**3. Vestibular evaluation**

Vestibular investigations are also recommended in Menière's disease patients not only as a recommended battery test for positive diagnosis, but also in order to evaluate the degree of vestibular lesion which is present from the beginning of the Menière's disease.

Both vestibulo-ocular reflex (VOR) and vestibulospinal reflex (VSR) should be evaluated. Besides bed-side evaluation, objective vestibular tests are performed for a quantitative measure of these two vestibular reflexes useful in understanding the vestibular deficits as the disease proceeds.

**Figure 11.** Nystagmus recording = variations of the corneo-retinian potential.

#### **3.1. Vestibulo-ocular reflex**

#### *3.1.1. Electronystagmography (ENG)/videonystagmography (VNG)*

Electro- or videonystagmography allows quantification of the nystagmus, as specific sign of vestibule-ocular reflex dysfunction. Nystagmus, as a conjugate movement of eyes with a slow and a fast phase provoked by vestibular asymmetry, reflects variations of the corneo-retinian potential during eyes movement (**Figure 11**). The slow phase is the effect of vestibular stimulation and its amplitude is proportional to the intensity of vestibular stimulation. The fast phase is central in origin and reflects only the reflex movement of the eyes to return to their normal position in the orbit. The fast phase direction gives the nystagmus direction.

The corneo-retinian potential can be measured by surface electrodes fixed around the eyes, horizontal and vertical or registered with infrared camera (**Figure 12**) in Refs. [15–17]. Conventionally, for horizontal electrodes, the upward fast phase is considered right beating nystagmus, while the downward fast phase is considered left beating nystagmus. For vertical electrodes, the upward fast phase is considered superior beating nystagmus, while the downward fast phase is considered inferior beating nystagmus.

Quantification of the nystagmus is based on several parameters:


**Figure 12.** Calculation of nystagmus slow phase velocity.

Several tests are included in the electro-/videonystagmography (ENG/VNG): spontaneous nystagmus, positional, and positioning nystagmus, as well as provoked nystagmus (post or perrotatory nystagmus and caloric nystagmus). The provoked test is recommended only if patient is not in an acute vertigo phase.

Rotatory and caloric testing evaluates semicircular canal function in response to rotation or irrigation with warm and cold water/air of the external ear canal. Bithermal irrigation causes convective movement of endolymph in the ipsilateral horizontal semicircular canal, caloric test being the only available test that gives information regarding each horizontal semicircular canal. The movement of the endolymph provoked by variation of temperature and, secondary, endolymph density results in deflection of the cupula of the irrigated semicircular canal. Motion of the cupula leads to vestibular hair cell excitation or inhibition with consecutive change of the discharge rate in the superior vestibular nerve fibers. The difference between the excitatory and inhibitory discharge rates of the two superior vestibular nerves reaches the vestibular nuclei. From here compensatory eye movements are elicited (slow phase of nystagmus), followed by rapid corrective saccades (fast phase of nystagmus).

**3.1. Vestibulo-ocular reflex**

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direction.

nystagmus.

*3.1.1. Electronystagmography (ENG)/videonystagmography (VNG)*

**Figure 11.** Nystagmus recording = variations of the corneo-retinian potential.

ward fast phase is considered inferior beating nystagmus.

Quantification of the nystagmus is based on several parameters:

• Velocity of the slow phase, vestibular in origin (**Figure 12**).

**Figure 12.** Calculation of nystagmus slow phase velocity.

Electro- or videonystagmography allows quantification of the nystagmus, as specific sign of vestibule-ocular reflex dysfunction. Nystagmus, as a conjugate movement of eyes with a slow and a fast phase provoked by vestibular asymmetry, reflects variations of the corneo-retinian potential during eyes movement (**Figure 11**). The slow phase is the effect of vestibular stimulation and its amplitude is proportional to the intensity of vestibular stimulation. The fast phase is central in origin and reflects only the reflex movement of the eyes to return to their normal position in the orbit. The fast phase direction gives the nystagmus

The corneo-retinian potential can be measured by surface electrodes fixed around the eyes, horizontal and vertical or registered with infrared camera (**Figure 12**) in Refs. [15–17]. Conventionally, for horizontal electrodes, the upward fast phase is considered right beating nystagmus, while the downward fast phase is considered left beating nystagmus. For vertical electrodes, the upward fast phase is considered superior beating nystagmus, while the down-

• Direction of the nystagmus—linear, vertical, rotatory; right-, left-, superior- or inferior-beating

In Menière's disease patients, results in ENG/VNG differ depending on the phase (acute, subacute, or chronic) and the duration of the disease.

