What visuospatial perception has taught us about the pathophysiology of vestibular migraine.

PURPOSE OF REVIEW: A decade has passed since vestibular migraine (VM) was formally established as a clinical entity. During this time, VM has emerged amongst the most common cause of episodic vertigo. Like all forms of migraine, VM symptoms are most prominent during individual attacks, however many patients may also develop persistent symptoms that are less prominent and can still interfere with daily activities. RECENT FINDINGS: Vestibular inputs are strongly multimodal, and because of extensive convergence with other sensory information, they do not result in a distinct conscious sensation. Here we review experimental evidence that supports VM symptoms are linked to multisensory mechanisms that control body motion and position in space. SUMMARY: Multisensory integration is a key concept for understanding migraine. In this context, VM pathophysiology may involve multisensory processes critical for motion perception, spatial orientation, visuospatial attention, and spatial awareness.

Focused Update on Migraine and Vertigo Comorbidity.

PURPOSE OF REVIEW: To provide an update on comorbidity of vestibular symptoms and migraine. RECENT FINDINGS: Multisensory processing and integration is a key concept for understanding mixed presentation of migraine and vestibular symptoms. Here, we discuss how vestibular migraine should be distinguished from a secondary migraine phenomenon in which migraine symptoms may coincide with or triggered by another vestibular disorder. We also have some updates on the diagnostic criteria of vestibular migraine, its pathophysiology, and common approaches used for its treatment. As a common clinical presentation of migraine and vestibular symptoms, vestibular migraine should be distinguished from a secondary migraine phenomenon, in which migraine symptoms may be triggered by or coincide with another vestibular disorder. Recent experimental evidence suggests vestibular symptoms in vestibular migraine are linked to multisensory mechanisms that control body motion and orientation in space.

Upbeat Nystagmus with an Unusual Velocity-Decreasing and Increasing Waveform: a Sign of Gaze-Holding Dysfunction in the Paramedian Tracts in the Medulla?

We report a patient with spontaneous upbeat nystagmus (UBN) due to an ischemic lesion involving the paramedian tract (PMT) in the medulla. Eye movement recordings, using an infrared video-oculography (VOG) system, showed that the slow phase of the nystagmus was initially velocity-decreasing but gradually became velocity-increasing. Simulation of the nystagmus with a mathematical model supports a role for the PMT in relaying premotor signals for vertical gaze holding to the cerebellum. Our model shows that the disruption in cerebellar input from PMT can lead to the velocity-increasing waveform of the nystagmus, whereas the velocity-decreasing waveform could be related to a mismatch between the innervational commands to the ocular muscles (the pulse and step) needed to hold gaze steady.

Sex-disease dimorphism underpins enhanced motion sickness susceptibility in primary adrenal insufficiency: a cross-sectional observational study.

Environmental motion can induce physiological stress and trigger motion sickness. In these situations, lower-than-normal levels of adrenocorticotropic hormone (ACTH) have been linked with increased susceptibility to motion sickness in healthy individuals. However, whether patients with primary adrenal insufficiency, who typically have altered ACTH levels compared to the normal population, exhibit alterations in sickness susceptibility remains unknown. To address this, we recruited 78 patients with primary adrenal insufficiency and compared changes in the motion sickness susceptibility scores from 10 years prior to diagnosis (i.e. retrospective sickness rating) with the current sickness measures (post-diagnosis), using the validated motion sickness susceptibility questionnaire (MSSQ). Group analysis revealed that motion sickness susceptibility pre-diagnosis did not differ between controls and patients. We observed that following treatment, current measures of motion sickness were significantly increased in patients and subsequent analysis revealed that this increase was primarily in female patients with primary adrenal insufficiency. These observations corroborate the role of stress hormones in modulating sickness susceptibility and support the notion of a sexually dimorphic adrenal cortex as we only observed selective enhancement in females. A potential mechanism to account for our novel observation remains obscure, but we speculate that it may reflect a complex sex-disease-drug interaction.

Consensus on Virtual Management of Vestibular Disorders: Urgent Versus Expedited Care.

