Leonardo Manzari

Ocular vestibular-evoked myogenic potentials to bone-conducted vibration in superior vestibular neuritis show utricular function:

OBJECTIVE: To determine whether the first negative component (n10) of the ocular vestibular-evoked myogenic potential (oVEMP) to bone-conducted vibration (BCV) is due primarily to activation of the utricular macula. STUDY DESIGN: The n10 was recorded in response to brief BCV at the midline of the forehead at the hairline (Fz). If the n10 is due primarily to utricular activation, then diseases that affect only the superior division of the vestibular nerve in which all utricular afferents course (i.e., superior vestibular neuritis [SVN]) should reduce or eliminate n10 beneath the contralesional eye, whereas the n10 beneath the ipsilesional eye and the sacculo-collic cervical vestibular-evoked myogenic potential (cVEMP) on the ipsilesional side should be preserved. SETTING: A prospective study at a tertiary neurotological referral center. SUBJECTS AND METHODS: The n10 component of the oVEMP was measured in 133 patients with unilateral SVN but with inferior vestibular nerve function preserved, as shown by ipsilesional cVEMPs. RESULTS: The n10 to Fz BCV of 133 SVN patients was reduced beneath the contralesional eye relative to the ipsilesional eye so that there was an n10 asymmetry that was significantly greater than the n10 asymmetry in the 50 healthy subjects. In terms of predicting the affected side (shown by canal paresis), using an n10 asymmetry ratio (asymmetry ratio for the relative size of the n10 of the oVEMPs for the two eyes [AR]) of 46.5 percent, the n10 AR has a diagnostic accuracy of 94 percent. CONCLUSION: The n10 component of the oVEMP to BCV is probably mediated by the superior vestibular nerve and so mainly by the utricular receptors. The n10 AR is almost as good as canal paresis in identifying the affected side in patients.

Ocular and cervical vestibular-evoked myogenic potentials to bone conducted vibration in Ménière’s disease during quiescence vs during acute attacks

OBJECTIVE Two indicators of otolithic function were used to measure dynamic otolith function in the same patients both during an acute attack of Ménières disease (MD) and in the quiescent period between attacks. METHODS The early negative component (n10) of the ocular vestibular-evoked myogenic potential (the oVEMP) to brief 500 Hz bone conducted vibration (BCV) stimulation of the forehead, in the midline at the hairline (Fz) was recorded by surface EMG electrodes just beneath both eyes while the patient looked up. It has been proposed that the n10 component of the oVEMP to 500 Hz Fz BCV indicates utricular function. It has been proposed that the early positive component (p13) of the cervical vestibular-evoked myogenic potential (the cVEMP) recorded by surface electrodes on both tensed SCM neck muscles to 500 Hz Fz BCV indicates saccular function. RESULTS Sixteen healthy control subjects tested on two occasions showed no detectable change in the symmetry of oVEMPs or cVEMPs to 500 Hz Fz BCV. In response to 500 Hz Fz BCV 15 early MD patients tested at both attack and quiescent phases showed a dissociation: there was a significant increase in contralesional of n10 of the oVEMP during the attack compared to quiescence but a significant decrease in the ipsilesional p13 of the cVEMP during the attack compared to quiescence. CONCLUSIONS During an MD attack, dynamic utricular function in the affected ear as measured by the n10 of the oVEMP to 500 Hz Fz BCV is enhanced, whereas dynamic saccular function in the affected ear as measured by the p13 of the cVEMP to 500 Hz Fz BCV is not similarly affected. SIGNIFICANCE The MD attack appears to affect different otolithic regions differentially.

The basis for using bone-conducted vibration or air-conducted sound to test otolithic function.

Extracellular single neuron recordings of primary vestibular neurons in Scarpas ganglion in guinea pigs show that low‐intensity 500 Hz bone‐conducted vibration (BCV) or 500 Hz air‐conducted sound (ACS) activate a high proportion of otolith irregular neurons from the utricular and saccular maculae but few semicircular canal neurons. In alert guinea pigs, and humans, 500 Hz BCV elicits otolith‐evoked eye movements. In humans, it also elicits a myogenic potential on tensed sternocleidomastoid muscles. Although BCV and ACS activate both utricular and saccular maculae, it is possible to probe the functional status of these two sense organs separately because of their differential neural projections. Saccular neurons have a strong projection to neck muscles and a weak projection to the oculomotor system. Utricular afferents have a strong projection to eye muscles. So measuring oculomotor responses to ACS and BCV predominantly probes utricular function, while measuring neck muscle responses to these stimuli predominantly probes saccular function.

