular aqueduct
● The ED ends in ES -> invaaginaation of the dura mater, leaving the temporal bone in the level of the foveate
fossa
● The ES can be divided into 3 portions based on the cellular lining:
○ The proximal (rugose), which lies within the vestibular aqueduct and is constituted by the same
epithelia of the ED
○ The intermediate, partly inside of the vestibular aqueduct and partly between layers of dura, which
consists of cuboidal cells
○ The distal, which lies within layers of dura mater and is lined by cuboidal cells

Endolymph production and regulation

● Radial (a rapid, ongoing process) -> energy metabolism and ion exchange around the sensory cell regions
● Longitudinal (slow) flow, which enables reabsorption of endolymph and disposal of high molecular waste
products and debris by the ES

Histopathology
 ● Observed dilation of the scala
media of the cochlea, with
displacement of Reissner
membrane into the vestibular
scala (EH)

● Severe cases -> Reissner

membrane bulge into the
helicotrema, -> the saccule ->
SCC (esp. HSCC) -> footplate
of the stapes

1 = saccule; 2 = utricle; 3 = LSCC; 4 =

PSCC; 5 = footplate of staps; 6 =
facial nerve; 7 = basal turn of the
cochlea; 8 = internal auditory canal; 9
= vestibular aqueduct and ED
Arrow = severe saccular dilatation

● The hair cells may or may not

further degenerate in the
organ of corti and in the
macula and crista ampullaris
of the vestibular system

1 = tectorial membrane; 2 = inner hair

cell; 3 = loss of the 3 rows of outer
hair cells -> A

● Bilateral ischemia of the stria

vascularis

Arrow = atrophy of stria vascularis

 ● Fibrous tissue proliferation
with the vestibule
● Focal loss of neurons
● Degeneration of the dendrite
in the upper middle and apical
turns of the cochlea

● Blockage of the ductus

reuniens

Upper B = open ductus reuniens

Lower B = blocked ductus reuniens

● Cupulolithiasis

Arrow = deposit on the cupula of the

crista ampullaris, cupulolithiasis in
the PSCC

● Hypoplasia of the vestibular

aqueduct
● Hypodevelopment of the
Trautmann trial, and altered
relationship between the
position of the posterior
fossa dural plate and the
position of the ES, and
aberrant (lateral)
displacement of the lateral
venous sinus

A= hypoplasia; B = normal
A = otosclerotic foci involving the
body areas around the cochlea of
vestibule -> blocking vestibular
aqueduct

A = severe otosclerosis involving the

inner ear -> distortion of the cochlea

B = severe distortion of the cochlea;

signs of EH -> dilation of the RM into
the scala vestibuli

A) Degeneration of organ corti,

focal areas of fibrous
proliferation and new bone
formation and EH
Squared = basal turn of
cochlea
B) Basal turn of cochlea showing
the presence of inflammatory
cells in the scala media and
scala vestibuli -> bulging of
the RM

1 = retraction pocket; 2 = fibrous

tissue; 3 = serous effusion; 4 =
tumoral cells; arrow = EH
 ● Bast valve seems to function
as a physiological mechanism
to prevent pars superior from
collapsing in case of sudden
decreased in its volume

A = open bast valve; B = closed bast

valve

Causative mechanisms

● Systemic administration of isotoprenol (a beta adrenergic agonist) increased endolymph pressure and
decreased the potential size of the sac’s lumen
● Longitudinal blockage (in the ED or bast valve) acts as dam, increasing retrograde volume and endolymph
pressure
● Given the distensible nature of its walls, associated with its position at the entrance of the ED, the sinus
might act as a reservoir
● Distended sinus could block the entrance of the ED by compressing bast valve
● Valve could open in response to increased pressure in the ES and ED -> allowing excess of endolymph to flow
backward
● Progression of MD and further impairment of the absorptive mechanisms of the sac could prevent it from
closing -> sensory epithelia could be more vulnerable to pressure changes -> vestibular symptoms
● Several enlarged saccules can also dislocate the utricular walls toward bast valve -> appear blocked
● Volume receptors in the inner ear -> inner ear can regulate the release of vasopressin
● Increased blood viscosity can result in inner ear dysfunction -> hearing loss, tinnitus, vertigo

