Hena Ahmad

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.

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.

Are white matter abnormalities associated with “unexplained dizziness”?

Introduction Although cerebral small vessel disease is a significant contributor to the development of imbalance and falls in the elderly, whether it causes dizziness is not known. Methods A retrospective case analysis was conducted for 122 dizzy patients referred to two neuro-otology tertiary centres in London and Pisa. Patients were divided into ‘explained’ causes of dizziness (e.g. benign positional vertigo, vestibular neuritis, orthostatic hypotension, cerebellar ataxias) and ‘unexplained’ dizziness. White matter hyperintensities (WMH) in MRI (T2 weighted and FLAIR sequences) were blindly rated according to the Fazekas scale. Results 122 patients; 58 (mean age = 72, SD = 7.95 years) in the ‘unexplained’ group and 64 (mean age = 72.01, SD = 8.28 years) in the ‘explained’ group were recruited. The overall frequency of lesions (Fazekas 1–3) significantly differed between groups (p = 0.011). The frequency of severe lesions (Fazekas 3) was significantly higher in the ‘unexplained’ group (22%) than in the ‘explained’ group (5%; p = 0.003). Conclusion Increased severity of WMH in cases of unexplained dizziness suggests that such abnormalities are likely contributory to the development of dizziness. WM lesions may induce dizziness either because patients perceive a degree of objective unsteadiness or by a disconnection syndrome involving vestibular or locomotor areas of the brain.

Applications of neuromodulation to explore vestibular cortical processing; new insights into the effects of direct current cortical modulation upon pursuit, VOR and VOR suppression

Functional imaging, lesion studies and behavioural observations suggest that vestibular processing is lateralised to the non-dominant hemisphere. Moreover, disruption of interhemispheric balance via inhibition of left parietal cortex using transcranial direct current stimulation (tDCS) has been associated with an asymmetric suppression of the vestibulo-ocular reflex (VOR). However, the mechanism by which the VOR was modulated remains unknown. In this paper we review the literature on non-invasive brain stimulation techniques which have been used to probe vestibular function over the last decade. In addition, we investigate the mechanisms whereby tDCS may modulate VOR, e.g. by acting upon pursuit, VOR suppression mechanisms or direct VOR modulation. We applied bi-hemispheric parietal tDCS in 11 healthy subjects and only observed significant effects on VOR gain (tdcs * condition p=0.041) - namely a trend for VOR gain increase with right anodal/left cathodal stimulation, and a decrease with right cathodal/left anodal stimulation. Hence, we suggest that the modulation of the VOR observed both here and in previous reports, is directly caused by top-down cortical control of the VOR as a result of disruption to interhemispheric balance, likely parietal.

Clinical and Functional Characterization of a Missense ELF2 Variant in a CANVAS Family

Cerebellar ataxia with neuropathy and bilateral vestibular areflexia syndrome (CANVAS) is a rare disorder with an unknown etiology. We present a British family with presumed autosomal dominant CANVAS with incomplete penetrance and variable expressivity. Exome sequencing identified a rare missense variant in the ELF2 gene at chr4:g.140058846 C > T, c.10G > A, p.A4T which segregated in all affected patients. By using transduced BE (2)-M17 cells, we found that the mutated ELF2 (mt-ELF2) gene increased ATXN2 and reduced ELOVL5 gene expression, the causal genes of type 2 and type 38 spinocerebellar ataxias. Both, western blot and confocal microscopy confirmed an increase of ataxin-2 in BE(2)-M17 cells transduced with lentivirus expressing mt-ELF2 (CEE-mt-ELF2), which was not observed in cells transduced with lentivirus expressing wt-ELF2 (CEE-wt-ELF2). Moreover, we observed a significant decrease in the number and size of lipid droplets in the CEE-mt-ELF2-transduced BE (2)-M17 cells, but not in the CEE-wt-ELF2-transduced BE (2)-M17. Furthermore, changes in the expression of ELOVL5 could be related with the reduction of lipid droplets in BE (2)-M17 cells. This work supports that ELF2 gene regulates the expression of ATXN2 and ELOVL5 genes, and defines new molecular links in the pathophysiology of cerebellar ataxias.

Differential effect of visual motion adaption upon visual cortical excitability

The objectives of this study were 1) to probe the effects of visual motion adaptation on early visual and V5/MT cortical excitability and 2) to investigate whether changes in cortical excitability following visual motion adaptation are related to the degree of visual dependency, i.e., an overreliance on visual cues compared with vestibular or proprioceptive cues. Participants were exposed to a roll motion visual stimulus before, during, and after visual motion adaptation. At these stages, 20 transcranial magnetic stimulation (TMS) pulses at phosphene threshold values were applied over early visual and V5/MT cortical areas from which the probability of eliciting a phosphene was calculated. Before and after adaptation, participants aligned the subjective visual vertical in front of the roll motion stimulus as a marker of visual dependency. During adaptation, early visual cortex excitability decreased whereas V5/MT excitability increased. After adaptation, both early visual and V5/MT excitability were increased. The roll motion-induced tilt of the subjective visual vertical (visual dependence) was not influenced by visual motion adaptation and did not correlate with phosphene threshold or visual cortex excitability. We conclude that early visual and V5/MT cortical excitability is differentially affected by visual motion adaptation. Furthermore, excitability in the early or late visual cortex is not associated with an increase in visual reliance during spatial orientation. Our findings complement earlier studies that have probed visual cortical excitability following motion adaptation and highlight the differential role of the early visual cortex and V5/MT in visual motion processing.NEW & NOTEWORTHY We examined the influence of visual motion adaptation on visual cortex excitability and found a differential effect in V1/V2 compared with V5/MT. Changes in visual excitability following motion adaptation were not related to the degree of an individuals visual dependency.

