Ménière's Disease - A Comprehensive ENT Textbook Review

1. Definition

2. Epidemiology

• Incidence varies widely: ~17/100,000 (Japan) to 513/100,000 (Finland). In the US, approximately 1 in 500 persons is affected.
• More prevalent in Caucasians, with roughly equal gender distribution (slight female predominance in some series).
• Peak age of onset: 4th and 5th decades (though it can occur at almost any age).
• Bilateral disease occurs in 19-24% of patients; onset of bilateral disease may occur decades after unilateral symptoms.
• Familial occurrence in 10-20% of cases, with autosomal dominant inheritance suggested; also autosomal recessive and mitochondrial patterns described.

3. Etiopathogenesis

3a. The Endolymphatic Hydrops Theory (Core Pathology)

• Endolymph is produced by the stria vascularis (cochlea) and dark cells (vestibular labyrinth), circulating in radial and longitudinal fashion.
• In hydrops, the pathophysiology is controversial, but inadequate absorption by the endolymphatic sac is the prevalent theory.
• The endolymphatic duct may act as a valve to regulate endolymph homeostasis.
• Distension occurs at the expense of the perilymphatic space.
• Endolymphatic hydrops is uniformly observed in temporal bones of MD patients - but it is not pathognomonic, as hydrops has been found in temporal bones of patients without the classic MD symptoms.
• Membrane ruptures were proposed to cause acute attacks (mixing of K+-rich endolymph with perilymph), but Merchant et al. found ruptures in patients without a history of vertigo, undermining this as the sole explanation.
• Current thinking: hydrops may be a marker of disordered inner ear homeostasis, with an unknown factor producing both the clinical symptoms and the hydrops. - Cummings Otolaryngology

3b. Contributing Etiological Factors

• Present in approximately 1 in 3 patients.
• Theories include cross-reactions between similar antigens, innocent bystander damage via cytokine release, acquired intolerance to inner ear antigens (sequestered antigens exposed by trauma/infection), and genetic MHC-linked factors.
• HLA associations: HLA B8/DR3 and Cw7 linked to MD (possibly autoimmune etiology in these individuals).
• Polymorphisms of heat-shock protein 70 gene, PTPN22, and interleukin-1 gene (IL1) have been implicated.

• Familial MD is more prone to bilateral presentation.
• MHC associations identified; COCH-gene mutations implicated in some hereditary cases.
• Gluten sensitivity has recently been implicated as a possible etiology.

• Herpes simplex virus most commonly implicated.
• Viral structures observed by electron microscopy in vestibular ganglion cells of one MD patient.
• Vertigo control in 91% of MD patients treated with acyclovir supports viral etiology.
• Delayed endolymphatic hydrops: symptomatic hydrops occurring many years after unexplained deafness, suggesting a viral insult can trigger late-onset hydrops.

• Derebery demonstrated association with allergy; vertigo control (Class A/B) achieved in 47.9% of patients accepting allergy treatment.
• Mechanisms: endolymphatic sac targeted by allergic reaction; deposition of circulating immune complexes in fenestrated blood vessels of the endolymphatic sac and stria vascularis; viral antigen-allergic T-cell interaction.

• Endolymphatic hydrops impairs blood flow autoregulation.
• Combination of hydrops + venous obstruction shown to induce Ménière-like vertigo attacks in animal models.

• Cone-beam CT studies identify anatomical variations in the temporal bone that may predispose to blockage of the endolymphatic canal.
• Foreign protein deposition in perilymph can also cause hydrops.

