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.

Using Smartphone Exophthalmometry to Measure Eyeball Protrusion.

Importance: The current clinical criterion standard for measuring abnormal eyeball protrusion is still the historic Hertel exophthalmometer, which is prone to reading errors. Therefore, a smartphone application has been developed to measure exophthalmos. Objective: To evaluate a relatively simple noninvasive measurement method for exophthalmos using a smartphone. Design, Setting, and Participants: This cross-sectional study compared smartphone exophthalmometry with the existing reference standard, the Hertel exophthalmometer, or a professional high-resolution 3-dimensional scanner. Participants were patients with exophthalmos due to Graves orbitopathy and other intraorbital conditions and healthy volunteers who were recruited between June 2019 and January 2022 from the Department of Ophthalmology, University Hospital Zurich. Interventions: All participants were examined twice by 3 different operators using 3 different methods (smartphone, high-resolution scanner, or Hertel exophthalmometer) at an interval of a minimum of 2 weeks or after exophthalmos-changing treatment. Main Outcome Measures: Accuracy and precision, test-retest reliability, and interoperator reliability of eyeball protrusion measurements obtained with the smartphone compared to the Hertel exophthalmometer and the high-resolution face scanner. Results: Of 39 participants, 23 patients (median [IQR] age, 54 [44-59] years; 15 [65%] female and 8 [35%] male) showed a mean difference in eyeball protrusion of 3.3 mm and 16 healthy volunteers (median [IQR] age, 32 [30-37] years; 11 [69%] female and 5 [31%] male) of 0.8 mm without any significant difference between the 3 methods. Accuracy and precision agreement between exophthalmos measures with the smartphone and the Hertel exophthalmometer showed an intraclass correlation coefficient (ICC) of 0.89 (95% CI, 0.80-0.94) and 0.93 (95% CI, 0.83-0.97) for the high-resolution scanner. Interoperator agreement was highest for the high-resolution scanner (ICC, 0.99 [95% CI, 0.98-0.99]), followed by the smartphone (ICC, 0.95 [95% CI, 0.92-0.97]) and the Hertel exophthalmometer (ICC, 0.91 [95% CI, 0.85-0.95]). Test retest reliability was similarly high for the smartphone (ICC, 0.93 [95% CI, 0.82-0.95]), the Hertel exophthalmometer (ICC, 0.92 [95% CI, 0.83-0.96]), and the high-resolution scanner (ICC, 0.95 [95% CI, 0.89-0.97]). Conclusions and Relevance: The findings of this study demonstrate relatively high accuracy and precision, interoperator reliability, and test-retest reliability for smartphone exophthalmometry. These data support the use of a smartphone in place of a Hertel exophthalmometer for measuring exophthalmos in the future.

Lesion follows function: video-oculography compared with MRI to diagnose internuclear ophthalmoplegia in patients with multiple sclerosis.

BACKGROUND: Video-oculography (VOG) is used to quantify functional deficits in internuclear ophthalmoplegia (INO), whereas MRI can detect the corresponding structural lesions in the medial longitudinal fasciculus (MLF). This study investigates the diagnostic agreement of MRI compared to VOG measurements. METHODS: We prospectively compared structural MRI findings and functional VOG measures of 63 MS patients to assess their diagnostic agreement for INO. RESULTS: MRI detected 12 true-positive and 92 true-negative MLF lesions for INO compared to VOG (12 true-positive and 38 true-negative patients) but identified one-third of the MLF lesions on the wrong side. MRI ratings were specific (92.0%) to detect MLF lesions but not sensitive (46.2%) for diagnosing INO (86.4% and 63.2% by patient). Accordingly, MRI has a high positive likelihood ratio of 5.77 but a modest negative likelihood ratio of 0.59 for the probability of INO (4.63 and 0.43) with an accuracy of 82.5% (79.4%). CONCLUSION: MRI assessments are highly specific but not sensitive for detecting INO compared to VOG. While MRI identifies MLF lesions in INO, VOG quantifies the deficit. As a simple, quick, and non-invasive test for diagnosing and tracking functional INO deficits, it will hopefully find its place in the diagnostic and therapeutic pathways of MS.