Downregulation of early visual cortex excitability mediates oscillopsia suppression

Objective: To identify in an observational study the neurophysiologic mechanisms that mediate adaptation to oscillopsia in patients with bilateral vestibular failure (BVF). Methods: We directly probe the hypothesis that adaptive changes that mediate oscillopsia suppression implicate the early visual-cortex (V1/V2). Accordingly, we investigated V1/V2 excitability using transcranial magnetic stimulation (TMS) in 12 avestibular patients and 12 healthy controls. Specifically, we assessed TMS-induced phosphene thresholds at baseline and cortical excitability changes while performing a visual motion adaptation paradigm during the following conditions: baseline measures (i.e., static), during visual motion (i.e., motion before adaptation), and during visual motion after 5 minutes of unidirectional visual motion adaptation (i.e., motion adapted). Results: Patients had significantly higher baseline phosphene thresholds, reflecting an underlying adaptive mechanism. Individual thresholds were correlated with oscillopsia symptom load. During the visual motion adaptation condition, no differences in excitability at baseline were observed, but during both the motion before adaptation and motion adapted conditions, we observed significantly attenuated cortical excitability in patients. Again, this attenuation in excitability was stronger in less symptomatic patients. Conclusions: Our findings provide neurophysiologic evidence that cortically mediated adaptive mechanisms in V1/V2 play a critical role in suppressing oscillopsia in patients with BVF.

ACQUIRED PENDULAR NYSTAGMUS IN STARGARDT'S SYNDROME SUPPRESSED BY ALCOHOL

Stargardts disease is the most common inherited form of juvenile macular degeneration leading to progressive visual loss. We describe a case of female twins aged 47 with Stargardts Type III (rare autosomal dominant form) who, aged 7, developed blurred vision leading to identical progressive macular dystrophy and deterioration in visual acuities (both 1/60). Pendular nystagmus, presumably secondary to visual deprivation, was observed 4 years ago in both although only one twin (AW) described worsening horizontal oscillopsia, reportedly improving following alcohol consumption. Here, we report measurements of eye movements using 3D video-oculography at baseline and post alcohol ingestion (Blood alcohol concentrations: pre <10 mg/dl, post AW=66 mg/dl and HW=49 mg/dl). Analysis software was used to determine the amplitude and frequency of the pendular nystagmus. In AW peak-to-peak horizontal amplitude decreased from 5° (3.13 Hz) to 0.8°, and vertical amplitude from 2.9° (3.13 Hz) to 0.5°. In HW, peak horizontal amplitude reduced from 4.2° (3.22 Hz) to 1.5° and vertical amplitude from 1.9° (6.25 Hz) to 1.7°. In AW the oscillopsia resolved completely post-alcohol with modified oscillopsia scale scores reduced by 50%. (21/28 to 10/28). The findings demonstrate the potential effects of alcohol in suppressing pendular nystagmus and oscillopsia which may guide pharmacological treatments with alcohol-mimetics.

ARE WHITE MATTER ABNORMALITIES A CAUSE OF ‘UNEXPLAINED DIZZINESS’? A RETROSPECTIVE BI–CENTRE STUDY

Introduction Although cerebral small vessel disease is a significant contributor to the development of imbalance and falls in the elderly, whether it also contributes to the development of dizziness is not known. Methods A retrospective case analysis was conducted for 125 dizzy patients referred to two neuro-otology tertiary centres in London and Pisa. Specific search criteria of “white matter disease” was applied to databases and patients were divided into ‘explained’ causes of dizziness (ie benign positional vertigo, orthostatic hypotension, cerebellar ataxias) and ‘unexplained’ causes of dizziness. White matter hyperintensities (WMH) in MRI (T2 weighted and FLAIR) were blindly rated according to the Fazekas scale. Results 61 patients (mean age=72SD=7.95 years) in the ‘unexplained’ group and 64 (mean age=72.01SD=8.28 years) in the ‘explained’ group were recruited. The overall frequency of lesions (Fazekas 1–3) differed between the groups (p=0.015). The frequency of severe lesions (Fazekas 3) was significantly higher in the unexplained group (21%) than in the explained group (5%; p=0.005). Conclusion Increased severity of WM abnormalities in cases of unexplained dizziness suggests that such abnormalities are contributory to the development of dizziness. WM lesions may induce dizziness either because patients perceive a degree of objective unsteadiness or by a cortical-subcortical disconnection syndrome.