MENIERE’S DISEASE

- DR. PRANEETH

CONTENTS

• INTRODUCTION• INCIDENCE• ANATOMY• PATHOGENESIS• INVESTIGATIONS• TREATMENT – MEDICAL & SURGICAL

INTRODUCTION• Meniere’s disease (idiopathic endolymphatic hydrops) is a disorder of

the inner ear where the endolymphatic system is distended with endolymph. • It is characterised by spontaneous, episodic attacks of vertigo;

sensorineural hearing loss which usually fluctuates; tinnitus; and often a sensation of aural fullness.• It is a common cause of the syndrome of spontaneous vertigo. • Despite this well-known symptom complex, it remains a controversial

and often difficult condition to diagnose and treat.

INCIDENCE• Wide variation exists from 17/100000 in the Japanese population to

513/100000 in the southern Finland.• M:F = 2:3• Most common age at presentation is 4th – 5th decade.• Familial occurrence 10 – 20 %. Autosomal dominant. • In familial cases, migraine is found to be more strongly associated. • HLA B8/DR3 & Cw7 have been associated. So, etiology in these

persons may be autoimmune.

ANATOMY OF ENDOLYMPHATIC SYSTEM• Inner ear consists of 2 parts – bony labyrinth & membranous

labyrinth.• Membranous labyrinth is filled with a clear fluid called endolymph

while space between membranous & bony labyrinths is filled with perilymph.• Membranous labyrinth consists of the cochlear duct, the utricle &

saccule, the 3 semi-circular ducts and the endolymphatic duct & sac.

• Cochlear duct is subdivided by two longitudinally running membranes that separate three chambers, the scala tympani, scala media and scala vestibuli.• The scala media is triangular in section, the

other boundaries represented by Reissner's membrane, which runs obliquely with respect to the basilar membrane from a ridge of tissue, the spiral limbus near the modiolus, to the lateral wall that runs along the inside of the bony wall.• The organ of Corti runs in a spiral along the floor

of the scala media, situated on its lower boundary, an acellular layer called the basilar membrane.

• The basilar membrane stretches across the cochlear duct from a bony shelf spiralling around the central bony modiolus, the osseous spiral lamina, to a bony promontory, the spiral prominence on the outer wall of the cochlea. • Cochlear duct widens substantially towards the basal end of the spiral but

the width of the basilar membrane decreases.• Organ of corti extends across the upper surface of basilar membrane from

the spiral limbus situated over the osseous spiral lamina to the Claudius cells that lie between the edge of the sensory region and the outer anchorage of the basilar membrane. • Underneath the basilar membrane is a layer of spindle shaped cells, the tympanic cells, whose long axes are orientated in an apical-basal direction along the cochlea. A branching spiral vessel lies under the basilar membrane.

• Reissner’s membrane consists of 2 layers of cells separated by a basement membrane.• The layer facing into the scala tympani is mesothelial cell layer and other layer facing scala media is the endothelial layer• Cells within each layer are joined by tight junctions which act as an impermeable barrier to ions and small molecules.• Stria vascularis is present on the lateral wall and consists of 3 layers of cells

composed of marginal cells, intermediate cells and basal cells. These cells have a variety of ion pumps, enzymes and transport proteins associated with homeostatic mechanisms for maintaining ionic composition of cochlear fluids.

• Fluid in scala media, endolymph contains high potassium and low sodium at an unusually high positive electrical potential (+80mV) called the endolymphatic potential (EP). This contrasts with the scala tympani and scala vestibuli, both of which are filled with perilymph that has high sodium and 0mV EP. • At the apex of cochlea, the 2 outer chambers are joined by an aperture called

helicotrema.• Maintenance of EP is crucial to hearing.• As with both the stria vascularis and reissner’s membrane, the cells of the organ

of corti facing scala media are joined by tight junctions. Thus the whole of the scala media is electrically and chemically isolated from other scalae, the only communication being through ion channels in the sensory cells of organ of corti.• EP is involved in driving currents through transduction channels that are

fundamental to hair-cell function.