Vestibular performance in high-level soccer and ice hockey players: Sport-specific norm values and implications.

OBJECTIVES: Quantitative vestibular testing in athletes after sports-related concussion (SRC) has become more popular due to accompanying injuries of the peripheral-vestibular organs that require targeted treatment. Sports-specific normative values are currently not available. Taking into account potential adaptational mechanisms, we obtained sports-specific, age- and peak-head-velocity-corrected normative values of peripheral-vestibular function and postural-stability in football (soccer, FB) and ice-hockey (IH) players. DESIGN: Retrospective single-center case-control study. METHOD: Pre-seasonal angular vestibulo-ocular reflex (aVOR) gains and cumulative-saccadic-amplitudes were obtained using the video-head-impulse test and performance in the balance-error-scoring-system (BESS) was recorded and compared in high-level FB-players (n = 510, 197 females) and IH-players (n = 210, males only) (age-range = 13-39y) and in healthy normals (n = 49, 22 females). Statistical analysis was performed using a generalized linear model. RESULTS: aVOR-gain values were significantly higher for FB-players than for IH-players (1.07 ±â€¯0.21 vs. 0.98 ±â€¯0.13, p < 0.001) and controls (1.07 ±â€¯0.21 vs. 0.97 ±â€¯0.17, p < 0.001). Significant age-related changes in aVOR-gains were only observed for the anterior and posterior canals in the IH-players. Cumulative-saccadic-amplitudes were clearly below established cut-off values (0.73°/trial). BESS scores were significantly higher in IH-players than in FB-players (15.4 ±â€¯5.1 vs. 11.2 ±â€¯4.9, p < 0.001). CONCLUSIONS: The significantly better performance of the FB players in the vertical aVOR-gains and the BESS compared to the IH-players could be related to sports-specific differences influencing visuo-vestibular and balance performance. Therefore, we recommend using the established normative aVOR-gain values for high-level FB-players, whereas in IH obtaining individual pre-seasonal (baseline) aVOR-gain values is proposed. Further studies should add sports-specific normative aVOR-gain values for IH and other sports.

Therapy-Resistant Atypical Downbeat Nystagmus with Vertigo Confined to Specific Head-Hanging Positions: Mapping to the Gravity Vector on a Multi-Axis Turntable.

Downbeat nystagmus (DBN) observed in head-hanging positions, may be of central or peripheral origin. Central DBN in head-hanging positions is mostly due to a disorder of the vestibulo-cerebellum, whereas peripheral DBN is usually attributed to canalolithiasis of an anterior semicircular canal. Here, we describe an atypical case of a patient who, after head trauma, experienced severe and stereotypic vertigo attacks after being placed in various head-hanging positions. Vertigo lasted 10-15 s and was always associated with a robust DBN. The provocation of transient vertigo and DBN, which both showed no decrease upon repetition of maneuvers, depended on the yaw orientation relative to the trunk and the angle of backward pitch. On a motorized, multi-axis turntable, we identified the two-dimensional Helmholtz coordinates of head positions at which vertigo and DBN occurred (y-axis: horizontal, space-fixed; z-axis: vertical, and head-fixed; x-axis: torsional, head-fixed, and unchanged). This two-dimensional area of DBN-associated head positions did not change when whole-body rotations took different paths (e.g., by forwarding pitch) or were executed with different velocities. Moreover, the intensity of DBN was also independent of whole-body rotation paths and velocities. So far, therapeutic approaches with repeated liberation maneuvers and cranial vibrations were not successful. We speculate that vertigo and DBN in this patient are due to macular damage, possibly an unstable otolithic membrane that, in specific orientations relative to gravity, slips into a position causing paroxysmal stimulation or inhibition of macular hair cells.

Effect of the Stimulus Duration on the Adaptation of the Optokinetic Afternystagmus.

