Role of cVEMP in Management of Balance Disorders

Abstract

Balance disorders may occur in a multitude of ENT-related diseases, thus making a correct diagnosis is challenging. In the last few decades, there has been a paradigm shift in the diagnostics of balance disorders due to the availability of better objective modalities that allow the assessment of different components of the complex vestibular labyrinth with relative ease. With the advent of vestibular-evoked myogenic potentials (VEMP) since the last few decades, it is possible to test otolith organs in isolation and objectively. This chapter will discuss the procedure, physiological basis, and effectiveness of cervical VEMP in the evaluation of saccular function in patients suffering from balance disorders.

1. Introduction

Balance disorders are one of the most common presentations to otolaryngology clinic. Inability to maintain balance or occurrence of vertigo has a considerable impact on social and working life. Imbalance is one of the most common symptoms which patients experience at some time or the other in their lifetime, with a lifetime prevalence of about 30% and an annual incidence that increases with age [1]. Despite this high prevalence and burden of disease, diagnosing the cause of imbalance remains a considerable challenge as the pathology may involve many sensory organs.

Most patients with balance disorders are uncertain who to consult, because their problem lies in between the specialties of neurology, otolaryngology, and in some cases, ophthalmology, general/internal medicine, endocrinology, or psychiatry. Imbalance, whether episodic or chronic, causes significant deterioration in the quality of life of a person and can cause anxiety, depression, reduced physical activity, and possible inability to work. In elderly population, falls due to imbalance add to existing morbidity to a great extent [2].

In the last few decades, availability of better objective modalities which help in assessing different components of complex vestibular labyrinth with relative ease have led to better diagnostics of balance disorders, and now precise localization of the vestibular disorders possible. These tests are rapid, reliable, and effective in diagnosing balance disorders.

The vestibular system consists of the three semicircular canals (lateral, superior, and posterior) and otolith organs (saccule and utricle). The majority of the clinical vestibular function tests for imbalance such as the caloric test, head impulse test, Dix-Hallpike test, supine roll test, subjective visual vertical, VNG, rotational tests mainly test the semicircular canals. But with the advent of vestibular-evoked myogenic potentials (VEMP), it is possible to test otolith organs separately and objectively. Various studies showed that high intensity sound stimulus resulted in activation of vestibule apart from stimulating cochlea and generated electromyographic reflexes in many muscles including sternocleidomastoid (SCM) and extraocular muscles. It was also possible to easily record these electromyographic reflexes with surface electrodes placed on SCM. The electromyographic reflexes recorded over SCM are called cervical VEMP or cVEMP, and they record sacculo-collic reflex, and those on the extra ocular muscles are called ocular VEMP or oVEMP and they record utriculo-collic reflex [3]. This chapter shall dwell upon cVEMP primarily.

2. Physiological basis of VEMP

The physiology of cVEMP generation has been hypothesized based on tendency of the animals to look in the direction of sound. Evolution has proved that vestibular system evolved earlier than the cochlear system. In reptiles and marine animals, the vestibular system served the purpose of hearing too. The saccule, which is part of otolithic organ, has remnants of these hearing receptors. These are transmitted via the inferior vestibular nerve, which eventually results in reflex turning of head in the direction of sound. This reflex is being commonly employed in our day-to-day clinical practice too. Turning of head in the direction of sound is a complex movement, which involves integration of auditory stimulus with vestibulo-spinal pathway. This is achieved by reflex inhibition of contraction of ipsilateral SCM muscle and contraction of contralateral SCM muscle, which results in turning of head toward the direction of sound. Cervical VEMP records the inhibitory signals of sacculo-collic reflex being generated from ipsilateral SCM in response to stimulation of saccule due to sound as it is situated very close to the oval window which itself is stimulated by sound. The reflex pathway is through inferior vestibular nerve (IVN) and the central nervous system (CNS), and is picked up by electrodes placed on ipsilateral SCM [4]. The neural pathway of cVEMP generation following presentation of sound stimulus given through insert earphones on the side to be tested is explained in the subsequent paragraph:

This recording is then used in the evaluation of saccular function in diagnosis of balance disorders by analyzing cVEMP parameters (threshold, latency of P13 and N23 peak, and the amplitude). The other parameters that can be derived from these basic parameters are: the interaural amplitude difference ratio that is calculated by dividing the interaural difference of P13-N23 interamplitude by the sum of P13-N23 interamplitude of both ears, P13-N23 interlatency, P13-N23 interamplitude, and absolute interear difference [5].

