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Treatment Controversies Treatment Controversies in Meniere’s Diseasein Meniere’s Disease

Shashidhar S. Reddy, MD, MPHShashidhar S. Reddy, MD, MPHShawn D. Newlands, MD, PhDShawn D. Newlands, MD, PhD

UTMB Otolaryngology UTMB Otolaryngology Grand RoundsGrand RoundsMay 18, 2005May 18, 2005

OutlineOutline

History and Meniere’sHistory and Meniere’sDefinition of Meniere’sDefinition of Meniere’sPhysiology, Pathophysiology of Meniere’sPhysiology, Pathophysiology of Meniere’sMedical Management of Meniere’sMedical Management of Meniere’sMeniet DeviceMeniet DeviceIntratympanic GentamicinIntratympanic GentamicinEndolymphatic Sac SurgeryEndolymphatic Sac SurgeryVestibular Nerve SectionVestibular Nerve SectionConclusionsConclusions

History of Meniere’sHistory of Meniere’s

1861 – Prosper Meniere describes classic 1861 – Prosper Meniere describes classic symptoms and attributes to labyrinthsymptoms and attributes to labyrinth1871 – Knappin theorizes dilatation of 1871 – Knappin theorizes dilatation of membranous Labyrinthmembranous Labyrinth1938 – Hallpike and Portman confirm 1938 – Hallpike and Portman confirm endolymphatic hydrops via temporal bone endolymphatic hydrops via temporal bone histologyhistology1995 – Latest revision of AAOHNS 1995 – Latest revision of AAOHNS definitiondefinition

Definition of Meniere’s DiseaseDefinition of Meniere’s DiseaseAAO-HNS Committee on Hearing and Equilibrium revised definition in AAO-HNS Committee on Hearing and Equilibrium revised definition in 19951995

Possible Meniere's diseasePossible Meniere's diseaseEpisodic vertigo of the Meniere's type without documented hearing loss, orEpisodic vertigo of the Meniere's type without documented hearing loss, orSensorineural hearing loss, fluctuating or fixed, with dysequilibrium but without Sensorineural hearing loss, fluctuating or fixed, with dysequilibrium but without definitive episodesdefinitive episodesOther causes excludedOther causes excluded

Probable Meniere's diseaseProbable Meniere's diseaseOne definitive episode of vertigoOne definitive episode of vertigoAudiometrically documented hearing loss on at least one occasionAudiometrically documented hearing loss on at least one occasionTinnitus or aural fullness in the treated earTinnitus or aural fullness in the treated earOther causes excluded Other causes excluded

Definite Meniere's diseaseDefinite Meniere's diseaseTwo or more definitive spontaneous episodes of vertigo 20 minutes or longerTwo or more definitive spontaneous episodes of vertigo 20 minutes or longerAudiometrically documented hearing loss on at least one occasionAudiometrically documented hearing loss on at least one occasionTinnitus or aural fullness in the treated earTinnitus or aural fullness in the treated earOther cases excluded Other cases excluded

Certain Meniere's diseaseCertain Meniere's diseaseDefinite Meniere's disease, plus histopathologic confirmationDefinite Meniere's disease, plus histopathologic confirmation

Committee on Hearing and Equilibrium Guidelines for Diagnoses and Evaluation of Therapy in Meniere’s Disease, AAOHNS Board of Directors March 1994

Definition of Meniere’sDefinition of Meniere’s

Staging of Hearing Loss in Definite/Certain Staging of Hearing Loss in Definite/Certain Meniere’s:Meniere’s:

StageStage Four Tone Average Four Tone Average dBdB

11 <=25<=25

22 26-4026-40

33 41-7041-70

44 >70>70


Definition of Meniere’sDefinition of Meniere’s

Functional Level ScaleFunctional Level Scale Regarding my current state of overall function, not just during attacks (check the Regarding my current state of overall function, not just during attacks (check the

ONE that best applies):ONE that best applies): 1. My dizziness has no effect on my activities at all.1. My dizziness has no effect on my activities at all. 2. When I am dizzy I have to stop what I am doing for a while, but it soon passes 2. When I am dizzy I have to stop what I am doing for a while, but it soon passes

and I can resume activities. I continue to work, drive, and engage in any activity I and I can resume activities. I continue to work, drive, and engage in any activity I choose without restriction. I have not changed any plans or activities to choose without restriction. I have not changed any plans or activities to accommodate my dizziness.accommodate my dizziness.