Ocular and cervical vestibular evoked myogenic potentials to 500 Hz fz bone-conducted vibration in superior semicircular canal dehiscence.

Objective: The aim of this study was to investigate the effect of superior semicircular canal dehiscence (SSCD) on the n10 component of the ocular vestibular evoked myogenic potential (oVEMP n10) and the p13-n23 component of the cervical vestibular evoked myogenic potential (cVEMP p13-n23) evoked by 500 Hz bone-conducted vibration (BCV) at the midline forehead at the hairline (Fz) in 26 patients with computed tomography-verified SSCD. Previous evidence has led to the proposal that the oVEMP n10 is of utricular origin whereas the cVEMP p13-n23 is of saccular origin. The question is can the oVEMP n10 to 500 Hz BCV indicate SSCD? Design: A hand-held Bruel & Kjaer 4810 Minishaker was used to provide BCV stimulation using surface electromyography electrodes to record oVEMP n10 and cVEMP p13-n23. The stimulus was 7 msec bursts of 500 Hz BCV at either Fz or at the vertex of the skull (Cz). Twenty-seven healthy subjects were tested in the same paradigm. Results: In response to 500 Hz Fz BCV in SSCD patients the oVEMP n10 amplitude beneath the contraSSCD eye was substantially and significantly larger than the oVEMP n10 beneath the ipsiSSCD eye, whereas in these same patients the cVEMP p13-n23 amplitude over the ipsiSSCD sternocleidomastoid muscle to Fz BCV was slightly but significantly larger than the cVEMP p13-n23 amplitude over the contraSSCD sternocleidomastoid muscle. In SSCD patients there was a significant relationship between the size of the dehiscence and the amplitude of the contralateral oVEMP n10 potential. The oVEMP n10 to Cz stimulation was still present in SSCD patients, but small or absent in healthy subjects. Conclusions: In response to 500 Hz Fz BCV an asymmetrical oVEMP n10 with a significantly increased amplitude of contralesional oVEMP n10 (compared with population values of healthy subjects) is a simple useful indicator of SSCD, confirmed by the Cz response. oVEMP testing with 500 Hz Fz BCV allows very simple, very fast identification of a probable unilateral SSCD.

Dissociation between cVEMP and oVEMP responses: different vestibular origins of each VEMP?

Recently two important tests of otolith function based on myogenic potentials have been reported, but the sensory origin of these potentials (saccular vs. utricular) is still controversial [1, 2]: (1) the cervical vestibular-evoked myogenic potential (cVEMP) from contracted sternocleidomastoid (SCM) muscles to either air-conducted sound (ACS) or bone-conducted vibration (BCV); (2) the ocular vestibular-evoked myogenic potential (oVEMP) to either BCV or ACS from contracted extraocular muscles beneath the eyes (inferior recti and inferior oblique muscles). It has been suggested that, in response to short tone burst (7 ms) 500 Hz BCV delivered to the midline of the forehead at the hairline (a location called Fz) or to 500 Hz ACS stimulation, the early negative potential of the oVEMP (called n10) indicates crossed utricular function, and the early positive potential of the cVEMP (called p13-n23) indicates uncrossed saccular function [1, 2]. Evidence supporting those suggestions comes from patients with reduced or absent superior vestibular function who have reduced or absent contralesional oVEMP n10 but whose cVEMP potentials are normal [3, 4]. Here we report an unusual patient with reduced inferior vestibular nerve function who provides the complementary but converse evidence for these suggestions by showing reduced cVEMP potentials but normal oVEMPs for both ACS and BCV stimuli. A 29-year-old female was referred to our tertiary outpatient otoneurology clinic (MSA ENT Academy Center, Cassino, Italy) with static and dynamic postural imbalance, feeling of subjective vertigo, nausea and vomiting. She denied having audiological symptoms such as hearing loss, aural fullness or tinnitus, and did not recall any history of head injury. Otoscopy findings were normal. Audiometric testing revealed normal: hearing levels, stapedial reflexes, tympanometry and auditory brainstem responses. She was then tested with written consent with vestibular tests, and the procedures described below have been approved by the local Ethics Committee. The tests were: spontaneous nystagmus (absent), head-shaking nystagmus (no nystagmus proved at cessation of the manoeuvre) and positional nystagmus (head roll manoeuvre failed to reveal any abnormal eye movement; Dix-Hallpike manoeuvre revealed, in the left head hanging, a quick phase downbeating nystagmus with a small rotatory CW component). Horizontal semicircular canal function was normal; she had no head impulse sign [5]; normal calorics (canal paresis = 3%), and subjective visual vertical was normal. cVEMPs and oVEMPs to ACS and BCV were carried out [1, 2]. BCV was applied to the midline of the forehead at the hairline (a location called Fz), using a hand-held mini-shaker [1, 4] (Bruel & Kjaer model 4810, Naerum, Denmark) consisting of 50 repetitions of a 500-Hz tone burst (MTB), lasting a total of 7 ms (including a 1-ms rise and 1 ms fall with zero-crossing start). For ACS, we used the same stimulus to drive a TDH 49 headphone. For both ACS and BCV, the EMG signals were amplified by two independent differential amplifiers (filter cut-offs 20–500 Hz), and the unrectified signals simultaneously acquired from the two eyes (oVEMPs), or the two sternocleidomastoid muscles L. Manzari (&) MSA ENT Academy Center, Via Riccardo da S.Germano 41, 03043 Cassino, FR, Italy e-mail: leonardomanzari@virgilio.it