3. Methodology

The test is usually done either in the sitting position or in the lying down position. When done in sitting position, the patient is made to turn his head to contralateral side from the ear being tested. The contraction of SCM muscle can also be monitored objectively by keeping inflated cuff of sphygmomanometer between shoulder and mandible and the patient is asked to maintain pressure at a constant level, maintaining a tonicity of SCM at 30–75 Μv [5]. While conducting the test in the lying down position, the patient may be made to lie down with head raised to about 30 degree without support and chin not touching the chest, and head turned contralaterally to the ear being tested to activate maximally the SCM muscle ipsilateral to the stimulation. However, it can be done in recumbent and prone positions too with head lifted or head turned [5].

There are no specific devices to be used in VEMP testing, and most of the centers use the Brainstem Evoked Response Audiometry (BERA) or Auditory Brainstem Response (ABR) equipment with special VEMP software to record these responses.

The electrode placed on the middle one-third of ipsilateral sternocleidomastoid muscle to be tested is called positive or active electrode, that on the sternal head of sternocleidomastoid muscle is called reference or inactive electrode and the one on forehead is called ground electrode (Figure 1). The stimulus in the form of tone bursts at an intensity of 98 dB nHL (120 dBSPL), using a 5 dB up, 10 dB down-step procedure is presented to the test ear by insert ear phone with foam ear tips. The tone bursts are given at 500 Hz as 200 stimuli of 0.2 milli-sec each [5]. The potentials are then recorded with standard disposable, self-adhesive surface electrodes. The electrode impedance is kept within optimum level by using conduction gel in all cases.

Figure 1.

Placement of electrodes.

The results are obtained from the software in the form of a graph showing latency on the X-axis measured in milli-seconds and amplitude on the Y-axis measured as microvolts. The first positive peak, that is, downward deflection is termed as P13 wave and is recorded at 13 millisec. N23 wave is the first negative peak and is recorded at 23 milli-sec. Both waves are recorded for each ear separately (Figures 2 and 3) [4]. The summation potentials recorded are then analyzed. The presence of cVEMP is confirmed by doing three consecutive summation potential recordings. Any prolongation of the positive peak or increase in latency or decrease in amplitude means that cVEMP is abnormal, and that there is saccular dysfunction. The interaural difference of latency from the peaks is associated with the speed of neuronal conduction, and any alteration in this speed may be a result of neurological disease process. The basic cVEMP parameters are threshold, latency of P13 and N23 peak and their amplitude. Other parameters that can be derived from these basic parameters are the interaural amplitude difference ratio which is calculated by dividing the interaural difference of P13-N23 interamplitude by the sum of P13-N23 interamplitude of both ears.

Figure 2.

cVEMP waveform showing latency and amplitude, P13 being the first positive peak and N23 the first negative peak.

Figure 3.

cVEMP waveform as seen on the computer screen showing P13 and N 23 waves.

4. Clinical applications

4.1 Benign paroxysmal positional vertigo

BPPV occurs due to the displacement of calcium-carbonate crystals or otoconia within the fluid-filled semicircular canals of the inner ear. These otoconia are essential for the proper functioning of the utricle of the otolithic membrane by helping deflect the hair cells within the endolymph, which relays positional changes of the head, including tilting, turning, and linear acceleration [6]. As cVEMP primarily detects saccular dysfunction, hence it is possible that the cVEMP parameters may be normal in BPPV. But there are studies which have shown abnormal cVEMP parameters in cases of BPPV. Yang et al. in their study found an increase in VEMP latencies, a finding which was also demonstrated by Godha et al. in their study. Godha et al. also showed high specificity and low sensitivity of VEMP for diagnosing BPPV [7, 8].