3. When I am dizzy, I have to stop what I am doing for a while, but it does pass 3. When I am dizzy, I have to stop what I am doing for a while, but it does pass and I can resume activities. I continue to work, drive, and engage in most and I can resume activities. I continue to work, drive, and engage in most activities I choose, but I have had to change some plans and make some activities I choose, but I have had to change some plans and make some allowance for my dizziness.allowance for my dizziness.

4. I am able to work, drive, travel, take care of a family, or engage in most 4. I am able to work, drive, travel, take care of a family, or engage in most essential activities, but I must exert a great deal of effort to do so. I must essential activities, but I must exert a great deal of effort to do so. I must constantly make adjustments in my activities and budge my energies. I am barely constantly make adjustments in my activities and budge my energies. I am barely making it.making it.

5. I am unable to work, drive, or take care of a family. I am unable to do most of 5. I am unable to work, drive, or take care of a family. I am unable to do most of the active things that I used to. Even essential activities must be limited. I am the active things that I used to. Even essential activities must be limited. I am disabled.disabled.

6. I have been disabled for 1 year or longer and/or I receive compensation 6. I have been disabled for 1 year or longer and/or I receive compensation (money) because of my dizziness or balance problem.(money) because of my dizziness or balance problem.


Definition of Meniere’sDefinition of Meniere’sReporting Results of Treatment:Reporting Results of Treatment: Divide frequency of spells 18-24months by Divide frequency of spells 18-24months by

number 6months prior to tx and multiplyx100number 6months prior to tx and multiplyx100

Numerical ValueNumerical Value ClassClass

00 AA

1 to 401 to 40 BB

41 to 8041 to 80 CC

81-12081-120 DD

>120>120 EE

Secondary TreatmentSecondary Treatment FFCommittee on Hearing and Equilibrium Guidelines for Diagnoses and Evaluation of Therapy in Meniere’s Disease, AAOHNS Board of Directors March 1994

PhysiologyPhysiology

Perilymph – Similar in composition to CSFPerilymph – Similar in composition to CSF High Na+, Low K+High Na+, Low K+

Endolymph – Similar in compostion to ICFEndolymph – Similar in compostion to ICF Low Na+ High K+Low Na+ High K+ Believed to be produced in Stria VascularisBelieved to be produced in Stria Vascularis

Membranous Labyrinth separates the twoMembranous Labyrinth separates the two Difference of 80mV in chargeDifference of 80mV in charge No difference in pressureNo difference in pressure

PhysiologyPhysiology

Production and flow of Endolymph - Production and flow of Endolymph - TheoriesTheories Longitudinal – produced in membranous Longitudinal – produced in membranous

labyrinth, flows to endolymphatic sac, then to labyrinth, flows to endolymphatic sac, then to dural venous sinusesdural venous sinuses

Diffuse – produced and absorbed along the Diffuse – produced and absorbed along the membranous labyrinthmembranous labyrinth

Periodic Flow – endolymph flows only with Periodic Flow – endolymph flows only with changes in volume or pressurechanges in volume or pressure

Andrews, JC, Intralabyrinthine fluid dynamics: Meniere disease 12(5) Oct 2004 pp408-412

PathophysiologyPathophysiology

Endolymphatic hydrops leads to distortion of Endolymphatic hydrops leads to distortion of membranous labyrinthmembranous labyrinth