Observing a rotating visual pattern covering a large portion of the visual field induces optokinetic nystagmus (OKN). If the lights are suddenly switched off, optokinetic afternystagmus (OKAN) occurs. OKAN is hypothesized to originate in the velocity storage mechanism (VSM), a central processing network involved in multi-sensory integration. During a sustained visual rotation, the VSM builds up a velocity signal. After the lights are turned off, the VSM discharges slowly, with OKAN as the neurophysiological correlate. It has been reported that the initial afternystagmus in the direction of the preceding stimulus (OKAN-I) can be followed by a reversed one (OKAN-II), which increases with stimulus duration up to 15 min. In 11 healthy adults, we investigated OKAN following optokinetic stimulus lasting 30 s, 3-, 5-, and 10-min. Analysis of slow-phase cumulative eye position and velocity found OKAN-II in only 5/11 participants. Those participants presented it in over 70% of their trials with longer durations, but only in 10% of their 30 s trials. While this confirms that OKAN-II manifests predominantly after sustained stimuli, it suggests that its occurrence is subject-specific. We also did not observe further increases with stimulus duration. Conversely, OKAN-II onset occurred later as stimulus duration increased (p = 0.02), while OKAN-II occurrence and peak velocity did not differ between the three longest stimuli. Previous studies on OKAN-I, used negative saturation models to account for OKAN-II. As these approaches have no foundation in the OKAN-II literature, we evaluated if a simplified version of a rigorous model of OKAN adaptation could be used in humans. Slow-phase velocity following the trials with 3-, 5-, and 10-min stimuli was fitted with a sum of two decreasing exponential functions with opposite signs (one for OKAN-I and one for OKAN-II). The model assumes separate mechanisms for OKAN-I, representing VSM discharge, and OKAN-II, described as a slower adaptation phenomenon. Although the fit was qualitatively imperfect, this is not surprising given the limited reliability of OKAN in humans. The estimated adaptation time constant seems comparable to the one describing the reversal of the vestibulo-ocular reflex during sustained rotation, suggesting a possible shared adaptive mechanism.

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.

Divergence bias in Hess compared to Harms screen strabismus testing.

The Hess and the Harms screen test each have different testing distances. While the Harms screen test is usually performed at 2.5 m, the Hess screen test is performed at 0.5 m. The geometry of the closer testing distance of the Hess screen test requires an increase of the convergence angle by 6°. This study investigates the quantitative differences between the two frequently employed screen tests. Ocular deviation of 18 normal subjects and 36 patients with congenital or acquired paralytic or concomitant strabismus were assessed with a complete orthoptic examination including alternate prism cover testing at near (nPCT) and far (fPCT), as well as Hess and Harms screen testing. One-way ANOVA was used for statistical analysis. The Hess test recorded more overall exodeviation compared to the Harms test for patients (mean difference -3.50°, 95% limits of agreement (CI) = [-4.79, -2.21], p < .001), and controls (mean difference -1.78°, CI = [-2.99, -0.56], p = .004). For vertical deviations, there was no statistically significant difference between the two tests for patients (mean difference +0.75°, CI = [-0.41, +1.91], p = .251), and controls (mean difference -0.28°, CI = [-0.68, -0.11], p = 0.231). This study emphasizes the importance to consider the divergence bias when comparing the Hess to the Harms screen test, which is likely explained by the greater vergence demand dependent on the closer testing distance. The exodeviation shift tended to be more pronounced in patients than controls, which may imply that patients with strabismus have an impaired convergence drive.

Beyond sensory conflict: The role of beliefs and perception in motion sickness.

Illusory self-motion often provokes motion sickness, which is commonly explained in terms of an inter-sensory conflict that is not in accordance with previous experience. Here we address the influence of cognition in motion sickness and show that such a conflict is not provocative when the observer believes that the motion illusion is indeed actually occurring. Illusory self-motion and motion sickness were elicited in healthy human participants who were seated on a stationary rotary chair inside a rotating optokinetic drum. Participants knew that both chair and drum could rotate but were unaware of the actual motion stimulus. Results showed that motion sickness was correlated with the discrepancy between participants' perceived self-motion and participants' beliefs about the actual motion. Together with the general motion sickness susceptibility, this discrepancy accounted for 51% of the variance in motion sickness intensity. This finding sheds a new light on the causes of visually induced motion sickness and suggests that it is not governed by an inter-sensory conflict per se, but by beliefs concerning the actual self-motion. This cognitive influence provides a promising tool for the development of new countermeasures.