4.2 Vestibular neuritis

The usual symptoms of vestibular neuritis (VN) are imbalance, vertigo, nausea, and vomiting, and these symptoms are present in many other clinical conditions such as labyrinthitis, Menier’s disease etc. To establish that these symptoms are due to inflammation of the vestibular nerve, complete or partial unilateral loss of vestibular function needs to be established. This cannot be done by Caloric test or head impulse test as they assess only lateral semicircular canal function and hence, these tests would be normal in patients of VN, thus creating a diagnostic dilemma. Hence, VEMP especially oVEMP which tests superior vestibular nerve function is useful for the diagnosis of VN patients. But in some cases, cVEMP parameters are also found to be abnormal. In a study by Tripathi et al., out of the 10 VN patients, cVEMP was bilaterally normal in seven patients indicating that they had superior vestibular neuritis, but in three patients, they found reduced amplitude in the effected ears indicating inferior vestibular neuritis (IVN) in these patients [9]. Halmagayi et al. published a similar study for the diagnosis of IVN [10]. Murofushi et al. in their study found normal latencies in VN patients and prolonged latencies only in retrolabyrinthine lesions [11]. Nola et al. in their study found that superior VN patients showed normal amplitude and latency on both sides, but IVN patients showed abnormal parameters which changed to normal once the acute attack was over [12]. This study suggested use of VEMP as a screening test for VN. Monstad et al. also reported similar findings in their case series [13].

4.3 Ménière’s disease (MD)

The most supported pathophysiological mechanism in MD is endolymphatic hydrops, characterized by excessive endolymphatic accumulation in the cochlea and vestibule [14]. The most commonly affected inner ear structures in MD are cochlea and the saccule, followed by utricle and semicircular canals [15, 16]. Hence, cVEMP parameters, if abnormal, support the diagnosis of MD in case of diagnostic dilemma. Saccular dysfunction causing saccular hydrops can cause cVEMP parameters to be abnormal in the effected ear, which may either be absent or may show reduced amplitude. Reduced peak-to-peak amplitudes as compared with controls were also found by Zuniga et al. and Salviz et al. in their respective studies [17, 18].

Absent or reduced cVEMP responses were also found by Angeli and Goncalves in 74% of the patients with active MD and 50% patients with stable MD [19].

Thus, cVEMP can be used to identify patients whose symptoms are suggestive, but not diagnostic for MD, and also to track saccular function over time. In case of unilateral MD, cVEMP can also be used to monitor the asymptomatic ear to know whether that ear will develop MD or nor not [20]. A study published by Rauch et al. in 2004 found VEMP parameters to be altered in about 94% of the patients with MD in the affected side in terms of increase in frequency thresholds between 250 and 2000 Hz. Also, about 27% of the asymptomatic ears with unilateral MD had altered cVEMP parameters. Thus, VEMP was found to be not only a diagnostic method for endolymphatic hydrops in initial stages, but also a prognostic factor for bilateral involvement in MD [21].

4.4 Superior semicircular canal dehiscence syndrome (SCD)

SCD is caused due to dehiscence of bone over superior semicircular canal, which creates a third mobile window in the labyrinth. Loud sounds or pressure changes in external auditory canal or middle ear may cause imbalance, vertigo, hearing loss, autophony, or pulsatile tinnitus as this third window serves as a low-resistance pathway for transmission of low-frequency sound energy through the labyrinth. This also lowers the threshold required for generation of cVEMP to a large extent and raises the resultant amplitude (Figure 4). Though the confirmatory investigation for SCD is HRCT temporal bone, it may over estimate the size of the dehiscence or can falsely detect dehiscence in patients with very thin bony covering, resulting in erroneous diagnosis of SCD. VEMP is uniquely suited for identification of SCD as it can be used to detect whether it is the dehiscence which is causing pathological pressure transmission in the vestibular labyrinth.

Figure 4.

cVEMP with recordable P13 and N23 waves obtained in a patient with left SCD at 60 dB.

SCD patients show reduced threshold and high amplitude in the effected ears, and normal parameters in contralateral healthy ears. Tripathi et al. in their study found the threshold to be as low as 50 dB [9]. The diagnosis of these cases was confirmed by doing HRCT temporal bone and they found dehiscence of superior semicircular canal in the images obtained (Figure 5). Similar findings were seen in studies done by Streubel et al. [22]. Also, Zhou et al. in their study of 65 patients, obtained abnormally low VEMP thresholds and found VEMP to be highly sensitive and specific for SCD, possibly better than CT [23]. Welgampola et al. in their study of 12 SCD cases found VEMP thresholds to be pathologically lowered in all, which normalized after corrective surgery [24].

Figure 5.