At the beginning of an acute phase, due to the minor ruptures in the Reissner's membrane and an increase of potassium concentration in the endolymph, the vestibular sensorial epithelium in the affected ear is stimulated and the spontaneous nystagmus beats toward the Menière's ear (**Figure 13**). Soon after, due to constantly increasing of the potassium concentration, the vestibular hair cells are intoxicated and their function decrease. In this stage, spontaneous nystagmus changes its direction toward the healthy ear.

In the next days after the acute spell of the Menière's disease results in rotatory and caloric test varies—either hypofunction in the affected ear (**Figure 14**), or symmetric functionality of the inner ears. The absence of a fixed vestibular lesion is the case in most of patients. In prolonged Menière's disease (long-term/chronic effect) usually patients' express caloric hypofunction of the affected ear (1/2—2/3 of patients) as VOR reflects the decreased input from the damaged

**Figure 13.** Spontaneous nystagmus: A—initial phase of the spell (towards the affected ear); B—end of the spell (towards the non-affected ear).

**Figure 14.** Left ear caloric hyporeflexia-hypofunction index > 30%.

ear. Caloric stimulation can be done sequential with warm and cold water, respectively, for each ear, or simultaneously. Bilateral cold water (30°C) irrigation shows rapidly the affected ear—the ear toward the nystagmus appears.

In rotatory chair test, results are usually normal. Directional preponderance is rarely seen, usually in long-duration Menière's disease, when vestibular lesion is stable at some extent (**Figure 15**). But immediately after an acute attack, VOR gain is increased in rotation toward the affected ear [18].

In between the acute spells, Menière's disease patients can experience positional vertigo, usually due to benign paroxysmal positional vertigo (BPPV). Disturbances in endolymph metabolism affect the function of the *stria vascularis* with secondary negative effects on the otolithic membrane. Still, BPPV is more frequently associated with vestibular migraine than Menière's disease.

#### *3.1.2. Video head impulse test*

The video head impulse test (HIT) evaluates as well semicircular canal function. Integrity of the VOR allows the tested subject to maintain sight fixed during high-acceleration high-velocity

**Figure 15.** Symmetrical VOR response in rotatory test.

head rotations in space (gain values close to 1.0, as the ratio between eye and head velocity). Rotation is performed in each plane with an excitatory effect on each of the six semicircular canals.

A positive HIT stands for complete lesion of the fibers connected with the tested semicircular canal. In comparison with caloric testing, video HIT is abnormal in much more small numbers of Menière's disease patients, maybe because vestibular lesion is not complete.

#### **3.2. Vestibulospinal reflex (VSR)**

ear. Caloric stimulation can be done sequential with warm and cold water, respectively, for each ear, or simultaneously. Bilateral cold water (30°C) irrigation shows rapidly the affected

In rotatory chair test, results are usually normal. Directional preponderance is rarely seen, usually in long-duration Menière's disease, when vestibular lesion is stable at some extent (**Figure 15**). But immediately after an acute attack, VOR gain is increased in rotation toward

In between the acute spells, Menière's disease patients can experience positional vertigo, usually due to benign paroxysmal positional vertigo (BPPV). Disturbances in endolymph metabolism affect the function of the *stria vascularis* with secondary negative effects on the otolithic membrane. Still, BPPV is more frequently associated with vestibular migraine than Menière's

The video head impulse test (HIT) evaluates as well semicircular canal function. Integrity of the VOR allows the tested subject to maintain sight fixed during high-acceleration high-velocity

ear—the ear toward the nystagmus appears.

**Figure 14.** Left ear caloric hyporeflexia-hypofunction index > 30%.

the affected ear [18].

110 Up to Date on Meniere's Disease

*3.1.2. Video head impulse test*

**Figure 15.** Symmetrical VOR response in rotatory test.

disease.

Equilibrium is a complex process, essential in human well-being and daily activities. It allows standing on different supports as well as walking and other movements without falling or disequilibrium.

Body and head position in space, related to gravity and environment landmarks (of verticality for example), is based on normal and correlated information's form sensorimotor, visual and vestibular systems. The most important, for sure until adult life, is the sensorimotor system proprioceptors from feet and neck contribute mostly in equilibrium as we move in space.

