Vestibular agnosia in traumatic brain injury and its link to imbalance.

Vestibular dysfunction, causing dizziness and imbalance, is a common yet poorly understood feature in patients with TBI. Damage to the inner ear, nerve, brainstem, cerebellum and cerebral hemispheres may all affect vestibular functioning, hence, a multi-level assessment-from reflex to perception-is required. In a previous report, postural instability was the commonest neurological feature in ambulating acute patients with TBI. During ward assessment, we also frequently observe a loss of vertigo sensation in patients with acute TBI, common inner ear conditions and a related vigorous vestibular-ocular reflex nystagmus, suggesting a 'vestibular agnosia'. Patients with vestibular agnosia were also more unbalanced; however, the link between vestibular agnosia and imbalance was confounded by the presence of inner ear conditions. We investigated the brain mechanisms of imbalance in acute TBI, its link with vestibular agnosia, and potential clinical impact, by prospective laboratory assessment of vestibular function, from reflex to perception, in patients with preserved peripheral vestibular function. Assessment included: vestibular reflex function, vestibular perception by participants' report of their passive yaw rotations in the dark, objective balance via posturography, subjective symptoms via questionnaires, and structural neuroimaging. We prospectively screened 918 acute admissions, assessed 146 and recruited 37. Compared to 37 matched controls, patients showed elevated vestibular-perceptual thresholds (patients 12.92°/s versus 3.87°/s) but normal vestibular-ocular reflex thresholds (patients 2.52°/s versus 1.78°/s). Patients with elevated vestibular-perceptual thresholds [3 standard deviations (SD) above controls' average], were designated as having vestibular agnosia, and displayed worse posturography than non-vestibular-agnosia patients, despite no difference in vestibular symptom scores. Only in patients with impaired postural control (3 SD above controls' mean), whole brain diffusion tensor voxel-wise analysis showed elevated mean diffusivity (and trend lower fractional anisotropy) in the inferior longitudinal fasciculus in the right temporal lobe that correlated with vestibular agnosia severity. Thus, impaired balance and vestibular agnosia are co-localized to the inferior longitudinal fasciculus in the right temporal lobe. Finally, a clinical audit showed a sevenfold reduction in clinician recognition of a common peripheral vestibular condition (benign paroxysmal positional vertigo) in acute patients with clinically apparent vestibular agnosia. That vestibular agnosia patients show worse balance, but without increased dizziness symptoms, explains why clinicians may miss treatable vestibular diagnoses in these patients. In conclusion, vestibular agnosia mediates imbalance in traumatic brain injury both directly via white matter tract damage in the right temporal lobe, and indirectly via reduced clinical recognition of common, treatable vestibular diagnoses.

Abnormal visuo-vestibular interactions in vestibular migraine: a cross sectional study.

Vestibular migraine is among the commonest causes of episodic vertigo. Chronically, patients with vestibular migraine develop abnormal responsiveness to both vestibular and visual stimuli characterized by heightened self-motion sensitivity and visually-induced dizziness. Yet, the neural mechanisms mediating such symptoms remain unknown. We postulate that such symptoms are attributable to impaired visuo-vestibular cortical interactions, which in turn disrupts normal vestibular function. To assess this, we investigated whether prolonged, full-field visual motion exposure, which has been previously shown to modulate visual cortical excitability in both healthy individuals and avestibular patients, could disrupt vestibular ocular reflex and vestibular-perceptual thresholds of self-motion during rotations. Our findings reveal that vestibular migraine patients exhibited abnormally elevated reflexive and perceptual vestibular thresholds at baseline. Following visual motion exposure, both reflex and perceptual thresholds were significantly further increased in vestibular migraine patients relative to healthy controls, migraineurs without vestibular symptoms and patients with episodic vertigo due to a peripheral inner-ear disorder. Our results provide support for the notion of altered visuo-vestibular cortical interactions in vestibular migraine, as evidenced by vestibular threshold elevation following visual motion exposure.

Electrophysiological markers of vestibular-mediated self-motion perception - A pilot study.

Peripheral vestibular activation results in multi-level responses, from brainstem-mediated reflexes (e.g. vestibular ocular reflex - VOR) to perception of self-motion. While VOR responses indicate preserved vestibular peripheral and brainstem functioning, there are no automated measures of vestibular perception of self-motion - important since some patients with brain disconnection syndromes manifest a vestibular agnosia (intact VOR but impaired self-motion perception). Electroencephalography ('EEG') - may provide a surrogate marker of vestibular perception of self-motion. A related objective is obtaining an EEG marker of vestibular sensory signal processing, distinct from vestibular-motion perception. We performed a pilot study comparing EEG responses in the dark when healthy participants sat in a vibrationless computer-controlled motorised rotating chair moving at near threshold of self-motion perception, versus a second situation in which subjects sat in the chair at rest in the dark who could be induced (or not) into falsely perceiving self-motion. In both conditions subjects could perceive self-motion perception, but in the second there was no bottom-up reflex-brainstem activation. Time-frequency analyses showed: (i) alpha frequency band activity is linked to vestibular sensory-signal activation; and (ii) theta band activity is a marker of vestibular-mediated self-motion perception. Consistent with emerging animal data, our findings support the role of theta activity in the processing of self-motion perception.