INNER EAR FLUIDS & THEIR CIRCULATIONPerilymph : • resembles extracellular fluid• Rich in Na ions• Fills space between bony & membranous labyrinth• Communicates with CSF through aqueduct of cochlea which opens

into scala tympani near the round window• Formation – 1)filtrate of blood serum formed by capillaries of spiral

ligament 2)direct continuation of CSF & reaches the labyrinth via aqueduct of cochlea

Endolymph : • Fills entire membranous labyrinth • Resembles ICF, rich in K ions• Secreted by secretory cells of stria vascularis of cochlea & by dark

cells.• Longitudinal flow – cochlea > saccule, utricle > E.duct > E.sac • Radial flow – secreted by stria vascularis & also gets absorbed by it

Composition of inner ear fluids

UTRICLE• lies in the posterior part of bony vestibule• Receives 5 openings from 3 semi-circular ducts• Connected to saccule through utriculo-saccular duct• Sensory epithelium of it is called macula that is concerned with linear

acceleration and deceleration

SACCULE• Lies in the bony vestibule, anterior to utricle & opposite the stapes

footplate• Its sensory epithelium is called macula• Exact function of it is not known , probably responds to linear

acceleration & deceleration• In Meniere’s, distended saccule lies against footplate & can be

surgically decompressed by perforating the footplate

SEMICIRCULAR DUCTS• 3 in number• Open in the utricle• Ampullated end of each duct contains a thickened ridge of

neuroepithelium called crista ampullaris

ENDOLYMPHATIC DUCT & SAC• E. duct is formed by union of 2 ducts – one each from saccule &

utricle.• It passes through the vestibular aqueduct.• Its terminal part is dilated to form endolymphatic sac, which lies

between the 2 layers of dura on the posterior surface of the petrous bone.• E. sac is surgically important. It is exposed for drainage or shunt

operation in Meniere’s disease.

BLOOD SUPPLY• Labyrinthine artery (br of AICA)

PATHOGENESIS

• Main pathology is distension of endolymphatic system due to increased volume of endolymph causing endolymphatic hypertension.• This may be due to either increased production or decreased

absorption or both.

• Defective absorption by endolymphatic sac – causing raised pressure in the cochlear duct -> Distension of it -> rupture of Reissner’s membrane -> mixing of endolymph & perilymph -> attack of vertigo. • Ischaemia of sac is seen in some cases indicating poor vascularity and

thus poor absorption by the sac. • Vasomotor disturbance – sympathetic overactivity -> spasm of

internal auditory artery -> impaired function of cochlear or vestibular sensory neuroepithelium -> deafness & vertigo.

• Anoxia of stria vascularis capillaries > increased permeability > transudation of fluid > increased production of endolymph.• Allergy – inner ear acts as a shock organ due to allergen causing increased

production of endolymph. • Na & water retention causes excessive fluid to get retained leading to

hydrops• Hypothyroidism – 3%• Autoimmune• Bacterial infections like syphilis• viral –mumps

• Electron microscopic studies have shown a reduction in the number of afferent nerve endings and synapses in the cochlea, but there are no reports regarding the vestibular hair cells.• Tsuji et al found type I hair cell densities within normal limits, but a

significant loss of type II hair cells in all sensory regions of the vestibular organ compared with age matched controls & a significant loss of vestibular ganglion cells.

• Meniere’s syndrome – Many different inner ear or temporal bone diseases, such as syphilis, mumps, Cogan's syndrome, trauma and even chronic suppurative otitis media, can, after many years, produce the clinical picture of Meniere's disease so-called Meniere's syndrome.

I/L delayed endolymphatic hydrops – • Patient describes attacks of spontaneous vertigo beginning many

years after the onset of unilateral hearing loss due to delayed endolymphatic hydrops on the abnormal side.

