Treating benign paroxysmal positional vertigo in acute traumatic brain injury: a prospective, randomised clinical trial assessing safety, feasibility, and efficacy.

Background: Benign paroxysmal positional vertigo (BPPV) affects approximately half of acute, moderate-severe traumatic brain injury (TBI) patients. To date, there have been no rigorous studies of BPPV assessment or treatment in this cohort. We aimed to determine the safety, practicability, and efficacy of therapist-led BPPV management in acute TBI and the feasibility of a larger effectiveness trial. Methods: This was a multi-centre, three-arm, parallel-groups, randomised, feasibility trial. Recruitment was via convenience sampling. The main inclusion criteria were age over 18 years and a confirmed, non-penetrating, acute TBI. BPPV-positive patients were randomly allocated to one of three interventions (repositioning manoeuvres, Brandt-Daroff exercises or advice) using minimisation criteria. Outcome assessors were blinded to the intervention. Results: Of 2014 patients screened for inclusion, 180 were assessed for BPPV. Of those assessed, 34% (62/180) had BPPV, and 58 patients received an intervention. Therapist-led interventions were delivered safely and accurately according to intervention monitoring criteria. Resolution of BPPV was observed in 35/58 (60%) patients. The resolution rate was highest following repositioning manoeuvres (78%), followed by the advice (53%) and Brandt-Daroff interventions (42%). 10 patients experienced recurrence. This was observed more frequently in those with skull fractures and bilateral or mixed BPPV. Conclusions: Overall, the results provide strong evidence for the feasibility of a future trial. Therapist-led management of BPPV in acute TBI was safe and practicable. Repositioning manoeuvres seemingly yielded a superior treatment effect. However, given the high recurrence rate of post-traumatic BPPV, the optimal time to treat according to patients' specific recurrence risk requires further investigation. Trial registration: ISRCTN91943864, https://doi.org/10.1186/ISRCTN91943864.

Sense of direction in vestibular disorders.

BACKGROUND: Our sense of direction (SOD) ability relies on the sensory integration of both visual information and self-motion cues from the proprioceptive and vestibular systems. Here, we assess how dysfunction of the vestibular system impacts perceived SOD in varying vestibular disorders, and secondly, we explore the effects of dizziness, migraine and psychological symptoms on SOD ability in patient and control groups. METHODS: 87 patients with vestibular disorder and 69 control subjects were assessed with validated symptom and SOD questionnaires (Santa Barbara Sense of Direction scale and the Object Perspective test). RESULTS: While patients with vestibular disorders performed significantly worse than controls at the group level, only central and functional disorders (vestibular migraine and persistent postural perceptual dizziness), not peripheral disorders (benign-paroxysmal positional vertigo, bilateral vestibular failure and Meniere's disease) showed significant differences compared to controls on the level of individual vestibular groups. Additionally, orientational abilities associated strongly with spatial anxiety and showed clear separation from general dizziness and psychological factors in both patient and control groups. CONCLUSIONS: SOD appears to be less affected by peripheral vestibular dysfunction than by functional and/or central diagnoses, indicating that higher level disruptions to central vestibular processing networks may impact SOD more than reductions in sensory peripheral inputs. Additionally, spatial anxiety is highly associated with orientational abilities in both patients and control subjects.

An assessment of the effects of neurokinin1 receptor antagonism against nausea and vomiting: Relative efficacy, sites of action and lessons for future drug development.

A broad-spectrum anti-vomiting effect of neurokinin1 receptor antagonists (NK1 RA), shown in pre-clinical animal studies, has been supported by a more limited range of clinical studies in different indications. However, this review suggests that compared with vomiting, the self-reported sensation of nausea is less affected or possibly unaffected (depending on the stimulus) by NK1 receptor antagonism, a common finding for anti-emetics. The stimulus-independent effects of NK1 RAs against vomiting are explicable by actions within the central pattern generator (ventral brainstem) and the nucleus tractus solitarius (NTS; dorsal brainstem), with additional effects on vagal afferent activity for certain stimuli (e.g., highly emetogenic chemotherapy). The central pattern generator and NTS neurones are multifunctional so the notable lack of obvious effects of NK1 RAs on other reflexes mediated by the same neurones suggests that their anti-vomiting action is dependent on the activation state of the pathway leading to vomiting. Nausea requires activation of cerebral pathways by projection of information from the NTS. Although NK1 receptors are present in cerebral nuclei implicated in nausea, and imaging studies show very high receptor occupancy at clinically used doses, the variable or limited ability of NK1 RAs to inhibit nausea emphasizes: (i) our inadequate understanding of the mechanisms of nausea; and (ii) that classification of a drug as an anti-emetic may give a false impression of efficacy against nausea vs. vomiting. We discuss the potential mechanisms for the differential efficacy of NK1 RA and the implications for future development of drugs that can effectively treat nausea, an area of unmet clinical need.