The virtual practice has made major advances in the way that we care for patients in the modern era. The culture of virtual practice, consulting, and telemedicine, which had started several years ago, took an accelerated leap as humankind was challenged by the novel coronavirus pandemic (COVID19). The social distancing measures and lockdowns imposed in many countries left medical care providers with limited options in evaluating ambulatory patients, pushing the rapid transition to assessments via virtual platforms. In this novel arena of medical practice, which may form new norms beyond the current pandemic crisis, we found it critical to define guidelines on the recommended practice in neurotology, including remote methods in examining the vestibular and eye movement function. The proposed remote examination methods aim to reliably diagnose acute and subacute diseases of the inner-ear, brainstem, and the cerebellum. A key aim was to triage patients into those requiring urgent emergency room assessment versus non-urgent but expedited outpatient management. Physicians who had expertise in managing patients with vestibular disorders were invited to participate in the taskforce. The focus was on two topics: (1) an adequate eye movement and vestibular examination strategy using virtual platforms and (2) a decision pathway providing guidance about which patient should seek urgent medical care and which patient should have non-urgent but expedited outpatient management.

Multisensory contribution in visuospatial orientation: an interaction between neck and trunk proprioception.

A coherent perception of spatial orientation is key in maintaining postural control. To achieve this the brain must access sensory inputs encoding both the body and the head position and integrate them with incoming visual information. Here we isolated the contribution of proprioception to verticality perception and further investigated whether changing the body position without moving the head can modulate visual dependence-the extent to which an individual relies on visual cues for spatial orientation. Spatial orientation was measured in ten healthy individuals [6 female; 25-47 years (SD 7.8 years)] using a virtual reality based subjective visual vertical (SVV) task. Individuals aligned an arrow to their perceived gravitational vertical, initially against a static black background (10 trials), and then in other conditions with clockwise and counterclockwise background rotations (each 10 trials). In all conditions, subjects were seated first in the upright position, then with trunk tilted 20° to the right, followed by 20° to the left while the head was always aligned vertically. The SVV error was modulated by the trunk position, and it was greater when the trunk was tilted to the left compared to right or upright trunk positions (p < 0.001). Likewise, background rotation had an effect on SVV errors as these were greater with counterclockwise visual rotation compared to static background and clockwise roll motion (p < 0.001). Our results show that the interaction between neck and trunk proprioception can modulate how visual inputs affect spatial orientation.

Vestibular migraine: An update on current understanding and future directions.

BACKGROUND: Vestibular migraine is among the most common causes of recurrent vertigo in the general population. Despite its prevalence and high impact on healthcare cost and utilization, it has remained an under-recognized condition with largely unknown pathophysiology. In the present article, we aim to provide an overview of the current understanding of vestibular migraine. METHODS: We undertook a narrative literature review on the epidemiology, presentations, clinical and laboratory findings, pathophysiology, and treatments of vestibular migraine. RESULTS: Currently, the diagnosis of vestibular migraine relies solely on clinical symptoms since clinical tests of vestibular function are typically normal, or difficult to interpret based on inconsistent results reported in earlier studies. The challenges related to diagnosis of vestibular migraine lie in its relatively broad spectrum of manifestations, the absence of typical migraine headaches with vestibular symptoms, and its very recent definition as a distinct entity. Here, we highlight these challenges, discuss common vestibular symptoms and clinical presentations in vestibular migraine, and review the current aspects of its clinical diagnosis and evaluation. The concepts related to the pathophysiology and treatment of vestibular migraine are also discussed. CONCLUSION: Vestibular migraine is still underdiagnosed clinically. Future studies are needed to address the pathophysiological mechanisms and investigate effective treatment regimens.

Venous hypertensive encephalopathy secondary to venous sinus thrombosis and dural arteriovenous fistula.

A 52-year-old man with a history of factor V Leiden thrombophilia, persistent headaches and papilloedema presented with worsening vision and confusion. MRI and MR angiography of the brain at the time of this presentation showed findings concerning for transverse sinus thrombosis and an associated dural arteriovenous fistula. Dural venous sinus thrombosis can lead to the formation of a dural arteriovenous fistula, which must be considered in the differential diagnosis for intracranial hypertension in patients with thrombophilia.

Transcranial magnetic stimulation (TMS) of the supramarginal gyrus: a window to perception of upright.