As long as the child grows, visual information becomes more important in equilibrium, especially when visual surroundings are difficult.

A vestibular system develops in function in the first year of life and contributes progressively more to equilibrium. Its contribution increases in the case of a lesion in either of the other two systems [15–17]. Besides this, a severe unilateral vestibular deficit or bilateral vestibular lesion has a huge impact on equilibrium, at least for several weeks until a unilateral vestibular deficit is compensated by the other ear.

In Menière's disease, pathophysiology of the disease explains the fluctuating vestibular function of the affected ear. So, we do not have a stable deficit, at least not a complete one, or from the very beginning of the disease. For this reason, vestibular investigations have different results, from patient to patient, as we discussed in the ENG section.

#### *3.2.1. Computerized dynamic posturography*

Computerized dynamic posturography (CDP) contributes with specific parameters in monitoring patients with Menière's disease—for appropriate diagnostic and management. CDP is based on a force plate system capable of measuring the antero-posterior balance of the center of gravity of the tested subject and automatically compare this balance with normal values for patient's group of age.

Sensory organization test (SOT) is the most common test of CDP. It allows a selective use of each of the three systems involved in equilibrium during six different conditions of testing (**Figure 16**) in [19] and thus a global and selective evaluation of equilibrium, based on the system used for maintaining the standing position during testing in [20].

As long as projection of the center of gravity (COG) during testing is inside the base support area and no external support is used for stabilize, patient is able to maintain his/her equilibrium and normal result will be displayed at the end of the test (**Figure 17**). When patient

**Figure 16.** CDP/SOT testing conditions (www.nervecenter.natus.com).

**Figure 17.** CDP—normal result.

cannot voluntary control its balance within the parameters described, he will obtain a pathological score of equilibrium, displayed at glance with colors convention and also with numeric values (**Figure 18**).

In Menière's disease patients, CDP usually display normal results, since in between the spells patient has no equilibrium problems and the acute vestibular deficit of the affected ear was

**Figure 18.** CDP—pathological result: vestibular deficit.

**Figure 19.** Montage and cVEMP biphasic potential.

compensated already. Immediately after the acute phase, vestibular scores can be abnormal, mainly in vestibular condition.

#### *3.2.2. Vestibular evoked miogenic potentials*

cannot voluntary control its balance within the parameters described, he will obtain a pathological score of equilibrium, displayed at glance with colors convention and also with numeric

In Menière's disease patients, CDP usually display normal results, since in between the spells patient has no equilibrium problems and the acute vestibular deficit of the affected ear was

values (**Figure 18**).

**Figure 17.** CDP—normal result.

112 Up to Date on Meniere's Disease

**Figure 16.** CDP/SOT testing conditions (www.nervecenter.natus.com).

Vestibular evoked miogenic potentials (VEMPs) area relatively new objective test designed to measure otolithic function in [21]. In response to loud sound stimulation (95–97dB nHL), saccular vestibular sensorial epithelium generates activity in the inferior vestibular nerve and further in the vestibulospinal and vestibule-ocular pathway.

Action potential transmitted through the vestibulospinal pathway generates muscular responses in the effectors of the vestibulospinal (cervical muscles—cervical vestibular evoked myogenic potential: cVEMP) or vestibule-ocular reflex (extraocular muscles—ocular vestibular evoked myogenic potential: oVEMP).

#### *3.2.2.1. Cervical VEMP*

cVEMP represents an inhibitory biphasic response in the ipsilateral sternocleidomastoid muscle after loud sound stimulation of the sacculae, which can be recorded by surface electrodes. A positive-negative P13-N23 potential is recorded with normal latencies of 13 and 23 ms, respectively (**Figure 19**). The greatest sensitivity of sacculocolic reflex is for 200–1000 Hz stimuli in Refs. [22, 23], a frequency range highly correlated with saccular function and resonance properties as well (which are correlated with saccular size).

Late N34-P44 potentials are not saccular in origins. The amplitude of the response varies with contraction level of the muscle (**Figure 20**).

A clinical value of cVEMP is based on comparison of cVEMP amplitude in response to each saccular stimulation. For this reason, contraction level should be measure as well and rectified traces are evaluated. A difference of more than 30% between cVEMP amplitudes is considered abnormal, in result either to saccular hypofunction or hyperfunction depending on the pathology.