Build up in pressure may lead to micro-Build up in pressure may lead to micro-ruptures of membranous labyrinth (Minor ruptures of membranous labyrinth (Minor et alet al)) Ruptures are confirmed by various histologic Ruptures are confirmed by various histologic

studiesstudies May responsible for episodic nature of attacksMay responsible for episodic nature of attacks Healing of ruptures may account for return of Healing of ruptures may account for return of

hearinghearing

Review Article: Minor, Lloyd et al, Meniere’s Disease, Current Opinion in Neurology 17(1) Feb2004


What causes hydrops?What causes hydrops? Obstruction of endolymphatic duct/sacObstruction of endolymphatic duct/sac

Obstruction of endolymphatic sac in does not Obstruction of endolymphatic sac in does not cause hydrops in all animals and causes vertigo in cause hydrops in all animals and causes vertigo in fewfew

Alteration of absorption of endolymphAlteration of absorption of endolymph Immunologic insult to inner earImmunologic insult to inner ear

Elevated levels of IG’s in endolymphElevated levels of IG’s in endolymph


Hydrops role in causation of Meniere’s is Hydrops role in causation of Meniere’s is not entirely clearnot entirely clear Rauche Rauche et alet al 1998 – Study of 19 temporal 1998 – Study of 19 temporal

bone histologies with hydrops-bone histologies with hydrops-13/19 patients with hydrops by histology showed 13/19 patients with hydrops by histology showed Meniere’s symptoms by chart reviewMeniere’s symptoms by chart review

6/19 showed no Meniere’s symptoms by chart 6/19 showed no Meniere’s symptoms by chart reviewreview

Rauch SD, et al Meniere’s syndrome and endolymphatic hydrops: double blind temporal bone study. Ann Otol Rhinol Laryngol 1989; 98:873-883


Silverstein Silverstein et alet al found that in pts. who found that in pts. who refused surgical tx., there was resolution refused surgical tx., there was resolution of vestibular symptoms of vestibular symptoms 57-60% of patients in 2 years57-60% of patients in 2 years 71% at eight years.71% at eight years. Long term PTA in affected ear is 50dBLong term PTA in affected ear is 50dB Speech discrimination is 53%Speech discrimination is 53% Caloric response reduction is 50%Caloric response reduction is 50%

Silverstein H., Smouha E. & Jones R. (1989) Natural history vs surgery for Ménière's disease. Otolaryngol. Head Neck Surg. 100, 6-16

Medical ManagementMedical Management

Acute TherapyAcute Therapy

Maintenance TherapyMaintenance Therapy


Acute TherapyAcute Therapy Relatively non-controversialRelatively non-controversial

Brookes, G.B. The pharmacological treatment of Meniere’s disease. Clinical Otolaryngology 21(1) Feb1996, pp3-11


Maintenance TherapyMaintenance Therapy No conclusive studies show efficacy of drugs No conclusive studies show efficacy of drugs

intended to alter disease course of Meniere’sintended to alter disease course of Meniere’s


Diuretics and Salt restrictionDiuretics and Salt restriction ? Alter fluid balance in inner ear leading to ? Alter fluid balance in inner ear leading to

depletion of endolymphdepletion of endolymph Shinkawa/Kimura unable to demonstrate Shinkawa/Kimura unable to demonstrate

beneficial effect on hydrops in animal modelbeneficial effect on hydrops in animal model

Shinkawa H. & Kimura R.S. (1986) Effect of diuretics on endolymphatic hydrops. Acta. Otolaryngol. (Stockh.)101, 43-52


Diuretics and Salt RestrictionDiuretics and Salt Restriction Ruckenstein Ruckenstein et alet al evaluated data from two double evaluated data from two double

blind studies by Klockhoff and Lindblom on HCTZ vs. blind studies by Klockhoff and Lindblom on HCTZ vs. Placebo and showed no difference in Diuretics vs. Placebo and showed no difference in Diuretics vs. placeboplacebo

Ruckenstein M.J., Rutka J.A. & Hawke M. (1991) The treatment of Meniere's disease: Torok revisited.