Measuring the susceptibility to visually induced motion sickness and its relationship with vertigo, dizziness, migraine, syncope and personality traits.

The widespread use of visual technologies such as Virtual Reality increases the risk of visually induced motion sickness (VIMS). Previously, the 6-item short version of the Visually Induced Motion Sickness Susceptibility Questionnaire (VIMSSQ short form) has been validated for predicting individual variation in VIMS. The aim of the current study was to investigate how the susceptibility to VIMS is correlated with other relevant factors in the general population. A total of 440 participants (201 M, 239F), mean age 33.6 (SD 14.8) years, completed an anonymous online survey of various questionnaires including the VIMSSQ, Motion Sickness Susceptibility Questionnaire (MSSQ), Vertigo in City questionnaire (VIC), Migraine (scale), Social & Work Impact of Dizziness (SWID), Syncope (faintness), and Personality ('Big Five' TIPI). The VIMSSQ correlated positively with the MSSQ (r = 0.50), VIC (r = 0.45), Migraine (r = 0.44), SWID (r = 0.28), and Syncope (r = 0.15). The most efficient Multiple Linear Regression model for the VIMSSQ included the predictors MSSQ, Migraine, VIC, and Age and explained 40% of the variance. Factor analysis of strongest correlates with VIMSSQ revealed a single factor loading with VIMSSQ, MSSQ, VIC, Migraine, SWID, and Syncope, suggesting a common latent variable of sensitivity. The set of predictors for the VIMSSQ in the general population has similarity with those often observed in patients with vestibular disorders. Based on these correlational results, we suggest the existence of continuum of underlying risk factors for sensitivity, from healthy population to patients with extreme visual vertigo and perhaps Persistent Postural-Perceptual Dizziness.

The Visually Induced Motion Sickness Susceptibility Questionnaire (VIMSSQ): Estimating Individual Susceptibility to Motion Sickness-Like Symptoms When Using Visual Devices.

OBJECTIVE: Two studies were conducted to develop and validate a questionnaire to estimate individual susceptibility to visually induced motion sickness (VIMS). BACKGROUND: VIMS is a common side-effect when watching dynamic visual content from various sources, such as virtual reality, movie theaters, or smartphones. A reliable questionnaire predicting individual susceptibility to VIMS is currently missing. The aim was to fill this gap by introducing the Visually Induced Motion Sickness Susceptibility Questionnaire (VIMSSQ). METHODS: A survey and an experimental study were conducted. Survey: The VIMSSQ investigated the frequency of nausea, headache, dizziness, fatigue, and eyestrain when using different visual devices. Data were collected from a survey of 322 participants for the VIMSSQ and other related phenomena such as migraine. Experimental study: 23 participants were exposed to a VIMS-inducing visual stimulus. Participants filled out the VIMSSQ together with other questionnaires and rated their level of VIMS using the Simulator Sickness Questionnaire (SSQ). RESULTS: Survey: The most prominent symptom when using visual devices was eyestrain, and females reported more VIMS than males. A one-factor solution with good scale reliability was found for the VIMSSQ. Experimental study: Regression analyses suggested that the VIMSSQ can be useful in predicting VIMS (R2 = .34) as measured by the SSQ, particularly when combined with questions pertaining to the tendency to avoid visual displays and experience syncope (R2 = .59). CONCLUSION: We generated normative data for the VIMSSQ and demonstrated its validity. APPLICATION: The VIMSSQ can become a valuable tool to estimate one's susceptibility to VIMS based on self-reports.

Motion sickness: current concepts and management.

