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.

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.

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.

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.

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.

Head shaking does not alter vestibulo ocular reflex gain in vestibular migraine.

Vestibular Migraine (VM) is the most common cause of non-positional episodic vestibular symptoms. Patients with VM commonly report increased motion sensitivity, suggesting that vestibular responses to head movement may identify changes specific to VM patients. Here we explore whether the vestibulo-ocular reflex (VOR) gain alters in response to a clinical "headshake" maneuver in patients with VM. Thirty patients with VM in the inter-ictal phase, 16 patients with Benign Positional Paroxysmal Vertigo (BPPV) and 15 healthy controls were recruited. Patients responded to the question "Do you feel sick reading in the passenger seat of a car?" and completed a validated motion sickness questionnaire as a measure of motion sensitivity. Lateral canal vHIT testing was performed before and after headshaking; the change in VOR gain was calculated as the primary outcome. Baseline VOR gain was within normal limits across all participants. There was no significant change in VOR gain after headshaking in any group (p = 0.264). Patients were 4.3 times more likely to be in the VM group than in the BPPV group if they reported nausea when reading in the passenger seat of a car. We postulate that a headshake stimulus may be insufficient to disrupt cortical interactions and induce a change in VOR gain. Alternatively, changes in VOR gain may only be apparent in the acute phase of VM. Reading in the passenger seat of a car was considered uncomfortable in all VM patients suggesting that this specific question may be useful for the diagnosis of VM.

Vestibular migraine treatment: a comprehensive practical review.

Vestibular migraine is an underdiagnosed but increasingly recognized neurological condition that causes episodic vertigo associated with other features of migraine. It is now thought to be the most common cause of spontaneous (non-positional) episodic vertigo, affecting up to 1% of the population. A meta-analysis of preventative treatments for vestibular migraine was published in 2021, but the authors were unable to establish a preferred treatment strategy due to low quality of evidence and heterogeneity of study design and outcome reporting. Therefore, there remains a clinical need for pragmatic management guidelines specific to vestibular migraine using the available evidence. Here, we provide a practical review utilizing a systematic qualitative assessment of the evidence for abortive and preventative interventions in adults. The overall evidence base for vestibular migraine treatment is of low quality. Nevertheless, we provide practical treatment recommendations based on the available evidence and our experience to help guide clinicians treating patients with vestibular migraine. We also discuss how future clinical trials could be designed to improve the quality of evidence in this condition.

Persistent Postural-Perceptual Dizziness (PPPD) from Brain Imaging to Behaviour and Perception.

Persistent postural-perceptual dizziness (PPPD) is a common cause of chronic dizziness associated with significant morbidity, and perhaps constitutes the commonest cause of chronic dizziness across outpatient neurology settings. Patients present with altered perception of balance control, resulting in measurable changes in balance function, such as stiffening of postural muscles and increased body sway. Observed risk factors include pre-morbid anxiety and neuroticism and increased visual dependence. Following a balance-perturbing insult (such as vestibular dysfunction), patients with PPPD adopt adaptive strategies that become chronically maladaptive and impair longer-term postural behaviour. In this article, we explore the relationship between behavioural postural changes, perceptual abnormalities, and imaging correlates of such dysfunction. We argue that understanding the pathophysiological mechanisms of PPPD necessitates an integrated methodological approach that is able to concurrently measure behaviour, perception, and cortical and subcortical brain function.

A link between frontal white matter integrity and dizziness in cerebral small vessel disease.

One in three older people (>60 years) complain of dizziness which often remains unexplained despite specialist assessment. We investigated if dizziness was associated with vascular injury to white matter tracts relevant to balance or vestibular self-motion perception in sporadic cerebral small vessel disease (age-related microangiopathy). We prospectively recruited 38 vestibular clinic patients with idiopathic (unexplained) dizziness and 36 age-matched asymptomatic controls who underwent clinical, cognitive, balance, gait and vestibular assessments, and structural and diffusion brain MRI. Patients had more vascular risk factors, worse balance, worse executive cognitive function, and worse ankle vibration thresholds in association with greater white matter hyperintensity in frontal deep white matter, and lower fractional anisotropy in the genu of the corpus callosum and the right inferior longitudinal fasciculus. A large bihemispheric white matter network had less structural connectivity in patients. Reflex and perceptual vestibular function was similar in patients and controls. Our results suggest cerebral small vessel disease is involved in the genesis of dizziness through its effect on balance.

Patient Experience of Flunarizine for Vestibular Migraine: Single Centre Observational Study.

