Loss of α-9 Nicotinic Acetylcholine Receptor Subunit Predominantly Results in Impaired Postural Stability Rather Than Gaze Stability

The functional role of the mammalian efferent vestibular system (EVS) is not fully understood. One proposal is that the mammalian EVS plays a role in the long-term calibration of central vestibular pathways, for example during development. Here to test this possibility, we studied vestibular function in mice lacking a functional α9 subunit of the nicotinic acetylcholine receptor (nAChR) gene family, which mediates efferent activation of the vestibular periphery. We focused on an α9 (−/−) model with a deletion in exons 1 and 2. First, we quantified gaze stability by testing vestibulo-ocular reflex (VOR, 0.2–3 Hz) responses of both α9 (−/−) mouse models in dark and light conditions. VOR gains and phases were comparable for both α9 (−/−) mutants and wild-type controls. Second, we confirmed the lack of an effect from the α9 (−/−) mutation on central visuo-motor pathways/eye movement pathways via analyses of the optokinetic reflex (OKR) and quick phases of the VOR. We found no differences between α9 (−/−) mutants and wild-type controls. Third and finally, we investigated postural abilities during instrumented rotarod and balance beam tasks. Head movements were quantified using a 6D microelectromechanical systems (MEMS) module fixed to the mouse’s head. Compared to wild-type controls, we found head movements were strikingly altered in α9 (−/−) mice, most notably in the pitch axis. We confirmed these later results in another α9 (−/−) model, with a deletion in the exon 4 region. Overall, we conclude that the absence of the α9 subunit of nAChRs predominately results in an impairment of posture rather than gaze.

Post-concussive Dizziness: A Review and Clinical Approach to the Patient

Dizziness is a frequent complaint after head trauma. Among patients who suffer a concussion (mild traumatic brain injury or mTBI), dizziness is second only to headache in symptom frequency. The differential diagnosis of post-concussive dizziness (PCD) can be divided into non-vestibular, central vestibular and peripheral vestibular causes with growing recognition that patients frequently exhibit both central and peripheral findings on vestibular testing. Symptoms that traditionally have been ascribed to central vestibular dysfunction may be due to peripheral dysfunction. Further, our ability to test peripheral vestibular function has improved and has allowed us to identify peripheral disorders that in the past would have remained unnoticed. The importance of the identification of the peripheral component in PCD lies in our ability to remedy the peripheral vestibular component to a much greater extent than the central component. Unfortunately, many patients are not adequately evaluated for vestibular disorders until long after the onset of their symptoms. Among the diagnoses seen as causes for PCD are (1) Central vestibular disorders, (2) Benign Paroxysmal Positional Vertigo (BPPV), (3) Labyrinthine dehiscence/perilymph fistula syndrome, (4) labyrinthine concussion, (5) secondary endolymphatic hydrops, (6) Temporal bone fracture, and (7) Malingering (particularly when litigation is pending). These diagnoses are not mutually exclusive and PCD patients frequently exhibit a combination of these disorders. A review of the literature and a general approach to the patient with post-concussive dizziness will be detailed as well as a review of the above-mentioned diagnostic categories.

Linking Vestibular Function and Subcortical Gray Matter Volume Changes in a Longitudinal Study of Aging Adults

Emerging evidence suggests a relationship between impairments of the vestibular (inner ear balance) system and alterations in the function and the structure of the central nervous system (CNS) in older adults. However, it is unclear whether age-related vestibular loss is associated with volume loss in brain regions known to receive vestibular input. To address this gap, we investigated the association between vestibular function and the volumes of four structures that process vestibular information (the hippocampus, entorhinal cortex, thalamus, and basal ganglia) in a longitudinal study of 97 healthy, older participants from the Baltimore Longitudinal Study of Aging. Vestibular testing included cervical vestibular-evoked myogenic potentials (cVEMP) to measure saccular function, ocular VEMP (oVEMP) to measure utricular function, and video head impulse tests to measure the horizontal semicircular canal vestibulo-ocular reflex (VOR). Participants in the sample had vestibular and brain MRI data for a total of one (18.6%), two (49.5%), and three (32.0%) visits. Linear mixed-effects regression was used to model regional volume over time as a function of vestibular physiological function, correcting for age, sex, intracranial volume, and intersubject random variation in the baseline levels and rates of change of volume over time. We found that poorer saccular function, characterized by lower cVEMP amplitude, is associated with reduced bilateral volumes of the basal ganglia and thalamus at each time point, demonstrated by a 0.0714 cm3 ± 0.0344 (unadjusted p = 0.038; 95% CI: 0.00397–0.139) lower bilateral-mean volume of the basal ganglia and a 0.0440 cm3 ± 0.0221 (unadjusted p = 0.046; 95% CI: 0.000727–0.0873) lower bilateral-mean volume of the thalamus for each 1-unit lower cVEMP amplitude. We also found a relationship between a lower mean VOR gain and lower left hippocampal volume (β = 0.121, unadjusted p = 0.018, 95% CI: 0.0212–0.222). There were no significant associations between volume and oVEMP. These findings provide insight into the specific brain structures that undergo atrophy in the context of age-related loss of peripheral vestibular function.