Hypothetical Mechanism for Vertigo in Meniere’s Disease (2010)

The physiologic of the ES and its role in longitudinal endolymph flow

● The ES secreted various substances, including aquaporins, glycoproteins, and even endolymph
● Glycoprotein is highly hydrophilic
○ Studied suggests that when longitudinal flow occurs, the glycoprotein is rapidly eaten away by
phagocytic activity
○ Glycoprotein is both produced and eaten away to cause longitudinal flow
● If excess endolymph volume occurs, this is reabsorbed back into the stria vascularis (radial flow)
● When there is a large volume increase -> endolymph move longitudinally to the ES
● People can maintain balance of endolymph by the radial mechanism alone
● The rate of longitudinal flow is restricted by the isthmus of the ED
Cochlear function before, during, and after vertigo attacks

● If a rupture or leakage of K+ thru the RM occurs, the endocochlear potential should crash -> severe loss of
hearing

C) ES secretes and macrophages

gobble away the glycoprotein ->
promote longitudinal flow of
endolymph
D) Meniere’s ear has a narrow
vestibular duct

● The increased volume of

endolymph in the utricle
stretches the cristae of the SCC
-> vertigo
● As the excess endolymph is
cleared, the amount of excess
endolymph decrease -> stretched
cristae reduce in size -> altering
the direction of the nystagmus
● As the disease progresses, the
functionality of the ES decreases
-> cellular damage resulting from
the frequent secretion of
glycoprotein -> attacks become
less severe
● The volume of endolymph
remaining in the cochlear duct
after each episode increases →
hearing deteriorates
● The valve of bast remains patent,
if there is any longitudinal flow ->
sudden drainage of endolymph
from the utricle -> drop attacks
(Tumarkin attacks

Etiology, Pathophysiology of Symptoms, and Pathogenesis of Meniere’s Disease (2002)

Endolymphatic malabsorption due

to physical or chemical obstruction
(“dam”)
 ● Drainage of endolymph toward the ES is an active process
● Osmotic gradients within the sac create longitudinal flow toward the sac
○ If the sac doesn;t receive enough endolymph because of an obstruction -> hormones (saccin) that
increase the production of endolymph
○ ES also produce glycoproteins that osmotically attract endolymph toward ES
○ When enough endolymph build up behind the obstruction -> sudden outflow across the obstruction
toward ES -> vertigo
○ EH in MD is a primary dysfunction of longitudinal flow
● Characteristic features in MD patients:
○ Lack of periaqueductal pneumatization
○ Lack of pneumatization medial to the arcuate eminence
○ Short vestibular aqueduct
○ Narrow external apertures of the vestibular aqueduct
○ Reduction in size of the mastoid air-cell system
● Endolymphatic malabsorption over a long period iif time -> developmental abnormality of the ED and ES in
association with a displaced lateral snus
● Unimpeded venous drainage of the vestibular system thru the paravestibular canaliculi vein is an important
aspect of homeostasis of fluids of the inner ear
● Abnormalities of the vasculature may contribute to the quantity of EH
● Osteogenesis, fibrosis, and granulation tissue -> greatly tightened dura, Trautmann’s triangle, and region
near the sac -> resultant pressure and obstruction of the area

Pathophysiology

● Attack of vertigo in MD -> simultaneous rupture of the cochlear duct and the saccule -> cochlear and
vestibular symptoms
● In advanced MD -> EH is seen in the scala media and saccule, vestibuli, and the scala vestibuli
● In advanced MD -> displacement of perilymph reduces radial flow and causes the longitudinal flow to
become dominant
○ Utricle or cochlear duct will less often extend to occupy the vestibule
● Saccule seems to function as a reservoir for endolymph trying to reach the ED and ES for outflow ->
stagnation of endolymphatic outflow occurs -> distention can mechanically interfere with traveling waves ->
changing cochlear function

Pathogenesis

Intrinsic or genetic

● Hypoplasia of mastoid air cells

● Hypoplasia of the vestibular aqueduct and ac
● Reduction or absence of Trautmann’s triangle and anteromedial displacement of sigmoid sinus
● Hypoplasia of the aditus ad antrum and the suprapyramidal (facial recess in contiguity)
Meniere Disease