Vestibular migraine (VM) is a leading cause of episodic vertigo, affecting up to 1% of the general population. Despite established diagnostic criteria, there is currently no evidence-based approach for acute treatment of VM, with treatment recommendations generally extrapolated from studies on classical migraine headache. Several small-scale studies have identified flunarizine as a potentially effective prophylactic medication in VM. We conducted a single-centre observational service evaluation study exploring patient experiences of preventative medications over a 28-month period, including flunarizine, for control of VM symptoms. To compare patient experience of flunarizine with other medications, data from patients taking flunarizine were separately analysed. A total of 90% of VM patients taking flunarizine reported symptomatic improvement, compared to only 32% of patients on other medications. Whilst 50% of patients on flunarizine reported side effects. these were not deemed to outweigh the clinical benefits, with most patients deciding to continue treatment. Our data supports the use of flunarizine in VM.

Visuospatial orientation: Differential effects of head and body positions.

To orientate in space, the brain must integrate sensory information that encodes the position of the body with the visual cues from the surrounding environment. In this process, the extent of reliance on visual information is known as the visual dependence. Here, we asked whether the relative positions of the head and body can modulate such visual dependence (VD). We used the effect of optokinetic stimulation (30°/s) on subjective visual vertical (SVV) to quantify VD as the average optokinetic-induced SVV bias in clockwise and counter-clockwise directions. The VD bias was measured in eight subjects with a head-on-body tilt (HBT) where only the head was tilted on the body, and also with a whole-body tilt (WBT) where the head and body were tilted together. The VD bias with HBT of 20° was in the same direction of the head tilt position (left tilt VD -1.35 ± 0.1.2°; right VD 1.60 ± 0.9°), whereas the VD bias with WBT of 20° was in a direction away from the body tilt position (left tilt VD 2.5 ± 1.1°; right tilt VD -2.1 ± 0.9°). These findings show differential effects of relative head and body positions on visual cue integration, a process which could facilitate optimal interaction with the surrounding environment for spatial orientation.

Priming overconfidence in belief systems reveals negative return on postural control mechanisms.

BACKGROUND: Modulation of postural control strategies and heightened perceptual ratings of instability when exposed to postural threats, illustrates the association between anxiety and postural control. RESEARCH QUESTION: Here we test whether modulating prior expectations can engender postural-related anxiety which, in turn, may impair postural control and dissociate the well-established relationship between sway and subjective instability. METHODS: We modulated expectations of the difficulty posed by an upcoming postural task via priming. In the visual priming condition, participants watched a video of an actor performing the task with either a stable or unstable performance, before themselves proceeding with the postural task. In the verbal priming paradigm, participants were given erroneous verbal information regarding the amplitude of the forthcoming platform movement, or no prior information. RESULTS: Following the visual priming, the normal relationship between trunk sway and subjective instability was preserved only in those individuals that viewed the stable but not the unstable actor. In the verbal priming experiment we observed an increase in subjective instability and anxiety during task performance in individuals who were erroneously primed that sled amplitude would increase, when in fact it did not. SIGNIFICANCE: Our findings show that people's subjective experiences of instability and anxiety during a balancing task are powerfully modulated by priming. The contextual provision of erroneous cognitive priors dissociates the normally 'hard wired' relationship between objective measures and subjective ratings of sway. Our findings have potential clinical significance for the development of enhanced cognitive retraining in patients with balance disorders, e.g. via modifying expectations.

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.

Prevalence of acute dizziness and vertigo in cortical stroke.

BACKGROUND AND PURPOSE: In posterior circulation stroke, vertigo can be a presenting feature. However, whether isolated hemispheric strokes present with vertigo is less clear, despite a few single case reports in the literature. Here, (a) the prevalence of vertigo/dizziness in acute stroke is explored and (b) the cortical distribution of the lesions in relation to both the known vestibular cortex and the evolution of the symptoms, are considered. METHODS: Structured interviews were conducted in 173 consecutive unselected patients admitted to the hyperacute stroke unit at the University College London Hospitals. The interview was used to evaluate whether the patient was suffering from dizziness and/or vertigo before the onset of the stroke and at the time of the stroke (acute dizziness/vertigo), and the nature of these symptoms. RESULTS: In all, 53 patients had cortical infarcts, of which 21 patients reported acute dizziness. Out of these 21, five patients reported rotational vertigo. Seventeen of the total 53 patients had lesions in known vestibular cortical areas distributed within the insular and parietal opercular cortices. CONCLUSIONS: The prevalence of vertigo in acute cortical strokes was 9%, with no single locus of lesion overlap. There is growing evidence supporting a lateralized vestibular cortex, with speculation that cortical strokes affecting the right hemisphere are more likely to cause vestibular symptoms than left hemispheric strokes. A trend was observed for this association, with the right hemisphere affected in four of five patients who reported spinning vertigo at the onset of the stroke.

