Meniere's disease pathophysiology

This explains the pathophysiology, histology and the diagnostic criteria of Meniere's disease

1. MÉNIÈRE’S DISEASE PATHOPHYSIOLOGY AND CLINICAL FEATURES Dr Prajwal Dange

2. INTRODUCTION Ménière’s disease is an idiopathic inner ear disorder characterized by recurrent spontaneous vertigo accompanied by fluctuating or progressive sensorineural hearing loss, tinnitus and aural fullness in the affected ear. The vertigo episodes - most incapacitating. Ménière’s disease is, by definition, the idiopathic type of endolymphatic hydrops. Ménière’s syndrome is secondary type presenting a similar clustering of symptoms caused by, for example, syphilis, trauma, autoimmune disorders.

3. HISTORY Prosper Meniere first described the symptom complex of the eponymous disease in 1861. Proposed the pathologic site to be in the labyrinth. Knapp advanced the hypothesis that hydrops was similar to ocular glaucoma. Histologically demonstrated in 1938.

4. INCIDENCE 4.3 per 100 000 population per year. More prevalent among whites Equal gender distribution. Age of onset - second to sixth decade. SPORADIC Majority of cases are sporadic. FAMILIAL Estimated 5–15% of cases are familial. Various genes are proposed which includes AQP2, KCNE1, KCNE3, HCFC1, COCH, ADD, HSPA1A, PTPTN22 and IL1.

5. The endolymphatic sac can be divided into 3 portions based on the cellular lining: (1) the proximal (rugose) portion, in vestibular aqueduct and is constituted by the same epithelia of the endolymphatic duct (2) the intermediate portion, partly inside of the vestibular aqueduct and partly between layers of dura, which consists of cuboidal cells (3) the distal portion, which lies within layers of dura mater and is lined by cuboidal cells.

6. PRODUCTION AND REGULATION OF ENDOLYMPH Endolymph is not only potassium-rich (150-180 mmol/L) but also nearly sodium-free. Evidence points toward the formation of endolymph from perilymph, rather than from plasma. The transepithelial K+ transportation from perilymph to endolymph through the Na+,K + ATPase ion pump is responsible for maintaining both the high endocochlear electric potential and the unique composition of endolymph.

7. The stria vascularis is responsible for the secretion of endolymph, with small contributions from the planum semilunatum and from dark vestibular cells. The rate of endolymph secretion seems to be influenced by a number of factors and hormones, including aldosterone and vasopressin.

8. Endolymph flows within the membranous labyrinth, by 2 concurrent mechanisms: (1) radial (a rapid, ongoing process), which is important for energy metabolism and ion exchange around the sensory cell regions; and (2) longitudinal (slow) flow, which enables reabsorption of endolymph and disposal of high-molecular waste products and debris by the endolymphatic sac. Those 2 mechanisms occur simultaneously, in a continuous fashion.

9. PATHOPHYSIOLOGY ENDOLYMPHATIC HYDROPS Obstruction of the endolymphatic duct is the basis for development of hydrops in experimental animals. Lesion producing failure of duct function by mechanical blockage, chemical fibrosis, viral inoculation, immunologically induced inflammation, and ischemia This theory remains controversial although it was observed in all temporal bones with Ménière’s disease.

10. Clinical data supporting this theory is based on delayed MRI after intratympanic or intravenous administration of gadolinium-based contrast agents. In electrocochleography, large summating potential has been observed in 50–70% of patients with Ménière’s disease, which can be reduced with administration of hyperosmotic substances.

11. Endolymphatic hydrops is not pathognomonic to Ménière’s disease. Endolymphatic hydrops was observed in a significant number of temporal bones from patients with hearing loss, without the classical symptoms of Ménière’s disease. Delayed MRI after intratympanic injection of gadolinium-based contrast agent in unilateral Ménière’s disease reveals bilateral endolymphatic hydrops quite frequently.

12. Schuknecht postulated Ruptures in the membranous labyrinth Leakage of the potassium rich endolymph into the perilymph bathes the eighth cranial nerve and lateral sides of the hair cells

13. High concentrations of K+ Depolarize the nerve cells Acute inactivation Decrease in auditory and vestibular neuronal outflow

14. Healing of the membranes Restitution of the normal chemical balance Termination of the attack Improvement in vestibular and auditory function Healed scars, have also been identified which supports this theory.

15. AUTOIMMUNE FACTOR In approximately 1 in 3 patients seems to have an autoimmune factor. Several theories were suggested, including cross-reactions between similar antigens, innocent bystander damage due to cytokine release, acquired intolerance to inner ear antigens (covert from the immunological system and exposed by trauma or infection)

16. VASCULAR FACTOR It has been observed that endolymphatic hydrops impairs blood flow autoregulation. The combination of endolymphatic hydrops and venous obstruction has shown to induce vertigo attacks similar to Ménière’s disease in an animal model.