HRCT temporal bone of the same patient confirming the diagnosis of left SCD.

4.5 Vestibular schwannoma

Vestibular schwannoma (VS), formerly known as acoustic neuroma, is a benign slow growing tumor that develops from Schwann cells of the vestibular nerve. The tumor arises within the internal auditory canal and grows into the cerebello-pontine angle, resulting in unilateral/asymmetric hearing loss and/or tinnitus and loss of balance. It is third most common intracranial benign tumor after meningioma and pituitary adenoma [25]. As the symptoms are subtle and varied, early detection of the tumor is sometimes difficult. Though the investigation of choice for the diagnosis of VS is MRI, it is costly and every suspected patient may not afford it, so other diagnostic modalities also play an important role in diagnosing vestibular schwannomas.

Knowing that VEMP neural pathways involve the inferior portion of the vestibular nerve, this diagnostic method can also be used to help in the diagnosis of VS. Murofushi et al. in their study published in 1998 noticed changes in VEMP parameters in 80% of their vestibular schwannoma patients [26]. Takeichi et al. published a study in 2001 in which they found alteration in VEMP parameters in 72% of their vestibular schwannoma patients [27].

Chiarovano et al. in their study published in 2014 to evaluate the role of Cervical and Ocular Vestibular-Evoked Myogenic Potentials in the assessment of patients with vestibular schwannomas conducted all oto-neurologic tests on 37 of the 63 unoperated patients of VS and made some important observations after analyzing their data which modified their clinical practice [28]. They found that inferior vestibular nerve (abnormal cVEMPs: 62%) was less frequently involved in the disease process as compared to the superior vestibular nerve (abnormal oVEMPs: 76%). Also, 16% percent of these patients had abnormal VEMP but normal hearing and normal caloric test. Thus, it is possible to use VEMP as a diagnostic test (as it may be the only abnormal vestibular finding) and also as a modality for follow up.

From then onwards they started doing VEMPs systematically in patients suffering from vertigo or imbalance and an MRI centered on the IAC was requested in the case of isolated abnormal cervical or ocular VEMPs. They also found that cVEMPs and oVEMPs allowed the evaluation of the effects of treatment on VS patients who had undergone stereotactic radiosurgery. They concluded that the role of the VEMPs in VS is not only in the diagnosis, but is also in assessment of the function of the superior and inferior vestibular nerves prior to surgery and/or microradiosurgery. VEMP testing as a baseline test for patients undergoing surgery and/or microradiosurgery had two distinct advantages: First, it served as a guide to how to assess residual vestibular function so that vestibular rehabilitation could be planned post-treatment, and, second, it helped to determine if the cause of imbalance was vestibular decompensation or further compromise of vestibular function and accordingly rehabilitation was planned. Though VEMPs can contribute to the diagnosis of vestibular tumors and serve as an excellent screening tool, they cannot be used as the sole diagnostic method, because they only assess the function of the inferior vestibular nerve. But when performed together with MRI, the ABR, audiometry and caloric test, they help in the exact location of the tumor in the vestibular pathways.

4.6 Perilymphatic fistula

A perilymphatic fistula is an abnormal communication between the perilymph-filled inner ear to outside, which causes perilymph to leak from the cochlea or vestibule, most commonly through the round or oval window, resulting in cochlear and vestibular symptoms [29]. The audiovestibular symptoms of perilymph fistula mimic various other conditions, which lack precise diagnostic tools such as Meniere’s disease, superior or posterior canal dehiscence, endolymphatic hydrops, Eustachian tube dysfunction, vestibular migraine, mal de debarquement, and persistent postural-perceptual dizziness. For decades, the gold standard for diagnosis of a perilymph fistula has been exploratory tympanotomy with intra-operative visualization of perilymph leakage with subsequent improvement in symptoms after the leak has been repaired. However, this test is not only invasive but also subjective as no established criteria exist for what constitutes a perilymphatic leak on observation. In 2006, Modugno et al. published a study in which VEMP testing was used for the diagnosis of endolymphatic fistula cases [30]. They reported four cases in which VEMP response thresholds were reduced with stimuli in the frequency of 500 Hz. The VEMP thresholds are lowered due to third window effect which reduces the impedance, similar to superior semicircular canal dehiscence. So cVEMP can be used as a screening tool prior to other sophisticated imaging modalities such as CT and MRI with axial and coronal Constructive Interference in Steady State (CISS), also called Fast Imaging Employing Steady-State Acquisition (FIESTA) or Magnetic Resonance Perfusion (MRP) sequence [29].