Although the pull of gravity, primarily detected by the labyrinth, is the fundamental input for our sense of upright, vision and proprioception must also be integrated with vestibular information into a coherent perception of spatial orientation. Here, we used transcranial magnetic stimulation (TMS) to probe the role of the cortex at the temporal parietal junction (TPJ) of the right cerebral hemisphere in the perception of upright. We measured the perceived vertical orientation of a visual line; that is, the subjective visual vertical (SVV), after a short period of continuous theta burst stimulation (cTBS) with the head upright. cTBS over the posterior aspect of the supramarginal gyrus (SMGp) in 8 right-handed subjects consistently tilted the perception of upright when tested with the head tilted 20° to either shoulder (right: 3.6°, left: 2.7°). The tilt of SVV was always in the direction opposite to the head tilt. On the other hand, there was no significant tilt after sham stimulation or after cTBS of nearby areas. These findings suggest that a small area of cerebral cortex--SMGp--has a role in processing information from different sensory modalities into an accurate perception of upright.

Knowing what the brain is seeing in three dimensions: A novel, noninvasive, sensitive, accurate, and low-noise technique for measuring ocular torsion.

Torsional eye movements are rotations of the eye around the line of sight. Measuring torsion is essential to understanding how the brain controls eye position and how it creates a veridical perception of object orientation in three dimensions. Torsion is also important for diagnosis of many vestibular, neurological, and ophthalmological disorders. Currently, there are multiple devices and methods that produce reliable measurements of horizontal and vertical eye movements. Measuring torsion, however, noninvasively and reliably has been a longstanding challenge, with previous methods lacking real-time capabilities or suffering from intrusive artifacts. We propose a novel method for measuring eye movements in three dimensions using modern computer vision software (OpenCV) and concepts of iris recognition. To measure torsion, we use template matching of the entire iris and automatically account for occlusion of the iris and pupil by the eyelids. The current setup operates binocularly at 100 Hz with noise <0.1° and is accurate within 20° of gaze to the left, to the right, and up and 10° of gaze down. This new method can be widely applicable and fill a gap in many scientific and clinical disciplines.

Ischemic stroke in evolution: predictive value of perfusion computed tomography.

BACKGROUND: Various perfusion computed tomography (PCT) parameters have been used to identify tissue at risk of infarction in the setting of acute stroke. The purpose of this study was to examine predictive value of the PCT parameters commonly used in clinical practice to define ischemic penumbra. The patient selection criterion aimed to exclude the effect of thrombolysis from the imaging data. METHODS: Consecutive acute stroke patients were screened and a total of 18 patients who initially underwent PCT and CT angiogram (CTA) on presentation but did not qualify to receive thrombolytic therapy were selected. The PCT images were postprocessed using a delay-sensitive deconvolution algorithm. All the patients had follow-up noncontrast CT or magnetic resonance imaging to delineate the extent of their infarction. The extent of lesions on PCT maps calculated from mean transit time (MTT), time to peak (TTP), cerebral blood flow, and cerebral blood volume were compared and correlated with the final infarct size. A collateral grading score was used to measure collateral blood supply on the CTA studies. RESULTS: The average size of MTT lesions was larger than infarct lesions (P < .05). The correlation coefficient of TTP/infarct lesions (r = .95) was better than MTT/infarct lesions (r = .66) (P = .004). CONCLUSIONS: A widely accepted threshold to define MTT lesions overestimates the ischemic penumbra. In this setting, TTP with appropriate threshold is a better predictor of infarct in acute stroke patients. The MTT/TTP mismatch correlates with the status of collateral blood supply to the tissue at risk of infarction.

Autokinesis Reveals a Threshold for Perception of Visual Motion.

In natural viewing conditions, the brain can optimally integrate retinal and extraretinal signals to maintain a stable visual perception. These mechanisms, however, may fail in circumstances where extraction of a motion signal is less viable such as impoverished visual scenes. This can result in a phenomenon known as autokinesis in which one may experience apparent motion of a small visual stimulus in an otherwise completely dark environment. In this study, we examined the effect of autokinesis on visual perception of motion in human observers. We used a novel method with optical tracking in which the visual motion was reported manually by the observer. Experiment results show at lower speeds of motion, the perceived direction of motion was more aligned with the effect of autokinesis, whereas in the light or at higher speeds in the dark, it was more aligned with the actual direction of motion. These findings have important implications for understanding how the stability of visual representation in the brain can affect accurate perception of motion signals.

