Practice Guideline: Cervical and Ocular Vestibular Evokedmyogenic Potential Testing: Report of the Guideline Development Dissemination and Implementation Subcommittee of the American Academy of Neurology

Objective: To systematically review the evidence and make recommendations with regard to diagnostic utility of cervical and ocular vestibular evoked myogenic potentials (cVEMP and oVEMP, respectively). Four questions were asked: Does cVEMP accurately identify superior canal dehiscence syndrome (SCDS)? Does oVEMP accurately identify SCDS? For suspected vestibular symptoms, does cVEMP/oVEMP accurately identify vestibular dysfunction related to the saccule/ utricle? For vestibular symptoms, does cVEMP/oVEMP accurately and substantively aid diagnosis of any specific vestibular disorder besides SCDS? Methods: The guideline panel identified and classified relevant published studies (January 1980- December 2016) according to the 2004 American Academy of Neurology process. Results and Recommendations: Level C positive: Clinicians may use cVEMP stimulus threshold values to distinguish SCDS from controls (2 Class III studies) (sensitivity 86%-91%, specificity 90%-96%). Corrected cVEMP amplitude may be used to distinguish SCDS from controls (2 Class III studies) (sensitivity 100%, specificity 93%). Clinicians may use oVEMP amplitude to distinguish SCDS from normal controls (3 Class III studies) (sensitivity 77%-100%, specificity 98%-100%). oVEMP threshold may be used to aid in distinguishing SCDS from controls (3 Class III studies) (sensitivity 70%-100%, specificity 77%-100%). Level U: Evidence is insufficient to determine whether cVEMP and oVEMP can accurately identify vestibular function specifically related to the saccule/utricle, or whether cVEMP or oVEMP is useful in diagnosing vestibular neuritis or M

Direction-dependent excitatory and inhibitory ocular vestibular-evoked myogenic potentials (oVEMPs) produced by oppositely directed accelerations along the midsagittal axis of the head

Oppositely directed displacements of the head need oppositely directed vestibulo-ocular reflexes (VOR), i.e. compensatory responses. Ocular vestibular-evoked myogenic potentials (oVEMPs) mainly reflect the synchronous extraocular muscle activity involved in the process of generating the VOR. The oVEMPs recorded beneath the eyes when looking up represent electro-myographic responses mainly of the inferior oblique muscle. We aimed: (1) to study the properties of these responses as they were produced by head acceleration impulses to the forehead and to the back of the head; (2) to investigate the relationships between these responses and the 3-D linear head accelerations that might reflect the true stimulus that acts on the vestibular hair cells. We produced backward- and forward-directed acceleration stimuli in four conditions (positive and negative head acceleration impulses to the hairline and to the inion) in 16 normal subjects. The oVEMPs produced by backward- and forward-directed accelerations of the head showed consistent differences. They were opposite in the phase. The responses produced by backward accelerations of the head began with an initial negativity, n11; conversely, those produced by accelerations directed forward showed initially a positive response, p11. There was a high inter-subject correlation of head accelerations along the head anteroposterior and transverse axes, but almost no correlation of accelerations along the vertical axis of the head. We concluded that backward-directed head accelerations produced an initial excitatory response, and forward-directed accelerations of the head were accompanied by an initial inhibitory response. These responses showed dependence on acceleration direction in the horizontal plane of the head. This could be consistent with activation of the utricle

Vestibular Perception following Acute Unilateral Vestibular Lesions.

Little is known about the vestibulo-perceptual (VP) system, particularly after a unilateral vestibular lesion. We investigated vestibulo-ocular (VO) and VP function in 25 patients with vestibular neuritis (VN) acutely (2 days after onset) and after compensation (recovery phase, 10 weeks). Since the effect of VN on reflex and perceptual function may differ at threshold and supra-threshold acceleration levels, we used two stimulus intensities, acceleration steps of 0.5°/s(2) and velocity steps of 90°/s (acceleration 180°/s(2)). We hypothesised that the vestibular lesion or the compensatory processes could dissociate VO and VP function, particularly if the acute vertiginous sensation interferes with the perceptual tasks. Both in acute and recovery phases, VO and VP thresholds increased, particularly during ipsilesional rotations. In signal detection theory this indicates that signals from the healthy and affected side are still fused, but result in asymmetric thresholds due to a lesion-induced bias. The normal pattern whereby VP thresholds are higher than VO thresholds was preserved, indicating that any 'perceptual noise' added by the vertigo does not disrupt the cognitive decision-making processes inherent to the perceptual task. Overall, the parallel findings in VO and VP thresholds imply little or no additional cortical processing and suggest that vestibular thresholds essentially reflect the sensitivity of the fused peripheral receptors. In contrast, a significant VO-VP dissociation for supra-threshold stimuli was found. Acutely, time constants and duration of the VO and VP responses were reduced - asymmetrically for VO, as expected, but surprisingly symmetrical for perception. At recovery, VP responses normalised but VO responses remained shortened and asymmetric. Thus, unlike threshold data, supra-threshold responses show considerable VO-VP dissociation indicative of additional, higher-order processing of vestibular signals. We provide evidence of perceptual processes (ultimately cortical) participating in vestibular compensation, suppressing asymmetry acutely in unilateral vestibular lesions