Prolonged Static Whole-Body Roll-Tilt and Optokinetic Stimulation Significantly Bias the Subjective Postural Vertical in Healthy Human Subjects.

Background: Prolonged static whole-body roll-tilt has been shown to bias estimates of the direction of gravity when assessed by static paradigms such as the subjective visual vertical and the subjective haptic vertical. Objective: We hypothesized that these shifts are paradigm-independent and thus predicted a post-tilt bias as well for self-adjustments along perceived vertical (subjective postural vertical, SPV). Likewise, rotatory optokinetic stimuli, which have been shown to shift the SPV when presented at the time of adjustments, may have an lasting effect on the SPV, predicting a shift in the perceived direction of gravity in the direction of the optokinetic rotatory stimulation. Methods: Self-adjustments along perceived vertical by use of a motorized turntable were recorded at baseline and after 5 min of static whole-body roll-tilt (orientation = ±90°, adaptation period) in 10 healthy human subjects. During adaptation subjects were either in darkness (no OKN stimulation) or were presented a full-field rotatory optokinetic stimulus (velocity = ±60°/s). Statistical analysis of adjustment errors for the different conditions was performed using a generalized linear model. Results: After 5 min of static whole-body roll-tilt in darkness, we observed significant (p < 0.001) shifts in the SPV averaging -2.8° (adaptation position: -90°) and 3.1° (+90°), respectively. Adding an optokinetic rotatory stimulus resulted in an additional, significant shift of SPV adjustments toward the direction of the previously presented optokinetic rotation (optokinetic clockwise rotation: 1.4°, p = 0.034; optokinetic counter-clockwise rotation: -1.3°, p = 0.037). Trial-to-trial variability of turntable adjustments was not significantly affected by adaptation. Conclusions: Prolonged static roll-tilt results in a significant post-tilt bias of the perceived direction of gravity when assessed by the SPV, confirming previous findings from other vision-dependent and vision-independent paradigms. This finding emphasizes the impact of recent whole-body roll orientations relative to gravity. Such adaptational shifts in verticality estimates may be explained in the context of Bayesian optimal observer theory with a bias of prior knowledge (i.e., expectation biased by experience). Our findings also have clinical implications, as the observed post-tilt bias may contribute to postural instability when standing up in the morning with an increasing risk for falls and fall-related injuries in humans with preexisting balance disorders.

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.

Distinct Vestibular Evoked Myogenic Potentials in Patients With Parkinson Disease and Progressive Supranuclear Palsy.

Background: Early brainstem neurodegeneration is common in Parkinson's disease (PD) and progressive supranuclear palsy (PSP). While previous work showed abnormalities in vestibular evoked myogenic potentials (VEMPs) in patients with either disorder as compared to healthy humans, it remains unclear whether ocular and cervical VEMPs differ between PD and PSP patients. Methods: We prospectively included 12 PD and 11 PSP patients, performed ocular and cervical VEMPs, and calculated specific VEMP scores (0 = normal, 12 = most pathological) based on latencies, amplitude, and absent responses. In addition, we assessed disease duration, presence of imbalance, motor asymmetry, and motor disability using the Movement Disorder Society Unified Parkinson's Disease Rating Scale, part III (MDS-UPDRS III). Moreover, we ascertained various sleep parameters by video-polysomnography. Results: PSP and PD patients had similar oVEMP scores (6 [3-6] vs. 3 [1.3-6], p = 0.06), but PSP patients had higher cVEMP scores (3 [0-6] vs. 0 [0-2.8], p = 0.03) and total VEMP scores (9 [5-12] vs. 4 [2-7.5], p = 0.01). Moreover, total VEMP scores >10 were only observed in PSP patients (45%, p = 0.01). MDS-UPDRS III correlated with cVEMP scores (rho = 0.77, p = 0.01) in PSP, but not in PD. In PD, but not in PSP, polysomnographic markers of disturbed sleep, including decreased rapid eye movement sleep, showed significant correlations with VEMP scores. Conclusions: Our findings suggest that central vestibular pathways are more severely damaged in PSP than in PD, as indicated by higher cervical and total VEMP scores in PSP than PD in a between-groups analysis. Meaningful correlations between VEMPs and motor and non-motor symptoms further encourage its use in neurodegenerative Parkinsonian syndromes.

