Charles C. Della Santina

Disorders of Balance and Vestibular Function in US Adults: Data From the National Health and Nutrition Examination Survey, 2001-2004

BACKGROUND Balance dysfunction can be debilitating and can lead to catastrophic outcomes such as falls. The inner ear vestibular system is an important contributor to balance control. However, to our knowledge, the prevalence of vestibular dysfunction in the United States and the magnitude of the increased risk of falling associated with vestibular dysfunction have never been estimated. The objective of this study was to determine the prevalence of vestibular dysfunction among US adults, evaluate differences by sociodemographic characteristics, and estimate the association between vestibular dysfunction and risk of falls. METHODS We included data from the 2001-2004 National Health and Nutrition Examination Surveys, which were cross-sectional surveys of US adults aged 40 years and older (n = 5086). The main outcome measure was vestibular function as measured by the modified Romberg Test of Standing Balance on Firm and Compliant Support Surfaces. RESULTS From 2001 through 2004, 35.4% of US adults aged 40 years and older (69 million Americans) had vestibular dysfunction. Odds of vestibular dysfunction increased significantly with age, were 40.3% lower in individuals with more than a high school education, and were 70.0% higher among people with diabetes mellitus. Participants with vestibular dysfunction who were clinically symptomatic (ie, reported dizziness) had a 12-fold increase in the odds of falling. CONCLUSIONS Vestibular dysfunction, as measured by a simple postural metric, is common among US adults. Vestibular dysfunction significantly increases the likelihood of falls, which are among the most morbid and costly health conditions affecting older individuals. These data suggest the importance of diagnosing, treating, and potentially screening for vestibular deficits to reduce the burden of fall-related injuries and deaths in the United States.

Mechanotransduction in mouse inner ear hair cells requires transmembrane channel–like genes

Inner ear hair cells convert the mechanical stimuli of sound, gravity, and head movement into electrical signals. This mechanotransduction process is initiated by opening of cation channels near the tips of hair cell stereocilia. Since the identity of these ion channels is unknown, and mutations in the gene encoding transmembrane channel-like 1 (TMC1) cause hearing loss without vestibular dysfunction in both mice and humans, we investigated the contribution of Tmc1 and the closely related Tmc2 to mechanotransduction in mice. We found that Tmc1 and Tmc2 were expressed in mouse vestibular and cochlear hair cells and that GFP-tagged TMC proteins localized near stereocilia tips. Tmc2 expression was transient in early postnatal mouse cochlear hair cells but persisted in vestibular hair cells. While mice with a targeted deletion of Tmc1 (Tmc1(Δ) mice) were deaf and those with a deletion of Tmc2 (Tmc2(Δ) mice) were phenotypically normal, Tmc1(Δ)Tmc2(Δ) mice had profound vestibular dysfunction, deafness, and structurally normal hair cells that lacked all mechanotransduction activity. Expression of either exogenous TMC1 or TMC2 rescued mechanotransduction in Tmc1(Δ)Tmc2(Δ) mutant hair cells. Our results indicate that TMC1 and TMC2 are necessary for hair cell mechanotransduction and may be integral components of the mechanotransduction complex. Our data also suggest that persistent TMC2 expression in vestibular hair cells may preserve vestibular function in humans with hearing loss caused by TMC1 mutations.

Symptoms and signs in superior canal dehiscence syndrome.

Abstract: Patients with superior canal dehiscence (SCD) syndrome experience vertigo and oscillopsia in response to loud sounds and to stimuli that result in changes in middle ear or intracranial pressure. They may also experience hyperacusis to bone‐conducted sounds. The evoked eye movements in this syndrome align with the plane of the dehiscent superior canal. The symptoms and signs can be understood in terms of the effect of the dehiscence in creation of a third mobile window into the inner ear. The SCD syndrome has been diagnosed in 28 patients who were examined in the neuro‐otology clinics at the Johns Hopkins Medical Institutions from May 1995 through January 2001. The diagnosis is best established based upon the symptoms that are characteristic for the syndrome, the vertical‐torsional eye movements evoked by sound or pressure stimuli noted on examination performed with Frenzel goggles, the lowered thresholds for responses to vestibular‐evoked myogenic potentials, and CT imaging of the temporal bones.

