Subjective visual horizontal correlates better with ocular than with cervical vestibular evoked myogenic potentials.

OBJECTIVE: To examine the relationship between widely used otolith function tests: the Subjective Visual Horizontal (SVH) and Vestibular Evoked Myogenic Potentials (VEMP). METHODS: A retrospective analysis was performed on 301 patients who underwent SVH, ocular and cervical VEMP (oVEMP and cVEMP) tests on the same day. Correlations between the mean SVH tilt and amplitude asymmetry ratios for bone-conducted (BC) oVEMP and air-conducted (AC) cVEMP were examined. Diagnoses included vestibular neuritis, stroke, vestibular migraine, Meniere's disease, sudden sensorineural hearing loss (SSNHL) and vestibular schwannoma. RESULTS: SVH results were concordant with the oVEMP in 64% of cases and the cVEMP in 51%. Across all patients, SVH demonstrated a significant moderate correlation with BC oVEMP amplitude asymmetry ratios (r = 0.55, p < 0.001) and a weak correlation with AC cVEMP amplitude asymmetry ratios (r = 0.35, p < 0.001). A stronger correlation between SVH and oVEMPs was observed in patients with vestibular neuritis (r = 0.67, p < 0.001) and SSNHL (r = 0.76, p = 0.001). CONCLUSIONS: SVH correlates better with oVEMP than cVEMP symmetry. SIGNIFICANCE: This finding reinforces the hypothesis of a common utricular origin for both SVH and oVEMPs which is distinct from the saccular origin of cVEMPs.

The human vestibulo-ocular reflex and compensatory saccades in schwannoma patients before and after vestibular nerve section.

OBJECTIVE: To examine the vestibulo-ocular reflex (VOR) and compensatory-saccades before and after complete unilateral vestibular deafferentation (UVD). METHODS: Forty patients were studied before and after surgery for vestibular or facial schwannoma using the video head-impulse test (vHIT) and multivariable regression. RESULTS: Prior to UVD (median(IQR), 14(58.4) days), the average VOR-gain towards the lesioned-ear was lower than in normal for all semicircular canals (lateral, anterior, posterior: 0.69, 0.72, 0.49). One-week after UVD (5(3.0) days) VOR gains were further reduced (0.22, 0.37, 0.27), however, within one-year after UVD (171(125.0) days) the lesioned-ear VOR gains had slightly increased (+0.08, +0.11, +0.03), maximally for the anterior-canal. After UVD, the VOR gain asymmetry (gain towards minus away from intact-ear) was lower for the intact posterior-canal plane (0.56, 0.56, 0.22). For the lesioned canals, the frequency and amplitude of the first compensatory-saccade increased from 61-93% and 1.9-3.6° pre-surgery, to 98-99% and to 3.1-5.9° one-week post-surgery and remained unchanged over one-year; second saccade frequency and amplitude decreased over the same timespan. CONCLUSIONS: After UVD the high-acceleration VOR for the intact posterior-canal plane is more symmetrical than the other canals. First compensatory-saccades adapt within one week and subsequently change only marginally. SIGNIFICANCE: Saccade compensation from surgical UVD is near complete by one-week.

A Window Into the Whole Story: Temporal Bone Plasmacytoma Presenting With a Mobile Third Window.

A 63-year-old man presented with imbalance when coughing due to a respiratory tract infection. He had a history of multiple myeloma with a plasmacytoma of the left temporal bone. Examination revealed a positive leftward head impulse test, no spontaneous nystagmus, left-beating positional nystagmus, and left-beating Valsalva-induced nystagmus. Videonystagmography, audiology, and comprehensive vestibular function tests revealed a subtotal left peripheral audio-vestibular loss. Temporal bone computed tomography showed an unchanged bony erosion of the left labyrinth from 2 years prior. Vertigo subsided after treatment of the respiratory tract infection. Although no tumor progression was evident, coughing had triggered a preexisting third mobile window to declare itself. Laryngoscope, 131:E966-E969, 2021.

Otolith Function Testing.