Migraine Associated Vertigo

The interrelations of migraine and vertigo are complex, eluding a simple localization either centrally or peripherally. Spontaneous episodic vertigo, benign paroxysmal positional vertigo, and Meniere's disease all occur more frequently in patients with migraine than in those without. Family studies support a hereditary predisposition to migraine associated vertigo. In this review, we discuss definitions, epidemiology, associated syndromes, neurootological abnormalities, genetics and treatment for patients with migraine and vertigo

Asymmetric vestibular evoked myogenic potentials in unilateral Menière patients

Vestibular evoked myogenic potentials (VEMPs) were measured in 22 unilateral Menière patients with monaural and binaural stimulation with 250 and 500 Hz tone bursts. For all measurement situations significantly lower VEMP amplitudes were on average measured at the affected side compared to the unaffected side. Unilateral Menière patients have, in contrast to normal subjects, asymmetric VEMPs, indicating a permanently affected vestibular (most likely otolith) system at the side of hearing loss. The diagnostic value of VEMP amplitude asymmetry measurement in individual patients is low, because of the large overlap of the VEMP amplitude asymmetry range for unilateral Menière patients with that for normal subjects

Homozygous Deletion of Six Olfactory Receptor Genes in a Subset of Individuals with Beta-Thalassemia

Progress in the functional studies of human olfactory receptors has been largely hampered by the lack of a reliable experimental model system. Although transgenic approaches in mice could characterize the function of individual olfactory receptors, the presence of over 300 functional genes in the human genome becomes a daunting task. Thus, the characterization of individuals with a genetic susceptibility to altered olfaction coupled with the absence of particular olfactory receptor genes will allow phenotype/genotype correlations and vindicate the function of specific olfactory receptors with their cognate ligands. We characterized a 118 kb β-globin deletion and found that its 3′ end breakpoint extends to the neighboring olfactory receptor region downstream of the β-globin gene cluster. This deletion encompasses six contiguous olfactory receptor genes (OR51V1, OR52Z1, OR51A1P, OR52A1, OR52A5, and OR52A4) all of which are expressed in the brain. Topology analysis of the encoded proteins from these olfactory receptor genes revealed that OR52Z1, OR52A1, OR52A5, and OR52A4 are predicted to be functional receptors as they display integral characteristics of G-proteins coupled receptors. Individuals homozygous for the 118 kb β-globin deletion are afflicted with β-thalassemia due to a homozygous deletion of the β-globin gene and have no alleles for the above mentioned olfactory receptors genes. This is the first example of a homozygous deletion of olfactory receptor genes in human. Although altered olfaction remains to be ascertained in these individuals, such a study can be carried out in β-thalassemia patients from Malaysia, Indonesia and the Philippines where this mutation is common. Furthermore, OR52A1 contains a γ-globin enhancer, which was previously shown to confer continuous expression of the fetal γ-globin genes. Thus, the hypothesis that β-thalassemia individuals, who are homozygous for the 118 kb deletion, may also have an exacerbation of their anemia due to the deletion of two copies of the γ-globin enhancer element is worthy of consideration

Benign Paroxysmal Positional Vertigo

Benign paroxysmal positional vertigo (BPPV) is characterized by brief recurrent episodes of vertigo triggered by changes in head position. BPPV is the most common etiology of recurrent vertigo and is caused by abnormal stimulation of the cupula by free-floating otoliths (canalolithiasis) or otoliths that have adhered to the cupula (cupulolithiasis) within any of the three semicircular canals. Typical symptoms and signs of BPPV are evoked when the head is positioned so that the plane of the affected semicircular canal is spatially vertical and thus aligned with gravity. Paroxysm of vertigo and nystagmus develops after a brief latency during the Dix-Hallpike maneuver in posterior-canal BPPV, and during the supine roll test in horizontal-canal BPPV. Positioning the head in the opposite direction usually reverses the direction of the nystagmus. The duration, frequency, and symptom intensity of BPPV vary depending on the involved canals and the location of otolithic debris. Spontaneous recovery may be expected even with conservative treatments. However, canalithrepositioning maneuvers usually provide an immediate resolution of symptoms by clearing the canaliths from the semicircular canal into the vestibule