Laryngoscope101, 211-218


Osmotic Diuretics (Urea, Glycerol)Osmotic Diuretics (Urea, Glycerol) Have been consistently shown to reduce Have been consistently shown to reduce

symptoms in a proportion of patients, but the symptoms in a proportion of patients, but the effects only last for a few hourseffects only last for a few hours

Objective data includes alteration of the Objective data includes alteration of the SP:AP ratio on ElectrocochleographySP:AP ratio on Electrocochleography

Acetazolamide – was actually shown to Acetazolamide – was actually shown to increase hydrops and hearing loss when increase hydrops and hearing loss when given IV and had no benefit p.o.given IV and had no benefit p.o.


VasodilatorsVasodilators Purported to work by decreasing ischemia in Purported to work by decreasing ischemia in

the inner ear and allowing better metabolism the inner ear and allowing better metabolism of endolymphof endolymph

Betahistine is a popular choice, with several Betahistine is a popular choice, with several studies showing decreased vertigo with usestudies showing decreased vertigo with use

Cochrane Database Review (2004) – Only one Cochrane Database Review (2004) – Only one Grade B study and four Grade C studies, none of Grade B study and four Grade C studies, none of which produced convincing evidence for use.which produced convincing evidence for use.

James, AL, et al. Betahistine for Meniere’s disease or syndrome. Cochrane Database of Systematic Reviews (2) 2005


Immunologic ManagementImmunologic Management Systemic steroids and intratympanic Systemic steroids and intratympanic

dexamethasone have been studied and dexamethasone have been studied and showed no conclusive benefit.showed no conclusive benefit.

Double-blinded prospective crossover study Double-blinded prospective crossover study by Silverstein by Silverstein et alet al showed no difference from showed no difference from placebo with intratympanic dexamethasone placebo with intratympanic dexamethasone injectionsinjections

Silverstein, Herbert et al Dexamethasone inner ear perfusion for the treatment of meniere’s disease: a prospective, randomized, double-blind, crossover trial. American Journal of Otology. 1998. 19:196-201

Mechanical ManagementMechanical Management

Transtympanic Transtympanic “Micropressure” “Micropressure” TreatmentTreatment

Meniett Device (Xomed) – Meniett Device (Xomed) – FDA approved in 1999 as a FDA approved in 1999 as a class II deviceclass II device

Advocates present no Advocates present no strong case for why the strong case for why the device should workdevice should work

Portably, low intensity Portably, low intensity alternating pressure alternating pressure generatorgenerator

Mechanical ManagementMechanical Management

Gates Gates et alet al 2004 2004 Prospective, randomized, placebo control trial of Prospective, randomized, placebo control trial of

Meniett deviceMeniett device

Gates GA. Green JD Jr. Tucci DL. Telian SA. The effects of transtympanic micropressure treatment in people with unilateral Meniere's disease. Archives of Otolaryngology -- Head & Neck Surgery. 130(6):718-25, 2004 Jun.

Did not use standardized vertigo assesment

Did not comment on severity of vertigo

Did not give good data on objective testing

Intratympanic TherapyIntratympanic Therapy

Goal is to maximize local effects in inner Goal is to maximize local effects in inner ear while minimizing systemic effectsear while minimizing systemic effects

Round window is point of diffusion to inner Round window is point of diffusion to inner earear

Intratympanic dexamethasone already Intratympanic dexamethasone already discusseddiscussed

Aminoglycoside Antibiotics: affect hair Aminoglycoside Antibiotics: affect hair cells of crista, ampulla, and cochleacells of crista, ampulla, and cochlea

Intratympanic TherapyIntratympanic Therapy

Fowler in 1948, and later Schuknecht Fowler in 1948, and later Schuknecht established role of systemic streptomycin established role of systemic streptomycin for bilateral disease (2gIVPB qd until for bilateral disease (2gIVPB qd until vestibular symptoms were noted)vestibular symptoms were noted)

Hearing loss and oscillopsia were a Hearing loss and oscillopsia were a problem with this therapy, though reducing problem with this therapy, though reducing dosage seemed to helpdosage seemed to help