Video ocular counter roll: A bedside test of otolith-ocular function.

Here we review the clinical value of a video-oculography test for clinical evaluation of vestibular otolith function. This test is known as the video ocular counter roll (vOCR) and is based on measurement of torsional vestibulo-ocular reflex with a lateral head tilt. The vOCR test consists of a simple maneuver during which the head and torso are tilted en bloc by the examiner. The pattern of vOCR deficit among patients highlights its clinical value in identifying the stage of vestibular loss and recovery. The quick application of vOCR allows examination of otolith-ocular function and assessment of vestibular recovery at the bedside.

Video Ocular Counter-Roll (vOCR): Otolith-Ocular Function and Compensatory Effect of the Neck Following Vestibular Loss.

OBJECTIVE: Assessment of recovery following vestibular loss has been limited by the lack of bedside measures in clinical settings. Here, we used the video ocular counter-roll (vOCR) test to study otolith-ocular function and compensatory effect of neck proprioception in patients at different stages of vestibular loss. STUDY DESIGN: Case-control study. SETTING: Tertiary care center. METHODS: Fifty-six subjects were recruited including patients with acute (9 ± 2 days [mean ± standard error of mean]), subacute (61 ± 11 days), and chronic (1009 ± 266 days) unilateral loss of vestibular function, as well as a group of healthy controls. We used a video-oculography method based on tracking the iris for vOCR measurement. To examine the effect of neck inputs, vOCR was recorded during two simple tilt maneuvers in all subjects while seated: 30° head-on-body tilt and 30° head-and-body tilt. RESULTS: The vOCR responses evolved at different stages following vestibular loss with improvement of the gains in the chronic stage. The deficit was more pronounced when the whole body was tilted (acute: 0.08 ± 0.01, subacute: 0.11 ± 0.01, chronic: 0.13 ± 0.02, healthy control: 0.18 ± 0.01), and the gain of vOCR improved when the head was tilted on the body (acute: 0.11 ± 0.01, subacute: 0.14 ± 0.01, chronic: 0.13 ± 0.02, healthy control: 0.17 ± 0.01). The time course of vOCR response was affected as well with reduced amplitude and slower response in the acute stage of vestibular loss. CONCLUSION: The vOCR test can be valuable as a clinical marker to measure vestibular recovery and compensatory effect of neck proprioception in patients at different stages following loss of vestibular function.

Altered visual conscious awareness in patients with vestibular dysfunctions; a cross-sectional observation study.

BACKGROUND: Patients with vestibular dysfunctions often experience visual-induced symptoms. Here we asked whether such visual dependence can be related to alterations in visual conscious awareness in these patients. METHODS: To measure visual conscious awareness, we used the effect of motion-induced blindness (MIB,) in which the perceptual awareness of the visual stimulus alternates despite its unchanged physical characteristics. In this phenomenon, a salient visual target spontaneously disappears and subsequently reappears from visual perception when presented against a moving visual background. The number of perceptual switches during the experience of the MIB stimulus was measured for 120 s in 15 healthy controls, 15 patients with vestibular migraine, 15 patients with benign positional paroxysmal vertigo (BPPV) and 15 with migraine without vestibular symptoms. RESULTS: Patients with vestibular dysfunctions (i.e., both vestibular migraine and BPPV) exhibited increased perceptual fluctuations during MIB compared to healthy controls and migraine patients without vertigo. In VM patients, those with more severe symptoms exhibited higher fluctuations of visual awareness (i.e., positive correlation), whereas, in BPPV patients, those with more severe symptoms had lower fluctuations of visual awareness (i.e., negative correlation). IMPLICATIONS: Taken together, these findings show that fluctuations of visual awareness are linked to the severity of visual-induced symptoms in patients with vestibular dysfunctions, and distinct pathophysiological mechanisms may mediate visual vertigo in peripheral versus central vestibular dysfunctions.

Association of SARS-CoV-2 Vaccination or Infection With Bell Palsy: A Systematic Review and Meta-analysis.