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.

The Tilted Self: Visuo-Graviceptive Mismatch in the Full-Body Illusion.

The bodily self is a fundamental part of human self-consciousness and relies on online multimodal information and prior beliefs about one's own body. While the contribution of the vestibular system in this process remains under-investigated, it has been theorized to be important. The present experiment investigates the influence of conflicting gravity-related visual and bodily information on the sense of a body and, vice versa, the influence of altered embodiment on verticality and own-body orientation perception. In a full-body illusion setup, participants saw in a head-mounted display a projection of their own body 2 m in front of them, on which they saw a tactile stimulation on their back displayed either synchronously or asynchronously. By tilting the seen body to one side, an additional visuo-graviceptive conflict about the body orientation was created. Self-identification with the seen body was measured explicitly with a questionnaire and implicitly with skin temperature. As measures of orientation with respect to gravity, we assessed subjective haptic vertical and the haptic body orientation. Finally, we measured the individual visual field dependence using the rod-and-frame test. The results show a decrease in self-identification during the additional visuo-graviceptive conflict, but no modulation of perceived verticality or subjective body orientation. Furthermore, explorative analyses suggest a stimulation-dependent modulation of the perceived body orientation in individuals with a strong visual field dependence only. The results suggest a mutual interaction of graviceptive and other sensory signals and the individual's weighting style in defining our sense of a bodily self.

Buzzing Sympathetic Nerves: A New Test to Enhance Anisocoria in Horner's Syndrome.

Introduction: Patients with suspected Horner's syndrome having equivocal pupil dilation lag and pharmacologic testing may undergo unnecessary MR imaging and work up in the case of false positive pupil test results. Our goal was to increase the diagnostic accuracy of pupillometry by accentuating the inter-ocular asymmetry of sympathetic innervation to the iris dilator with surface electrical stimulation of the median nerve using a standard electromyography machine. We hypothesized that an accentuated difference in sympathetic response between the two eyes would facilitate the diagnosis of Horner's syndrome. Methods: Eighteen patients with pharmacologically proven Horner's syndrome were compared to ten healthy volunteers tested before and after monocular instillation of 0.2% brimonidine tartrate ophthalmic solution to induce pharmacological Horner's syndrome. Pupillary responses were measured with binocular pupillometry in response to sympathetic activation by electrical stimulation of the median nerve in darkness and at various times after extinction of a light stimulus. Sudomotor sympathetic responses from the palm of the stimulated arm were recorded simultaneously. Results: In subjects with Horner's syndrome and pharmacologically induced unilateral sympathetic deficit, electrical stimulation in combination with the extinction of light greatly enhanced the anisocoria during the evoked pupil dilation, while there was no significant increase in anisocoria in healthy subjects. The asymmetry of the sympathetic response was greatest when the electrical stimulus was given 2 s after termination of the light or under constant low light conditions. When given 2 s after termination of light, the electrical stimulation increased the mean anisocoria from 1.0 to 1.2 mm in Horner's syndrome (p = 0.01) compared to 0.22-0.26 mm in healthy subjects (p = 0.1). In all subjects, the maximal anisocoria induced by the electrical stimulation appeared within a 2 s interval after the stimulus. Correspondingly, the largest change in anisocoria between light and dark without electrical stimulation was seen between 3 and 4 s after light-off. While stronger triple stimulation further enhanced the anisocoria, it was less well tolerated. Conclusions: Electrical stimulation 2 s after light-off greatly enhances the sensitivity of pupillometry for diagnosing Horner's syndrome. This new method may help to rule in or rule out a questionable Horner's syndrome, especially if the results of topical pharmacological testing are inconclusive.

Effects of Optokinetic Stimulation on Verticality Perception Are Much Larger for Vision-Based Paradigms Than for Vision-Independent Paradigms.