4. Diagnostic Criteria

• Scott-Brown's, Table 63.1

AAO-HNS Staging (Hearing Level Staging)

5. Clinical Features

Triad / Tetrad

1. Episodic vertigo (96.2%): most distressing symptom
2. Fluctuating SNHL (87.7%): low-frequency, typically unilateral
3. Tinnitus (91.1%): low-pitched, roaring quality, ipsilateral
4. Aural fullness/pressure: a sense of pressure or plugging in the affected ear

The Typical Attack

• Often preceded by an aura: increasing fullness in the ear, rising tinnitus, hearing change
• Attacks may also be sudden without warning
• Duration: 20 minutes to several hours (most commonly 2-3 hours)
• Attacks lasting >24 hours should cast doubt on the diagnosis
• Accompanied by nausea, vomiting, diaphoresis, diarrhea
• Horizontal nystagmus is the cardinal finding; direction varies over the course of an attack (initially toward the affected ear, then away)
• No loss of consciousness
• Post-attack: fatigue, disequilibrium, which may persist for days

Variable Presentation

• Early disease may show predominantly either vestibular or auditory complaints.
• Kitahara series: 50% presented with vertigo + hearing loss together; 19% with vertigo only; 26% with only deafness.
• "Cochlear Ménière" and "vestibular Ménière" are subtypes not endorsed by AAO-HNS.

Special Presentations

• Sudden unexplained falls without loss of consciousness or vertigo
• Reported in 2-6% of MD patients
• Due to abrupt utriculosaccular dysfunction generating an erroneous vertical gravity reference via the vestibulospinal pathway
• Occur in clusters then spontaneously remit
• Risk of significant injury

• Tinnitus and hearing loss precede the onset of vertigo; when the vertiginous episode occurs, the tinnitus and hearing loss dramatically resolve
• Attributed to hydrops and membrane ruptures isolated to the basal cochlear turns and saccule

Natural History

• Highly variable; patients often have clusters of attacks separated by long remissions
• Vertigo ceases spontaneously in 57% within 2 years, and 71% by 8.3 years (Silverstein)
• Progressive sensorineural hearing loss accumulates over time, typically beginning in low frequencies and eventually becoming flat or all-frequency
• Vestibular responsiveness of the affected ear decreases over time (partial compensation)
• Disease is emotionally disabling in addition to physically incapacitating

6. Investigations

Pure Tone Audiometry (PTA)

• Low-frequency SNHL initially (250-1000 Hz affected first)
• Fluctuating pattern early; becomes flat at later stages
• "Tent-shaped" audiogram (poorer at low and high frequencies, relative preservation at 2 kHz) in early disease
• Minimum of 30 dB hearing loss at two frequencies distinguishing from the better ear required for diagnosis by AAO-HNS

Electrocochleography (ECoG)

• Records sound-evoked electrical activity near the cochlea (transtympanic or extratympanic)
• Evaluates SP/AP (summating potential / action potential) ratio - enlarged SP reflects basilar membrane displacement toward scala tympani (hydrops marker)
• Diagnostic thresholds: SP/AP ratio >0.42 (extratympanic) or >0.35 (transtympanic) using click stimuli
• Elevated SP on tone-burst stimuli: <-2 µV (<-3 µV at 1 kHz) transtympanically
• Sensitivity: large SP found in approximately 50-70% of MD patients
• SP can be reduced with hyperosmotic substances (e.g., glycerol), a diagnostic maneuver

COCHLEAR HYDROPS ANALYSIS MASKING PROCEDURE (CHAMP)

• Alternative ECoG-based diagnostic tool

Vestibular Testing

• Caloric testing: may show canal paresis (reduced response) on the affected side
• VEMP (Vestibular Evoked Myogenic Potentials): can assess saccular and utricular function
• vHIT (Video Head Impulse Test): may show reduced gain on affected side in later disease
• Rotational chair testing

Imaging

• MRI with gadolinium (IV or intratympanic):
  • Delayed MRI after intratympanic/IV gadolinium injection visualizes endolymphatic hydrops in vivo
  • Can confirm endolymphatic hydrops as in vivo surrogate for histopathologic confirmation
  • Unilateral MD often shows bilateral hydrops on delayed Gd-MRI
  • Mandatory to exclude vestibular schwannoma and other CPA lesions, inner ear malformations, neurovascular conflicts
  • Rule out white matter lesions (inflammatory, vasculoischaemic)

Blood Tests

• Thyroid function tests (if thyroid disease suspected)
• Immunological panel (if autoimmune disease suspected)
• HLA typing in familial cases
• COCH-gene mutation screening in familial MD

