Bevacizumab in NF2-related vestibular schwannomas: a nationally coordinated approach to delivery and prospective evaluation

Background: NF2 patients develop multiple nervous system tumors including bilateral vestibular schwannomas (VS). The tumors and their surgical treatment are associated with deafness, neurological disability, and mortality. Medical treatment with bevacizumab has been reported to reduce VS growth and to improve hearing. In addition to evaluating these effects, this study also aimed to determine other important consequences of treatment including patient-reported quality of life and the impact of treatment on surgical VS rates. Methods: Patients treated with bevacizumab underwent serial prospective MRI, audiology, clinical, CTCAE-4.0 adverse events, and NFTI-QOL quality-of-life assessments. Tumor volumetrics were classified according to the REiNs criteria and annual VS surgical rates reviewed. Results: Sixty-one patients (59% male), median age 25 years (range, 10–57), were reviewed. Median follow-up was 23 months (range, 3–53). Partial volumetric tumor response (all tumors) was seen in 39% and 51% had stabilization of previously growing tumors. Age and pretreatment growth rate were predictors of response. Hearing was maintained or improved in 86% of assessable patients. Mean NFTI-QOL scores improved from 12.0 to 10.7 (P < .05). Hypertension was observed in 30% and proteinuria in 16%. Twelve treatment breaks occurred due to adverse events. The rates of VS surgery decreased after the introduction of bevacizumab. Conclusion: Treatment with bevacizumab in this large, UK-wide cohort decreased VS growth rates and improved hearing and quality of life. The potential risk of surgical iatrogenic damage was also reduced due to an associated reduction in VS surgical rates. Ongoing follow-up of this cohort will determine the long-term benefits and risks of bevacizumab treatment.

Visual Dependency and Dizziness after Vestibular Neuritis

Symptomatic recovery after acute vestibular neuritis (VN) is variable, with around 50% of patients reporting long term vestibular symptoms; hence, it is essential to identify factors related to poor clinical outcome. Here we investigated whether excessive reliance on visual input for spatial orientation (visual dependence) was associated with long term vestibular symptoms following acute VN. Twenty-eight patients with VN and 25 normal control subjects were included. Patients were enrolled at least 6 months after acute illness. Recovery status was not a criterion for study entry, allowing recruitment of patients with a full range of persistent symptoms. We measured visual dependence with a laptop-based Rod-and-Disk Test and severity of symptoms with the Dizziness Handicap Inventory (DHI). The third of patients showing the worst clinical outcomes (mean DHI score 36–80) had significantly greater visual dependence than normal subjects (6.35° error vs. 3.39° respectively, p = 0.03). Asymptomatic patients and those with minor residual symptoms did not differ from controls. Visual dependence was associated with high levels of persistent vestibular symptoms after acute VN. Over-reliance on visual information for spatial orientation is one characteristic of poorly recovered vestibular neuritis patients. The finding may be clinically useful given that visual dependence may be modified through rehabilitation desensitization techniques.

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.

Invited lectures from a spatial orientation symposium in honor of Frederick Guedry, Day 2

This report contains the invited lectures from day 2 of a Spatial Orientation Symposium in honor of the late Dr. Frederick Guedry, held at the Institute of Human and Machine Cognition (IHMC) in Pensacola, Florida in November of 2010. The conference was sponsored by the Coalition Warfare Program of the Office of the Under Secretary of Defense for Acquisition, Technology, and Logistics. It was organized by Drs. Angus Rupert and Ben Lawson (USAARL) and hosted by Drs. Anil Raj and Ken Ford (IHMC). The lectures from day 1 are in Lawson et al., 2014. Day 2 includes lectures by Drs. Scott, Ben Lawson, Angus Rupert, Owen Black, Karen Atkins, Kim Gottshall, Anil Raj, and Måns Magnusson. The lectures focus on the structure, function and reflexes of the vestibular system, orientation perceptions, motion sickness, adaptation, and rehabilitation. This report also features banquet talks given by Drs. Lawson and Rupert, in which they honor Dr. Fred Guedry. Also featured is an interview with Dr. Guedry, conducted by a Navy historian, in which the reader can catch a glimpse into Dr. Guedry's wartime experiences and early days as a researcher.

Motion Sickness

Over 2000 years ago the Greek physician Hippocrates wrote, “sailing on the sea proves that motion disorders the body.” Indeed, the word “nausea” derives from the Greek root word naus, hence “nautical,” meaning a ship. The primary signs and symptoms of motion sickness are nausea and vomiting. Motion sickness can be provoked by a wide variety of transport environments, including land, sea, air, and space. The recent introduction of new visual technologies may expose more of the population to visually induced motion sickness. This chapter describes the signs and symptoms of motion sickness and different types of provocative stimuli. The “how” of motion sickness (i.e., the mechanism) is generally accepted to involve sensory conflict, for which the evidence is reviewed. New observations concern the identification of putative “sensory conflict” neurons and the underlying brain mechanisms. But what reason or purpose does motion sickness serve, if any? This is the “why” of motion sickness, which is analyzed from both evolutionary and nonfunctional maladaptive theoretic perspectives. Individual differences in susceptibility are great in the normal population and predictors are reviewed. Motion sickness susceptibility also varies dramatically between special groups of patients, including those with different types of vestibular disease and in migraineurs. Finally, the efficacy and relative advantages and disadvantages of various behavioral and pharmacologic countermeasures are evaluated.

Meniere’s, Migraine & Motion Sickness

CONCLUSION Elevated MSS in MD is likely to be a consequence of the onset of MD and not migraine per se. OBJECTIVES Pathologies of the vestibular system influence motion sickness susceptibility (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 Meniere’s disease (MD), a condition in which many patients experience vestibular loss and migraine symptoms. METHODS We 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.