The Effects of Vibro-Tactile Biofeedback Balance Training on Balance Control and Dizziness in Patients with Persistent Postural-Perceptual Dizziness (PPPD).

BACKGROUND: Patients with persistent postural-perceptual dizziness (PPPD) frequently report having problems with balance control. Artificial systems providing vibro-tactile feedback (VTfb) of trunk sway to the patient could aid recalibration of "falsely" programmed natural sensory signal gains underlying unstable balance control and dizziness. Thus, the question we examine, retrospectively, is whether such artificial systems improve balance control in PPPD patients and simultaneously reduce the effects of dizziness on their living circumstances. Therefore, we assessed in PPPD patients the effects of VTfb of trunk sway on balance control during stance and gait tests, and on their perceived dizziness. METHODS: Balance control was assessed in 23 PPPD patients (11 of primary PPPD origin) using peak-to-peak amplitudes of trunk sway measured in the pitch and roll planes with a gyroscope system (SwayStar™) during 14 stance and gait tests. The tests included standing eyes closed on foam, walking tandem steps, and walking over low barriers. The measures of trunk sway were combined into a Balance Control Index (BCI) and used to determine whether the patient had a quantified balance deficit (QBD) or dizziness only (DO). The Dizziness Handicap Inventory (DHI) was used to assess perceived dizziness. The subjects first underwent a standard balance assessment from which the VTfb thresholds in eight directions, separated by 45 deg, were calculated for each assessment test based on the 90% range of the trunk sway angles in the pitch and roll directions for the test. A headband-mounted VTfb system, connected to the SwayStar™, was active in one of the eight directions when the threshold for that direction was exceeded. The subjects trained for 11 of the 14 balance tests with VTfb twice per week for 30 min over a total of 2 consecutive weeks. The BCI and DHI were reassessed each week and the thresholds were reset after the first week of training. RESULTS: On average, the patients showed an improved balance control in the BCI values after 2 weeks of VTfb training (24% p = 0.0001). The improvement was greater for the QBD patients than for the DO patients (26 vs. 21%), and greater for the gait tests than the stance tests. After 2 weeks, the mean BCI values of the DO patients, but not the QBD patients, were significantly less (p = 0.0008) than the upper 95% limit of normal age-matched reference values. A subjective benefit in balance control was spontaneously reported by 11 patients. Lower (36%), but less significant DHI values were also achieved after VTfb training (p = 0.006). The DHI changes were identical for the QBD and DO patients and approximately equal to the minimum clinical important difference. CONCLUSIONS: These initial results show, as far as we are aware for the first time, that providing VTfb of trunk sway to PPPD subjects yields a significant improvement in balance control, but a far less significant change in DHI-assessed dizziness. The intervention benefitted the gait trials more than the stance trials and benefited the QBD group of PPPD patients more than the DO group. This study increases our understanding of the pathophysiologic processes underlying PPPD and provides a basis for future interventions.

Acute unilateral vestibular neuritis contributes to alterations in vestibular function modulating circumvention around obstacles: A pilot study suggesting a role for vestibular signals in the spatial perception of orientation during circumvention.

Background: Walking among crowds avoiding colliding with people is described by patients with vestibular disorders as vertigo-inducing. Accurate body motion while circumventing an impeding obstacle in the gait pathway is dependent on an integration of multimodal sensory cues. However, a direct role of vestibular signals in spatial perception of distance or orientation during obstacle circumvention has not been investigated to date. Materials and methods: We examined trunk yaw motion during circumvention in patients with acute unilateral vestibular loss (aUVL) and compared their results with age-matched healthy controls (HCs). Subjects performed five gait tasks with eyes open two times: walk 6 m in total, but after 3 m, circumvent to the left or right, as closely as possible, a cylindrical obstacle representing a person, and then veer back to the original path; walk 6 m, but after left and right circumvention at 3 m, veer, respectively, to the right, and left 45 deg; and walk 6 m without circumvention. Trunk yaw angular velocities (YAVs) were measured using a gyroscope system. Results: Yaw angular velocity peak amplitudes approaching to, and departing from, the circumvented object were always greater for patients with aUVL compared to HCs, regardless of whether passing was to the aUVLs' deficit or normal side. The departing peak YAV was always greater, circa 52 and 87%, than the approaching YAV for HCs when going straight and veering 45 deg (p ≤ 0.0006), respectively. For patients with aUVL, departing velocities were marginally greater (12%) than approaching YAVs when going straight (p < 0.05) and were only 40% greater when veering 45 deg (p = 0.05). The differences in departing YAVs resulted in significantly lower trajectory-end yaw angles for veering trials to the deficit side in patients with aUVL (34 vs. 43 degs in HCs). Conclusion: The results demonstrate the effects of vestibular loss on yaw velocity control during the three phases of circumvention. First, approaching an obstacle, a greater YAV is found in patients with aUVL. Second, the departing YAV is found to be less than in HCs with respect to the approaching velocity, resulting in larger deficit side passing yaw angles. Third, patients with UVLs show yaw errors returning to the desired trajectory. These results could provide a basis for rehabilitation protocols helping to avoid collisions while walking in crowded spaces.