Two technically simple tests, vestibular evoked myogenic potential (VEMP) and subjective visual vertical/horizontal (SVV/H) test, have the potential to transform otolith function testing from the research laboratory to the outpatient clinic. Cervical- and ocular-VEMPs are short latency surface potentials produced through the activation of saccular and utricular afferents by sound and vibration. They are tests of dynamic otolith function. The SVV/H test in peripheral lesions probes static asymmetries in utricular function and represents a perceptual error in perceived gravitational vertical/horizontal. VEMPs and SVV/H enable the characterization of patterns and severity of otolith dysfunction in common vestibular disorders. Combined with tests of semicircular canal function, they provide a useful tool for eliciting diagnostic profiles in vestibular neuritis and Ménière's disease. VEMPs are valuable in the pre-surgical confirmation of superior semicircular canal dehiscence and in some cases, may alert the clinician to the presence of a vestibular schwannoma in patients with symmetrical hearing.

TRAK2, a novel regulator of ABCA1 expression, cholesterol efflux and HDL biogenesis.

Aims: The recent failures of HDL-raising therapies have underscored our incomplete understanding of HDL biology. Therefore there is an urgent need to comprehensively investigate HDL metabolism to enable the development of effective HDL-centric therapies. To identify novel regulators of HDL metabolism, we performed a joint analysis of human genetic, transcriptomic, and plasma HDL-cholesterol (HDL-C) concentration data and identified a novel association between trafficking protein, kinesin binding 2 (TRAK2) and HDL-C concentration. Here we characterize the molecular basis of the novel association between TRAK2 and HDL-cholesterol concentration. Methods and results: Analysis of lymphocyte transcriptomic data together with plasma HDL from the San Antonio Family Heart Study (n = 1240) revealed a significant negative correlation between TRAK2 mRNA levels and HDL-C concentration, HDL particle diameter and HDL subspecies heterogeneity. TRAK2 siRNA-mediated knockdown significantly increased cholesterol efflux to apolipoprotein A-I and isolated HDL from human macrophage (THP-1) and liver (HepG2) cells by increasing the mRNA and protein expression of the cholesterol transporter ATP-binding cassette, sub-family A member 1 (ABCA1). The effect of TRAK2 knockdown on cholesterol efflux was abolished in the absence of ABCA1, indicating that TRAK2 functions in an ABCA1-dependent efflux pathway. TRAK2 knockdown significantly increased liver X receptor (LXR) binding at the ABCA1 promoter, establishing TRAK2 as a regulator of LXR-mediated transcription of ABCA1. Conclusion: We show, for the first time, that TRAK2 is a novel regulator of LXR-mediated ABCA1 expression, cholesterol efflux, and HDL biogenesis. TRAK2 may therefore be an important target in the development of anti-atherosclerotic therapies.

Vertigo with sudden hearing loss: audio-vestibular characteristics.

Acute vertigo with sudden sensorineural hearing loss (SSNHL) is a rare clinical emergency. Here, we report the audio-vestibular test profiles of 27 subjects who presented with these symptoms. The vestibular test battery consisted of a three-dimensional video head impulse test (vHIT) of semicircular canal function and recording ocular and cervical vestibular-evoked myogenic potentials (oVEMP, cVEMP) to test otolith dysfunction. Unlike vestibular neuritis, where the horizontal and anterior canals with utricular function are more frequently impaired, 74 % of subjects with vertigo and SSNHL demonstrated impairment of the posterior canal gain (0.45 ± 0.20). Only 41 % showed impairment of the horizontal canal gains (0.78 ± 0.27) and 30 % of the anterior canal gains (0.79 ± 0.26), while 38 % of oVEMPs [asymmetry ratio (AR) = 41.0 ± 41.3 %] and 33 % of cVEMPs (AR = 47.3 ± 41.2 %) were significantly asymmetrical. Twenty-three subjects were diagnosed with labyrinthitis/labyrinthine infarction in the absence of evidence for an underlying pathology. Four subjects had a definitive diagnosis [Ramsay Hunt Syndrome, vestibular schwannoma, anterior inferior cerebellar artery (AICA) infarction, and traction injury]. Ischemia involving the common-cochlear or vestibulo-cochlear branches of the labyrinthine artery could be the simplest explanation for vertigo with SSNHL. Audio-vestibular tests did not provide easy separation between ischaemic and non-ischaemic causes of vertigo with SSNHL.

Prevalence of vestibular dysfunction in patients with vestibular schwannoma using video head-impulses and vestibular-evoked potentials.