PURPOSE OF REVIEW: Motion sickness is an ancient phenomenon that affects many people. Nausea, vomiting, disorientation, sweating, fatigue, and headache are just few of the many signs and symptoms that are commonly experienced during an episode of motion sickness. In the present review, we will provide an overview of the current research trends and topics in the domain of motion sickness, including theoretical considerations, physiological and neural mechanisms, individual risk factors, and treatment options, as well as recommendations for future research directions. RECENT FINDINGS: More recently, motion sickness has been in the focus of attention in the context of two global technological trends, namely automated vehicles and virtual reality. Both technologies bear the potential to revolutionize our daily lives in many ways; however, motion sickness is considered a serious concern that threatens their success and acceptance. The majority of recent research on motion sickness focuses on one of these two areas. SUMMARY: Aside from medication (e.g. antimuscarinics, antihistamines), habituation remains the most effective nonpharmacological method to reduce motion sickness. A variety of novel techniques has been investigated with promising results, but an efficient method to reliably prevent or minimize motion sickness has yet to emerge.

Motion Sickness Lessons from the Southern Ocean.

BACKGROUND: The objectives were to assess the prevalence, severity, and medication taken, and to look for predictive factors in order to better identify characteristics of passengers at risk of motion sickness during transport from Hobart in Tasmania to the French polar stations in Antarctica. METHODS: There were 239 passengers who were surveyed over 4 yr with 4 round trips per year using the Motion Sickness Susceptibility Questionnaire (MSSQ), Simulator Sickness Questionnaire (SSQ), state-trait anxiety test (STAI-Trait and STAI-State), and general parameters (age, gender, number of trips, jet-lag, direction of the trip), medication, calculation of the distance of each passengers cabin to the center of gravity (CoG). RESULTS: While the passengers had a low intrinsic sensitivity to motion sickness (MSSQ), 94 reported at least one SSQ symptom of motion sickness, and 38 vomited. Five associated factors were discovered: greater initial sensitivity (MSSQ), anticipation of being ill, younger age, higher level of anxiety at midtrip, and greater distance from the CoG. Of the passengers, there were 54 who took anti-motion sickness medication at different times of the trip, however, these passengers experienced more nausea. This could be due to self-selection since they were more sensitive to motion sickness. CONCLUSION: We identified three predictive factors of motion sickness (greater intrinsic susceptibility, younger age, and greater cabin distance from the CoG). For preventive purposes, two associated factors of MS (anticipation of being ill, MSSQ score) were determined to classify three groups of risk of MS to improve passenger care during the trip. Besnard S, Bois J, Hitier M, Vogt J, Laforet P, Golding JF. Motion sickness lessons from the Southern Ocean. Aerosp Med Hum Perform. 2021; 92(9):720727.

Smaller Cortisol Awakening Responses Are Associated with Greater Visual Dependence in Postural Control.

There are known links between the hypothalamic-pituitary-adrenal (HPA) axis and systems responsible for regulating posture. Our aim was to explore directly, for the first time, whether an aspect of circadian HPA axis activity (the cortisol awakening response: CAR) was associated with greater visual dependency in postural control. For measurement of the CAR, electronically monitored saliva samples were collected by participants following morning awakening in their home environment. On the afternoons of the same days, postural sway was measured in the laboratory by exposing participants to static (control) and moving visual stimuli whilst standing still and upright on a force platform. Visual dependence was assessed as the increase in postural sway (path length) during exposure to the moving compared with the static condition. The 44 measurement days were derived from four days for each of eleven healthy participants (mean ± SD age: 51.18 ± 3.3 years). As expected, postural sway was greater when exposed to moving versus static cues. Mixed regression modelling showed that participants with smaller four day average CARs had greater deterioration in postural sway when presented with moving stimuli. These data are the first to document associations between the CAR and visual dependency in postural sway.

Motion sickness diagnostic criteria: Consensus Document of the Classification Committee of the Bárány Society.