Subclinical Vestibular Deficits Illustrated in Patients With Exercise Intolerance After mTBI Using Force Plate Protocols

ObjectiveInvestigate the changes in sway velocity vestibular markers in mTBI patients with exercise intolerance (EI) during exertional testing as part of a 5-Step Exertional Rehab Protocol (ERP).BackgroundExertional testing can be used to determine one's therapeutic exercise threshold. A number of systems have been shown to be related to Exercise Intolerance (EI) including autonomic, cervical, and vestibular, and visual. Vestibular function can be measured before and after exercise and may shed light into its impact on EI.Design/MethodsRetrospective review of 342 trials of exertional testing in mTBI patients, ages 10–60, in 2020. Exertional testing was completed with pre/post force plate sway velocity calculated. Protocol A involved single leg stances, while protocol B involved 2 feet stances. A concussion specialist determined exercise tolerance (ET) by evaluating for the onset of signs/symptoms or cardiovagal dysautonomia.ResultsOf 342 exertional test trials, 34.8% exhibited EI due to symptom exacerbation and/or signs of autonomic dysfunction. Vestibular Force Plate sway velocities in both protocol A and B were significantly worsened in the EI group by an average change of 0.32 deg/sec, compared to those in the ET group who exhibited only an average change of 0.03 deg/sec sway velocity (p = 0.0004). The EI group using protocol A, showed an average change of 0.86 deg/sec compared to those in the ET group using protocol A, who exhibited only an average change of 0.03 deg/sec sway velocity (p = 0.0041). EI group using protocol B, showed an average change of 0.12 deg/sec sway velocity compared to those in the ET group using protocol B, who also exhibited an average change of 0.03 deg/sec (p = 0.0013).ConclusionsSubclinical vestibular markers such as sway velocity measures may be used to identify etiologies for EI in mTBI. Furthermore, these vestibular testing may be a subclinical measure that can aid exercise and sport clearance decisions.

The Effect of a Home Exercise Program on Visio-Vestibular Function in Concussed Pediatric Patients

ObjectiveTo explore if a home exercise program (HEP) affects visio-vestibular function in concussed pediatric patients.BackgroundA HEP can provide an equitable and cost-effective method for therapy targeted towards visio-vestibular deficits that are common following concussion. It is unclear if pediatric patients prescribed a HEP demonstrate improved visio-vestibular function.Design/MethodsThis observational study included 1,041 patients (59% female; age = 14.0 ± 2.5 years) reporting to a specialty care concussion center for an initial visit ≤28 days post-injury and follow-up ≤60 days post-injury. All patients completed a Visio-Vestibular Examination (VVE) at both timepoints consisting of 9 subtests: smooth pursuit, horizontal/vertical saccades and gaze stability, binocular convergence, left/right monocular accommodation, and complex tandem gait. Patients were prescribed a HEP (1–2 times/day) at initial visit consisting of exercises addressing visio-vestibular deficits. At follow-up, patients reported their progress: (1) has not done the HEP, (2) is currently doing the HEP, or (3) has completed the HEP. Primary outcomes included HEP progress, VVE subtests (normal/abnormal), and total VVE (abnormal = 2 + abnormal subtests). Chi-square tests with Bonferroni corrections were used to determine if abnormal VVE outcomes were associated with HEP status.ResultsAt initial visit, 81 2(77.6%) patients presented with abnormal total VVE. At follow-up, the proportion of abnormal total VVE did not differ among patients not doing the HEP (101 [62.0%]), patients currently doing the HEP (516 [69.0%]), and patients who had completed the HEP (51 [69.0%]). However among VVE subtests, a lower proportion who completed the HEP presented with abnormal smooth pursuit (7.5%), horizontal (3.8%) and vertical (3.8%) saccades, and complex tandem gait (0%) relative to patients currently doing the HEP (p = 0.003) and patients not doing the HEP (p = 0.01).ConclusionsOur findings indicate that patients who completed the HEP presented with improved elements of visio-vestibular function relative to those who did not start or were currently doing the HEP.

Enhanced Eye Velocity With Backup Saccades in vHIT Tests of a Menière Disease Patient: A Case Report

Reduced eye velocity and overt or covert compensatory saccades during horizontal head impulse testing are the signs of reduced vestibular function. However, here we report the unusual case of a patient who had enhanced eye velocity during horizontal head impulses followed by a corrective saccade. We term this saccade a “backup saccade” because it acts to compensate for the gaze position error caused by the enhanced velocity (and enhanced VOR gain) and acts to return gaze directly to the fixation target as shown by eye position records. We distinguish backup saccades from overt or covert compensatory saccades or the anticompensatory quick eye movement (ACQEM) of Heuberger et al. (1) ACQEMs are anticompensatory in that they are in the same direction as head velocity and so, act to take gaze off the target and thus require later compensatory (overt) saccades to return gaze to the target. Neither of these responses were found in this patient. The patient here was diagnosed with unilateral definite Meniere's disease (MD) on the right and had enhanced VOR (gain of 1.17) for rightward head impulses followed by backup saccades. For leftwards head impulses eye velocity and VOR gain were in the normal range (VOR gain of 0.89). As further confirmation, testing with 1.84 Hz horizontal sinusoidal head movements in the visual-vestibular (VVOR) paradigm also showed these backup saccades for rightwards head turns but normal slow phase eye velocity responses without backup saccades for leftwards had turns. This evidence shows that backup saccades can be observed in some MD patients who show enhanced eye velocity responses during vHIT and that these backup saccades act to correct for gaze position error caused by the enhanced eye velocity during the head impulse and so have a compensatory effect on gaze stabilization.