C/L delayed endolymphatic hydrops• Sometimes attacks of vertigo coincide with onset of fluctuating

hearing loss in the other, previously normal ear which is thought to be due to development of autoimmunity to inner ear antigens.

• Histopathology reveals pathological changes in deaf ears that are similar to those known to occur in mumps and measles labyrinthitis. These observations support the proposItIon that Meniere's disease may occur as a delayed sequela of inner ear damage sustained during an attack of subclinical viral labyrinthitis occurring in childhood.

CLINICAL FEATURES

• Recurrent attacks of spontaneous vertigo heralded by lateralised low-frequency fluctuating hearing loss, tinnitus and aural fullness. An attack typically increases in intensity over a period of minutes and then usually lasts for several hours.• Hearing loss and tinnitus may persist for days.• Associated nausea and vomiting.

An attack of vertigo• A typical vertigo attack has 3 phases.• initial irritative phase due to increased potassium concentration – nystagmus usually

horizontal or horizontal-torsional & beats towards the affected ear; usually lasts less than an hour.• second paretic phase nystagmus beats away from affected ear because of peripheral

hypofunction and reduced spontaneous neural activity (due to blockade of neurotransmitter release) in the right vestibular nucleus relative to the left & lasts usually several hours or sometimes 1 or 2 days. • Third recovery phase in which nystagmus again beats towards affected site; brainstem

compensation lasts for several hours or sometimes 1 or 2 days. • Healing of rupture then allows restitution of normal chemical composition of both

fluids terminating an attack and improvement in symptoms.

• In the national temporal bone registry containing 119 bones of Meniere’s disease, it was found that there are structural defects or holes in the wall of the membranous labyrinth that may be covered with new membranes. Such healed discontinuities seem consistent with a rupture theory.

• Diplacusis or double hearing is a phenomenon of altered sound perception, which differs from that of a presented sound. • Diplacusis could be manifested as binaural or mon aural. In binaural

diplacusis, the same tone is perceived differently in each ear. It is most frequently reported in Meniere's disease. • Evaluation – • Patients typically complain of 'distorted' sounds. Dipla cusis can be easily

identified using the tuning fork test, when the patient is able to report whether the tone presented to each ear sounds different.

• Hyperacusis is an intensity-related dysacusis and can be defined as a reduced tolerance to noise, or an increased sensitivity to sounds in levels that would not cause discomfort in a normal individual. • It is characterized by an increased growth in loudness but, unlike loudness

recruitment when patients report oversensitivity to loud sounds, patients with hyperacusis complain of excessively loud perception of ordinary environmental sounds. • The essence of hyperacusis is the lack or insufficiency of adaptive (inhibitory)

mechanisms, which normally limit the sound input and prevent overstimulation of the auditory system.• Treatment of hyperacusis is difficult – desensitization involves the application of a

low-noise generator, with a gradual increase in the level of noise.

CLASSIFICATIONGuidelines were given by AAOHNS.

Definite Meniere’s – • > 2 spontaneous attacks of vertigo each lasting > 20 min• Hearing loss documented by PTA on atleast 1 occasion• Tinnitus or aural fullness on affected side

Probable Meniere’s – • > 2 spontaneous attacks of vertigo + U/L hearing loss + tinnitus + aural fullness,

all at the same timePossible Meniere’s – • > 2 attacks of spontaneous attacks of vertigo without any auditory impairment

EXAMINATION

• Otoscopy – no abnormality in TM• Nystagmus – seen only during acute attack, quick component is

towards unaffected ear• Tuning fork tests – indicate SNHL. Rinne +, ABC reduced, weber

lateralised to better ear.

INVESTIGATIONS• PURE TONE AUDIOMETRY – SNHL• Early stages – lower frequencies affected & curve is rising type• When higher frequencies involved, curve becomes a flat or a falling type.