17. VIRAL FACTOR A viral etiology has been suggested as well, most often involving the herpes simplex virus . Viral structures have been observed by means of transmission electron microscopy in the vestibular ganglion cells of Ménière’s disease patient, which supports this theory. ALLERGIC FACTOR

18. HISTOPATHOLOGY Hallpike, Cairns and Yamakawa report considered hallmarks of the disease (dilation of the scala media of the cochlea, with displacement of Reissners membrane into the vestibular scala ).

19. CLINICAL PRESENTATION No single test makes the diagnosis of Meniere disease. Clinical presentation The typical history consists of Recurring attacks of vertigo (96.2%) with Tinnitus (91.1%) and Sensory neural hearing loss (87.7%).

20. VERTIGO Attacks are often preceded by an aura that consists of a sense of fullness in the ear, increasing tinnitus, and a decrease in hearing. However, onset may be sudden with little or no warning. The classic presentation is not always detailed by the patient.

21. A typical attack of Ménière’s disease can be defined by the direction of the spontaneous nystagmus. Irritative phase - The nystagmus will beat towards the affected ear in a horizontal or horizontal–torsional direction, a finding which usually lasts less than 1  hour. Paretic phase - The nystagmus will beat away from the affected ear and last hours to days. Recovery phase - The nystagmus again beats towards the affected side because peripheral vestibular function recovers.

22. The clinical course is highly variable. Long remissions. Silverstein and colleagues found that vertigo ceased spontaneously in 57% of patients in 2 years and in 71% after 8.3 years.

23. Sudden unexplained falls without loss of consciousness or associated vertigo are occasionally described. Tumarkin attributed these to acute utriculosaccular dysfunction, so-called otolithic crises of Tumarkin or drop attacks. It is thought that an erroneous vertical gravity reference occurs as a consequence of an abrupt change in otolithic input. This in turn generates an inappropriate postural adjustment via the vestibulospinal pathway, which results in a sudden fall.

24. Attacks are so sudden that injury can occur, and the patient often describes being pushed or feeling the world moving. The spells are short lived with little associated vertigo. Drop attacks have been reported in 2% to 6% of people with Meniere disease, and they tend to occur in clusters and then spontaneously remit.

25. Lermoyez described an unusual clinical presentation in which tinnitus and hearing loss precede and worsen with the onset of vertigo: when the vertiginous episode occurs, the tinnitus and hearing loss dramatically resolve. The temporal bone studies of one individual with such attacks noted hydrops and membrane ruptures isolated to the basal turns of the cochlea and the saccule.

26. HEARING LOSS Low-frequency sensorineural hearing loss is defined as increases in pure-tone thresholds for bone-conducted sound that are higher (i.e.  worse) in the affected ear than the contralateral ear by at least 30 dBHL at each of two contiguous frequencies below 2 kHz. In cases of bilateral low-frequency sensorineural hearing loss, the absolute thresholds for bone-conducted sound must be 35 dBHL or higher at each of two contiguous frequencies below 2000 Hz.

27. If multiple audiograms are available, demonstration of recovery of low-frequency sensorineural hearing loss at some point in time further supports the diagnosis of Ménière’s disease. Bilateral synchronous sensorineural hearing loss (symmetric or asymmetric) can occur in some patients.

28. Additional features include diplacusis, a difference in the perception of pitch between the ears (43.6%), and recruitment (56%). Tinnitus tends to be non pulsatile and is variously described as whistling or roaring. It may be continuous or intermittent. Tinnitus often begins, gets louder, or changes pitch as an attack approaches; after the attack, a period of improvement is common.

29. CRITERIA FOR DIAGNOSIS Vertigo • Recurrent, well-defined episodes of spinning or rotation • Duration from 20 minutes to 24 hours • Nystagmus associated with attacks • Nausea and vomiting during vertigo spells (common) • No neurologic symptoms with vertigo Deafness • Fluctuating hearing deficits • Sensorineural hearing loss • Progressive hearing loss, usually unilateral Tinnitus • Variable, often low pitched and louder during attacks • Usually unilateral • Subjective

30. DIAGNOSIS OF MENIERE DISEASE Possible Meniere Disease • Episodic vertigo without hearing loss or • Sensorineural hearing loss, fluctuating or fixed, with dysequilibrium but without definite episodes • Other causes excluded Probable Meniere Disease • One definitive episode of vertigo • Hearing loss documented by audiogram at least once • Tinnitus or aural fullness in the suspected ear • Other causes excluded

31. Definite Meniere Disease • Two or more definitive spontaneous episodes of vertigo lasting at least 20 minutes • Audiometrically documented hearing loss on at least one occasion • Tinnitus or aural fullness in the suspected ear • Other causes excluded Certain Meniere Disease • Definite Meniere disease plus histopathologic confirmation

32. The most recent guidelines for the diagnosis in patients with Ménière’s disease were issued in 2015.