Vestibulo-perceptual influences upon the vestibulo-spinal reflex.

The vestibular system facilitates gaze and postural stability via the vestibulo-ocular (VOR) and vestibulo-spinal reflexes, respectively. Cortical and perceptual mechanisms can modulate long-duration VOR responses, but little is known about whether high-order neural phenomena can modulate short-latency vestibulo-spinal responses. Here, we investigate this by assessing click-evoked cervical vestibular myogenic-evoked potentials (VEMPS) during visual roll motion that elicited an illusionary sensation of self-motion (i.e. vection). We observed that during vection, the amplitude of the VEMPs was enhanced when compared to baseline measures. This modulation in VEMP amplitude was positively correlated with the subjective reports of vection strength. That is, those subjects reporting greater subjective vection scores exhibited a greater increase in VEMP amplitude. Control experiments showed that simple arousal (cold-induced discomfort) also increased VEMP amplitude but that, unlike vection, it did not modulate VEMP amplitude linearly. In agreement, small-field visual roll motion that did not induce vection failed to increase VEMP amplitude. Taken together, our results demonstrate that vection can modify the response of vestibulo-collic reflexes. Even short-latency brainstem vestibulo-spinal reflexes are influenced by high-order mechanisms, illustrating the functional importance of perceptual mechanisms in human postural control. As VEMPs are inhibitory responses, we argue that the findings may represent a mechanism whereby high-order CNS mechanisms reduce activity levels in vestibulo-collic reflexes, necessary for instance when voluntary head movements need to be performed.

Universal newborn hearing screening in South Africa: a single-centre study.

Hearing screening for newborn babies is an established protocol in many high-income countries. Implementing such screening has yielded significant socioeconomic advantages at both an individual and societal level. This has yet to permeate low/middle-income countries (LMIC). Here, we illustrate how newborn hearing screening needs to be contextually adapted for effective utilisation and implementation in an LMIC. Specifically, this advocates the use of auditory brainstem testing as the first-line approach. We propose that such adaptation serves to maximise clinical efficacy and community participation at a reduced cost.

Vestibular agnosia in traumatic brain injury and its link to imbalance.

Vestibular dysfunction, causing dizziness and imbalance, is a common yet poorly understood feature in patients with TBI. Damage to the inner ear, nerve, brainstem, cerebellum and cerebral hemispheres may all affect vestibular functioning, hence, a multi-level assessment-from reflex to perception-is required. In a previous report, postural instability was the commonest neurological feature in ambulating acute patients with TBI. During ward assessment, we also frequently observe a loss of vertigo sensation in patients with acute TBI, common inner ear conditions and a related vigorous vestibular-ocular reflex nystagmus, suggesting a 'vestibular agnosia'. Patients with vestibular agnosia were also more unbalanced; however, the link between vestibular agnosia and imbalance was confounded by the presence of inner ear conditions. We investigated the brain mechanisms of imbalance in acute TBI, its link with vestibular agnosia, and potential clinical impact, by prospective laboratory assessment of vestibular function, from reflex to perception, in patients with preserved peripheral vestibular function. Assessment included: vestibular reflex function, vestibular perception by participants' report of their passive yaw rotations in the dark, objective balance via posturography, subjective symptoms via questionnaires, and structural neuroimaging. We prospectively screened 918 acute admissions, assessed 146 and recruited 37. Compared to 37 matched controls, patients showed elevated vestibular-perceptual thresholds (patients 12.92°/s versus 3.87°/s) but normal vestibular-ocular reflex thresholds (patients 2.52°/s versus 1.78°/s). Patients with elevated vestibular-perceptual thresholds [3 standard deviations (SD) above controls' average], were designated as having vestibular agnosia, and displayed worse posturography than non-vestibular-agnosia patients, despite no difference in vestibular symptom scores. Only in patients with impaired postural control (3 SD above controls' mean), whole brain diffusion tensor voxel-wise analysis showed elevated mean diffusivity (and trend lower fractional anisotropy) in the inferior longitudinal fasciculus in the right temporal lobe that correlated with vestibular agnosia severity. Thus, impaired balance and vestibular agnosia are co-localized to the inferior longitudinal fasciculus in the right temporal lobe. Finally, a clinical audit showed a sevenfold reduction in clinician recognition of a common peripheral vestibular condition (benign paroxysmal positional vertigo) in acute patients with clinically apparent vestibular agnosia. That vestibular agnosia patients show worse balance, but without increased dizziness symptoms, explains why clinicians may miss treatable vestibular diagnoses in these patients. In conclusion, vestibular agnosia mediates imbalance in traumatic brain injury both directly via white matter tract damage in the right temporal lobe, and indirectly via reduced clinical recognition of common, treatable vestibular diagnoses.