• SPEECH AUDIOMETRY – Discrimination score is usually 55-85% between attacks but impaired during & immediately following an attack.• To differentiate from retrocochlear• Recruitment positive• SISI >70%• Tone decay test – decay < 20dB

Audiogram

Electrocochleography• Most sensitive & specific for

Meniere’s when tone-burst and click stimuli are used, and when the responses are recorded transtympanically at the promontory.• Giving 4g oral NaCl for 3 days prior to

ECoG may increase the sensitivity of the test.

Electrocochleography

• SEROLOGY. Fluorescent treponemal antibody absorption is mandatory in any patient given the diagnosis of an idiopathic disease since syphilis may perfectly imitate Meniere’s disease. Autoimmune inner ear disease may present initially with a Meniere’s picture. The distinguishing characteristics of an autoimmune inner ear disease include a more aggressive course and early bilateral involvement. Autoimmune serologic tests may also be helpful. A promising test is a Western blot looking for anticochlear antibodies that can bind to a 68 to 70 kD antigen.

• Caloric test• It shows reduced response on the affected side in 75% of cases. • Often, it reveals a canal paresis on the affected side (most common) but sometimes there is directional

preponderance to healthy side or a combination of both canal paresis on the affected side and directional preponderance on the opposite side.

• Glycerol test• Glycerol is a dehydrating agent. • When given orally, it reduces endolymph pressure and thus causes an improvement in hearing. • Patient is given glycerol (1.5 mL/kg) with an equal amount of water and a little flavouring agent or lemon

juice. • Audiogram and speech discrimination scores are recorded before and 1–2 h after ingestion of glycerol. • An improvement of 10 dB in two or more adjacent octaves or gain of 10% in discrimination score makes the

test positive. • There is also improvement in tinnitus and in the sense of fullness in the ear. • The test has a diagnostic and prognostic value.

• These days, glycerol test is combined with electrocochleography.

VARIANTS OF MENIERE’S DISEASE• Cochlear hydrops – • Only cochlear symptoms present • Vertigo is absent, may appear after several years• Block at level of ductus reuniens, confining increased pressure to cochlea only.

• Vestibular hydrops – • Typical attacks of episodic vertigo• Cochlear functions normal

• Lermoyez syndrome – • Symptoms of menier’s appear in reverse order• Hearing loss -> vertigo attack (hearing recovers by this time)

VARIANTS OF MENIERE’S DISEASE• Drop attacks • a/k/a tumarkin or otolithic crises • Reason - acute otolithic dysfunction of utricle or saccule due to changes in

endolymphatic pressure• Occur in the later stages of the disease• Patient simply drops to the ground without warning and can sustain a fracture

or a serious injury.• Sensation of being pushed to the ground by some external force during these

attacks.• No associated vertigo or loss of consciousness.• Number of attacks varies

STAGING OF MENIERE’S DISEASE• It is based on average of the pure tone thresholds at 0.5, 1, 2, 3 kHz

(rounded to nearest whole) of the worst audiogram during interval of 6 months before treatment.

MANAGEMENT

GENERAL MEASURES• The treatment of Meniere's disease should be preceded by diagnosis

on the basis of strict criteria and after Exclusion of retrocochlear pathology and of causes such as Cogan's syndrome or syphilis.• Level of anxiety correlates with severity of symptoms • Stress may contribute via autonomic mechanisms in the genesis of

endolymphatic hydrops, thus indicating the need for lifestyle adaptations.• restrict salt intake to 1 mg or 1.5-2 mg per day

MEDICAL TREATMENTAim – to decrease production or accumulation of endolymphDrug therapy for Meniere's disease may include:• acute vestibular symptoms suppression, • drugs that aim to influence endolymphatic hydrops, which include

diuretics and betahistine • suppression of immunological reactions with steroids or

methotrexate; • destruction of the vestibular end organ by intratympanic injection of

aminoglycosides.

acute vertigo suppression• Drugs that control vertigo suppress integration of sensory stimuli by

targeting acetylcholine, histamine and y GABA neurotransmitter action at the level of primary to secondary vestibular neurons and the vestibular nuclei.• Antiemetics block three major afferent pathways that conduct the

emetic signals to the medullary vomiting centre:• the chemoreceptor zone in the area postrema blocked by dopamine agonists; • the gastrointestinal tract: blocked by serotonin 5-hydroxytryptamine (HT3)• from the labyrinth leading to stimulation of the vestibular nuclei: blocked by

antihistamine and glutamate antagonists.

