Visual Vertigo, Motion Sickness and Disorientation in vehicles

The normal vestibular system may be adversely affected by environmental challenges which have characteristics that are unfamiliar or ambiguous in the patterns of sensory stimulation they provide. A disordered vestibular system lends susceptibility even to quotidian environmental experiences as the sufferer becomes dependent on potentially misleading, non-vestibular sensory stimuli. In both cases the sequela may be dizziness, incoordination, imbalance and unpleasant autonomic responses. Many forms of visual environmental motion, particularly busy places such as supermarkets, readily induce inappropriate sensations of sway or motion and imbalance referred to as visual vertigo. All people with intact vestibular function can become motion sick although individual susceptibility varies widely and is partially determined by inheritance. Motorists learn to interpret sensory stimuli in the context of the car stabilised by its suspension and guided by steering. A type of motorist disorientation occurs in some individuals that develop a heightened awareness of false perceptions of car orientation, readily experiencing stereotypical symptoms of threatened rolling over on corners and veering on open highways or in streaming traffic. This article discusses the putative mechanisms, consequences and approach to managing patients with visual vertigo, motion sickness and motorist disorientation syndrome in the context of chronic dizziness and motion sensitivity

The “broken escalator” phenomenon: Vestibular dizziness interferes with locomotor adaptation

BACKGROUND: Although vestibular lesions degrade postural control we do not know the relative contributions of the magnitude of the vestibular loss and subjective vestibular symptoms to locomotor adaptation. OBJECTIVE: To study how dizzy symptoms interfere with adaptive locomotor learning. METHODS: We examined patients with contrasting peripheral vestibular deficits, vestibular neuritis in the chronic stable phase (n = 20) and strongly symptomatic unilateral Meniere’s disease (n = 15), compared to age-matched healthy controls (n = 15). We measured locomotor adaptive learning using the “broken escalator” aftereffect, simulated on a motorised moving sled. RESULTS: Patients with Meniere’s disease had an enhanced “broken escalator” postural aftereffect. More generally, the size of the locomotor aftereffect was related to how symptomatic patients were across both groups. Contrastingly, the degree of peripheral vestibular loss was not correlated with symptom load or locomotor aftereffect size. During the MOVING trials, both patient groups had larger levels of instability (trunk sway) and reduced adaptation than normal controls. CONCLUSION: Dizziness symptoms influence locomotor adaptation and its subsequent expression through motor aftereffects. Given that the unsteadiness experienced during the “broken escalator” paradigm is internally driven, the enhanced aftereffect found represents a new type of self-generated postural challenge for vestibular/unsteady patients

Factors influencing clinical outcome in vestibular neuritis – A focussed review and reanalysis of prospective data

Following vestibular neuritis (VN), long term prognosis is not dependent on the magnitude of the residual peripheral function as measured with either caloric or the video head-impulse test. Rather, recovery is determined by a combination of visuo-vestibular (visual dependence), psychological (anxiety) and vestibular perceptual factors. Our recent research in healthy individuals has also revealed a strong association between the degree of lateralisation of vestibulo-cortical processing and gating of vestibular signals, anxiety and visual dependence. In the context of several functional brain changes occurring in the interaction between visual, vestibular and emotional cortices, which underpin the aforementioned psycho-physiological features in patients with VN, we re-examined our previous published findings focusing on additional factors impacting long term clinical outcome and function. These included: (i) the role of concomitant neuro-otological dysfunction (i.e. migraine and benign paroxysmal positional vertigo (BPPV)) and (ii) the degree to which brain lateralisation of vestibulo-cortical processing influences gating of vestibular function in the acute stage. We found that migraine and BPPV interfere with symptomatic recovery following VN. That is, dizziness handicap at short-term recovery stage was significantly predicted by migraine (r=0.523, n=28, p=.002), BPPV (r=0.658, n=31, p0.05). In left-sided VN patients, we observed a negative correlation between visual dependence and ipsilesional oculomotor thresholds (R2 0.459; p0.05). To summarise, our findings illustrate that in VN, neuro-otological co- morbidities retard recovery, and that measures of the peripheral vestibular system are an aggregate of residual function and cortically mediated gating of vestibular input

Long-term follow-up of intratympanic methylprednisolone versus gentamicin in patients with unilateral Menière’s disease

Objectives: To determine whether long term (>48 months) symptomatic vertigo control is sustained in patients with Menie`re’s disease from a previous comparative trial of intratympanic methylprednisolone versus gentamicin, and if the two treatments remain nonsignificantly different at longterm follow-up. Study Design: Mail survey recording vertigo frequency in the previous one and six months, further intratympanic treatment received, and validated symptom questionnaires. Setting: Outpatient hospital clinic setting. Patients: Adult patients with definite unilateral refractory Menie`re’s disease, who previously received in tratympanic treatment in a comparative trial. Intervention: A survey of trial participants who received intratympanic gentamicin (40 mg/mL) or methylprednisolone (62.5 mg/mL). Outcome measures: Primary: number of vertigo attacks in the 6 months prior to receiving this survey compared with the 6 months before the first trial injection. Secondary: : Number of vertigo attacks over the previous 1 month; validated symptom questionnaire scores of tinnitus, dizziness, vertigo, aural fullness, and functional disability. Results: Average follow-up was 70.8 months (standard deviation 17.0) from the first treatment injection. Vertigo attacks in the 6 months prior to receiving the current survey reduced by 95% compared to baseline in both drug groups (intention-to-treat analysis, both p<0.001). No significant difference between drugs was found for the primary and secondary outcomes. Eight participants (methylprednisolone ¼ 5 and gentamicin ¼ 3) required further injections for relapse after completing the original trial. Conclusion: Intratympanic methylprednisolone treatment provides effective long-lasting relief of vertigo, without the known inner-ear toxicity associated with gentamicin. There are no significant differences between the two treatments at long term follow-up