4.7 Monitoring after treatment with intratympanic gentamicin

In Ménière’s disease, those cases with intolerable vertigo and resistance to clinical treatment, administration of intratympanic gentamicin is done in an attempt to reduce vertigo symptoms in these patients [31]. After this therapy, VEMP can be used to confirm if the gentamicin dose employed was enough to cause damage to the vestibular cells. In 2002, De Waele et al. showed that 92% of the patients submitted to intratympanic injection of gentamicin had absent responses in VEMP testing [32].

5. Clinical applications in pediatric population

Balance disorders in children due to vestibular disorders are not well documented as compared to the adult population. It is so because clinicians often rely on parent’s inputs to screen for vestibular dysfunction, especially when the child is too young to verbalize their symptoms. Vestibular function testing in children is not an easy task as they may not self-report or even be aware that their symptoms are abnormal. Also, their short attention span makes any test more challenging. The prevalence of balance and vestibular disorders in children is estimated between 0.45 and 5.3%, with a slightly higher prevalence in females over males, which tends to rise with age [33, 34]. VEMP forms an important part of pediatric vestibular testing battery right from the birth of the child. Early development of the Vestibular Colic Reflex facilitates the ability to use cVEMP testing in children younger than 12 months. Pediatric normative amplitude ranges are approximately 208.5 to 285.00 μV, and normative cVEMP threshold responses are at approximately 105 to 110 dB SPL [35, 36].

As in the adults, cVEMPs are considered abnormal if responses are absent or low in amplitude; however, with third window disorders, such as enlarged vestibular aqueduct or superior canal dehiscence, large amplitudes and low thresholds are considered abnormal.

VEMP testing in children provides the clinician with diagnostic information about otolith function that cannot be identified by other tests. It is well received by children because the testing procedure does not require that they be in the dark, does not induce symptoms of dizziness, and they can sit with or close to their parent. Also it is quick, painless and non-invasive.

5.1 Neonatal vestibular screening

Verrecchia et al. in their pilot study published in 2019 used VEMP for newborn vestibular screening alongside the regional newborn hearing screening program. They used bone-conducted stimuli to test VEMP. The tonicity of neck muscles was maintained by resting the infants unconstrained in their parents´ arms, while the operator supported the infant’s head with his hand. Performed this way, they found VEMP protocol to be highly viable and reproducible. They concluded that VEMP can be used for large-scale assessment of vestibular function in infants if integrated into the newborn hearing screening program [37].

5.2 Cochlear implant surgery

Assessment of vestibular function is also done in children pre- and post-cochlear implantation. Otolith damage may occur during cochlear implant surgery as saccule lies very close to the insertion pathway of the implant’s electrode array. cVEMP responses are absent in about 40 to 80% of children following cochlear implantation. Wolter et al. in their retrospective study compared 35 children with CI failure to 165 children who did not experience CI failure. Saccular function was assessed by VEMP. They found that a greater proportion of children with CI failure had abnormal saccular function compared to those without CI failure (81 vs. 46%, p = 0.003). They suggested early identification and treatment of such impairments so as to avoid or delay implant failures and prevent children from experiencing periods of sound deprivation that could impact speech and language acquisition [38].

In addition VEMP has also been used to demonstrate vestibular dysfunction in conditions such as autism and spastic cerebral palsy [39, 40].

6. Conclusion

VEMP is a relatively newer vestibular function test, which can test otolith organs in isolation and objectively. oVEMP is the objective test for utricle and superior vestibular nerve, whereas cVEMP tests saccule and the inferior vestibular nerve. As it does not induce vertigo, it is more acceptable and comfortable for the patients. It is a non-invasive test and the electromyographic potentials are stable and repeatable, can be documented, and reproduced objectively. The cost is very less as it uses hardware of ABR testing. It is also an excellent tool for screening of vestibular system in newborns and has extensive applications in pediatric population. These advantages make it an excellent tool in management of vestibular disorders. However, in many clinical conditions it cannot be used as the sole diagnostic modality, but is a complementary test, which when done along with other investigative procedures, points to a diagnosis in case of balance disorders.