We present diagnostic criteria for motion sickness, visually induced motion sickness (VIMS), motion sickness disorder (MSD), and VIMS disorder (VIMSD) to be included in the International Classification of Vestibular Disorders. Motion sickness and VIMS are normal physiological responses that can be elicited in almost all people, but susceptibility and severity can be high enough for the response to be considered a disorder in some cases. This report provides guidelines for evaluating signs and symptoms caused by physical motion or visual motion and for diagnosing an individual as having a response that is severe enough to constitute a disorder.   The diagnostic criteria for motion sickness and VIMS include adverse reactions elicited during exposure to physical motion or visual motion leading to observable signs or symptoms of greater than minimal severity in the following domains: nausea and/or gastrointestinal disturbance, thermoregulatory disruption, alterations in arousal, dizziness and/or vertigo, headache and/or ocular strain. These signs and/or symptoms occur during the motion exposure, build as the exposure is prolonged, and eventually stop after the motion ends. Motion sickness disorder and VIMSD are diagnosed when recurrent episodes of motion sickness or VIMS are reliably triggered by the same or similar stimuli, severity does not significantly decrease after repeated exposure, and signs/symptoms lead to activity modification, avoidance behavior, or aversive emotional responses.   Motion sickness/MSD and VIMS/VIMSD can occur separately or together. Severity of symptoms in reaction to physical motion or visual motion stimuli varies widely and can change within an individual due to aging, adaptation, and comorbid disorders. We discuss the main methods for measuring motion sickness symptoms, the situations conducive to motion sickness and VIMS, and the individual traits associated with increased susceptibility. These additional considerations will improve diagnosis by fostering accurate measurement and understanding of the situational and personal factors associated with MSD and VIMSD.

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.

Abnormal visuo-vestibular interactions in vestibular migraine: a cross sectional study.

Vestibular migraine is among the commonest causes of episodic vertigo. Chronically, patients with vestibular migraine develop abnormal responsiveness to both vestibular and visual stimuli characterized 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 been previously shown to modulate visual cortical excitability in both healthy individuals and avestibular patients, could disrupt vestibular ocular reflex 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.

Reliability of functional outcome measures in adults with neurofibromatosis 1.

OBJECTIVES: To determine intra-rater and inter-rater reliability of functional outcome measures in adults with neurofibromatosis 1 and to ascertain how closely objective and subjective measures align. METHODS: A total of 49 ambulant adults with neurofibromatosis 1 aged 16 years and over were included in this observational study: median age 31 years (range: 16-66 years), 29 females, 20 males. Participants were video-recorded or photographed performing four functional outcome measures. Four raters from the neurofibromatosis centre multi-disciplinary team independently scored the measures to determine inter-rater reliability. One rater scored the measures a second time on a separate occasion to determine intra-rater reliability. The measures evaluated were the functional reach, timed up and go, 10 m walk and a modified nine-hole peg tests. Participants also completed a disease-specific quality-of-life questionnaire. RESULTS: Inter-rater reliability and intra-rater reliability scores (intra-class coefficient) were similar for each outcome measure. Excellent rater agreement (intra-class coefficient, r ⩾ 0.9) was found for the functional reach, timed up and go and the 10 m walk tests. Rater agreement was good for the modified nine-hole peg test: intra-class coefficient r = 0.75 for intra-rater reliability and 0.76 for inter-rater reliability. The timed up and go and the 10 m walk tests correlated highly with perceived mobility challenges in the quality-of-life questionnaire. CONCLUSION: The functional reach, timed up and go and 10 m walk tests are potentially useful outcome measures for monitoring neurofibromatosis 1 treatment and will be assessed in multi-centre and longitudinal studies.

The effects of the selective muscarinic M3 receptor antagonist darifenacin, and of hyoscine (scopolamine), on motion sickness, skin conductance & cognitive function.

AIMS: The aim of this study was to compare the effects of the selective M3 muscarinic acetylcholine receptor antagonist darifenacin, oral hyoscine hydrobromide and placebo on motion sickness induced by cross-coupled stimulation. METHODS: The effects of darifenacin 10 mg or 20 mg, hyoscine hydrobromide 0.6 mg and placebo were assessed in a randomized, double-blind, four-way cross over trial of 16 healthy subjects. Motion sickness, skin conductance (a measure of sweating) and psychomotor cognitive function tests were investigated. RESULTS: Hyoscine hydrobromide produced significantly increased tolerance to motion versus placebo (P < 0.05 to P < 0.01). The motion protection effect of darifenacin (10 or 20 mg) was approximately one third that of hyoscine hydrobromide but was not significant versus placebo. Darifenacin and hyoscine hydrobromide both significantly reduced skin conductance versus placebo. Darifenacin produced either no effect or an enhanced effect on cognitive function in contrast to hyoscine hydrobromide, where there was significant impairment of psychomotor performance. CONCLUSION: The results suggest that selective antagonism of the M3 receptor may not be important in the prevention of motion sickness. However, selective M3 antagonism does not impair cognitive function. These observations may be important given that long-term treatment with non-selective anti-muscarinic agents such as oxybutynin may lead to an increased incidence of dementia.

Evaluation of quality of life in adults with neurofibromatosis 1 (NF1) using the Impact of NF1 on Quality Of Life (INF1-QOL) questionnaire.