Differential diagnosis

● Basilar migraine : Associated with vertigo but without aural symptoms

● Vestibular neuronitis : Associated with vertigo lasting for several days, no aural symptoms
● BPPV : Associated with vertigo related to head movements, lasting seconds to minutes, no aural symptoms
● Central vertigo : causes include stroke, multiple sclerosis, seizure disorders, other
● Peripheral vertigo of non-otogenic origin: Commonly seen in elderly patients with peripheral neuropathy and
deconditioning

Meniere’s Disease (2012)

Overproduction of endolymph

● Presence of 2 osmotic gradients in the cochlea

○ Between perilymphatic space and ES
○ Inside the endolymphatic space between the apex and the base of the cochlea

Possible local causes

● Endolymphatic sector hypertension would lead to a rupture of the membranous labyrinth -> blend of
perilymph and endolymph fluids -> decrease K+ levels in endolymph sector -> increase K+ levels in
perilymphatic sector
● Followed by a depolarization of vestibular nerve fibers -> irritative vestibular syndrome
● The absence of repolarisation would explain the decreased vestibular excitability observed secondarily

Role of the CNS

● Vertigo is thought to result from a functional imbalance between the labyrinths of the 2 ears
● NT in central compensatory mechanisms -> histamine, acetylcholine, and GABA
● The post-synaptic histamine H1 and H2 receptors and the pre-synaptic H3 receptors -> present in the
vestibular nuclei
● Histamine modulates vestibular nuclei neuron activity via H1 and H2 receptors
● Increase in histamine synthesis and release by the tuberomammillary neurons projecting to the vestibular
nuclei, promoting vestibular recovery
● Cholinergic receptors have been also identified in the vestibular nuclei and the midbrain
● Vestibular compensatory process -> modification of cholinergic brainstem synapses occurs -> new synapses
with an asymmetric pattern of distribution both in number and sensitivity
● The afferent neurons fire again at a normal rate under the control of the contralateral non-damaged
labyrinth
● At the same time, inhibitory synapses coming from the cerebellar Purkinje cells are mediated, at the
vestibular nuclei level, via GABA
Pharmacological treatment

Benzodiazepines (Diazepam)

● Central vestibular sedative effect

● Benzodiazepines act on the cerebellar GABA-ergic system that mediates inhibition on the vestibular
response -> bind to a specific site on the GABA receptor to potentiate the effect of the endogenous ligand
● Effect may offer benefits for vertigo and emesis

Antiemetic agents

● Controlling the MD bt reducing stress and anxiety, and treating nausea

● Sedative, anticholinergic, and antiemetic properties
● Meclizine = the antivertiginous and antiemetic effects are believed to be linked to a decrease in the
excitability of the middle ear labyrinth and an inhibition of conduction in the middle ear
vestibular-cerebellar pathways -> 25 to 100 mg/day in divided doses
● Dimenhydrinate = an antihistamine; preventing and treating vertigo associated with MD, as well as nausea
and vomiting -> PO of 50 to 100mg, 3 - 4 times daily
● Metoclopramide = antidopaminergic drug; doesn’t cross the blood-brain barrier, but exerts its antiemetic
property at the area prostema of the brainstem -> for acute treatment, 20 - 40 mg/day in 2 - 3 doses
● Promethazine = phenothiazine with pronounced antihistaminic properties in addition to a strong
anticholinergic activity; significant dopamine blocking activity

Vasodilators

● Betahistine blocks H1 and H3 receptors -> increase cochlear blood flow

Diuretics

● Acetazolamide = carbonic anhydrase inhibitor; induce diuresis by virtue of a decrease in sodium-hydrogen

exchange in the renal tubules

Meniere’s Disease

● The spiral ganglions and the

scarpa ganglion contain
bipolar neurons connected to
sensory cells in the cochlea
and vestibular apparatus
● Cochlea consists of the scala
vestibuli and scala tympani,
which are filled with
perilymph, and the scala
media, which is filled with
endolymph
Clinical symptoms

Hearing loss

● The OHC of basilar membrane amplify the stimuli and transmit the fluid vibration to the IHC
● The BM is wider and softer in the apex than in the vase of the cochlea
● Distention of the membranes in EH start within the apex -> hearing loss too
● The suggested mechanism for low-tone hearing loss and fluctuating hearing loss indicated that EH disturbs
sound transmission in the inner ear -> bulging of the BM