Importance: Bell palsy (BP) has been reported as an adverse event following the SARS-CoV-2 vaccination, but neither a causative relationship nor a higher prevalence than in the general population has been established. Objective: To compare the incidence of BP in SARS-CoV-2 vaccine recipients vs unvaccinated individuals or placebo recipients. Data Sources: A systematic search of MEDLINE (via PubMed), Web of Science, Scopus, Cochrane Library, and Google Scholar from the inception of the COVID-19 report (December 2019) to August 15, 2022. Study Selection: Articles reporting BP incidence with SARS-CoV-2 vaccination were included. Data Extraction and Synthesis: This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline and was conducted with the random- and fixed-effect models using the Mantel-Haenszel method. The quality of the studies was evaluated by the Newcastle-Ottawa Scale. Main Outcomes and Measures: The outcomes of interest were to compare BP incidence among (1) SARS-CoV-2 vaccine recipients, (2) nonrecipients in the placebo or unvaccinated cohorts, (3) different types of SARS-CoV-2 vaccines, and (4) SARS-CoV-2-infected vs SARS-CoV-2-vaccinated individuals. Results: Fifty studies were included, of which 17 entered the quantitative synthesis. Pooling 4 phase 3 randomized clinical trials showed significantly higher BP in recipients of SARS-CoV-2 vaccines (77 525 vaccine recipients vs 66 682 placebo recipients; odds ratio [OR], 3.00; 95% CI, 1.10-8.18; I2 = 0%). There was, however, no significant increase in BP after administration of the messenger RNA SARS-CoV-2 vaccine in pooling 8 observational studies (13 518 026 doses vs 13 510 701 unvaccinated; OR, 0.70; 95% CI, 0.42-1.16; I2 = 94%). No significant difference was found in BP among 22 978 880 first-dose recipients of the Pfizer/BioNTech vaccine compared with 22 978 880 first-dose recipients of the Oxford/AstraZeneca vaccine (OR, 0.97; 95% CI, 0.82-1.15; I2 = 0%). Bell palsy was significantly more common after SARS-CoV-2 infection (n = 2 822 072) than after SARS-CoV-2 vaccinations (n = 37 912 410) (relative risk, 3.23; 95% CI, 1.57-6.62; I2 = 95%). Conclusions and Relevance: This systematic review and meta-analysis suggests a higher incidence of BP among SARS-CoV-2-vaccinated vs placebo groups. The occurrence of BP did not differ significantly between recipients of the Pfizer/BioNTech vs Oxford/AstraZeneca vaccines. SARS-CoV-2 infection posed a significantly greater risk for BP than SARS-CoV-2 vaccination.

Deep Learning Model for Static Ocular Torsion Detection Using Synthetically Generated Fundus Images.

Purpose: The objective of the study is to develop deep learning models using synthetic fundus images to assess the direction (intorsion versus extorsion) and amount (physiologic versus pathologic) of static ocular torsion. Static ocular torsion assessment is an important clinical tool for classifying vertical ocular misalignment; however, current methods are time-intensive with steep learning curves for frontline providers. Methods: We used a dataset (n = 276) of right eye fundus images. The disc-foveal angle was calculated using ImageJ to generate synthetic images via image rotation. Using synthetic datasets (n = 12,740 images per model) and transfer learning (the reuse of a pretrained deep learning model on a new task), we developed a binary classifier (intorsion versus extorsion) and a multiclass classifier (physiologic versus pathologic intorsion and extorsion). Model performance was evaluated on unseen synthetic and nonsynthetic data. Results: On the synthetic dataset, the binary classifier had an accuracy and area under the receiver operating characteristic curve (AUROC) of 0.92 and 0.98, respectively, whereas the multiclass classifier had an accuracy and AUROC of 0.77 and 0.94, respectively. The binary classifier generalized well on the nonsynthetic data (accuracy = 0.94; AUROC = 1.00). Conclusions: The direction of static ocular torsion can be detected from synthetic fundus images using deep learning methods, which is key to differentiate between vestibular misalignment (skew deviation) and ocular muscle misalignment (superior oblique palsies). Translational Relevance: Given the robust performance of our models on real fundus images, similar strategies can be adopted for deep learning research in rare neuro-ophthalmologic diseases with limited datasets.

Pearls & Oy-sters: Vertical Diplopia and Ocular Torsion: Peripheral vs Central Localization.

