Qadeer Arshad

Motion sickness in migraine and vestibular disorders

Motion sickness is a syndrome provoked by sensory conflict that involves the vestibular system with symptoms resembling those of common neuro-otological disorders including vestibular neuritis (VN) and vestibular migraine (VM). By contrast, it is generally believed that bilateral vestibular failure (BVF) causes reduced motion sickness susceptibility. We investigate differences between these conditions with a single protocol using validated objective experimental (off-vertical axis rotation, OVAR1) and validated patient-centred measures of motion sickness susceptibility.2 Five groups were studied: 1. Normal healthy controls ( n=12; mean age 51, SD 17.2; 4/12 women). 2. VN (history of acute vertigo without neurological features or hearing loss; none treated with steroids acutely; positive head thrust test; spontaneous unidirectional horizontal nystagmus; acute caloric canal paresis >30%, mean canal paresis repeated in chronic phase after 6 weeks was 38% (SD 31); n=12; disease duration range 10–33 months; mean age 45, SD 15.3; 5/12 women). 3. BVF (absent caloric or rotational responses; confirmed in chronic phase; n=8; mean age 51, SD 11.5; 3/8 women). 4. VM (recurrent episodic vestibular symptoms in association with migraine according to published criteria with no vestibular test abnormalities3; n=12; mean age 45, SD 15.3; 11/12 women). 5. Migraine without vestibular symptoms ( M ; recurrent headaches meeting International Headache Society (IHS) 2004 criteria; with/without aura but with no significant vestibular symptoms3; n=12; mean age 41, SD 13.6; 8/12 women. Two groups of patient with migraine were studied (one with vestibular symptoms, VM, and one without vestibular symptoms, M) to determine whether the presence of vestibular symptoms in the setting of migraine influences motion sickness susceptibility. The normal controls and the migraine group were screened for vestibular symptoms but did not undergo formal vestibular testing. Participants were …

Vestibular Activation Differentially Modulates Human Early Visual Cortex and V5/MT Excitability and Response Entropy

Head movement imposes the additional burdens on the visual system of maintaining visual acuity and determining the origin of retinal image motion (i.e., self-motion vs. object-motion). Although maintaining visual acuity during self-motion is effected by minimizing retinal slip via the brainstem vestibular-ocular reflex, higher order visuovestibular mechanisms also contribute. Disambiguating self-motion versus object-motion also invokes higher order mechanisms, and a cortical visuovestibular reciprocal antagonism is propounded. Hence, one prediction is of a vestibular modulation of visual cortical excitability and indirect measures have variously suggested none, focal or global effects of activation or suppression in human visual cortex. Using transcranial magnetic stimulation-induced phosphenes to probe cortical excitability, we observed decreased V5/MT excitability versus increased early visual cortex (EVC) excitability, during vestibular activation. In order to exclude nonspecific effects (e.g., arousal) on cortical excitability, response specificity was assessed using information theory, specifically response entropy. Vestibular activation significantly modulated phosphene response entropy for V5/MT but not EVC, implying a specific vestibular effect on V5/MT responses. This is the first demonstration that vestibular activation modulates human visual cortex excitability. Furthermore, using information theory, not previously used in phosphene response analysis, we could distinguish between a specific vestibular modulation of V5/MT excitability from a nonspecific effect at EVC.

Left Cathodal Trans-Cranial Direct Current Stimulation of the Parietal Cortex Leads to an Asymmetrical Modulation of the Vestibular-Ocular Reflex

Multi-sensory visuo-vestibular cortical areas within the parietal lobe are important for spatial orientation and possibly for descending modulation of the vestibular-ocular reflex (VOR). Functional imaging and lesion studies suggest that vestibular cortical processing is localized primarily in the non-dominant parietal lobe. However, the role of inter-hemispheric parietal balance in vestibular processing is poorly understood. Therefore, we tested whether experimentally induced asymmetries in right versus left parietal excitability would modulate vestibular function. VOR function was assessed in right-handed normal subjects during caloric ear irrigation (30 °C), before and after trans-cranial direct current stimulation (tDCS) was applied bilaterally over the parietal cortex. Bilateral tDCS with the anode over the right and the cathode over the left parietal region resulted in significant asymmetrical modulation of the VOR, with highly suppressed responses during the right caloric irrigation (i.e. rightward slow phase nystagmus). In contrast, we observed no VOR modulation during either cathodal stimulation of the right parietal cortex or SHAM tDCS conditions. Application of unilateral tDCS revealed that the left cathodal stimulation was critical in inducing the observed modulation of the VOR. We show that disruption of parietal inter-hemispheric balance can induce asymmetries in vestibular function. This is the first report using neuromodulation to show right hemisphere dominance for vestibular cortical processing.