Vertigo

● Abnormal excitability or cessation of sensory input from the affected ear as a result of fluid disturbance
in the inner ear
● Nausea and vomiting is mediated by the fastigial nucleus in the cerebellum and the nucleus of the solitary
tract in the brainstem
● Lermoyez syndrome = movement of endolymph from the cochlea towards the SCC -> reduction of EH in the
cochlea; increase in EH SCC
● Tumarkin attacks = otolith organs disorders in the utricle and saccule

Pathology and Pathophysiology of Meniere’s Disease (2002)

Histopathology

The organ of corti and the cochlear nerve

● Patients with SNHL -> loss of cochlear HC and spiral GC, mainly in the apical turn of cochlea
● Primary dendritic neuronal degenerations spreads in a broad range along the cochlea -> decrease
innervation density of HC
● Patients with EH -> the permanent threshold shift of hearing is related to degeneration of sensory
elements
● Damage to GC rather than damage to sensory HC is directly associated with the initiation and
progression of symptoms

Stria Vascularis
● Significantly atrophic in MD
● Poor vascularity in the stria vascularis is significantly
correlated with strial atrophy in MD
● Stria vascularis -> organ that changes the perilymph
coming thru RM into endolymph by ion exchange (radial
flow theory)
● Pathology of SV -> dysregulation of ion change -> EH

Dark cells
● Significantly lower in MD, and many are abnormal
● Present at the periphery of the macula of the utricle and
the cristae of SCC
● Active transport of electrolytes in the vestibular
labyrinth -> production of endolymph
 Vein in paravestibular canaliculus
● The vein in the PVC is one of the two major veins that
drain blood flow from the inner ear
● Starts from the vestibule and runs in PVC adjacent to VA
toward the posterior cranial fossa
● Communicated with the venous plexus of the ES before it
exists the sigmoid sinus, the inferior petrous sinus, or
the jugular bulb

Pneumatization of the petrous bone

● Poor pneumatization appears to be closely associated
with hypoplasia of the VA
● Lateral sinus in MD cases is anteromedially displaced ->
reduces area of Trautmann’s triangle
● Displaced sinus is closely associated with hypo
development of the ED and ES

High jugular bulb

● The jugular bulb is normally located at the base of the temporal bone, inferior to the vestibular
structure and the hypotympanum
● The jugular bulb in its lateral part may be bulging superiorly up to the level of the mesotympanum -> its
bony covering may be thinned or completely lacking
○ Compress the vessels in the rugose part of the ES

Pathophysiology and Treatment of Tinnitus (2014)

● Perception of sound in proximity to the head with the absence of an external source
● Objective tinnitus = generation of noise near the ear
○ Uncommon occurrence -> audible, pulsatile hum and can be caused by turbulent flow thru the carotid
artery or jugular vein
● Subjective tinnitus = perception of sound in the absence of an acoustic stimulus and is heard only b the
patient
Pathophysiology

● Loss of cochlear input to neurons in the central auditory system

(occur in cochlear HC damage or lesion to the vestibulocochlear
nerve -> abnormal neural activity in the auditory cortex
● Loss of suppression of the neural feedback loops which help tune
and reinforce auditory memory in the central auditory cortex ->
disinhibition of normal synapses and the creation of uncontrolled
alternative neural synapses -> tinnitus
● A decrease in inhibition or increase in excitation may lead to an
excitatory-inhibitory imbalance -> neuronal hyperexcitability in
these regions -> tinnitus
Aural Fullness in Meniere’s Disease
● Hyperacusis, tinnitus, drop attacks, and moving difficulties were connected with aural fullness
● Learning to relax -> alleviate aural fullness
● The ophthalmic division of the trigeminal nerve innervate the cochlea and mandibular division of the
middle ear mucosa
● EH may cause aural fullness via sensory trigeminal fibers
● Stimulation of the trigeminal ganglion -> changes in cochlear flow that can restore the fluid dynamics in
endolymphatic space
● Changes in the EH may underlie an increased sensitivity -> further damage from environmental stress
such as noise