Neural basis of new clinical vestibular tests: otolithic neural responses to sound and vibration.

Extracellular single neuron recording and labelling studies of primary vestibular afferents in Scarpas ganglion have shown that guinea‐pig otolithic afferents with irregular resting discharge are preferentially activated by 500 Hz bone‐conducted vibration (BCV) and many also by 500 Hz air‐conducted sound (ACS) at low threshold and high sensitivity. Very few afferent neurons from any semicircular canal are activated by these stimuli and then only at high intensity. Tracing the origin of the activated neurons shows that these sensitive otolithic afferents originate mainly from a specialized region, the striola, of both the utricular and saccular maculae. This same 500 Hz BCV elicits vestibular‐dependent eye movements in alert guinea‐pigs and in healthy humans. These stimuli evoke myogenic potentials, vestibular‐evoked myogenic potentials (VEMPs), which are used to test the function of the utricular and saccular maculae in human patients. Although utricular and saccular afferents can both be activated by BCV and ACS, the differential projection of utricular and saccular afferents to different muscle groups allows for differentiation of the function of these two sensory regions. The basic neural data support the conclusion that in human patients in response to brief 500 Hz BCV delivered to Fz (the midline of the forehead at the hairline), the cervical VEMP indicates predominantly saccular function and the ocular VEMP indicates predominantly utricular function. The neural, anatomical and behavioural evidence underpins clinical tests of otolith function in humans using sound and vibration.

Vestibular function after vestibular neuritis.

Abstract Objective: To measure horizontal semicircular canal function over days, weeks, and months after an acute attack of vestibular neuritis. Design: The video head impulse test (vHIT) was used to measure the eye movement response to small unpredictable passive head turns at intervals after the attack. Study sample: Two patients diagnosed with acute right unilateral vestibular neuritis. Results: There was full restoration of horizontal canal function in one patient (A) as shown by the return of the slow phase eye velocity response to unpredictable head turns, while in the other patient (B) there was little or no recovery of horizontal canal function. Instead this second patient generated covert saccades during head turns. Conclusion: Despite the objective evidence of their very different recovery patterns, both patients reported, at the final test, being happy and feeling well recovered, even though in one of the patients there was clear absence of horizontal canal function. The results indicate covert saccades seem a successful way of compensating for loss of horizontal canal function after unilateral vestibular neuritis. Factors other than recovery of the slow phase eye velocity are significant for patient recovery.

Rapid fluctuations in dynamic semicircular canal function in early Ménière’s disease