INTRODUCTION: Verticality perception as assessed by the subjective visual vertical (SVV) is significantly biased by a rotating optokinetic stimulus. The underlying mechanisms of this effect remain open. Potentially, the optokinetic stimulus induces a shift of the internal estimate of the direction of gravity. This hypothesis predicts a shift of perceived vertical using other, non-vision dependent, paradigms as well. Alternatively, an optokinetic stimulus may only induce a shift of visual orientation, and so would be task specific. METHODS: To test this prediction, both vision-dependent SVV and vision-independent [subjective haptic vertical (SHV)] paradigms were applied. In 12 healthy human subjects, perceived vertical was measured in different whole-body roll positions (up to ±120°, steps = 30°) while watching a clockwise or counterclockwise rotating optokinetic stimulus. For comparison, baseline trials were collected in darkness. A generalized linear model was applied for statistical analysis. RESULTS: A significant main effect for optokinetic stimulation was noted both for the SVV paradigm (p < 0.001) and the SHV paradigm (p = 0.013). However, while pairwise comparisons demonstrated significant optokinetic-induced shifts (p ≤ 0.035) compared to baseline in all roll-tilted orientations except 30° and 60° left-ear-down position and counterclockwise optokinetic stimulation for the SVV paradigm, significant shifts were found in only 1 of the 18 test conditions (120° left-ear-down roll orientation, counterclockwise optokinetic stimulation) for the SHV paradigm. Compared to the SHV, the SVV showed significantly (p < 0.001) larger shifts of perceived vertical when presenting a clockwise (15.3 ± 16.0° vs. 1.1 ± 5.2°, mean ± 1 SD) or counterclockwise (-12.6 ± 7.7° vs. -2.6 ± 5.4°) rotating optokinetic stimulus. CONCLUSION: Comparing the effect of optokinetic stimulation on verticality perception in both vision-dependent and vision-independent paradigms, we demonstrated distinct patterns. While significant large and roll-angle dependent shifts were noted for the SVV, offsets were minor and reached significance only in one test condition for the SHV. These results suggest that optokinetic stimulation predominately affects vision-related mechanisms, possibly due to induced torsional eye displacements, and that any shifts of the internal estimate of the direction of gravity are relatively minor.

Hierarchical Cluster Analysis of Semicircular Canal and Otolith Deficits in Bilateral Vestibulopathy.

BACKGROUND: Gait imbalance and oscillopsia are frequent complaints of bilateral vestibular loss (BLV). Video-head-impulse testing (vHIT) of all six semicircular canals (SCCs) has demonstrated varying involvement of the different canals. Sparing of anterior-canal function has been linked to aminoglycoside-related vestibulopathy and Menière's disease. We hypothesized that utricular and saccular impairment [assessed by vestibular-evoked myogenic potentials (VEMPs)] may be disease-specific also, possibly facilitating the differential diagnosis. METHODS: We searched our vHIT database (n = 3,271) for patients with bilaterally impaired SCC function who also received ocular VEMPs (oVEMPs) and cervical VEMPs (cVEMPs) and identified 101 patients. oVEMP/cVEMP latencies above the 95th percentile and peak-to-peak amplitudes below the 5th percentile of normal were considered abnormal. 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: Rates of utricular and saccular loss of function were similar (87.1 vs. 78.2%, p = 0.136, Fisher's exact test). oVEMP abnormalities were found more frequent in aminoglycoside-related bilateral vestibular loss (BVL) compared with Menière's disease (91.7 vs. 54.6%, p = 0.039). Hierarchical cluster analysis indicated distinct patterns of vestibular end-organ impairment, showing that the results for the same end-organs on both sides are more similar than to other end-organs. Relative sparing of anterior-canal function was reflected in late merging with the other end-organs, emphasizing their distinct state. An anatomically corresponding pattern of SCC/otolith hypofunction was present in 60.4% (oVEMPs vs. horizontal SCCs), 34.7% (oVEMPs vs. anterior SCCs), and 48.5% (cVEMPs vs. posterior SCCs) of cases. Average (±1 SD) number of damaged sensors was 6.8 ± 2.2 out of 10. Significantly (p < 0.001) more sensors were impaired in patients with aminoglycoside-related BVL (8.1 ± 1.2) or inner-ear infections (8.7 ± 1.8) compared with Menière-related BVL (5.5 ± 1.5). DISCUSSION: Hierarchical cluster analysis may help differentiate characteristic patterns of BVL. With a prevalence of ≈80%, utricular and/or saccular impairment is frequent in BVL. The extent of SCC and otolith impairment was disease-dependent, showing most extensive damage in BVL related to inner-ear infection and aminoglycoside-exposure and more selective impairment in Menière's disease. Specifically, assessing utricular function may help in the distinction between aminoglycoside-related BVL and bilateral Menière's disease.

