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.

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.

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.

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.

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.

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.

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.

Pathophysiology and treatment of motion sickness.

PURPOSE OF REVIEW: Motion sickness remains bothersome in conventional transport and is an emerging hazard in visual information technologies. Treatment remains unsatisfactory but advances in brain imaging, neurophysiology, and neuropharmacology may provide insights into more effective drug and behavioural management. We review these major developments. RECENT FINDINGS: Recent progress has been in identifying brain mechanisms and loci associated with motion sickness and nausea per se. The techniques have included conventional neurophysiology, pathway mapping, and functional MRI, implicating multiple brain regions including cortex, brainstem, and cerebellum. Understanding of the environmental and behavioural conditions provocative of and protective against motion sickness and how vestibular disease may sensitize to motion sickness has increased. The problem of nauseogenic information technology has emerged as a target for research, motivated by its ubiquitous applications. Increased understanding of the neurophysiology and brain regions associated with motion sickness may provide for more effective medication in the future. However, the polysymptomatic nature of motion sickness, high interindividual variability, and the extensive brain regions involved may preclude a single, decisive treatment. SUMMARY: Motion sickness is an emerging hazard in information technologies. Adaptation remains the most effective countermeasure together with established medications, notably scopolamine and antihistamines. Neuropharmacological investigations may provide more effective medication in the foreseeable future.

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.

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.

Sleep disturbance as part of the neurofibromatosis type 1 phenotype in adults.

Neurofibromatosis type 1 (NF1) is an autosomal dominant condition with a wide array of neurological complications, including cognitive dysfunction, tumors, malformations, neuropathy, neurovascular disease, and epilepsy. Many of these complications may impact on sleep quality and cause sleep disturbance. Previously sleep disturbance in NF1 has been specifically addressed solely in children. We performed a prospective study of sleep quality in 114 consecutive out-patients with NF1 attending our national neurofibromatosis service. The Epworth sleepiness scale (ESS) and the Pittsburgh sleep quality index (PSQI) were administered, and information was obtained from patient records on drugs potentially impacting on sleep, complications directly affecting sleep and employment status. The mean ESS was 6.8, and 21% had an abnormally high ESS of 10 or more. The mean global PSQI score was 8.4 (norm mean 2.67), with abnormally high scores in all sleep domains. Thirty-nine patients had a bed partner and 54% reported features suggestive of periodic limb movements of sleep, 43% had features suggestive of obstructive sleep apnoea, and 10.8% experienced confusion on waking. There was no evidence of phase shift. The ESS did not correlate with the PSQI, but unemployment status was associated with worse global PSQI score and multiple domain sub-scales of sleep quality in the PSQI. We conclude that sleep disturbance and poor sleep quality are significantly more frequent in the adult NF1 patient population. It is likely to be multi-factorial, related to pain, anxiety, depression, cognitive issues, and organic sleep pathology. We recommend careful assessment of patients to determine underlying triggers and possible treatment strategies.

Vertigo and dizziness from environmental motion: visual vertigo, motion sickness, and drivers' disorientation.

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, nonvestibular sensory stimuli. In both cases, the sequelae may be vertigo, incoordination, imbalance, and unpleasant autonomic responses. Common environmental motion conditions include visual vertigo, motion sickness, and motorists' disorientation. The core therapy for visual vertigo, motion sickness, and drivers' disorientation is progressive desensitization within a cognitive framework of reassurance and explanation, plus anxiolytic tactics and autogenic control of autonomic symptoms.

Cognitive cues and visually induced motion sickness.

BACKGROUND: The importance of cognitive processing of orientation cues in visually induced motion sickness and vection is often overlooked. Upright versus inverted visual scenes containing cues of different levels of salience were compared. METHODS: Panoramic scenes of 360 degrees were projected in the visual equivalent to the nauseogenic situation of rotating about an axis tilted from the vertical with a field of view of 84 degrees rotating at 0.2 Hz (72 degrees x s(-1)). Exposures were for 10 min or until moderate nausea developed. The design was counterbalanced repeated measures. Pilot Study: Subjects (N = 12) viewed visual conditions: a distant bland coastline scene as from an aircraft, tilted 30 degrees (Up); the same scene but inverted (Invert); and the scene morphed with no obvious orientation cues (Abstract). Main Experiment: Subjects (N = 22) viewed a city street scene containing numerous unambiguous and strong verticality cues under two conditions: upright (Up) and inverted (Invert), with 18 degrees tilt of rotational axis. RESULTS: Pilot Study: there were no significant differences between conditions in time (mean +/- SD min) to nausea endpoint (Up: 7.4 +/- 3.1; Invert: 7.1 +/- 3.1;Abstract: 7.8 +/- 2.4), nor for total symptom scores, nor for vection. Main Experiment: the upright scene was significantly more nauseogenic than the inverted, with shorter times to nausea endpoint (Up: 8.7 +/- 2.3; Invert: 9.2 +/- 2.2) and greater total symptom scores. Vection was marginally greater for Up than Invert. CONCLUSIONS: Salient and unambiguous higher order cognitive cues may modulate the development of motion sickness induced by optokinetic stimuli. There was no one-to-one correspondence between vection and motion sickness.

