Exposure to Intense Noise Causes Vestibular Loss.

INTRODUCTION: The vestibular system is essential for normal postural control and balance. Because of their proximity to the cochlea, the otolith organs are vulnerable to noise. We previously showed that head jerks that evoke vestibular nerve activity were no longer capable of inducing a response after noise overstimulation. The present study adds a greater range of jerk intensities to determine if the response was abolished or required more intense stimulation (threshold shift). MATERIALS AND METHODS: Vestibular short-latency evoked potential (VsEP) measurements were taken before noise exposure and compared to repeated measurements taken at specific time points for 28 days after noise exposure. Calretinin was used to identify changes in calyx-only afferents in the sacculus. RESULTS: Results showed that more intense jerk stimuli could generate a VsEP, although it was severely attenuated relative to prenoise values. When the VsEP was evaluated 4 weeks after noise exposure, partial recovery was observed. CONCLUSION: These data suggest that noise overstimulation, such as can occur in the military, could introduce an increased risk of imbalance that should be evaluated before returning a subject to situations that require normal agility and motion. Moreover, although there is recovery with time, some dysfunction persists for extended periods.

Head impulse compensatory saccades: Visual dependence is most evident in bilateral vestibular loss.

The normal vestibulo-ocular reflex (VOR) generates almost perfectly compensatory smooth eye movements during a 'head-impulse' rotation. An imperfect VOR gain provokes additional compensatory saccades to re-acquire an earth-fixed target. In the present study, we investigated vestibular and visual contributions on saccade production. Eye position and velocity during horizontal and vertical canal-plane head-impulses were recorded in the light and dark from 16 controls, 22 subjects after complete surgical unilateral vestibular deafferentation (UVD), eight subjects with idiopathic bilateral vestibular loss (BVL), and one subject after complete bilateral vestibular deafferentation (BVD). When impulses were delivered in the horizontal-canal plane, in complete darkness compared with light, first saccade frequency mean(SEM) reduced from 96.6(1.3)-62.3(8.9) % in BVL but only 98.3(0.6)-92.0(2.3) % in UVD; saccade amplitudes reduced from 7.0(0.5)-3.6(0.4) ° in BVL but were unchanged 6.2(0.3)-5.5(0.6) ° in UVD. In the dark, saccade latencies were prolonged in lesioned ears, from 168(8.4)-240(24.5) ms in BVL and 177(5.2)-196(5.7) ms in UVD; saccades became less clustered. In BVD, saccades were not completely abolished in the dark, but their amplitudes decreased from 7.3-3.0 ° and latencies became more variable. For unlesioned ears (controls and unlesioned ears of UVD), saccade frequency also reduced in the dark, but their small amplitudes slightly increased, while latency and clustering remained unchanged. First and second saccade frequencies were 75.3(4.5) % and 20.3(4.1) %; without visual fixation they dropped to 32.2(5.0) % and 3.8(1.2) %. The VOR gain was affected by vision only in unlesioned ears of UVD; gains for the horizontal-plane rose slightly, and the vertical-planes reduced slightly. All head-impulse compensatory saccades have a visual contribution, the magnitude of which depends on the symmetry of vestibular-function and saccade latency: BVL is more profoundly affected by vision than UVD, and second saccades more than first saccades. Saccades after UVD are probably triggered by contralateral vestibular function.

Nerve ultrasound as a diagnostic tool for sensory neuronopathy in spinocerebellar ataxia syndrome.

OBJECTIVE: The objective was to assess if nerve ultrasound has a role in diagnosing sensory neuronopathy in spinocerebellar ataxia syndrome (SCA) by examining if proposed diagnostic cut-off criteria of ultrasound in sensory neuronopathy caused by cerebellar ataxia neuropathy vestibular areflexia syndrome (CANVAS) were also discriminatory for SCA-related sensory neuronopathy. METHODS: Optimal diagnostic cut-off criteria for nerve size measured by diagnostic ultrasound were developed in 14 patients with CANVAS and 42 healthy controls using six peripheral nerve sites; and logistic regression and receiver operating characteristic (ROC) curves. These proposed cut-off values were tested in seven patients with spinocerebellar ataxia type 2 (SCA2) patients with sensory neuronopathy. RESULTS: Ultrasound of upper limb nerves was highly accurate in differentiating between CANVAS and healthy controls with areas under the ROC curves between 0.97 and 0.99. Optimal cut-off measurements from the CANVAS patients also accurately diagnosed sensory neuronopathy in all patients with SCA2. CONCLUSIONS: Upper limb ultrasound is a sensitive tool for detecting sensory neuronopathy in established cases of CANVAS and SCA2. SIGNIFICANCE: Ultrasound could aid the diagnosis of sensory neuronopathy in spinocerebellar ataxias.