Intratympanic methylprednisolone versus gentamicin in patients with unilateral Ménière's disease: a randomised, double-blind, comparative effectiveness trial

BACKGROUND Ménières disease is characterised by severe vertigo attacks and hearing loss. Intratympanic gentamicin, the standard treatment for refractory Ménières disease, reduces vertigo, but damages vestibular function and can worsen hearing. We aimed to assess whether intratympanic administration of the corticosteroid methylprednisolone reduces vertigo compared with gentamicin. METHODS In this double-blind comparative effectiveness trial, patients aged 18-70 years with refractory unilateral Ménières disease were enrolled at Charing Cross Hospital (London, UK) and Leicester Royal Infirmary (Leicester, UK). Patients were randomly assigned (1:1) by a block design to two intratympanic methylprednisolone (62·5 mg/mL) or gentamicin (40 mg/mL) injections given 2 weeks apart, and were followed up for 2 years. All investigators and patients were masked to treatment allocation. The primary outcome was vertigo frequency over the final 6 months (18-24 months after injection) compared with the 6 months before the first injection. Analyses were done in the intention-to-treat population, and then per protocol. This trial is registered with ClinicalTrials.gov, number NCT00802529. FINDINGS Between June 19, 2009, and April 15, 2013, 256 patients with Ménières disease were screened, 60 of whom were enrolled and randomly assigned: 30 to gentamicin and 30 to methylprednisolone. In the intention-to-treat analysis (ie, all 60 patients), the mean number of vertigo attacks in the final 6 months compared with the 6 months before the first injection (primary outcome) decreased from 19·9 (SD 16·7) to 2·5 (5·8) in the gentamicin group (87% reduction) and from 16·4 (12·5) to 1·6 (3·4) in the methylprednisolone group (90% reduction; mean difference -0·9, 95% CI -3·4 to 1·6). Patients whose vertigo did not improve after injection (ie, non-responders) after being assessed by an unmasked clinician were eligible for additional injections given by a masked clinician (eight patients in the gentamicin group vs 15 in the methylprednisolone group). Two non-responders switched from methylprednisolone to gentamicin. Both drugs were well tolerated with no safety concerns. Six patients reported one adverse event each: three in the gentamicin group and three in the methylprednisolone group. The most common adverse event was minor ear infections, which was experienced by one patient in the gentamicin group and two in the methylprednisolone group. INTERPRETATION Methylprednisolone injections are a non-ablative, effective treatment for refractory Ménières disease. The choice between methylprednisolone and gentamicin should be made based on clinical knowledge and patient circumstances. FUNDING Ménières Society and National Institute for Health Research Imperial Biomedical Research Centre.

Chronic symptoms after vestibular neuritis and the high velocity vestibulo-ocular reflex

Hypothesis: As the anterior and posterior semicircular canals are vital to the regulation of gaze stability, particularly during locomotion or vehicular travel, we tested whether the high-velocity vestibulo-ocular reflex (VOR) of the three ipsilesional semicircular canals elicited by the modified Head Impulse Test would correlate with subjective dizziness or vertigo scores after vestibular neuritis (VN). Background: Recovery after acute VN varies with around half reporting persistent symptoms long after the acute episode. However, an unanswered question is whether chronic symptoms are associated with impairment of the high-velocity VOR of the anterior or posterior canals. Methods: Twenty patients who had experienced an acute episode of VN at least 3 months earlier were included in this study. Participants were assessed with the video head impulse test (vHIT) of all six canals, bithermal caloric irrigation, the Dizziness Handicap Inventory (DHI), and the Vertigo Symptoms Scale short-form (VSS). Results: Of these 20 patients, 12 thought that they had recovered from the initial episode whereas 8 did not and reported elevated DHI and VSS scores. However, we found no correlation between DHI or VSS scores and the ipsilesional single or combined vHIT gain, vHIT gain asymmetry orcaloric paresis. The high-velocity VOR was not different between patients who thought they had recovered and patients who thought they had not. Conclusion: Our findings suggest that chronic symptoms of dizziness after VN are not associated with the high-velocity VOR of the single or combined ipsilesional horizontal, anterior, or posterior semicircular canals.