Neurofibromatosis 2: a novel risk factor for hypertension?

There are anecdotal reports of neurofibromatosis 2 (NF2) patients and vascular disease, but no previous studies have compared blood pressure (BP) in people with NF2 and in the general population. This study is the first to show that BP is significantly higher in patients with NF2 than in matched control patients. This is important for the management of patients with NF2, and in the differential diagnosis of secondary hypertension.

Respiratory vulnerability to vehicle buffeting.

OBJECTIVE: Buffeting in a jerky ride in a bus or ambulance normally provokes a sustained tachypnoea driven by vibration and sensory mechanisms including vestibular signals. Tachypnoea reinforces the torso against mechanical shocks but results in overbreathing, causing a mild fall in CO(2). However, normal CO(2) is rapidly restored by a reduction in depth of breathing. We test the hypothesis that vulnerable subjects, exemplified by elderly individuals and patients with vestibular disorders, may fail to adapt to buffeting. METHODS: Respiratory and cardiovascular functions were recorded from five elderly subjects, two patients with bilateral loss of vestibular function and five patients with 'BPPV,' while being exposed to 15-min buffeting in a flight simulator which simulated transport in an ambulance over rough pavement. Results were compared with published norms. RESULTS: Some subjects sustained overbreathing during motion, through either tachypnoea or deep breathing, causing a marked reduction in CO(2) levels (3/5, 2/2 avestibular, 4/5 elderly, 4/5 BPPV). Others failed to raise breathing frequency which would render them susceptible to mechanical shock (4/5 elderly, 1/2 avestibular). Overbreathing was particularly evident in three anxious subjects. INTERPRETATION: Overbreathing during buffeting could be caused by (1) resetting of CO(2) rest levels lower; (2) change in receptor sensitivity; (3) adjustment of central drive to breathing; and (4) stiffening of posture because of motion discomfort reduced the ability to modulate breathing. The buffeting experienced was moderately violent. More profound hypocapnia and mechanical shock are likely to result in vulnerable individuals failing to adapt to severe buffeting in transport on unpaved roads, in war zones or by sea ambulance.

Off vertical axis rotation motion sickness and field dependence.

BACKGROUND: Our study probed the relationship between field dependence and the development of nausea in light and dark during whole-body, off vertical axis rotation (OVAR). METHODS: There were 24 subjects who underwent OVAR at 0.2 Hz, 18 degree tilt. Exposures were undertaken in both light and darkness in sessions spaced 5 d apart in balanced order design. During rotation, nausea was rated at 1-min intervals to a cut off at 20 min or a level of 'moderate nausea' was attained, at which point motion stopped. Before and after OVAR sessions field dependence was rated with the rod and frame test (RFT) with head upright or tilted 28 degree to induce a head-centric bias. RESULTS: Subjects tolerated OVAR longer in the light (mean 13.3 min +/- 6.8 SD) than in darkness (11.1 min +/- 7.2). Motion sickness susceptibility evaluated by questionnaire was inversely correlated with tolerance of OVAR in the light. There was a tendency for subjects who were visual field dependent to fare better with OVAR in the light than in darkness. Subjects whose RFT estimates with head tilted tended to incline the visual vertical to the direction of head tilt better tolerated OVAR in darkness. DISCUSSION: The results suggest that susceptibility, as evaluated by questionnaires probing motion sickness experiences in daily life, is influenced by visual factors. Assessments of sensitivity to reference frames for orientation, either visual or ego-centered, show promise for markers of motion sickness susceptibility according to the visual surround rather than to absolute levels of susceptibility to motion sickness.