Hair cell specific NTPDase6 immunolocalisation in vestibular end organs: Potential role of purinergic signaling in vestibular sensory transductionO'Keeffe, Mary G.; Thorne, Peter R.; Housley, Gary D.; Robson, Simon C.; Vlajkovic, Srdjan M.
doi: 10.3233/ves-2012-00461pmid: 23302703
A complex extracellular nucleotide signalling system acting on P2 receptors is involved in regulation of cochlear function in the mammalian inner ear. Ectonucleoside triphosphate diphosphohydrolases (E-NTPDases) are ectonucleotidases that regulate P2 receptor signalling pathways in mammalian tissues by hydrolysing extracellular nucleotides to the respective nucleosides. All enzymes from the CD39/ENTPD family (NTPDase1-8) are expressed in the adult rat cochlea, but their expression and distribution in the vestibular end organ is unknown. This report demonstrates selective expression of NTPDase6 by rat vestibular hair cells. Hair cells transducing both angular acceleration (crista ampullaris) and static head position (maculae of the utricle and saccule) exhibited strong immunolabelling with a bias towards the sensory pole and in particular, the hair cell bundle. NTPDase6 is an intracellular enzyme that can be released in a soluble form from cell cultures and shows an enzymatic preference for nucleoside 5'-diphosphates, such as guanosine 5'-diphosphate (GDP) and uridine 5'-diphosphate (UDP). The main function of NTPDase6 may be the regulation of nucleotide levels in cellular organelles by regulating the conversion of nucleotides to nucleosides. NTPDase6 immunolocalisation in the vestibular end organ could be linked to the regulation of P2 receptor signalling and sensory transduction, including maintenance of vestibular hair bundles.
The ataxic mouse as a model for studying downbeat nystagmusStahl, John S.; Thumser, Zachary C.; Oommen, Brian S.
doi: 10.3233/ves-120463pmid: 23302704
Downbeat nystagmus (DBN) is a common eye movement complication of cerebellar disease. Use of mice to study pathophysiology of vestibulocerebellar disease is increasing, but it is unclear if mice can be used to study DBN; it has not been reported in this species. We determined whether DBN occurs in the ataxic mutant tottering, which carries a mutation in the Cacna1a gene for P/Q calcium channels. Spontaneous DBN occurred only rarely, and its magnitude did not exhibit the relationship to head tilt seen in human patients. DBN during yaw rotation was more common and shares some properties with the tilt-independent, gaze-independent component of human DBN, but differs in its dependence on vision. Hyperactivity of otolith circuits responding to pitch tilts is hypothesized to contribute to the gaze-independent component of human DBN. Mutants exhibited hyperactivity of the tilt maculo-ocular reflex (tiltMOR) in pitch. The hyperactivity may serve as a surrogate for DBN in mouse studies. TiltMOR hyperactivity correlates with hyperdeviation of the eyes and upward deviation of the head during ambulation; these may be alternative surrogates. Muscimol inactivation of the cerebellar flocculus suggests a floccular role in the tiltMOR hyperactivity and provides insight into the rarity of frank DBN in ataxic mice.
Visual-vestibular stimulation influences spatial and non-spatial cognitive processingFurman, Joseph M.; Redfern, Mark S.; Fuhrman, Susan I.; Jennings, J. Richard
doi: 10.3233/ves-2012-00460pmid: 23302706
This study investigated the impact of visual-vestibular stimulation on performance of an auditory information processing task in young and older adults. Performance on a spatial choice reaction time task was compared to performance on a non-spatial choice reaction time task. The tasks were performed during simultaneous rotational and moving visual stimulation. The non-spatial task was an auditory frequency discrimination task while the spatial task was a right-left lateralization task. Visual and vestibular conditions consisted of a non-movement baseline, sinusoidal earth-vertical axis rotation (EVAR) in darkness, off-vertical axis rotation (OVAR) in darkness at a constant velocity, OVAR in darkness with a sinusoidal profile, EVAR with a lighted visual surround, constant velocity optokinetic stimulation, and sinusoidal optokinetic stimulation. Baseline reaction times were subtracted from reaction times during each stimulus condition to yield “task cost”, which was analyzed statistically. Subjects were healthy young (n=20; 24 ± 2.7 yrs; 10F) and older (n=29; 73 ± 6.0 yrs; 18F) adults. Results indicated that task cost was affected by the visual-vestibular condition and a task x condition interaction. There was no main effect of task or age group and no significant interaction with age. Otolithic stimulation and visual stimulation were associated with greater task cost compared to semicircular canal stimulation. Combining semicircular canal with otolithic or visual stimulation had no additional effect beyond otolithic or visual stimulation alone. This pattern of task cost being larger for otolith or visual vs. semicircular canal stimulation was found for both the spatial and non-spatial tasks. The significant interaction between condition and task type revealed that the task cost for the spatial task was larger than the task cost for the non-spatial task during visual conditions but not during non-visual conditions although the visual and non-visual conditions were not entirely comparable. This study suggests that interference of vestibular stimulation with cognitive processing is especially prominent for otolithic and visual stimulation although the strength of the various visual-vestibular stimuli may not have been uniform. Also, spatial tasks are more affected than non-spatial tasks during visual stimulation and interference between vestibular stimulation and cognitive processing is not age dependent for these relatively easy tasks.