MRI Magnetic Field Stimulates Rotational Sensors of the Brain

Vertigo in and around magnetic resonance imaging (MRI) machines has been noted for years [1, 2]. Several mechanisms have been suggested to explain these sensations [3, 4], yet without direct, objective measures, the cause is unknown. We found that all of our healthy human subjects developed a robust nystagmus while simply lying in the static magnetic field of an MRI machine. Patients lacking labyrinthine function did not. We use the pattern of eye movements as a measure of vestibular stimulation to show that the stimulation is static (continuous, proportional to static magnetic field strength, requiring neither head movement nor dynamic change in magnetic field strength) and directional (sensitive to magnetic field polarity and head orientation). Our calculations and geometric model suggest that magnetic vestibular stimulation (MVS) derives from a Lorentz force resulting from interaction between the magnetic field and naturally occurring ionic currents in the labyrinthine endolymph fluid. This force pushes on the semicircular canal cupula, leading to nystagmus. We emphasize that the unique, dual role of endolymph in the delivery of both ionic current and fluid pressure, coupled with the cupulas function as a pressure sensor, makes magnetic-field-induced nystagmus and vertigo possible. Such effects could confound functional MRI studies of brain behavior, including resting-state brain activity.

Changes in the three-dimensional angular vestibulo-ocular reflex following intratympanic gentamicin for Ménière's disease

The 3-dimensional angular vestibulo-ocular reflexes (AVOR) elicited by rapid rotary head thrusts were studied in 17 subjects with unilateral Ménières disease before and 2–10 weeks after treatment with intratympanic gentamicin and in 13 subjects after surgical unilateral vestibular destruction (SUVD). Each head thrust was in the horizontal plane or in either diagonal plane of the vertical semicircular canals, so that each head thrust effectively stimulated only one pair of canals. The AVOR gains (eye velocity/head velocity during the 30 ms before peak head velocity) for the head thrusts exciting each individual canal were averaged and taken as a measure of the function of that canal. Prior to intratympanic gentamicin, gains for head thrusts that excited canals on the affected side were 0.91 ± 0.20 (horizontal canal, HC), 0.78 ± 0.20 (anterior canal, AC), and 0.83 ± 0.10 (posterior canal, PC). The asymmetries between these gain values and those for head thrusts that excited the contralateral canals were <2%. In contrast, caloric asymmetries averaged 40% ± 32%. Intratympanic gentamicin resulted in decreased gains attributable to each canal on the treated side: 0.40 ± 0.12 (HC), 0.35 ± 0.14 (AC), 0.31 ± 0.14 (PC) (p <0.01). However, the gains attributable to contralateral canals dropped only slightly, resulting in marked asymmetries between gains for excitation of ipsilateral canals versus their contralateral mates: HC: 34% ± 12%, AC: 24% ± 25%, and PC: 42% ± 13%. There was no difference in the AVOR gain for excitation of the ipsilateral HC after gentamicin in patients who received a single intratympanic injection (0.39 ± 0.11, n = 12) in comparison to those who received 2–3 injections (0.42 ± 0.15, n = 5, p = 0.7). Gain decreases attributed to the gentamicin-treated HC and AC were not as severe as those observed after SUVD. This finding suggests that intratympanic gentamicin causes a partial vestibular lesion that may involve preservation of spontaneous discharge and/or rotational sensitivity of afferents.

Diabetes, vestibular dysfunction, and falls: analyses from the National Health and Nutrition Examination Survey.

Objective: Patients with diabetes are at increased risk both for falls and for vestibular dysfunction, a known risk factor for falls. Our aims were 1) to further characterize the vestibular dysfunction present in patients with diabetes and 2) to evaluate for an independent effect of vestibular dysfunction on fall risk among patients with diabetes. Study Design: National cross-sectional survey. Setting: Ambulatory examination centers. Patients: Adults from the United States aged 40 years and older who participated in the 2001-2004 National Health and Nutrition Examination Survey (n = 5,86). Interventions: Diagnosis of diabetes, peripheral neuropathy, and retinopathy. Main Outcome Measures: Vestibular function measured by the modified Romberg Test of Standing Balance on Firm and Compliant Support Surfaces and history of falling in the previous 12 months. Results: We observed a higher prevalence of vestibular dysfunction in patients with diabetes with longer duration of disease, greater serum hemoglobin A1c levels and other diabetes-related complications, suggestive of a dose-response relationship between diabetes mellitus severity and vestibular dysfunction. We also noted that vestibular dysfunction independently increased the odds of falling more than 2-fold among patients with diabetes (odds ratio, 2.3; 95% confidence interval, 1.1-5.1), even after adjusting for peripheral neuropathy and retinopathy. Moreover, we found that including vestibular dysfunction, peripheral neuropathy, and retinopathy in multivariate models eliminated the significant association between diabetes and fall risk. Conclusion: Vestibular dysfunction may represent a newly recognized diabetes-related complication, which acts as a mediator of the effect of diabetes mellitus on fall risk.