In Menière's disease, endolymphatic hydrops involves the sacculae from the very initial stages of the disease with secondary variations in sacculae's mechanical properties. Since cervical VEMP depends on the physical characteristics of the sacculae, cVEMP is included in the vestibular battery test for Menière's disease diagnosis. In more than 50% of Menière's disease patients, click-evoked cVEMP is abnormal or absent in Refs. [24, 25].

It also has been studied frequency tuning of cVEMP in endolymphatic hydrops and it appears that VEMP is recorded at higher frequencies and across broader frequency ranges than in normal inner ears due to changes in saccular resonance characteristics [26].

These two changes (blunting and frequency shift of cVEMP) are greater as the Menière's disease has a longer evolution and greater severity in [27]. Additionally, over 20% of Menière's disease patients have abnormal cVEMP results in the non-affected ear in Ref. [28], recommending VEMP as a predictor test for bilateral Menière's disease.

**Figure 20.** Amplitude variation in relation with muscle contraction.

**Figure 21.** VEMP amplitude variation in positive glycerol test.

Another study revealed a correlation between cVEMP threshold variations in between affected and nonaffected ear and the severity of Menière's disease in Ref. [29].

In a small series of Menière's disease patients, VEMP increased in amplitude, even three times at the end of positive glycerol test (**Figure 21**) as an argument of presence of the endolymphatic hydrops in the sacculae in Ref. [30].

#### *3.2.2.2. Ocular VEMP*

*3.2.2.1. Cervical VEMP*

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pathology.

cVEMP represents an inhibitory biphasic response in the ipsilateral sternocleidomastoid muscle after loud sound stimulation of the sacculae, which can be recorded by surface electrodes. A positive-negative P13-N23 potential is recorded with normal latencies of 13 and 23 ms, respectively (**Figure 19**). The greatest sensitivity of sacculocolic reflex is for 200–1000 Hz stimuli in Refs. [22, 23], a frequency range highly correlated with saccular function and reso-

Late N34-P44 potentials are not saccular in origins. The amplitude of the response varies with

A clinical value of cVEMP is based on comparison of cVEMP amplitude in response to each saccular stimulation. For this reason, contraction level should be measure as well and rectified traces are evaluated. A difference of more than 30% between cVEMP amplitudes is considered abnormal, in result either to saccular hypofunction or hyperfunction depending on the

In Menière's disease, endolymphatic hydrops involves the sacculae from the very initial stages of the disease with secondary variations in sacculae's mechanical properties. Since cervical VEMP depends on the physical characteristics of the sacculae, cVEMP is included in the vestibular battery test for Menière's disease diagnosis. In more than 50% of Menière's disease

It also has been studied frequency tuning of cVEMP in endolymphatic hydrops and it appears that VEMP is recorded at higher frequencies and across broader frequency ranges than in

These two changes (blunting and frequency shift of cVEMP) are greater as the Menière's disease has a longer evolution and greater severity in [27]. Additionally, over 20% of Menière's disease patients have abnormal cVEMP results in the non-affected ear in Ref. [28], recom-

nance properties as well (which are correlated with saccular size).

patients, click-evoked cVEMP is abnormal or absent in Refs. [24, 25].

mending VEMP as a predictor test for bilateral Menière's disease.

**Figure 20.** Amplitude variation in relation with muscle contraction.

normal inner ears due to changes in saccular resonance characteristics [26].

contraction level of the muscle (**Figure 20**).

Ocular VEMP (oVEMP) is a newer variant of VEMP which measures saccular function in response to very loud sound stimulation (about 120–130 dB SPL) or utricular function in response to vibrations applied to the cochlea. Electrodes placed below the orbit record excitatory response in the contralateral inferior oblique muscle when in a flexed state by looking upward in Ref. [31].

The first negative (excitatory) component of the oVEMP at a latency of about 10 ms is called n10. This n10 component most likely indicates the myogenic potentials of inferior oblique muscle.

Additionally, in patients with early Menière's disease tested at attack, the contralateral oVEMP n10 is enhanced compared to measures in the same patients at quiescence. We speculate that this enhancement by Menière's disease attack could be due to mechanical changes in the labyrinth that enhance the sensitive response of utricular receptors to bone conduction vibrator stimulation. It seems that alterations in frequency tuning discussed in cVEMP are also present in sound-evoked oVEMP in Menière's disease patients in Ref. [32].