Predictors of clinical recovery from vestibular neuritis: a prospective study

We sought to identify predictors of symptomatic recovery in vestibular neuritis. Forty VN patients were prospectively studied in the acute phase (median = 2 days) and 32 in the recovery phase (median = 10 weeks) with vestibulo‐ocular reflex, vestibular‐perceptual, and visual dependence tests and psychological questionnaires. Clinical outcome was Dizziness Handicap Inventory score at recovery phase. Acute visual dependency and autonomic arousal predicted outcome. Worse recovery was associated with a combination of increased visual dependence, autonomic arousal, anxiety/depression, and fear of bodily sensations, but not with vestibular variables. Findings highlight the importance of early identification of abnormal visual dependency and concurrent anxiety.

Bidirectional Modulation of Numerical Magnitude

Numerical cognition is critical for modern life; however, the precise neural mechanisms underpinning numerical magnitude allocation in humans remain obscure. Based upon previous reports demonstrating the close behavioral and neuro-anatomical relationship between number allocation and spatial attention, we hypothesized that these systems would be subject to similar control mechanisms, namely dynamic interhemispheric competition. We employed a physiological paradigm, combining visual and vestibular stimulation, to induce interhemispheric conflict and subsequent unihemispheric inhibition, as confirmed by transcranial direct current stimulation (tDCS). This allowed us to demonstrate the first systematic bidirectional modulation of numerical magnitude toward either higher or lower numbers, independently of either eye movements or spatial attention mediated biases. We incorporated both our findings and those from the most widely accepted theoretical framework for numerical cognition to present a novel unifying computational model that describes how numerical magnitude allocation is subject to dynamic interhemispheric competition. That is, numerical allocation is continually updated in a contextual manner based upon relative magnitude, with the right hemisphere responsible for smaller magnitudes and the left hemisphere for larger magnitudes.

Right hemisphere dominance directly predicts both baseline V1 cortical excitability and the degree of top-down modulation exerted over low-level brain structures

Highlights • Line bisection predicts V1 excitability.• Line bisection predicts degree of VOR modulation.• Line bisection correlates with tDCS-mediated vestibular-nystagmus suppression.• Degree of nystagmus suppression is a bio-marker of right hemisphere dominance.

A brief review of the clinical anatomy of the vestibular-ocular connections—how much do we know?

The basic connectivity from the vestibular labyrinth to the eye muscles (vestibular ocular reflex, VOR) has been elucidated in the past decade, and we summarise this in graphic format. We also review the concept of ‘velocity storage’, a brainstem integrator that prolongs vestibular responses. Finally, we present new discoveries of how complex visual stimuli, such as binocular rivalry, influence VOR processing. In contrast to the basic brainstem circuits, cortical vestibular circuits are far from being understood, but parietal-vestibular nuclei projections are likely to be involved.

Functional neuroimaging of visuo-vestibular interaction.

The brain combines visual, vestibular and proprioceptive information to distinguish between self- and world motion. Often these signals are complementary and indicate that the individual is moving or stationary with respect to the surroundings. However, conflicting visual motion and vestibular cues can lead to ambiguous or false sensations of motion. In this study, we used functional magnetic resonance imaging to explore human brain activation when visual and vestibular cues were either complementary or in conflict. We combined a horizontally moving optokinetic stimulus with caloric irrigation of the right ear to produce conditions where the vestibular activation and visual motion indicated the same (congruent) or opposite directions of self-motion (incongruent). Visuo-vestibular conflict was associated with increased activation in a network of brain regions including posterior insular and transverse temporal areas, cerebellar tonsil, cingulate and medial frontal gyri. In the congruent condition, there was increased activation in primary and secondary visual cortex. These findings suggest that when sensory information regarding self-motion is contradictory, there is preferential activation of multisensory vestibular areas to resolve this ambiguity. When cues are congruent, there is a bias towards visual cortical activation. The data support the view that a network of brain areas including the posterior insular cortex may play an important role in integrating and disambiguating visual and vestibular cues.