We describe a case with torsional deviation of the eyes from a brainstem lesion. Torsional eye movement refers to changes in the position of the eyes in the roll plane around the visual axis. When the head is tilted laterally (that is, rolled towards the shoulder), the eyes roll in the opposite direction as part of the torsional vestibulo-ocular reflex known as the ocular counter-roll (OCR). Pathologies that affect the otolith-ocular pathway can lead to a torsional deviation of the eyes as part of the ocular tilt reaction (OTR) that also cause vertical deviation of the eyes (skew deviation) and head tilt. Lesions caudal to the pontomedullary junction (such as the labyrinth, eighth cranial nerve, or vestibular nucleus) result in an OTR with ipsiversive torsional deviation, whereas lesions rostral to the junction result in an OTR with contraversive torsional deviation. Furthermore, torsional deviation of the eyes in OTR is conjugate (incyclotorsion in the higher eye and excyclotorsion in the lower eye), whereas torsional deviation from ocular palsy in peripheral lesions is disconjugate (e.g., exyclotorsion only in the higher eye with superior oblique palsy). Therefore, the pattern of torsional eye deviation can be helpful in localizing the lesion. Several techniques including fundus photography, double Maddox rod testing, optical coherence tomography (OCT), and video-oculography are used to measure torsional eye position.

Psychophysical Haptic Measurement of Vertical Perception: Elucidating a Hand Sensory Bias.

The primary sensory modality for probing spatial perception can vary among psychophysical paradigms. In the subjective visual vertical (SVV) task, the brain must account for the position of the eye within the orbit to generate an estimate of a visual line orientation, whereas in the subjective haptic vertical (SHV) task, the position of the hand is used to sense the orientation of a haptic bar. Here we investigated whether a hand sensory bias can affect SHV measurement. We measured SHV in 12 subjects (6 left-handed and 6 right-handed) with a forced-choice paradigm using their left and right hands separately. The SHV measurement was less accurate than the SVV measurements (-0.6 ± 0.7) and it was biased in the direction of the hand used in the task but was not affected by handedness; SHV left hand -6.8 ± 2.1° (left-handed -7.9 ± 3.6°, right-handed -5.8 ± 2.5°) and right hand 9.8 ± 1.5° (left-handed 7.4 ± 2.2°, right-handed 12.3 ± 1.8°). SHV measurement with the same hand was also affected by the haptic bar placement on the left or right side versus midline, showing a side effect (left vs midline -2.0 ± 1.3°, right vs midline 3.8 ± 1.7°). Midline SHV measures using the left and right hands were different, confirming a laterality effect (left hand -4.5 ± 1.7°, right hand 6.4 ± 2.0°). These results demonstrate a sensory bias in SHV measurement related to the effects of both hand-in-body (i.e., right vs left hand) and hand-in-space positions. Such modality-specific bias may result in disparity between SHV and SVV measurements, and therefore cannot be generalized to vertical or spatial perception.

Measures of Spatial Orientation: Spatial Bias Analogs in Visual and Haptic Tasks.

The primary sensory modality for probing spatial orientation can vary among psychophysical tasks. In the subjective visual vertical (SVV) task, a visual stimulus is used to measure perceived vertical orientation, while a haptic stimulus is used in the subjective haptic vertical (SHV) task. Here we examined disparity in SHV and SVV task results and asked whether it could be related to biases in probing different spatial estimates by each task. Forty-two healthy volunteers (mean ± SD age, 25 ± 10 years; 19 females; 21 left handed) were recruited. The effect of a task to measure spatial orientation was calculated as the difference between SHV and SVV values, and with the head upright and tilted 20° laterally. There was a task bias regardless of head position related to hand use in the haptic task but not handedness (mean head upright ± SEM: left hand, -3.7 ± 1.1°; right hand, 7.9 ± 1.0°). When this task bias was subtracted out, there was a similar spatial bias using each hand in the SHV task that was also comparable to the SVV task (mean head with left tilt: left hand, 3.9 ± 0.7°; right hand, 4.4 ± 0.7°; SVV, 4.9 ± 0.7°; mean head with right tilt: left hand, -4.6 ± 0.9°; right hand, -4.6 ± 0.8°; SVV, -4.7 ± 1.0°). These findings show that the disparity in visual and haptic measures of spatial orientation is primarily related to a modality-specific bias, and once the effect of hand use is removed from the haptic measurements, the spatial bias becomes comparable to the visual task.