Background and Objectives:One year since the onset of the COVID-19 pandemic, we aimed to summarize the frequency of neurological manifestations reported in COVID-19 patients and investigate the association of these manifestations with disease severity and mortality.Methods:We searched PubMed, Medline, Cochrane library, clinicaltrials.gov and EMBASE from 31st December 2019 to 15th December 2020 for studies enrolling consecutive COVID-19 patients presenting with neurological manifestations. Risk of bias was examined using Joanna Briggs Institute (JBI) scale. A random-effects meta-analysis was performed, and pooled prevalence and 95% Confidence Intervals (CI) were calculated for neurological manifestations. Odds ratio (OR) and 95%CI were calculated to determine the association of neurological manifestations with disease severity and mortality. Presence of heterogeneity was assessed using I-square, meta-regression, and subgroup analyses. Statistical analyses were conducted in R version 3.6.2.Results:Of 2,455 citations, 350 studies were included in this review, providing data on 145,721 COVID-19 patients, 89% of whom were hospitalized. Forty-one neurological manifestations (24 symptoms and 17 diagnoses) were identified. Pooled prevalence of the most common neurological symptoms included: fatigue (32%), myalgia (20%), taste impairment (21%), smell impairment (19%) and headache (13%). A low risk of bias was observed in 85% of studies; studies with higher risk of bias yielded higher prevalence estimates. Stroke was the most common neurological diagnosis (pooled prevalence- 2%). In COVID-19 patients aged ≥60, the pooled prevalence of acute confusion/delirium was 34% and the presence of any neurological manifestations in this age group was associated with mortality (OR 1.80; 95%CI 1.11 to 2.91).Discussion:Up to one-third of COVID-19 patients analysed in this review experienced at least one neurological manifestation. One in 50 patients experienced stroke. In those over 60, more than one-third had acute confusion/delirium; the presence of neurological manifestations in this group was associated with near doubling of mortality. Results must be interpreted keeping in view the limitations of observational studies and associated bias.

An intact cerebellum is a prerequisite for optimal ocular motor performance. The cerebellum fine-tunes each of the subtypes of eye movements so they work together to bring and maintain images of objects of interest on the fovea. Here we review the major aspects of the contribution of the cerebellum to ocular motor control. The approach will be based on structural–functional correlation, combining the effects of lesions and the results from physiologic studies, with the emphasis on the cerebellar regions known to be most closely related to ocular motor function: (1) the flocculus/paraflocculus for high-frequency (brief) vestibular responses, sustained pursuit eye movements, and gaze holding, (2) the nodulus/ventral uvula for low-frequency (sustained) vestibular responses, and (3) the dorsal oculomotor vermis and its target in the posterior portion of the fastigial nucleus (the fastigial oculomotor region) for saccades and pursuit initiation.

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.

We inherently maintain a stable perception of the world despite frequent changes in the head, eye, and body positions. Such "orientation constancy" is a prerequisite for coherent spatial perception and sensorimotor planning. As a multimodal sensory reference, perception of upright represents neural processes that subserve orientation constancy through integration of sensory information encoding the eye, head, and body positions. Although perception of upright is distinct from perception of body orientation, they share similar neural substrates within the cerebral cortical networks involved in perception of spatial orientation. These cortical networks, mainly within the temporo-parietal junction, are crucial for multisensory processing and integration that generate sensory reference frames for coherent perception of self-position and extrapersonal space transformations. In this review, we focus on these neural mechanisms and discuss (i) neurobehavioral aspects of orientation constancy, (ii) sensory models that address the neurophysiology underlying perception of upright, and (iii) the current evidence for the role of cerebral cortex in perception of upright and orientation constancy, including findings from the neurological disorders that affect cortical function.

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.

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.

We maintain a stable perception of the visual world despite continuous movements of our eyes, head and body. Perception of upright is a key aspect of such orientation constancy. Here we investigated whether changes in upright perception during sustained head tilt were related to simultaneous changes in torsional position of the eyes. We used a subjective visual vertical (SVV) task, modified to track changes in upright perception over time, and a custom video method to measure ocular torsion simultaneously. We tested 12 subjects in upright position, during prolonged (~15 min) lateral head tilts of 20 degrees, and also after the head returned to upright position. While the head was tilted, SVV drifted in the same direction as the head tilt (left tilt: −5.4 ± 1.4° and right tilt: +2.2 ± 2.1°). After the head returned to upright position, there was an SVV aftereffect with respect to the pre-tilt baseline, which was also in the same direction as the head tilt (left tilt: −3.9 ± 0.6° and right tilt: +2.55 ± 1.0°). Neither the SVV drift nor the SVV aftereffect were correlated with the changes in ocular torsion. Using the Bayesian spatial-perception model we show that the pattern of SVV drift and aftereffect in our results could be explained by a drift and an adaptation in sensory inputs that encode head orientation. The fact that ocular torsion (mainly driven by the otoliths) could not account for the perceptual changes suggests that neck proprioception could be the primary source of drift in upright perception during head tilt, and subsequently the aftereffect in upright position.

Conclusion vOCR can detect loss of otolith-ocular function without specifying the side of vestibular loss. Since vOCR is measured with a simple head tilt maneuver, it can be potentially used as a bedside clinical test in combination with video head impulse test. Objective Video-oculography (VOG) goggles are being integrated into the bedside assessment of patients with vestibular disorders. Lacking, however, is a method to evaluate otolith function. This study validated a VOG test for loss of otolith function. Methods VOG was used to measure ocular counter-roll (vOCR) in 12 healthy controls, 14 patients with unilateral vestibular loss (UVL), and six patients with bilateral vestibular loss (BVL) with a static lateral head tilt of 30°. The results were compared with vestibular evoked myogenic potentials (VEMP), a widely-used laboratory test of otolith function. Results The average vOCR for healthy controls (4.6°) was significantly different from UVL (2.7°) and BVL (1.6°) patients (p < 0.0001). The vOCR and VEMP measurements were correlated across subjects, especially the click and tap oVEMPs (click oVEMP R = 0.45, tap oVEMP R = 0.51; p < 0.0003). The receiver operator characteristic (ROC) analysis showed that vOCR and VEMPs detected loss of otolith function equally well. The best threshold for vOCR to detect vestibular loss was at 3°. The vOCR values from the side of vestibular loss and the healthy side were not different in UVL patients (2.53° vs 2.8°; p = 0.59).