Intratympanic GentamicinIntratympanic Gentamicin

Preferred because of Gentamicin’s Preferred because of Gentamicin’s vestibuloselectivityvestibuloselectivity

Side effects can include temporary Side effects can include temporary imbalance or nystagmusimbalance or nystagmus

Hearing lossHearing loss

Many methods of delivery existMany methods of delivery exist


Titration TherapyTitration Therapy Martin and Perez 2003 (prospective study, Martin and Perez 2003 (prospective study,

n=71)n=71)Serial daily injections of buffered (pH 6.4) Serial daily injections of buffered (pH 6.4) 26.7mg/cc gentamicin solution via 27 gauge 26.7mg/cc gentamicin solution via 27 gauge needle into middle earneedle into middle earInjections repeated until vestibular symptoms Injections repeated until vestibular symptoms developed (spontaneous or evoked nystagmus)developed (spontaneous or evoked nystagmus)At 2 years, 69% had Class A vertigo control, At 2 years, 69% had Class A vertigo control, 14.1% had Class B14.1% had Class B32.4% had hearing loss32.4% had hearing loss

Martin E, Perez N: Hearing loss after intratympanic gentamicin therapy for unilateral Meniere’s Disease. Otol Neurotol 2003, 24:800-806


Ablation via Multiple Daily DosingAblation via Multiple Daily Dosing Jackson and Silverstein – Study on 92 Jackson and Silverstein – Study on 92

patients who underwent myringotomy and patients who underwent myringotomy and wick placement through to round window wick placement through to round window niche.niche.

Pts. self-administered gentamicin drops TID until Pts. self-administered gentamicin drops TID until 100% reduction on ENG of vestibular response100% reduction on ENG of vestibular response

85% relief of vertigo, 67% improvement in aural 85% relief of vertigo, 67% improvement in aural pressurepressure

36% hearing loss36% hearing loss

Jackson, LE; Silverstein, H: Chemical perfusion of the inner ear. Otolaryngol Clin North Am 2002, 35:639-653


Low dose therapyLow dose therapy Harner Harner et alet al 2001 – retrospective study of 51 2001 – retrospective study of 51

patients who received 1 dose of 40mg/mL patients who received 1 dose of 40mg/mL injection and were re-evaluated in 1 month injection and were re-evaluated in 1 month and given another if neededand given another if needed

At 2 years, 86% had vertigo class A or BAt 2 years, 86% had vertigo class A or B He reported minimal change in PTA but drop He reported minimal change in PTA but drop

in SRT’sin SRT’s Claimed better hearing preservation with thisClaimed better hearing preservation with this

Harner, Stephen et al: Long-term follow-up of transtympanic gentamicin for Meniere’s Syndrome. Otology & Neurotol 22:210-214, 2001


Other methods of deliveryOther methods of delivery Weekly administrationWeekly administration

Single dose of gentamicin once a week for four Single dose of gentamicin once a week for four treatmentstreatments

Continuous administrationContinuous administrationMicrocatheter delivery of gentamicin using a Microcatheter delivery of gentamicin using a continuous perfusion methodcontinuous perfusion method

Results in extremely variable amount of gentamicin Results in extremely variable amount of gentamicin deliverydelivery

Better perfusion techniques may be neededBetter perfusion techniques may be needed

Intratympanic GentamicinIntratympanic GentamicinChia Chia et alet al performed a meta-analysis of different performed a meta-analysis of different modalities of application in 2004modalities of application in 2004

Chia, Stanley H, et al Intratympanic Gentamicin Therapy for Meniere’s Disease: a Meta-Analysis. Otology&Neurotol 25(4) July 2004 pp 544-552

Class A or BVertigo Control


Hearing loss was greatest for multiple Hearing loss was greatest for multiple daily dosingdaily dosing

Hearing loss was least for titration therapyHearing loss was least for titration therapy

Hearing loss was not lower than average Hearing loss was not lower than average for low-dose therapyfor low-dose therapy