International Classification of Functioning, Disability and Health (ICF) Core Set for patients with vertigo, dizziness and balance disorders1Grill, Eva; Bronstein, Adolfo; Furman, Joseph; Zee, David S.; Müller, Martin
doi: 10.3233/ves-120459pmid: 23302707
Vertigo, dizziness and balance disorders have major impact on independence, employability, activities and participation. There are many measures for the assessment of the impact of vertigo, but no consensus exists on which aspects should be measured. The objective of this study was to develop international standards (ICF Core Sets) for patients with vertigo and dizziness to describe functioning. The development of the ICF Core Sets involved a formal decision-making and consensus process, integrating evidence from preparatory studies including qualitative interviews with patients, a systematic review of the literature, a survey with health professionals, and empirical data collection from patients. Twenty-seven experts selected 100 second level categories for the comprehensive Core Set and 29 second level categories for the Brief Core Set. The largest number of categories was selected from the ICF component Activities and Participation (40). Twenty-five categories were selected from the component Body Functions, six from Body Structures, and 29 from Environmental Factors. The ICF Core Set for vertigo is designed for physicians, nurses, therapists and other health professionals working in inpatient or ambulatory settings. ICF Core Sets create patient-relevant outcomes that can be used as evidence for the success of treatments.
The effect of virtual reality on visual vertigo symptoms in patients with peripheral vestibular dysfunction: A pilot studyPavlou, M.; Kanegaonkar, R.G.; Swapp, D.; Bamiou, D.E.; Slater, M.; Luxon, L.M.
doi: 10.3233/ves-120462pmid: 23302708
Individuals with vestibular dysfunction may experience visual vertigo (VV), in which symptoms are provoked or exacerbated by excessive or disorientating visual stimuli (e.g. supermarkets). VV can significantly improve when customized vestibular rehabilitation exercises are combined with exposure to optokinetic stimuli. Virtual reality (VR), which immerses patients in realistic, visually challenging environments, has also been suggested as an adjunct to VR to improve VV symptoms. This pilot study compared the responses of sixteen patients with unilateral peripheral vestibular disorder randomly allocated to a VR regime incorporating exposure to a static (Group S) or dynamic (Group D) VR environment. Participants practiced vestibular exercises, twice weekly for four weeks, inside a static (Group S) or dynamic (Group D) virtual crowded square environment, presented in an immersive projection theatre (IPT), and received a vestibular exercise program to practice on days not attending clinic. A third Group D1 completed both the static and dynamic VR training. Treatment response was assessed with the Dynamic Gait Index and questionnaires concerning symptom triggers and psychological state. At final assessment, significant between-group differences were noted between Groups D (p=0.001) and D1 (p=0.03) compared to Group S for VV symptoms with the former two showing a significant 59.2% and 25.8% improvement respectively compared to 1.6% for the latter. Depression scores improved only for Group S (p=0.01) while a trend towards significance was noted for Group D regarding anxiety scores (p=0.07). Conclusion: Exposure to dynamic VR environments should be considered as a useful adjunct to vestibular rehabilitation programs for patients with peripheral vestibular disorders and VV symptoms.
The effect of vestibular rehabilitation on adults with bilateral vestibular hypofunction: A systematic reviewPorciuncula, Franchino; Johnson, Connie C.; Glickman, Leslie B.
doi: 10.3233/ves-120464pmid: 23302709
Purpose:Adults with bilateral vestibular hypofunction (BVH) experience significant disability. A systematic review assessed evidence for vestibular rehabilitation (VR). Number of studies:14 studies. Materials/methods:Search identification of studies based on inclusion criteria: (a) population: adults with BVH of peripheral origin; (b) interventions: vestibular exercises, balance training, education, or sensory prosthetics; (c) comparison: single interventions or compared to another psychophysical intervention, placebo, or healthy population; (d) outcomes: based on International Classification of Functioning, Disability and Health (ICF) Body Functions and Structure, Activity, and Participation; (e) study designs: prospective and interventional, Levels of Evidence I to III per Centre of Evidence-based Medicine grading. Coding and appraisal based on ICF framework and strength of evidence synthesis. Results:Five Level II studies and nine Level III studies: All had outcomes on gaze and postural stability, five with outcomes on gait speed and perceptions of oscillopsia and disequilibrium.Conclusions:(a) Moderate evidence strength on improved gaze and postural stability (ICF-Body Functions) following exercise-based VR; (b) Inadequate number of studies supporting benefit of VR on ICF-Participation outcomes; (c) Sensory prosthetics in early phase of development. Clinical relevance:Moderate evidence strength in support of VR from an impairment level; clinical practice and research needed to explore interventions extending to ICF-Activity and Participation.