Accuracy of Repetitive Ocular Vestibular-Evoked Myogenic Potentials to Diagnose Myasthenia Gravis in Patients With Ptosis or Diplopia.

BACKGROUND AND OBJECTIVES: We developed repetitive ocular vestibular-evoked myogenic potentials (roVEMP) as an electrophysiologic test that allows us to elicit the characteristic decrement of extraocular muscles in patients with ocular myasthenia gravis (OMG). Case-control studies demonstrated that roVEMP reliably differentiates patients with OMG from healthy controls. We now aimed to evaluate the diagnostic accuracy of roVEMP for OMG diagnosis in patients with ptosis and/or diplopia. METHODS: In this blinded prospective diagnostic accuracy trial, we compared roVEMP in 89 consecutive patients presenting with ptosis and/or diplopia suspicious of OMG with a multimodal diagnostic approach, including clinical examination, antibodies, edrophonium testing, repetitive nerve stimulation of accessory and facial nerves, and single-fiber EMG (SFEMG). We calculated the roVEMP decrement as the ratio between the mean of the first 2 responses compared with the mean of the sixth-ninth responses in the train and used cutoff of >9% (unilateral decrement) in a 30 Hz stimulation paradigm. RESULTS: Following a complete diagnostic work-up, 39 patients (44%) were diagnosed with ocular MG, while 50 patients (56%) had various other neuro-ophthalmologic conditions, but not MG (non-MG). roVEMP yielded 88.2% sensitivity, 30.2% specificity, 50% positive predictive value (PPV), and 76.5% negative predictive value (NPV). For comparison, SFEMG resulted in 75% sensitivity, 56% specificity, 55.1% PPV, and 75.7% NPV. All other diagnostic tests (except for the ice pack test) also yielded significantly higher positive results in patients with MG compared with non-MG. DISCUSSION: The study revealed a high sensitivity of 88.2% for roVEMP in OMG, but specificity and PPV were too low to allow for the OMG diagnosis as a single test. Thus, differentiating ocular MG from other neuro-ophthalmologic conditions remains challenging, and the highest diagnostic accuracy is still obtained by a multimodal approach. In this study, roVEMP can complement the diagnostic armamentarium for the diagnosis of MG. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that in patients with diplopia and ptosis, roVEMP alone does not accurately distinguish MG from non-MG disorders. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov: NCT03049956.

Pre-habilitation Before Vestibular Schwannoma Surgery-Impact of Intratympanal Gentamicin Application on the Vestibulo-Ocular Reflex.

Background: Patients with vestibular schwannoma that show residual peripheral-vestibular function before surgery may experience sudden and substantial vestibular loss of function after surgical resection. To alleviate the sudden loss of peripheral-vestibular function after vestibular-schwannoma (VS) resection, pre-surgical intratympanic gentamicin application was proposed. Objective: We hypothesized that this approach allows for a controlled reduction of peripheral-vestibular function before surgery but that resulting peripheral-vestibular deficits may be canal-specific with anterior-canal sparing as observed previously in systemic gentamicin application. Methods: Thirty-four patients (age-range = 27-70 y) with unilateral VS (size = 2-50 mm) were included in this retrospective single-center trial. The angular vestibulo-ocular reflex (aVOR) was quantified before and after (29.7 ± 18.7 d, mean ± 1SD) a single or two sequential intratympanic gentamicin applications by use of video-head-impulse testing. Both aVOR gains, cumulative saccadic amplitudes, and overall aVOR function were retrieved. Statistical analysis was done using a generalized linear model. Results: At baseline, loss of function of the horizontal (20/34) and posterior (21/34) canal was significantly (p < 0.001) more frequent than that of the anterior canal (5/34). After gentamicin application, loss of function of the horizontal (32/34) or posterior (31/34) canal remained significantly (p ≤ 0.003) more frequent than that of the anterior canal (18/34). For all ipsilesional canals, significant aVOR-gain reductions and cumulative-saccadic-amplitude increases were noted after gentamicin. For the horizontal canal, loss of function was significantly larger (increase in cumulative-saccadic-amplitude: 1.6 ± 2.0 vs. 0.8 ± 1.2, p = 0.007) or showed a trend to larger changes (decrease in aVOR-gain: 0.24 ± 0.22 vs. 0.13 ± 0.29, p = 0.069) than for the anterior canal. Conclusions: Intratympanic gentamicin application resulted in a substantial reduction in peripheral-vestibular function in all three ipsilesional canals. Relative sparing of anterior-canal function noted at baseline was preserved after gentamicin treatment. Thus, pre-surgical intratympanic gentamicin is a suitable preparatory procedure for reducing the drop in peripheral-vestibular function after VS-resection. The reasons for relative sparing of the anterior canal remain unclear.

Vestibular mapping in patients with unilateral peripheral-vestibular deficits.