Differential Diagnosis

1. Vestibular migraine (headache features, photophobia/phonophobia with vestibular episodes)
2. Vestibular paroxysmia (very short <1 min attacks, neurovascular conflict on MRI)
3. Chronic subjective dizziness
4. Labyrinthitis, perilymphatic fistula, autoimmune inner ear disease, superior canal dehiscence

7. Medical Management

Step 1 - Lifestyle and Dietary Measures (First Line)

• Traditional cornerstone of MD management
• Reduces endolymphatic pressure/volume
• Recommended sodium intake: <1500-2000 mg/day (typically <2 g/day)
• Luxford et al. demonstrated that compliance with low-sodium and caffeine-free diet for >6 months produced statistically significant improvement in vertigo frequency and functional level, with higher Class A/B vertigo outcomes - Scott-Brown's
• Avoidance of caffeine (vasoconstrictive, may exacerbate hydrops)
• Avoid alcohol, monosodium glutamate, and nicotine

• Stress is a well-recognized precipitant of attacks
• Relaxation techniques, vestibular rehabilitation, and cognitive behavioral therapy are adjuncts

Step 2 - Pharmacological Medical Management

• Hydrochlorothiazide (alone or combined with triamterene - Dyazide/Maxzide)
• Acetazolamide (carbonic anhydrase inhibitor)
• Mechanism: reduce endolymphatic volume and pressure
• Cochrane analysis (Thirwall & Kundu, 2006): insufficient high-quality evidence of effect, yet diuretics remain first-line in many clinics due to clinical experience
• Monitor for: electrolyte disturbances, drug interactions

• Oral histamine analogue - weak H1 agonist, potent H3 receptor antagonist
• H3 antagonism increases histamine release at the stria vascularis, improving microcirculation; also proposed to increase endolymphatic absorption
• Marketed specifically for MD in Europe (not approved in the US)
• Standard dose: 16 mg three times daily; high-dose regimens up to 480 mg/day reported effective in refractory cases (case series)
• Cochrane analysis (James & Burton, 2001): insufficient high-quality evidence; most trials showed some vertigo control but methodology was flawed
• Very well tolerated; generally considered safe

• Antihistamines: meclizine (25-50 mg), dimenhydrinate, promethazine
• Benzodiazepines: diazepam, lorazepam (reduce vestibular excitability, useful acutely)
• Antiemetics: prochlorperazine, ondansetron
• These are used for symptom relief during attacks and are not disease-modifying

• In patients with identified allergic etiology, allergy immunotherapy/desensitization
• Derebery reported Class A/B vertigo control in 47.9% with allergy treatment

• Acyclovir considered in cases suspected of viral etiology

Step 3 - Intratympanic (IT) Therapies (Salvage Medical Treatment)

• Recommended as first-line salvage treatment (recommendation grade A) when medical management fails
• Achieves substantial long-term vertigo control in ~80% of refractory cases without significant hearing loss
• Dexamethasone (4 mg/mL or higher) is the preferred agent because it is better tolerated by middle ear tissues vs. methylprednisolone
• Methylprednisolone achieves higher perilymph/endolymph concentrations but no demonstrated superior clinical results
• First IT steroid protocol (Itoh & Sakata, 1987): 4-5 weekly injections of dexamethasone 2 mg - resulted in vertigo relief in 80%, tinnitus reduction in 74%
• Various protocols described (Table 158.2 in Cummings) including daily × 5 days, weekly × 4 weeks, on-demand
• Possible mechanism: besides anti-inflammatory effect, Na+/K+ channel modulation altering endolymph homeostasis
• No significant permanent hearing loss risk

• Indicated when IT steroids fail, or in end-stage MD with drop attacks
• Gentamicin selectively destroys vestibular hair cells (vestibulotoxic), producing partial chemolabyrinthectomy
• Typical Ménière's vertigo attacks cease because the peripheral vestibular input is ablated
• Patient may develop some imbalance or visual-vestibular mismatch post-treatment (vestibular compensation required)
• Recommendation grade A evidence for vertigo control
• Sensorineural hearing loss is a significant risk (dose-dependent) - must be factored into patient counseling
• "As-needed" or titration protocols preferred over fixed-dose to minimize cochlear toxicity
• Not indicated in the only-hearing ear

