Treatment Controversies in Menieres Disease

Shashidhar S. Reddy, MD, MPH Shawn D. Newlands, MD, PhD UTMB Otolaryngology Grand Rounds May 18, 2005

Outline
History and Menieres Definition of Menieres Physiology, Pathophysiology of Menieres Medical Management of Menieres Meniet Device Intratympanic Gentamicin Endolymphatic Sac Surgery Vestibular Nerve Section Conclusions

History of Menieres
1861 Prosper Meniere describes classic symptoms and attributes to labyrinth 1871 Knappin theorizes dilatation of membranous Labyrinth 1938 Hallpike and Portman confirm endolymphatic hydrops via temporal bone histology 1995 Latest revision of AAOHNS definition

Definition of Menieres Disease

AAOAAO-HNS Committee on Hearing and Equilibrium revised definition in 1995


Possible Meniere's disease

Episodic vertigo of the Meniere's type without documented hearing loss, or Sensorineural hearing loss, fluctuating or fixed, with dysequilibrium but without definitive episodes Other causes excluded

Probable Meniere's disease

One definitive episode of vertigo Audiometrically documented hearing loss on at least one occasion Tinnitus or aural fullness in the treated ear Other causes excluded

Definite Meniere's disease

Two or more definitive spontaneous episodes of vertigo 20 minutes or longer Audiometrically documented hearing loss on at least one occasion Tinnitus or aural fullness in the treated ear Other cases excluded

Certain Meniere's disease

Definite Meniere's disease, plus histopathologic confirmation

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

Definition of Menieres
Staging of Hearing Loss in Definite/Certain Menieres: Stage 1 2 3 4 Four Tone Average dB <=25 26-40 2641-70 41>70

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

Definition of Menieres
Functional Level Scale
  

Regarding my current state of overall function, not just during attacks (check the ONE that best applies): 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 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 accommodate my dizziness. 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 activities I choose, but I have had to change some plans and make some allowance for my dizziness. 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 constantly make adjustments in my activities and budge my energies. I am barely making it. 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 disabled. 6. I have been disabled for 1 year or longer and/or I receive compensation (money) because of my dizziness or balance problem.

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

Definition of Menieres
Reporting Results of Treatment:


Divide frequency of spells 18-24months by 18number 6months prior to tx and multiplyx100

Numerical Value 0 1 to 40 41 to 80 8181-120 >120 Secondary Treatment

Class A B C D E F

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

Physiology
Perilymph Similar in composition to CSF


High Na+, Low K+ Low Na+ High K+ Believed to be produced in Stria Vascularis Difference of 80mV in charge No difference in pressure

Endolymph Similar in compostion to ICF

 

Membranous Labyrinth separates the two

 

Physiology
Production and flow of Endolymph Theories


Longitudinal produced in membranous labyrinth, flows to endolymphatic sac, then to dural venous sinuses Diffuse produced and absorbed along the membranous labyrinth Periodic Flow endolymph flows only with changes in volume or pressure

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

Pathophysiology
Endolymphatic hydrops leads to distortion of membranous labyrinth

Pathophysiology
Build up in pressure may lead to micromicroruptures of membranous labyrinth (Minor et al) al)


 

Ruptures are confirmed by various histologic studies May responsible for episodic nature of attacks Healing of ruptures may account for return of hearing

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

Pathophysiology
What causes hydrops?


Obstruction of endolymphatic duct/sac

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

 

Alteration of absorption of endolymph Immunologic insult to inner ear

Elevated levels of IGs in endolymph

Pathophysiology
Hydrops role in causation of Menieres is not entirely clear


Rauche et al 1998 Study of 19 temporal bone histologies with hydropshydrops13/19 patients with hydrops by histology showed Menieres symptoms by chart review 6/19 showed no Menieres symptoms by chart review

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

Pathophysiology
Silverstein et al found that in pts. who refused surgical tx., there was resolution of vestibular symptoms
    

5757-60% of patients in 2 years 71% at eight years. Long term PTA in affected ear is 50dB Speech discrimination is 53% Caloric response reduction is 50%

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

Medical Management
Acute Therapy Maintenance Therapy

Medical Management
Acute Therapy


Relatively non-controversial non-

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

Medical Management
Maintenance Therapy


No conclusive studies show efficacy of drugs intended to alter disease course of Menieres

Medical Management
Diuretics and Salt restriction


? Alter fluid balance in inner ear leading to depletion of endolymph Shinkawa/Kimura unable to demonstrate beneficial effect on hydrops in animal model

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

Medical Management
Diuretics and Salt Restriction


Ruckenstein et al evaluated data from two double blind studies by Klockhoff and Lindblom on HCTZ vs. Placebo and showed no difference in Diuretics vs. placebo

Ruckenstein M.J., Rutka J.A. & Hawke M. (1991) The treatment of Meniere's disease: Torok revisited. Laryngoscope101, 211-218

Medical Management
Osmotic Diuretics (Urea, Glycerol)


Have been consistently shown to reduce symptoms in a proportion of patients, but the effects only last for a few hours Objective data includes alteration of the SP:AP ratio on Electrocochleography

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

Medical Management
Vasodilators


Purported to work by decreasing ischemia in the inner ear and allowing better metabolism of endolymph Betahistine is a popular choice, with several studies showing decreased vertigo with use
Cochrane Database Review (2004) Only one Grade B study and four Grade C studies, none of which produced convincing evidence for use.