OBJECTIVE: To test the hypothesis that patterns of semicircular canal (SCC) and otolith impairment in unilateral vestibular loss depend on the underlying disorders, we analyzed peripheral-vestibular function of all 5 vestibular sensors. METHODS: For this retrospective case series, we screened the hospital video-head-impulse test database (n = 4,983) for patients with unilaterally impaired SCC function who also received ocular vestibular-evoked myogenic potentials and cervical vestibular-evoked myogenic potentials (n = 302). Frequency of impairment of vestibular end organs (horizontal/anterior/posterior SCC, utriculus/sacculus) was analyzed with hierarchical cluster analysis and correlated with the underlying etiology. RESULTS: Acute vestibular neuropathy (AVN) (37.4%, 113 of 302), vestibular schwannoma (18.2%, 55 of 302), and acute cochleovestibular neuropathy (6.6%, 20 of 302) were most frequent. Horizontal SCC impairment (87.4%, 264 of 302) was more frequent (p < 0.001) than posterior (47.4%, 143 of 302) and anterior (37.8%, 114 of 302) SCC impairment. Utricular damage (58%, 175 of 302) was noted more often (p = 0.003) than saccular impairment (32%, 98 of 302). On average, 2.6 (95% confidence interval 2.48-2.78) vestibular sensors were deficient, with higher numbers (p ≤ 0.017) for acute cochleovestibular neuropathy and vestibular schwannoma than for AVN, Menière disease, and episodic vestibular syndrome. In hierarchical cluster analysis, early mergers (posterior SCC/sacculus; anterior SCC/utriculus) pointed to closer pathophysiologic association of these sensors, whereas the late merger of the horizontal canal indicated a more distinct state. CONCLUSIONS: While the extent and pattern of vestibular impairment critically depended on the underlying disorder, more limited damage in AVN and Menière disease was noted, emphasizing the individual range of loss of function and the value of vestibular mapping. Likely, both the anatomic properties of the different vestibular end organs and their vulnerability to external factors contribute to the relative sparing of the vertical canals and the sacculus.

Constant severe imbalance following traumatic otoconial loss: a new explanation of residual dizziness.

Benign paroxysmal positional vertigo (BPPV) is the most common type of vertigo, caused by otoconia falling from the utricle into a semicircular canal (SCC). After successful repositioning maneuvers residual dizziness (RD) has been described and several reasons are used to explain RD. It can last for only a few days or weeks, but also much longer. We present a patient with a severe traumatic loss of otoconia from both maculae utriculi and a persistent imbalance more than 9 years. We think that the loss of otoconia from the utricular and probably also saccular macula induced a sudden reduction of her ability to sense gravity thus logically explaining her symptoms. We show the vestibular test results also supporting our hypothesis and we extrapolate this support to other forms of so far unexplained dizziness especially increasing imbalance with aging. We also discuss the normal c- and oVEMP indicating intact haircell function and supporting our hypothesis of isolated otoconial loss as the major cause for imbalance.

Repetitive ocular vestibular evoked myogenic potential stimulation for the diagnosis of myasthenia gravis: Optimization of stimulation parameters.

OBJECTIVE: To determine the most effective stimulation parameters for the diagnosis of ocular myasthenia gravis (MG) using repetitive ocular vestibular evoked myogenic potentials (oVEMP) for quantification of the extraocular muscle response decrement. METHODS: Repetitive bone-conducted oVEMPs were elicited in 18 MG patients and 20 healthy subjects. We compared four different stimulus repetition rates (20 Hz, 30 Hz, 40 Hz, 50 Hz) and 100 Hz continuous stimulation, as well as recordings from the inferior oblique muscles and the lateral rectus muscles to determine the most sensitive and specific oVEMP parameters for decrement detection. RESULTS: Repetitive stimulation at all tested repetition rates with recordings from inferior oblique muscles allowed for effective differentiation between MG patients and healthy subjects. Among all repetition rates, 30 Hz showed a trend towards superiority, with a sensitivity of 71% and a specificity of 94% (area under the curve (AUC) 0.88) when using the smaller decrement of the two eyes and -10% as cutoff. Considering the larger decrement for analysis (-9% as cutoff), sensitivity increased to 82%, but specificity decreased to 78% (AUC 0.81). CONCLUSIONS: Our study demonstrates, that repetitive oVEMP stimulation elicits a robust decrement in the inferior oblique muscles of MG patients at repetition rates between 20 Hz and 50 Hz, with a probable optimum at 30 Hz. SIGNIFICANCE: Repetitive inferior oblique oVEMP stimulation with optimal stimulus parameters facilitates early and accurate diagnosis of ocular MG.

Association of posterior semicircular canal hypofunction on video-head-impulse testing with other vestibulo-cochlear deficits.