Ménière’s disease (MD) is characterized by fluctuations in labyrinthine function which are well known and objectively established for the auditory symptoms [1, 2]. It is also well known that it is disorders of balance, rather than hearing, which are the major symptoms during the early stages of the disease [3]. But to date there have been only a few measurements of the fluctuations in vestibular function around the time of the attack. This has been due to two factors. First, the difficulty of testing early MD patients around the time of their attack, which can have highly variable duration: each attack may last from 10 min to hours [2, 3]. Second, the limited range of vestibular tests available and the fact that the usual tests of vestibular function are so demanding that they are not feasible in patients around the time of the attack. However, recently, we published results of a new nondemanding test of otolith function—the n10 of the ocular vestibular-evoked myogenic potential which showed that there are fluctuations in vestibular function, with enhanced dynamic utricular function at the time of the attack compared to quiescence [4]. Here, we wish to address the complementary question as to whether dynamic semicircular canal function fluctuates as auditory and dynamic otolith function does and we present evidence of variations in dynamic semicircular canal function around the time of the MD attack. The development of the video head impulse test (vHIT) has allowed non-demanding objective measures of semicircular canal function [5]. This is a very simple, fast way of measuring dynamic semicircular canal function accurately and has been validated by directly comparing it to simultaneous measures by the ‘‘gold standard’’ search coil test [6]. The gain measurements of the two tests are not significantly different and show very high concordance correlations [6]. With vHIT it is possible to test patients very quickly at short intervals and this kind of easily repeatable, high accuracy, minimally demanding test allows the measurement of the sequential changes in semicircular canal function at the time of the attack. The vHIT test involves the clinician delivering brief, passive, high acceleration head impulses of yaw head rotation unpredictably to the right or left through an angle of about 10 –20 while the patient is instructed to keep looking at an earth-fixed target. The patient wears a set of minimal-slip goggles to which is attached a small lightweight high speed video camera to measure eye position and a 3-d sensor to measure head velocity. We used vHIT to measure the yaw VOR response of patients with evidence of early MD, both at quiescence and during an acute attack. Here, we report that the repeated tests at short intervals show that the VOR response changes substantially around the time of an attack (Fig. 1). One important issue is that the patients for this study were a homogeneous group with early MD (6 subjects, 3 L. Manzari (&) MSA ENT Academy Center Cassino, Via Riccardo da S.Germano 41, 03043 Cassino (FR), Italy e-mail: leonardomanzari@virgilio.it

Ocular and cervical vestibular evoked myogenic potentials in response to bone-conducted vibration in patients with probable inferior vestibular neuritis.

BACKGROUND AND AIMS Previous evidence shows that the n10 component of the ocular vestibular evoked myogenic potential indicates utricular function, while the p13 component of the cervical vestibular evoked myogenic potential indicates saccular function. This study aimed to assess the possibility of differential utricular and saccular function testing in the clinic, and whether loss of saccular function affects utricular response. METHODS Following vibration conduction from the mid-forehead at the hairline, the ocular n10 component was recorded by surface electromyograph electrodes beneath both eyes, while the cervical p13-n23 component was recorded by surface electrodes over the tensed sternocleidomastoid muscles. RESULTS Fifty-nine patients were diagnosed with probable inferior vestibular neuritis, as their cervical p13-n23 component was asymmetrical (i.e. reduced or absent on the ipsilesional side), while their ocular n10 component was symmetrical (i.e. normal beneath the contralesional eye). CONCLUSION The sense organ responsible for the cervical and the ocular vestibular evoked myogenic potentials cannot be the same, as one response was normal while the other was not. Reduced or absent saccular function has no detectable effect on the ocular n10 component. On vibration stimulation, the ocular n10 component indicates utricular function and the cervical p13-n23 component indicates saccular function.

A new saccadic indicator of peripheral vestibular function based on the video head impulse test

Objective: While compensatory saccades indicate vestibular loss in the conventional head impulse test paradigm (HIMP), in which the participant fixates an earth-fixed target, we investigated a complementary suppression head impulse paradigm (SHIMP), in which the participant is fixating a head-fixed target to elicit anticompensatory saccades as a sign of vestibular function. Methods: HIMP and SHIMP eye movement responses were measured with the horizontal video head impulse test in patients with unilateral vestibular loss, patients with bilateral vestibular loss, and in healthy controls. Results: Vestibulo-ocular reflex gains showed close correlation (R2 = 0.97) with slightly lower SHIMP than HIMP gains (mean gain difference 0.06 ± 0.05 SD, p < 0.001). However, the 2 paradigms produced complementary catch-up saccade patterns: HIMP elicited compensatory saccades in patients but rarely in controls, whereas SHIMP elicited large anticompensatory saccades in controls, but smaller or no saccades in bilateral vestibular loss. Unilateral vestibular loss produced covert saccades in HIMP, but later and smaller saccades in SHIMP toward the affected side. Cumulative HIMP and SHIMP saccade amplitude differentiated patients from controls with high sensitivity and specificity. Conclusions: While compensatory saccades indicate vestibular loss in conventional HIMP, anticompensatory saccades in SHIMP using a head-fixed target indicate vestibular function. SHIMP saccades usually appear later than HIMP saccades, therefore being more salient to the naked eye and facilitating vestibulo-ocular reflex gain measurements. The new paradigm is intuitive and easy to explain to patients, and the SHIMP results complement those from the standard video head impulse test. Classification of evidence: This case-control study provides Class III evidence that SHIMP accurately identifies patients with unilateral or bilateral vestibulopathies.