• Anticholinergics • target the efferent feedback from the brainstem to the vestibular labyrinth, parts of

the vestibulocochlear nucleus and the muscarinic receptors of autonomic effector sites innervated by parasympathetic nerves, both centrally and peripherally.

• The main drug in this category, hyoscine, was one of the first to be used for treatment of vertigo and remains the most effective drug for treatment of motion sickness.

• The most common mode of administration is transdermal as it achieves continuous release of the drug into the blood stream for up to 72 hours.

• Scopolamine nasal spray also has a rapid onset of action, within 30 minutes after administration, and is an effective treatment for motion sickness, with no signs of nasal or pharyngeal mucous membrane irritation.

• Hyoscine is more effective than cinnarizine in protecting against the symptoms of seasickness.

• Antihistamines • The phenothiazines are dopamine antagonists with significant antimuscarinic

effects that act centrally in the dopamine receptors in the area postrema of the brainstem, and are effective in controlling nausea and vomiting.

• They include promethazine, a long-acting antihistamine with antiemetic, central sedative and anticholinergic properties and prochlorperazine, a dopa mine and histamine antagonist, with weak anticholinergic action.

• buccal pro chlorperazine is faster acting, significantly more effective in nausea and severity of vomiting control, and slightly more effective in frequency of vomiting control.

• Piperazines include cyclizine, a histamine HI receptor antagonist characterized by a low incidence of drowsiness. Dimenhydrinate (Dramamine) is another HI receptor blocker. Sedation is the most common reported side effect and patients who take this drug are advised not to drive.• Cyclizine is more effective in controlling gastrointestinal symptoms and

caused less drowsiness than dimenhydrinate.• Cyclizine, at doses used for the relief of motion sickness, may have minimal

suppressive effects on visual-vestibular interaction. • Dimenhydrinate significantly impairs decision reaction time, subjective well -

being and general performance abilities.

• Metoclopramide is a benzamide closely associated with the parasympathetic nervous control of the upper gastrointestinal system.

• Calcium channel antagonists • Cinnarizine and flunarazine inhibit the influx of calcium intracellularly.• Cinnarizine is less effective than hyoscine in the prevention of motion

sickness.• Flunarizine and cinnarizine have been well documented to cause

extrapyramidal side effects.• While 15 mg cinnarizine has no effects on mental and vigilance performance,

30 mg cinnarizine or more may impair performance in tasks which require continued attention and may increase sleepiness.

• Other drugs • Diazepam acts by reducing neural activity and causing inhibition throughout

the CNS, including the vestibular nerve and nuclei.• Steroids may also be used to control vertigo, on the basis of an assumption

that the vestibular disorder is due to an autoimmune process.

• Diuretics • may be effective in the long-term control of vertigo but not of cochlear

symptoms.• Bendroflurazide is a thiazide diuretic which reduces the absorption of

electrolytes from the renal tubules, thereby increasing the excretion of sodium, chloride ions and water.• Dyazide (a combination of 50 mg triamterene and 25 mg hydro chlorthiazide)

is a potassium-conserving diuretic.• Chlorthalidone is a sulphonamide derivative. • Acetazola mide is a carbonic anhydrase inhibitor.