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

Medical Management
Immunologic Management


Systemic steroids and intratympanic dexamethasone have been studied and showed no conclusive benefit. DoubleDouble-blinded prospective crossover study by Silverstein et al showed no difference from placebo with intratympanic dexamethasone injections

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

Mechanical Management
Transtympanic Micropressure Treatment


Meniett Device (Xomed) FDA approved in 1999 as a class II device Advocates present no strong case for why the device should work Portably, low intensity alternating pressure generator

Mechanical Management
Gates et al 2004


Prospective, randomized, placebo control trial of Meniett device

Did not use standardized vertigo assesment Did not comment on severity of vertigo Did not give good data on objective testing

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.

Intratympanic Therapy
Goal is to maximize local effects in inner ear while minimizing systemic effects Round window is point of diffusion to inner ear Intratympanic dexamethasone already discussed Aminoglycoside Antibiotics: affect hair cells of crista, ampulla, and cochlea

Intratympanic Therapy
Fowler in 1948, and later Schuknecht established role of systemic streptomycin for bilateral disease (2gIVPB qd until vestibular symptoms were noted) Hearing loss and oscillopsia were a problem with this therapy, though reducing dosage seemed to help

Intratympanic Gentamicin
Preferred because of Gentamicins vestibuloselectivity Side effects can include temporary imbalance or nystagmus Hearing loss Many methods of delivery exist

Intratympanic Gentamicin
Titration Therapy


Martin and Perez 2003 (prospective study, n=71)

Serial daily injections of buffered (pH 6.4) 26.7mg/cc gentamicin solution via 27 gauge needle into middle ear Injections repeated until vestibular symptoms developed (spontaneous or evoked nystagmus) At 2 years, 69% had Class A vertigo control, 14.1% had Class B 32.4% had hearing loss

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

Intratympanic Gentamicin
Ablation via Multiple Daily Dosing


Jackson and Silverstein Study on 92 patients who underwent myringotomy and wick placement through to round window niche.
Pts. self-administered gentamicin drops TID until self100% reduction on ENG of vestibular response 85% relief of vertigo, 67% improvement in aural pressure 36% hearing loss

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

Intratympanic Gentamicin
Low dose therapy


 

Harner et al 2001 retrospective study of 51 patients who received 1 dose of 40mg/mL injection and were re-evaluated in 1 month reand given another if needed At 2 years, 86% had vertigo class A or B He reported minimal change in PTA but drop in SRTs Claimed better hearing preservation with this

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

Intratympanic Gentamicin
Other methods of delivery


Weekly administration
Single dose of gentamicin once a week for four treatments

Continuous administration
Microcatheter delivery of gentamicin using a continuous perfusion method Results in extremely variable amount of gentamicin delivery Better perfusion techniques may be needed

Intratympanic Gentamicin
Chia et al performed a meta-analysis of different metamodalities of application in 2004

Class A or B Vertigo Control

Chia, Stanley H, et al Intratympanic Gentamicin Therapy for Menieres Disease: a MetaAnalysis. Otology&Neurotol 25(4) July 2004 pp 544-552

Intratympanic Gentamicin
Hearing loss was greatest for multiple daily dosing Hearing loss was least for titration therapy Hearing loss was not lower than average for low-dose therapy low-

Endolymphatic Sac Surgery

Purported to address the site of obstruction causing hydrops


4 types:
Decompression removal of bone around the sac Shunting placement of synthetic shunt to drain endolymph into mastoid Drainage incision of the sac to allow drainage Removal of sac to address the possibility that the sac may actually play a role in endolymph production

Endolymphatic Sac Surgery

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

Endolymphatic Sac Surgery

Jens Thomsen et al 1981


DoubleDouble-blinded placebo-control study with placebosham surgery (cortical mastoidectomy) vs endolymphatic shunt placement in 30 patients No difference in any outcome between sham surgery and endolymphatic sac shunt group

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

Vestibular Nerve Section

Can achieve vestibular suppression without any effect on hearing Single step procedure Can have intraoperative complications of damage to facial nerve, cochlear nerve, or CSF leak (rate of CSF leak is about 13%) Approaches: Middle Fossa, Retrolabyrinthine/Retrosigmoid

Vestibular Nerve Section

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

Vestibular Nerve Section

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


Performed via combined mastoidectomy/retrosig approach

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

Vestibular Nerve Section

Hillman et al continued

Vestibular Nerve Section

Hillman et al continued


No incidence of wound infection or meningitis in this group 12.6% incidence of CSF leak requiring LP and extended hospitalization Rates of disequilibrium were similar but persisted longer in the nerve section group

Other Ablative Surgeries

Labyrinthectomy


Useful in patients with no serviceable hearing and those who cannot tolerate intracranial procedure Similar in efficacy to vestibular nerve section

Conclusions
Therapies that definitely reduce vertigo in Menieres Disease:
 

 

Vestibular suppressant medications Intratympanic Gentamicin (especially when titrated) Vestibular Nerve Section Labyrinthectomy

Other therapies discussed are unproven or controversial