Endolymphatic Sac SurgeryEndolymphatic Sac Surgery

Purported to address the site of Purported to address the site of obstruction causing hydropsobstruction causing hydrops 4 types:4 types:

Decompression – removal of bone around the sacDecompression – removal of bone around the sac

Shunting – placement of synthetic shunt to drain Shunting – placement of synthetic shunt to drain endolymph into mastoidendolymph into mastoid

Drainage – incision of the sac to allow drainageDrainage – incision of the sac to allow drainage

Removal of sac – to address the possibility that the Removal of sac – to address the possibility that the sac may actually play a role in endolymph sac may actually play a role in endolymph productionproduction


Coker, Newton J. et al Atlas of Otologic Surgery. W.B. Saunders 2001


Jens Thomsen Jens Thomsen et alet al 1981 1981 Double-blinded placebo-control study with Double-blinded placebo-control study with

sham surgery (cortical mastoidectomy) vs sham surgery (cortical mastoidectomy) vs endolymphatic shunt placement in 30 patientsendolymphatic shunt placement in 30 patients

No difference in any outcome between sham No difference in any outcome between sham surgery and endolymphatic sac shunt groupsurgery and endolymphatic sac shunt group

Thomsen, Jen et al. Placebo Effect in Surgery for Meniere’s Disease. Arch Otolaryngol – Vol 107, May 1981, pp271-277

Vestibular Nerve SectionVestibular Nerve Section

Can achieve vestibular suppression Can achieve vestibular suppression without any effect on hearingwithout any effect on hearing

Single step procedureSingle step procedure

Can have intraoperative complications of Can have intraoperative complications of damage to facial nerve, cochlear nerve, or damage to facial nerve, cochlear nerve, or CSF leak (rate of CSF leak is about 13%)CSF leak (rate of CSF leak is about 13%)

Approaches: Middle Fossa, Approaches: Middle Fossa, Retrolabyrinthine/RetrosigmoidRetrolabyrinthine/Retrosigmoid


Coker, Newton J. et al Atlas of Otologic Surgery. W.B. Saunders 2001


Hillman Hillman et al et al 2004 retrospectively compared v. nerve 2004 retrospectively compared v. nerve section to intratymp. Gent.section to intratymp. Gent.

Performed via combined mastoidectomy/retrosig approachPerformed via combined mastoidectomy/retrosig approach

Hillman, Todd A, et al. Vestibular Nerve Section Versus Intratympanic Gentamicin for Meniere’s Disease. Laryngoscope 114:pp 216-224


Hillman Hillman et alet al continuedcontinued


Hillman Hillman et alet al continued continued No incidence of wound infection or meningitis No incidence of wound infection or meningitis

in this groupin this group 12.6% incidence of CSF leak requiring LP and 12.6% incidence of CSF leak requiring LP and

extended hospitalizationextended hospitalization Rates of disequilibrium were similar but Rates of disequilibrium were similar but

persisted longer in the nerve section grouppersisted longer in the nerve section group

Other Ablative SurgeriesOther Ablative Surgeries

LabyrinthectomyLabyrinthectomy Useful in patients with no serviceable hearing Useful in patients with no serviceable hearing

and those who cannot tolerate intracranial and those who cannot tolerate intracranial procedureprocedure

Similar in efficacy to vestibular nerve sectionSimilar in efficacy to vestibular nerve section

ConclusionsConclusions

Therapies that definitely reduce vertigo in Therapies that definitely reduce vertigo in Meniere’s Disease:Meniere’s Disease: Vestibular suppressant medicationsVestibular suppressant medications Intratympanic Gentamicin (especially when Intratympanic Gentamicin (especially when

titrated)titrated) Vestibular Nerve SectionVestibular Nerve Section LabyrinthectomyLabyrinthectomy

Other therapies discussed are unproven or Other therapies discussed are unproven or controversialcontroversial

menieres slides-050518

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menieres symptoms

history of menieres

menieres disease shashidhar

probable menieres disease

disease course of menieres

definitecertain menieres

menieres type

causation of menieres