• Betahistine • is a histamine analogue with weak agonistic action of both HI and H2 and

moderate antagonistic action of H3 histamine receptors. • The drug may owe its antivertigo properties in Meniere's disease to

• a reduction of the asymmetric functioning of the vestibular end organs; • improved microvascular circulation in the stria vascularis of the cochlea; • inhibition of the activity in the vestibular nuclei;• less specific effects on alertness through cerebral H(l) receptors.

Intratympanic injection of AG• Gentamicin is predomi nantly vestibulotoxic and acts by destroying the

dark cells of the secretory epithelium, thus decreasing en dolymph production.• high efficacy in controlling the vertigo of up to 90 percent,• profound sensorineural hearing loss may develop in 3-30 percent

treated cases.• This treatment should be reserved for patients who have failed

medical therapy.

Other means of treatment.

• Alternobaric oxygen therapy with continuous variations in pressure• treatment with the Meniett device, which applies intermittent micro

pressure pulses to the inner ear through a tympanostomy tube.• Inhalation of carbogen ( 5% CO2 + 95% O2 ).

SURGICAL• Endolymphatic sac surgery – reduction in frequency, duration &

intensity of vertigo attacks.• Selective vestibular neurectomy – stops vertigo attacks but hearing

loss & facial paralysis may occur as potential complications.• Surgical Labyrinthectomy – stop vertigo attacks at the expense of

losing any remaining hearing on that side.

ENDOLYMPHATIC SAC SURGERY• Endolymphatic sac surgery involves a mastoidectomy and

locating the ES on the posterior fossa dura. • The sac is medial to the sigmoid sinus and inferior to the

PSCC. • The ES is also located along an imaginary line (Donaldson’s

line) in the plane of the horizontal semicircular canal. • The ES may be decompressed or have a shunt placed that

communicates into the subarachnoid space or mastoid cavity.

• The “sham” study, a double-masked, placebo-controlled comparison of the endolymphatic mastoid shunt versus a cortical mastoidectomy, by Thomsen et al showed that ES surgery provides no greater benefit than per- forming a cortical mastoidectomy.

• A 9-year followup showed 70% control of vertigo in both surgical groups. Reanalysis of the sham study suggested a greater benefit in the ES surgery group, and a recent study with a 5-year follow-up showed an 88% functional Level 1 or 2 response After an endolymphatic Mastoid Shunt operation. The success rates have great variation in the literature, so the benefit of ES surgery is not universally accepted. Endolymphatic shunt surgery provides a nondestructive option for patients who fail medical or aminoglycoside therapy and have good hearing. The role of endolymphatic surgery is currently in decline with the renewed interest in intratympanic aminoglycoside therapy.

VESTIBULAR NERVE SECTION. • Vestibular nerve section provides a

definitive treatment of unilateral Meniere’s disease in patients with serviceable hearing.

• Ninety-five Percent of patients achieve vertigo control, and hearing is preserved in over 95% of patients.

• The vestibular neurectomy may be approached via a retrosigmoid or middle fossa approach. These procedures are described in detail in the CPA section.

• The risk to the facial nerve is less than 1% in the retrosigmoid approach and less than 5% in the middle fossa approach.

• The advantage of the middle fossa approach is sectioning the vestibular nerves in the IAC lateral to where they join the cochlear nerve in the CPA. • The patients are acutely vertiginous and have nystagmus (fast phase

away from the operated ear) for a few days until central compensation takes effect. • The hearing appears to degenerate in the postoperative patient in

accordance with the natural history of Meniere’s disease.

LABYRINTHECTOMY. • A transmastoid labyrinthectomy with fenestration of the bony

semicircular canals and vestibule and removal of the membranous neuroepithelium provides control of vertigo in nearly all patients with unilateral Meniere’s disease and poor hearing. • The rate of control may decline by 10 years owing to development of

vertebral basilar artery insufficiency (aging), poorer vision, and development of Meniere’s disease in the contralateral ear. • The complete loss of unilateral vestibular function owing to the

labyrinthectomy leads to unsteadiness in up to 30% of patients.

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