BACKGROUND: Neurofibromatosis 1 (NF1) is an inherited, multi-system, tumour suppressor disorder with variable complications that cause psychological distress and social isolation. The study aim was to develop and validate a disease-specific questionnaire to measure quality of life (QOL) in NF1 that is suitable both as an assessment tool in clinical practice and in clinical trials of novel therapy. METHODS: The Impact of NF1 on Quality of Life (INF1-QOL) questionnaire was developed by a literature search for common terms, focus group (n = 6), semi-structured interviews (n = 21), initial drafts (n =50) and final 14 item questionnaire (n = 50). Bivariate correlations between items, exploratory factor analysis, correlations with severity and EuroQol were employed. RESULTS: INF1-QOL showed good internal reliability (Cronbach's alpha 0.87), mean total INF1-QOL score was 8.64 (SD 6.3), median 7.00, range 0-30 (possible range 0-42); no significant correlations with age or gender. The mean total EuroQol score was 7.38 (SD 2.87), median 6.5, mean global EuroQol score was 76.34 (SD 16.56), median 80. Total INF1-QOL score correlated with total EuroQol r = 0.82, p < 0.0001. The highest impact on QOL was moderate or severe problems with anxiety and depression (32%) and negative effects of NF1 on role and outlook on life (42%). The mean inter-relater reliability for grading of clinical severity scores was 0.71 (range 0.65-0.79), and intra-class correlation was 0.92. The mean clinical severity score was 1.95 (SD 0.65) correlating r = 0.34 with total INF1-QOL score p < 0.05 and correlated 0.37 with total EuroQol score p < 0.01. The clinical severity score was mild in 17 (34%), moderate in 16 (32%) and 17 (34%) individuals had severe disease. CONCLUSIONS: INF1-QOL is a validated, reliable disease specific questionnaire that is easy and quick to complete. Role and outlook on life and anxiety and depression have the highest impact on QOL indicating the variability, severity and unpredictability of NF1. INFI-QOL correlates moderately with clinical severity. The moderate relationship between INF1-QOL and physician rated severity emphasizes the difference between clinical and patient perception. INFI-QOL will be useful in individual patient assessment and as an outcome measure for clinical trials.

Prevalence, Predictors, and Prevention of Motion Sickness in Zero-G Parabolic Flights.

INTRODUCTION: Zero-G parabolic flight reproduces the weightlessness of space for short periods. However, motion sickness may affect some fliers. The aim was to assess the extent of this problem and to find possible predictors and modifying factors. METHODS: Airbus zero-G flights consist of 31 parabolas performed in blocks. Each parabola consisted of 20 s of 0 g sandwiched by 20 s of hypergravity of 1.5-1.8 g. The survey covered N = 246 person-flights (193 men, 53 women), ages (M ± SD) 36.0 ± 11.3 yr. An anonymous questionnaire included motion sickness rating (1 = OK to 6 = vomiting), Motion Sickness Susceptibility Questionnaire (MSSQ), antimotion sickness medication, prior zero-G experience, anxiety level, and other characteristics. RESULTS: Participants had lower MSSQ percentile scores (27.4 ± 28.0) than the population norm of 50. Motion sickness was experienced by 33% and 12% vomited. Less motion sickness was predicted by older age, greater prior zero-G flight experience, medication with scopolamine, lower MSSQ scores, but not gender or anxiety. Sickness ratings in fliers pretreated with scopolamine (1.81 ± 1.58) were lower than for nonmedicated fliers (2.93 ± 2.16), and incidence of vomiting in fliers using scopolamine treatment was reduced by half to a third. Possible confounding factors including age, sex, flight experience, and MSSQ could not account for this. CONCLUSION: Motion sickness affected one-third of zero-G fliers despite being intrinsically less motion sickness susceptible compared to the general population. Susceptible individuals probably try to avoid such a provocative environment. Risk factors for motion sickness included younger age and higher MSSQ scores. Protective factors included prior zero-G flight experience (habituation) and antimotion sickness medication.Golding JF, Paillard AC, Normand H, Besnard S, Denise P. Prevalence, predictors, and prevention of motion sickness in zero-G parabolic flights. Aerosp Med Hum Perform. 2017; 88(1):3-9.

Embodied perspective-taking indicated by selective disruption from aberrant self motion.