We sought to investigate the utility of new non-invasive tests of semicircular-canal and otolith function that are usable in the neuro-otology office practice in patients with vestibular schwannoma. Fifty patients with vestibular schwannoma were assessed using a 5-item battery consisting of air-conducted cervical- and bone conducted ocular-vestibular-evoked myogenic potentials (AC cVEMPs and BC oVEMPs) and video head impulse testing (vHIT) in all three canal planes. VEMP asymmetry ratios, latencies, and vHIT gains were used to determine the test sensitivity, relationship with tumour size and the pattern of vestibular nerve involvement. The percentage of abnormalities for each of the five tests for the entire sample ranged between 36.2-61.7%. In 58.3 % of patients, test abnormalities were referable to both superior and inferior vestibular nerve divisions. Selective inferior nerve dysfunction was identified in 10.4% and superior nerve dysfunction in 12.5%. The remaining 18.8% of patients demonstrated a normal test profile. The sensitivity of the 5-item battery increased with tumour size and all patients with medium to large (>14 mm) schwannoma had at least two abnormal vestibular test result. Our results indicate that dysfunction of the superior and inferior vestibular nerve evolves in parallel for most patients with schwannoma. Unexplained vHIT and VEMP asymmetry should alert otologists and neurologists to undertake imaging in patients presenting with non-specific disequilibrium or vertigo.

Lhermitte-Duclos disease presenting with atypical positional nystagmus.

We describe a patient with dysplastic cerebellar gangliocytoma (Lhermitte-Duclos disease) who presented with an acute onset of positional disequilibrium. Video-oculography in the right Hallpike position revealed rightward torsional down-beat nystagmus, initially thought to be right anterior canal benign positional vertigo. However, the presence of spontaneous nystagmus, the persistent character of the positional nystagmus and the absence of fatigability indicated central positional nystagmus, attributable to his right-sided Lhermitte-Duclos disease. These findings emphasise the need for clinicians to reconsider a central cause before diagnosing the rare anterior canal benign positioning vertigo variant.

Causes and characteristics of horizontal positional nystagmus.

Direction changing horizontal positional nystagmus can be observed in a variety of central and peripheral vestibular disorders. We tested sixty subjects with horizontal positional nystagmus and vertigo on the Epley Omniax(®) rotator. Monocular video recordings were performed with the right or left ear down, in the supine and prone positions. Nystagmus slow-phase velocity (SPV) was plotted as a function of time. Thirty-one subjects diagnosed with horizontal canalolithiasis had paroxysmal horizontal geotropic nystagmus with the affected ear down (onset 0.8 ± 1 s, range 0-4.9 s, duration 11.7-47.9 s, peak SPV 79 ± 67°/s). The SPV peaked at 5-20 s and declined to 0 by 60 s; at 40 s from onset, the average SPV was 1.8 % of the peak. Nine subjects diagnosed with cupulolithiasis had persistent apogeotropic horizontal nystagmus (onset 0.7 ± 1.4 s, range 0-4.3 s). Peak SPV was 54.2 ± 31.8°/s and 26.6 ± 12.2°/s with unaffected and affected ears down, respectively. At 40 s, the average SPV had decayed to only 81 % (unaffected ear down) and 65 % (affected ear down) of the peak. Twenty subjects were diagnosed with disorders other than benign positional vertigo (BPV) [vestibular migraine (VM), Ménière's Disease, vestibular schwannoma, unilateral or bilateral peripheral vestibular loss]. Subjects with VM (n = 13) had persistent geotropic or apogeotropic horizontal nystagmus. On average, at 40 s from nystagmus onset, the SPV was 61 % of the peak. Two patients with Ménière's Disease had persistent apogeotropic horizontal nystagmus; the peak SPV at 40 s ranged between 28.6 and 49.5 % of the peak. Symptomatic horizontal positional nystagmus can be observed in canalolithiasis, cupulolithiasis and diverse central and peripheral vestibulopathies; its temporal and intensity profile could be helpful in the separation of these entities.

Vestibular schwannoma mimicking horizontal cupulolithiasis.

Positional vertigo and nystagmus can be due to canalithiasis, cupulolithiasis and less commonly, an underlying peripheral or central vestibular disorder. We present a patient with vestibular schwannoma who initially sought treatment for positioning vertigo. Video-oculography on the roll-test revealed direction-changing horizontal apogeotropic nystagmus, consistent with horizontal cupulolithiasis. However, further audio-vestibular investigations and imaging confirmed a right vestibulopathy attributable to a schwannoma of the right vestibular nerve. This case report suggests that vestibular schwannoma should be considered as another potential mimicker of horizontal cupulolithiasis.