• Delivers repetitive 0.6-second pulses of low pressure (0-20 cm H2O) via a ventilation tube
• Proposed mechanism: alters endolymphatic pressure via round window
• Requires a pre-existing or surgically placed grommet
• Some positive results but Cochrane analysis results were mixed

8. Surgical Management

8a. Endolymphatic Sac Surgery (Hearing-Preserving)

• The endolymphatic sac, located on the posterior surface of the temporal bone (Trautmann's triangle), is surgically decompressed by removing overlying bone via mastoidectomy
• Rationale: improves endolymph reabsorption by relieving pressure on the endolymphatic sac

• A silicone or Dacron wick/tube is placed from the endolymphatic sac into the mastoid cavity or subarachnoid space, theoretically providing a drainage pathway for excess endolymph

• ESD: vertigo control (Class A+B) of 79.3% at 12 months, 81.6% at 24 months
• Mastoid shunting: 76.4% at 12 months, 75.7% at 24 months
• Hearing preservation (within 10 dB of preoperative thresholds): ~71-73%

8b. Tenotomy of Tensor Tympani and Stapedial Muscle Tendons

• Sectioning the tensor tympani and/or stapedius tendons to relieve increased cochlear pressure transmitted via the ossicular chain
• Proposed mechanism: increased cochlear pressure pushes the tympanic membrane laterally against the ossicles; tenotomy alleviates this
• Conflicting evidence: positive results reported only by one centre; a randomized study of IT gentamicin with vs. without simultaneous tenotomy showed no statistically significant difference

8c. Selective Vestibular Nerve Section (Hearing-Preserving Destructive)

• Surgical section of the vestibular division of CN VIII while preserving the cochlear nerve and facial nerve
• Produces vestibular areflexia on the operated side; central compensation follows
• Approaches: retrosigmoid (posterior fossa), middle fossa, or retrolabyrinthine
• Indications: disabling vertigo with useful hearing in the affected ear, failure of medical and IT therapies
• Outcomes: vertigo control comparable to IT gentamicin in case-control studies, but with greater surgical morbidity
• Risks: CSF leak, meningitis, facial nerve injury, hearing loss, headache
• Rarely performed today given effectiveness of IT gentamicin

8d. Labyrinthectomy (Destructive, Non-Hearing Preserving)

• Surgical destruction of the entire membranous labyrinth (cochlear + vestibular)
• Definitively ablates all peripheral inner ear function on the affected side
• Indicated only when:
  • Hearing in the affected ear is severely impaired (Stage 4, non-serviceable hearing)
  • IT gentamicin has failed or is contraindicated
  • The contralateral ear has serviceable hearing
• Approaches: transmastoid labyrinthectomy (most common) or transcanal
• Vertigo control: >95% - most definitive vestibular ablation procedure
• Permanent total deafness on the operated side is certain
• Vestibular rehabilitation required post-operatively for central compensation

Summary Algorithm for Surgical Decision-Making

Disabling MD, failed medical therapy
           |
           ↓
  IT Dexamethasone (Grade A)
           |
     Still failing?
           ↓
  IT Gentamicin (Grade A)  ←— Especially if drop attacks
           |
     Still failing?
           ↓
  Hearing in affected ear?
    |                  |
   Yes                 No
    |                  |
Endolymphatic     Labyrinthectomy
Sac Surgery /    (>95% vertigo control)
Vestibular Nerve
Section

9. Summary Table

• Cummings Otolaryngology Head and Neck Surgery, 6th Ed. (Flint et al.), Chapters 158 & 167
• Scott-Brown's Otorhinolaryngology Head & Neck Surgery, 8th Ed., Vol. 2, Chapter 63
• K.J. Lee's Essential Otolaryngology, 11th Ed.