Spatial perspective-taking that involves imagined changes in one's spatial orientation is facilitated by vestibular stimulation inducing a congruent sensation of self-motion. We examined further the role of vestibular resources in perspective-taking by evaluating whether aberrant and conflicting vestibular stimulation impaired perspective-taking performance. Participants (N = 39) undertook either an "own body transformation" (OBT) task, requiring speeded spatial judgments made from the perspective of a schematic figure, or a control task requiring reconfiguration of spatial mappings from one's own visuo-spatial perspective. These tasks were performed both without and with vestibular stimulation by whole-body Coriolis motion, according to a repeated measures design, balanced for order. Vestibular stimulation was found to impair performance during the first minute post stimulus relative to the stationary condition. This disruption was task-specific, affecting only the OBT task and not the control task, and dissipated by the second minute post-stimulus. Our experiment thus demonstrates selective temporary impairment of perspective-taking from aberrant vestibular stimulation, implying that uncompromised vestibular resources are necessary for efficient perspective-taking. This finding provides evidence for an embodied mechanism for perspective-taking whereby vestibular input contributes to multisensory processing underlying bodily and social cognition. Ultimately, this knowledge may contribute to the design of interventions that help patients suffering sudden vertigo adapt to the cognitive difficulties caused by aberrant vestibular stimulation.

Meniere's, migraine, and motion sickness.

CONCLUSION: Elevated Motion Sickness Susceptibility (MSS) in Meniere?s disease (MD) is likely to be a consequence of the onset of MD and not migraine per se. OBJECTIVES: Pathologies of the vestibular system influence MSS. Bilateral vestibular deficits lower MSS, vestibular neuritis or benign paroxysmal positional vertigo have little overall effect, whereas vestibular migraine elevates MSS. However, less is known about MSS in MD, a condition in which many patients experience vestibular loss and migraine symptoms. METHODS: The authors conducted an online survey that posed diagnostic and disease questions before addressing frequency of headaches, migraines, visual display dizziness (VDD), syncope, social life, and work impact of dizziness (SWID4) and motion sickness susceptibility (MSSQ). The two groups were: diagnosed MD individuals with hearing loss (n = 751) and non-MD individuals in the control group (n = 400). RESULTS: The MD group showed significantly elevated MSS, more headache and migraine, increased VDD, higher SWID4 scores, and increased syncope. MSS was higher in MD than controls only after the development of MD, but not before, nor in childhood. Although elevated in MD compared with controls, MSS was lower than migraine patients from past data. Multivariate analysis revealed VDD, SWID4, and MSS in adulthood as the strongest predictors of MD, but not headache nor migraine.

Toxicity profile of bevacizumab in the UK Neurofibromatosis type 2 cohort.

Bevacizumab is considered an established part of the treatment strategies available for schwannomas in patients with Neurofibromatosis type 2 (NF2). In the UK, it is available through NHS National Specialized Commissioning to NF2 patients with a rapidly growing target schwannoma. Regrowth of the tumour on suspension of treatment is often observed resulting in prolonged periods of exposure to bevacizumab to control the disease. Hypertension and proteinuria are common events with bevacizumab use and there are concerns with regards to the long-term risks of prolonged treatment. Dosing, demographic and adverse event (CTCAE 4.03) data from the UK NF2 bevacizumab cohort are reviewed with particular consideration of renal and cardiovascular complications. Eighty patients (48 male:32 female), median age 24.5 years (range 11-66 years), were followed for a median of 32.7 months (range 12.0-60.2 months). The most common adverse events were fatigue, hypertension and infection. A total of 19/80 patients (24 %) had either a grade 2 or grade 3 hypertension event and 14/80 patients (17.5 %) had proteinuria. Of 36 patients followed for 36 months, 78 % were free from hypertension and 86 % were free of proteinuria. Logistic regression modeling identified age and induction dosing regime to be independent predictors of development of hypertension with dose of 7.5 mg/kg 3 weekly and age >30years having higher rates of hypertension. Proteinuria persisted in one of three patients after cessation of bevacizumab. One patient developed congestive heart failure and the details of this case are described. Further work is needed to determine optimal dosing regimes to limit toxicity without impacting on efficacy.

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 effectiveness 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 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 Ménière's disease. The choice between methylprednisolone and gentamicin should be made based on clinical knowledge and patient circumstances. FUNDING: Ménière's Society and National Institute for Health Research Imperial Biomedical Research Centre.