Electrocortical therapy for motion sickness

Given a sufficiently provocative stimulus, almost everyone can be made motion sick, with approximately one-third experiencing significant symptoms on long bus trips, on ships, or in light aircraft.1–4 Current countermeasures are either behavioral or pharmacologic. Behavioral measures include habituation/desensitization treatment protocols5 as well as positioning the head in alignment with the direction of the gravito-inertial force and maintaining a stable horizontal reference frame.5 Pharmacologic measures include antimuscarinics, H1 antihistamines, and sympathomimetics, which all detrimentally impact upon cognitive function, rendering them inappropriate for occupational use.5 All current therapies are only partially effective

Effects of Prochlorperazine on Normal Vestibular Ocular and Perceptual Responses: A Randomised, Double-Blind, Crossover, Placebo-Controlled Study

Background: The present study investigated whether prochlorperazine affects vestibular-ocular reflex (VOR) and vestibulo-perceptual function. Methods: We studied 12 healthy naïve subjects 3 hours after a single dose of oral prochlorperazine 5mg in a randomised, placebo-controlled, double-blind, cross-over study in healthy young subjects. Two rotational tests in yaw were used: 1) a Threshold task investigating perceptual motion detection and nystagmic thresholds (acceleration steps of 0.5deg/s/s) and 2) Suprathreshold responses to velocity steps of 90deg/s in which vestibulo-ocular (VO) and vestibulo-perceptual (VP) time constants of decay, as well as VOR gain, were measured. Results: Prochlorperazine had no effect upon any measure of nystagmic or perceptual vestibular function compared to placebo. This lack of effects on vestibular-mediated motion perception suggests that the drug is likely to act more as an antiemetic than as an anti-vertiginous agent

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

Background Ménière’s disease is characterised by severe vertigo attacks and hearing loss. Intratympanic gentamicin,the standard treatment for refractory Ménière’s 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 eff ectiveness trial, patients aged 18–70 years with refractory unilateral Ménière’s 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 Ménière’s 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 fi nal 6 months compared with the 6 months before the fi rst 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 diff erence –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 Ménière’s disease. The choice between methylprednisolone and gentamicin should be made based on clinical knowledge and patient circumstances

Abnormal Visuo-vestibular Interactions in Vestibular Migraine: a Cross Sectional Study

Vestibular migraine is amongst the commonest causes of episodic vertigo. Chronically, patients with vestibular migraine develop abnormal responsiveness to both vestibular and visual stimuli characterised by heightened self-motion sensitivity and visually-induced dizziness. Yet, the neural mechanisms mediating such symptoms remain unknown. We postulate that such symptoms are attributable to impaired visuo-vestibular cortical interactions, which in-turn disrupts normal vestibular function. To assess this, we investigated whether prolonged, full-field visual motion exposure, which has previously been shown to modulate visual cortical excitability in both healthy individuals and avestibular patients, could disrupt vestibular ocular reflex (VOR) and vestibular-perceptual thresholds of self-motion during rotations. Our findings reveal that vestibular migraine patients exhibited abnormally elevated reflexive and perceptual vestibular thresholds at baseline. Following visual motion exposure, both reflex and perceptual thresholds were significantly further increased in vestibular migraine patients relative to healthy controls, migraineurs without vestibular symptoms and patients with episodic vertigo due to a peripheral inner-ear disorder. Our results provide support for the notion of altered visuo-vestibular cortical interactions in vestibular migraine, as evidenced by vestibular threshold elevation following visual motion exposure

Assessing the impact of digital patient monitoring on health outcomes and healthcare resource usage in addition to the feasibility of its combination with at-home treatment, in participants receiving systemic anticancer treatment in clinical practice: protocol for an interventional, open-label, multicountry platform study (ORIGAMA).

Digital patient monitoring (DPM) tools can enable more effective clinical care and improved patient outcomes in cancer. However, their broad adoption requires ease of use and demonstration of real-world clinical utility/impact. ORIGAMA (MO42720) is an interventional, open-label, multicountry platform study investigating the clinical utility of DPM tools and specific treatments. ORIGAMA will begin with two cohorts that aim to assess the impact of the atezolizumab-specific Roche DPM Module (hosted on the Kaiku Health DPM platform (Helsinki, Finland)) on health outcomes and healthcare resource usage, and its feasibility to support at-home treatment administration, in participants receiving systemic anticancer treatment. Other digital health solutions may be added to future cohorts. In Cohort A, participants with metastatic non-small cell lung cancer (NSCLC), extensive-stage SCLC or Child Pugh A unresectable hepatocellular carcinoma will be randomised to a locally approved anticancer regimen containing intravenous atezolizumab (TECENTRIQ, F. Hoffmann-La Roche Ltd/Genentech) and local standard-of-care support, with/without the Roche DPM Module. Cohort B will assess the feasibility of the Roche DPM Module in supporting administration of three cycles of subcutaneous atezolizumab (1875 mg; Day 1 of each 21-day cycle) in the hospital, followed by 13 cycles at home by a healthcare professional (ie, flexible care), in participants with programmed cell-death ligand 1-positive, early-stage NSCLC. The primary endpoints are the mean difference in change of the participant-reported Total Symptom Interference Score at Week 12 from baseline (Cohort A) and flexible care adoption rate at Cycle 6 (Cohort B). This study will be conducted according to the Declaration of Helsinki, and/or the applicable laws and regulations of the country in which the research is conducted, whichever affords the greater protection to the individual. The study received its first Ethics Committee approval in Spain in October 2022. Participants will provide written informed consent in a face-to-face setting. The results of this study will be presented at national and/or international congresses and disseminated via publication in peer-reviewed journals. NCT05694013