Effects of Biphasic Current Pulse Frequency, Amplitude, Duration, and Interphase Gap on Eye Movement Responses to Prosthetic Electrical Stimulation of the Vestibular Nerve

An implantable prosthesis that stimulates vestibular nerve branches to restore sensation of head rotation and vision-stabilizing reflexes could benefit individuals disabled by bilateral loss of vestibular (inner ear balance) function. We developed a prosthesis that partly restores normal function in animals by delivering pulse frequency modulated (PFM) biphasic current pulses via electrodes implanted in semicircular canals. Because the optimal stimulus encoding strategy is not yet known, we investigated effects of varying biphasic current pulse frequency, amplitude, duration, and interphase gap on vestibulo-ocular reflex (VOR) eye movements in chinchillas. Increasing pulse frequency increased response amplitude while maintaining a relatively constant axis of rotation. Increasing pulse amplitude (range 0-325 μA) also increased response amplitude but spuriously shifted eye movement axis, probably due to current spread beyond the target nerve. Shorter pulse durations (range 28-340 μs) required less charge to elicit a given response amplitude and caused less axis shift than longer durations. Varying interphase gap (range 25-175 μs) had no significant effect. While specific values reported herein depend on microanatomy and electrode location in each case, we conclude that PFM with short duration biphasic pulses should form the foundation for further optimization of stimulus encoding strategies for vestibular prostheses intended to restore sensation of head rotation.

Dynamic Visual Acuity during Passive Head Thrusts in Canal Planes

We sought to determine whether the dynamic visual acuity (DVA) test, which has been used to measure the function of the two horizontal semicircular canals (SCCs), could be adapted to measure the individual function of all six SCCs using transient, rapid, unpredictable head rotation stimuli (head thrusts) in the direction of maximum sensitivity of each SCC. We examined head-thrust DVA (htDVA) performance in 19 healthy control subjects, five patients before and six patients after plugging of one superior SCC for treatment of superior canal dehiscence, and two subjects with unilateral vestibular deafferentation (UVD) by vestibular neurectomy. We compared htDVA results for each SCC to vestibulo-ocular reflex gains measured using 3-D scleral coil recordings during a passive head-thrust-test paradigm. Individuals with normal vestibular function had similar htDVA scores for each of the six directions (canals) tested (mean 0.058 ± 0.050 LogMAR). Individuals tested after surgical plugging of one superior SCC were similar to normal for all SCCs except the plugged SCC, which had significantly worse htDVA scores (mean 0.270 ± 0.08 LogMAR). Individuals with UVD had significantly worse htDVA scores for head rotations maximally exciting any of the ipsilesional SCC (mean 0.317 ± 0.129 LogMAR) and scores similar to normal subjects for contralesional rotations (0.063 ± 0.051 LogMAR). These findings suggest that the htDVA test, which does not require scleral coil placement, magnetic field coils, or expensive oculography equipment, can provide a useful quantitative measure of individual SCC function.

Disruption of the Head Direction Cell Signal after Occlusion of the Semicircular Canals in the Freely Moving Chinchilla

Head direction (HD) cells in the rat anterodorsal thalamic nucleus (ADN) fire relative to the animals directional heading. Lesions of the entire vestibular labyrinth have been shown to severely alter VIIIth nerve input and disrupt these HD signals. To assess the specific contributions of the semicircular canals without altering tonic VIIIth nerve input, ADN cells were recorded from chinchillas after bilateral semicircular canal occlusion. Although ADN HD cells (and also hippocampal place cells and theta cells) were identified in intact chinchillas, no direction-specific activity was seen after canal occlusions. Instead, “bursty” cells were observed that exhibited burst-firing patterns similar to normal HD cells but with firing unrelated to the animals actual head direction. Importantly, when pairs of bursty cells were recorded, the temporal order of their firing was dependent on the animals turning direction, as is the case for pairs of normal HD cells. These results suggest that bursty cells are actually disrupted HD cells. The present findings further suggest that the HD cell network is still able to generate spiking activity after canal occlusions, but the semicircular canal input is critical for updating the network activity in register with changes in the animals HD.

Vestibulo-Ocular Reflex Responses to a Multichannel Vestibular Prosthesis Incorporating a 3D Coordinate Transformation for Correction of Misalignment

There is no effective treatment available for individuals unable to compensate for bilateral profound loss of vestibular sensation, which causes chronic disequilibrium and blurs vision by disrupting vestibulo-ocular reflexes that normally stabilize the eyes during head movement. Previous work suggests that a multichannel vestibular prosthesis can emulate normal semicircular canals by electrically stimulating vestibular nerve branches to encode head movements detected by mutually orthogonal gyroscopes affixed to the skull. Until now, that approach has been limited by current spread resulting in distortion of the vestibular nerve activation pattern and consequent inability to accurately encode head movements throughout the full 3-dimensional (3D) range normally transduced by the labyrinths. We report that the electrically evoked 3D angular vestibulo-ocular reflex exhibits vector superposition and linearity to a sufficient degree that a multichannel vestibular prosthesis incorporating a precompensatory 3D coordinate transformation to correct misalignment can accurately emulate semicircular canals for head rotations throughout the range of 3D axes normally transduced by a healthy labyrinth.