**2. A short introduction of Ménière's disease (MD)**

MD is an idiopathic disorder of the inner ear. It is characterized by paroxysmal unpredictable crisis, with a typical symptomatological triad: tinnitus, hearing loss associated to fullness and objective vertigo with neurovegetative symptoms [6]. The crises have a variable duration (from few minutes to 24 h) and the intercritical periods are characterized by residual dizziness or wellness, configuring, anyway, a particularly invalidating disease, particularly considering the unpredictability of the crisis.

MD occurs typically between the fourth and sixth decades of life, with a mild prevalence in women. It is frequently unilateral, but both ears may be affected with the progression of the disease. Although most cases of MD are sporadic, a 5-15% has a familiar configuration and seems to have a hereditary transmission.

acoustic energy is transformed by the middle ear in acoustic pressure applied to the stapes footplate. The pressure wave inside the cochlea stimulates the OAE generators and a reverse acoustic energy (the OAE response) propagates from the inner ear, through the stapes and the middle ear structures, to the tympanic membrane. There it can be recorded by a sensitive

The classical classification scheme categorizes OAEs according to their evoking stimulus [3]. In this context, the OAE responses can be elicited by transient clicks (TEOAEs), transient tone bursts (TBOAEs), or by pure tones (distortion product OAEs – DPOAEs). Responses evoked by random thermal noise in the cochlea are called Spontaneous OAEs (SOAEs), which have limited clinical applications. The newest and most accepted taxonomy classifies the responses according to their generation mechanisms [4]. According to Shera and Guinnan [4], the OAE responses are evoked by a linear reflection (of the travelling wave energy) on the basilar membrane, or by nonlinear processes "orchestrated" by nonlinear characteristics of the outer hair cells (OHCs) and the cochlear amplifier per se. The clinically used responses (TEOAEs or

The OAE values, express a measure/metric of the cochlear amplifier functionality, which has found numerous applications in Audiology and Hearing Science. The most known application is in the area of hearing screening. TEOAEs can detect sensorineural deficits up to 35 dB HL; DPOAEs are more sensitive and can detect deficits up to 40 dB HL [3]. The great advantage of OAEs, in comparison to traditional audiometry tests, is that they can detect a deficit before it registers as a hearing deficit (i.e., it is in a subclinical phase) [3]. When an external or internal stressor causes severe mechanical alterations on the functionality of the OHCs, intrinsic and extrinsic apoptotic processes are initiated [5]. Within the next time-frames (days/months), the corresponding OAEs are severely altered and gradually, the OHC damage induces an intrinsic neural apoptosis and a subsequent hearing deficit.

Therefore, the OAE response characteristics are altered by inner ear disorders, such as Meniere's disease (MD), a condition in which the whole inner ear can be damaged, including

This chapter is an excursus of the current scientific findings relating vestibular and middle ear alterations, as observed in various stages of the Ménière's disease, with measurements of otoacoustic emissions. The latter are considered the test of choice to identify preclinical effects

MD is an idiopathic disorder of the inner ear. It is characterized by paroxysmal unpredictable crisis, with a typical symptomatological triad: tinnitus, hearing loss associated to fullness and objective vertigo with neurovegetative symptoms [6]. The crises have a variable duration (from few minutes to 24 h) and the intercritical periods are characterized by residual dizziness or wellness, configuring, anyway, a particularly invalidating disease, particularly considering

MD occurs typically between the fourth and sixth decades of life, with a mild prevalence in women. It is frequently unilateral, but both ears may be affected with the progression of the

all the structures of the cochlea (outer and inner hair cells) and the vestibular system.

on the human hearing threshold and alterations in the inner ear.

**2. A short introduction of Ménière's disease (MD)**

the unpredictability of the crisis.

probe (microphone), inserted in the acoustic meatus.

138 Up to Date on Meniere's Disease

DPOAEs) are a mixture of these two mechanisms.

To date, the etiology of MD is unknown, but anatomopathological and histopathological studies on Menieric patients temporal bones, have revealed an enlargement of the membranous labyrinth due to an endolymphatic hydrops [7, 8]. Therefore, the most accredited theory about MD pathogenetic mechanism is the increase of the endolymphatic volume, due to a disorder of either production or reabsorption mechanisms of endolymph, with an expansion and a possible rupture of the membranous labyrinth [9–11]. The damage to the hair cells may be due to both the pressure, during the hydrops phase, and the mixture of endolymph and perilymph, if the membrane rupture occurs. In this case particularly, it has been stated that the crisis may be produced by a potassium intoxication of the labyrinth sensorial epithelium, after the Reissner's membrane rupture [12, 13].

Even though infrequent, endolymphatic hydrops can be congenital and it may be consequent to inner ear malformations, such as Mondini dysplasia [14]. More frequently, the acquired hydrops can be a consequence of viral or bacterial labyrinth infections, or traumas [15].

It has been reported that endolymphatic hydrops has been observed also in asymptomatic patients; this suggests that there should be many 'triggering factors' that may rouse a MD crisis, such as hydric retention, viral infections, stress, cranial traumas, vitamin deficiency, and endocrine disorders [16].

The diagnosis of MD is difficult and it can be defined only after some vestibular crisis with the typical triad. In 1995, the American Academy of Otolaryngology-Head and Neck Surgery published the diagnostic criteria for MD, then updated in 2015, defining a "possible", "probable", and "definite" MD, depending on the frequency of the typical symptoms, until the "confirmed" diagnosis of MD, achievable only with a histopathological examination [17, 18]. A careful history taking and the audiovestibular instrumental examination are recommended. Otoscopy is usually negative.

In the initial phases of MD, the tonal audiometry finds a unilateral cochlear sensorineural hearing loss, affecting the low frequencies. At the beginning, the MD hearing loss is typically fluctuating, reflecting the inner ear hydrops phase: only during this phase, it is possible to perform an osmotic test (Glycerol test) and to observe the improvement of 10 dB in the hearing threshold, at least on two frequencies between 500 Hz and 2000 Hz, within 3 hours, after the administration of 1.5 ml/Kg of body weight of oral glycerol (a potent osmotic agent) with the same volume of isotonic saline solution [19, 20]. The glycerol test is not a diagnostic evaluation, but it allows in determining the reversibility of the early phase of MD and, therefore, it has a prognostic and therapeutic significance. The verbal discrimination is initially preserved at the vocal audiometry. In an advanced MD, hearing loss becomes permanent, pantonal, and often bilateral [21, 22]. The evaluation of the acoustic reflex threshold also demonstrates the recruitment phenomenon, typical of cochlear lesions. Auditory brainstem responses (ABR) can exclude a retrocochlear disease. The vestibular instrumental examinations could be normal at the beginning; during the progress of MD, it reveals a unilateral vestibular hyporeflectivity. Electrocochleography can determine, during the hydropic phase, an increased summating potential, due to the distension of basilar membrane into the scala tympani and then an increased action potential/summating potential ratio [23].

Neuroimaging, such as laboratory exams, are recommended during the differential diagnosis in order to exclude other diseases causing Ménière's-like symptoms or congenital malformation/anatomic variations of the inner ear or metabolic, electrolytic, endocrine, vitaminic, immunologic disorders potentially implicated in MD [24].