OBJECTIVES: The video-head-impulse test (vHIT) provides a functional assessment of all six semicircular canals (SCC). Occasionally isolated loss of the posterior canal(s) (ILPC) is diagnosed, though this finding is poorly characterized. Here we assessed how accurate that diagnosis is by measuring the co-occurrence of abnormalities on caloric irrigation, vestibular-evoked myogenic-potentials and audiometry. METHODS: We identified 52 patients with ILPC (unilateral=40, bilateral=12). We determined vHIT-gains and saccade-amplitudes and correlated vHIT-findings with other vestibulo-cochlear tests. RESULTS: The most frequent diagnoses were history of vestibular neuritis (13/52), Menière's disease (12/52) and vertigo/dizziness of unclear origin (13/52). Unilateral ILPC on vHIT was accompanied by a deficient horizontal canal on calorics, saccular and/or utricular deficits ipsilesionally in 33/40 (83%), while ipsilesional hearing-loss was noted in 24/40 (60%). Involvement of other sensors was highest for vestibular schwannoma (100%) and history of vestibular neuritis (92%). Bilateral deficits in ≥1 vestibulo-cochlear sensor(s) were noted in 2/12 cases with bilateral ILPC. CONCLUSIONS: >80% of patients with unilateral ILPC had additional deficits of other parts of the vestibular organ, while this rate was ≤20% for patients with bilateral ILPC. SIGNIFICANCE: Dizzy patients should receive testing of the posterior canals and if abnormalities are observed, additional vestibulo-cochlear testing should be obtained.

Hysteresis of haptic vertical and straight ahead in healthy human subjects.

BACKGROUND: The subjective haptic vertical (SHV) task requires subjects to adjust the roll orientation of an object, mostly in the roll plane, in such a way that it is parallel to perceived direction of gravity. Previously we found a tendency for clockwise rod rotations to deviate counter-clockwise and vice versa, indicating hysteresis. However, the contributing factors remained unclear. To clarify this we characterized the SHV in terms of handedness, hand used, direction of hand rotation, type of grasping (wrap vs. precision grip) and gender, and compared findings with perceived straight-ahead (PSA). Healthy subjects repetitively performed adjustments along SHV (n = 21) and PSA (n = 10) in complete darkness. RESULTS: For both SHV and PSA significant effects of the hand used and the direction of rod/plate rotation were found. The latter effect was similar for SHV and PSA, leading to significantly larger counter-clockwise shifts (relative to true earth-vertical and objective straight-ahead) for clockwise rotations compared to counter-clockwise rotations irrespective of the handedness and the type of grip. The effect of hand used, however, was opposite in the two tasks: while the SHV showed a counter-clockwise bias when the right hand was used and no bias for the left hand, in the PSA a counter-clockwise bias was obtained for the left hand without a bias for the right hand. No effects of grip and handedness (studied for SHV only) on accuracy were observed, however, SHV precision was significantly (p < 0.005) better in right-handed subjects compared to left-handed subjects and in male subjects. CONCLUSIONS: Unimanual haptic tasks require control for the hand used and the type of grip as these factors significantly affect task performance. Furthermore, aligning objects with the SHV and PSA resulted in systematic direction-dependent deviations that could not be attributed to handedness, the hand used, or the type of grip. These deviations are consistent with hysteresis and are likely not related to gravitational pull, as they were observed in both planes tested, i.e. parallel and perpendicular to gravity. Short-term adaptation that shifts attention towards previous adjustment positions may provide an explanation for such biases of spatial orientation in both the horizontal and frontal plane.

A new dynamic visual acuity test to assess peripheral vestibular function.

OBJECTIVE: To evaluate a novel test for dynamic visual acuity (DVA) that uses an adaptive algorithm for changing the size of Landolt rings presented during active or passive head impulses, and to compare the results with search-coil head impulse testing. DESIGN: Prospective study in healthy individuals and patients with peripheral vestibular deficits. SETTING: Tertiary academic center. PARTICIPANTS: One hundred neuro-otologically healthy individuals (age range, 19-80 years) and 15 patients with bilateral (n = 5) or unilateral (n = 10) peripheral vestibular loss (age range, 27-72 years). INTERVENTIONS: Testing of static visual acuity (SVA), DVA during active and passive horizontal head rotations (optotype presentation at head velocities >100 degrees/s and >150 degrees/s), and quantitative horizontal head impulse testing with scleral search coils. MAIN OUTCOME MEASURE: Difference between SVA and DVA, that is, visual acuity loss (VA loss), gain of the high-acceleration vestibulo-ocular reflex. RESULTS: Passive head impulses and higher velocities were more effective than active impulses and lower velocities. Using passive head impulses and velocities higher than 150 degrees/s, the DVA test discriminated significantly (P < .001) among patients with bilateral vestibulopathy, those with unilateral vestibulopathy, and normal individuals. The DVA test sensitivity was 100%, specificity was 94%, and accuracy was 95%, with search-coil head impulse testing used as a reference. In healthy individuals, VA loss increased significantly with age (P < .001; R(2) = 0.04). CONCLUSION: Dynamic visual acuity testing with Landolt rings that are adaptively changed in size enables detection of peripheral vestibular dysfunction in a fast and simple way.