More far is more right: Manual and ocular line bisections, but not the Judd illusion, depend on radial space.

Line bisection studies generally find a left-to-right shift in bisection bias with increasing distance between the observer and the target line, which may be explained by hemispheric differences in the processing of proximo-distal information. In the present study, the segregation between near and far space was further characterized across the motor system and contextual cues. To this aim, 20 right-handed participants were required to perform a manual bisection task of simple lines presented at three different distances (60, 90, 120 cm). Importantly, the horizontal spatial location of the line was manipulated along with the viewing distance to investigate more deeply the hemispheric engagement in the transition from near to far space. As the motoric component of the manual task producing activations of left premotor and motor areas may be partially responsible for the observed transition, participants were also involved in an ocular bisection task. Further, participants were required to bisect Judd variants of the target lines, which are known to elicit a Müller-Lyer-type illusion. Since the Judd illusion depends on areas in the ventral visual stream, we predicted that line bisections of Judd-type lines would be unaffected by viewing distance. Results showed that manual bisection of simple lines was modulated separately by viewing distance and the hemispace of presentation, with this pattern being similar for ocular bisection. Critically, bisections in the Judd illusion task were not modulated by viewing distance, whether performed by hand or by eye. Overall, these findings support the hypothesis that the right hemisphere plays a dominant role in the processing of space close to the body. They also present novel evidence for a general reduction of this dominance at farther distances, whether hand motor actions are involved or not. Finally, our study documents a dissociation between the processing of pure visuospatial information and that of a visual illusion as a function of viewing distance, supporting more generally the dorsal/near space and the ventral/far space segregation.

Strabismus Measurements with Novel Video Goggles.

PURPOSE: To assess the validity of a novel, simplified, noninvasive test for strabismus using video goggles. DESIGN: Cross-sectional method comparison study in which the new test, the strabismus video goggles, is compared with the existing reference standard, the Hess screen test. PARTICIPANTS: We studied 41 adult and child patients aged ≥6 years with ocular misalignment owing to congenital or acquired paralytic or comitant strabismus and 17 healthy volunteers. METHODS: All participants were tested with binocular infrared video goggles with built-in laser target projection and liquid crystal display shutters for alternate occlusion of the eyes and the conventional Hess screen test. In both tests, ocular deviations were measured on a 9-point target grid located at 0±15° horizontal and vertical eccentricity. MAIN OUTCOME MEASURES: Horizontal and vertical ocular deviations at 9 different gaze positions of each eye were measured by the strabismus video goggles and the Hess screen test. Agreement was quantified as the intraclass correlation coefficient. Secondary outcomes were the utility of the goggles in patients with visual suppression and in children. RESULTS: There was good agreement between the strabismus video goggles and the Hess screen test in the measurements of horizontal and vertical deviation (intraclass correlation coefficient horizontal 0.83, 95% confidence interval [0.77, 0.88], vertical 0.76, 95% confidence interval [0.68, 0.82]). Both methods reproduced the characteristic strabismus patterns in the 9-point grid. In contrast to Hess screen testing, strabismus video goggle measurements were even possible in patients with comitant strabismus and visual suppression. CONCLUSIONS: The new device is simple and is fast and accurate in measuring ocular deviations, and the results are closely correlated with those obtained using the conventional Hess screen test. It can even be used in patients with visual suppression who are not suitable for the Hess screen test. The device can be applied in children as young as 6 years of age.