Strain and Sex Differences in the Vestibular and Systemic Toxicity of 3,3'-Iminodipropionitrile in Mice.

The nitrile 3,3'-iminodipropionitrile (IDPN) causes a loss of hair cells in the vestibular epithelium of the inner ear in several species of both mammals and nonmammals. It is of interest as a model compound in ototoxicity and vestibular regeneration research, but its effects on the mouse, including the potential relevance of strain and sex differences for susceptibility, have not yet been thoroughly characterized. In this study, we compared the vestibular toxicity of IDPN in dose-response studies (0, 8, 12, 16, and 24 mmol/kg IDPN p.o.) in males and females of 2 different mouse strains (RjOrl:Swiss/CD-1 and 129S1/SvImJ). 3,3'-Iminodipropionitrile caused a dose-dependent loss of vestibular function in all sex and strain groups, as assessed by a specific battery of behavioral tests. However, large differences in systemic toxicity were recorded, with high systemic toxicity in 129S1 mice of both sexes compared to limited effects on the Swiss mice. Both male and female Swiss mice showed a marked increase of hindlimb stride width after exposure. The Swiss, but not the 129S1, mice treated with IDPN showed hyperactivity in the open field. The dose-response relationships in the behavioral effects were matched by the extent of hair cell loss assessed by scanning electron microscopy. Altogether, the data demonstrated prominent strain-dependent differences in the systemic toxicity of IDPN between 129S1 and Swiss mice, in contrast to no differences between the strains and small differences between the sexes in its vestibular toxicity. These results support the use of Swiss mice exposed to IDPN as a mouse lesion model for research in vestibular therapy and regeneration.

Hippocampal and striatal M1 -muscarinic acetylcholine receptors are down-regulated following bilateral vestibular loss in rats.

Permanent vestibular loss has detrimental effects on the hippocampus, resulting in a disruption to spatial learning and memory, hippocampal theta rhythm and place cell field spatial coherence. Little is known about the vestibular system-related hippocampal cholinergic transmission. Since the pharmacological blockade of muscarinic acetylcholine (ACh) receptors within the hippocampus produces deficits in learning and memory, we hypothesized that ACh receptors may at least partly support the integration of vestibular input. Consequently, we examined the expression of M1 muscarinic ACh receptors in the hippocampus at 7 and 30 days following bilateral vestibular lesions (BVL) in rats using autoradiography. Animals were divided into sham (n = 12) and BVL (n = 11) groups. BVL animals received intratympanic injections of sodium arsanilate (30 mg/0.1 ml) under isoflurane anesthesia and sham animals received the same volume of saline. Analysis of the brain tissue revealed a significant reduction in the number of M1 receptors throughout the hippocampus and striatum at 30 days (P ≤ 0.0001), but not at 7 days following BVL. This suggests that the changes in learning and memory seen following vestibular damage may be in part due to the loss of M1 muscarinic receptors in the hippocampus and striatum. © 2016 Wiley Periodicals, Inc.

Hippocampal gray matter volume in bilateral vestibular failure.

Bilateral vestibular failure (BVF) is a severe chronic disorder of the labyrinth or the eighth cranial nerve characterized by unsteadiness of gait and disabling oscillopsia during head movements. According to animal data, vestibular input to the hippocampus is proposed to contribute to spatial memory and spatial navigation. Except for one seminal study showing the association of impaired spatial navigation and hippocampal atrophy, patient data in BVF are lacking. Therefore, we performed a voxel-wise comparison of the hippocampal gray matter volume (GMV) in a clinically representative sample of 27 patients with incomplete BVF and 29 age- and gender-matched healthy controls to test the hypothesis of hippocampal atrophy in BVF. Although the two groups did not generally differ in their hippocampal GMV, a reduction of GMV in the bilateral hippocampal CA3 region was significantly correlated with increased vestibulopathy-related clinical impairment. We propose that GMV reduction in the hippocampus of BVF patients is related to the severity of vestibular-induced disability which is in line with combined hippocampal atrophy and disorders of spatial navigation in complete vestibular deafferentation due to bilateral nerve section. Clinically, however, the most frequent etiologies of BVF cause incomplete lesions. Accordingly, hippocampus atrophy and deficits in spatial navigation occur possibly less frequently than previously suspected. Hum Brain Mapp 37:1998-2006, 2016. © 2016 Wiley Periodicals, Inc.