2 Clinical Trials for Various Conditions
Bilateral vestibular hypofunction affects more than 64,000 adults in the US and leads to a substantial decline in quality of life. Bilateral vestibular hypofunction (BVH) is a condition characterized by a bilateral impairment of vestibular sensory function2. BVH often occurs without a known cause but can result from a viral infection, exposure to ototoxic drugs, vestibulo-cochlear nerve tumors, Meningitis, or Meniere's disease2. The results of a nationally representative survey estimate that between 64,000 and 193,000 adults in the US (28 to 85 per 100,000) are affected2. However, due to a lack of standardized vestibular screenings in older adult populations, the true prevalence of BVH is likely underestimated. Aging is also capable of producing a bilateral reduction in vestibular function, yielding a sub-type of BVH labeled as "Presbyvestibulopathy". In fact, more than 50% of adults over the age of 65 show evidence of vestibular impairment3 and recent data suggest that age-related vestibular declines may begin as early as age 403. The symptoms of BVH - oscillopsia (bouncing vision whilst the head is moved), imbalance, gait instability, and dizziness - manifest secondary to an insensitivity of the vestibular system to self-motion cues (i.e., rotation, translation, or tilting of the head). Relative to unilateral vestibular lesions, the symptoms of BVH lead to greater perceived disability and a worsened health-related quality of life4; the economic burden of BVH has been estimated to be $13,019 per patient, nearly 4-times the burden of unilateral vestibular disease4. Adding to the economic and health-related burden is the substantial increase in fall risk; Ward, et al. (2015) showed that patients with BVH display an age-adjusted fall risk that is 9.9x higher than patients without a diagnosis of BVH but who report imbalance/dizziness, and 31x higher than the asymptomatic general population2; Sun, et al. (2015) reported that patients with BVH experience an average of 19 falls per year and Herdman and colleagues showed that over half of patients with BVH aged 65-74 reported a history of falls5. Given the substantial burden of BVH, the identification of new approaches for improving the functional status of these individuals is critically important. To meet this need, we propose to investigate the use of subthreshold vestibular stimulation as a novel strategy for improving vestibular function in patients with bilateral vestibular dysfunction. The nervous system responds to changes in external or internal conditions by altering the behavior of neurons through multiple forms of neural plasticity. A specific form of plasticity, "homeostatic plasticity", stabilizes neural activity by driving the excitability of neurons toward a "set-point" level of activity6. Over the last six years, new data have come to light showing that the vestibular system also possess a robust capacity to modulate sensitivity to self-motion cues in response to prolonged periods of motion. Dietrich and Straka showed direct evidence of a bidirectional modulation of neuronal firing rates in the oculomotor neurons of Xenopus laevis (i.e., via the lateral canal driven aVOR) following subthreshold and suprathreshold yaw rotations7. In a sample of healthy adults, Fitzpatrick and Watson (2015) showed a 248% decrease in perceptual sensitivity and a 50% decrease in the sensitivity of the descending vestibular pathways (elicited by galvanic vestibular stimulation) following a single ten-minute period of large amplitude (suprathreshold) rotations8. Recently, Keywan and colleagues found that the sensitivity to interaural (IA) translation cues was increased 28.8% immediately following a 20-minute block of low-amplitude (subthreshold) translations9; a follow up study using the same subthreshold IA translation stimulus yielded an average improvement in sensitivity (i.e., reduction in self-motion perceptual thresholds) of 39%10. Collectively, these results demonstrate a capacity to use motion perturbations (i.e., low, or high levels of vestibular stimulation) to dynamically adjust the sensitivity of the vestibular system on both the single neuron and behavioral levels. The ability to use subthreshold motion stimuli to drive plasticity in the vestibular system motivates this study. We aim to determine if the delivery of a subthreshold motion stimulus before balance training leads to greater improvements in postural control for individuals with bilateral vestibular hypofunction.
Although cochlear implants can restore hearing to individuals who have lost cochlear hair cell function, there is no widely available, adequately effective treatment for individuals suffering chronic imbalance, postural instability and unsteady vision due to bilateral vestibular hypofunction. Prior research has demonstrated that electrical stimulation of the vestibular nerve via a chronically implanted multichannel vestibular implant can partially restore vestibular reflexes that normally maintain steady posture and vision; improve performance on objective measures of postural stability and gait; and improve patient-reported disability and health-related quality of life. This single-arm open-label study extends that research to evaluate outcomes for up to fifteen older adults (age 65-90 years at time of enrollment) with ototoxic or non-ototoxic bilateral vestibular hypofunction.