The human brain networks mediating the vestibular sensation of self-motion.

Vestibular Agnosia - where peripheral vestibular activation triggers the usual reflex nystagmus response but with attenuated or no self-motion perception - is found in brain disease with disrupted cortical network functioning, e.g. traumatic brain injury (TBI) or neurodegeneration (Parkinson's Disease). Patients with acute focal hemispheric lesions (e.g. stroke) do not manifest vestibular agnosia. Thus, brain network mapping techniques, e.g. resting state functional MRI (rsfMRI), are needed to interrogate functional brain networks mediating vestibular agnosia. Hence, we prospectively recruited 39 acute TBI patients with preserved peripheral vestibular function and obtained self-motion perceptual thresholds during passive yaw rotations in the dark and additionally acquired whole-brain rsfMRI in the acute phase. Following quality-control checks, 26 patient scans were analyzed. Using self-motion perceptual thresholds from a matched healthy control group, 11 acute TBI patients were classified as having vestibular agnosia versus 15 with normal self-motion perception thresholds. Using independent component analysis on the rsfMRI data, we found altered functional connectivity in bilateral lingual gyrus and temporo-occipital fusiform cortex in the vestibular agnosia patients. Moreover, regions of interest analyses showed both inter-hemispheric and intra-hemispheric network disruption in vestibular agnosia. In conclusion, our results show that vestibular agnosia is mediated by bilateral anterior and posterior network dysfunction and reveal the distributed brain mechanisms mediating vestibular self-motion perception.

Functional Testing of Vestibulo-Spinal Contributions to Balance Control: Insights From Tracking Improvement Following Acute Bilateral Peripheral Vestibular Loss.

Background: A battery of stance and gait tasks can be used to quantify functional deficits and track improvement in balance control following peripheral vestibular loss. An improvement could be due to at least 3 processes: partial peripheral recovery of sensory responses eliciting canal or otolith driven vestibular reflexes; central compensation of vestibular reflex gains, including substitution of intact otolith responses for pathological canal responses; or sensory substitution of visual and proprioceptive inputs for vestibular contributions to balance control. Results: We describe the presumed action of all 3 processes observed for a case of sudden incapacitating acute bilateral peripheral loss probably due to vestibular neuritis. Otolith responses were largely unaffected. However, pathological decreases in all canal-driven vestibular ocular reflex (VOR) gains were observed. After 3 months of vestibular rehabilitation, balance control was normal but VOR gains remained low. Conclusions: This case illustrates the difficulty in predicting balance control improvements from tests of the 10 vestibular end organs and emphasizes the need to test balance control function directly in order to determine if balance control has improved and is normal again despite remaining vestibular sensory deficits. This case also illustrates that the presence of residual otolithic function may be crucial for balance control improvement in cases of bilateral vestibular hypofunction.

Theoretical framework for "unexplained" dizziness in the elderly: The role of small vessel disease.

In this paper we postulate that disruption of connectivity in the human brain can lead to dizziness, a symptom normally associated with focal disease of the vestibular system. The specific case that we will examine is the development of "unexplained" dizziness in the elderly-an extremely common clinical problem. Magnetic resonance imaging of the brain in the elderly usually show variable degrees of multifocal micro-angiopathy (small vessel white matter disease, SVD); thus, we review the literature, present a conceptual model and report preliminary quantitative EEG data in support of the hypothesis that such hemispheric SVD leads to central nervous system disconnection that elderly patients report as dizziness. Loss of connectivity by age-related build-up of SVD could lead to dizzy feelings through one or more of the following mechanisms: disconnection of cortical vestibular centers, disconnection between frontal gait centers and the basal ganglia, and disconnection between intended motor action (efference copy) and sensory re-afference. Finally, we propose that SVD-mediated dysregulation of cerebral blood pressure is linked to dizziness during standing and walking in elderly patients with "unexplained" dizziness.

Vestibular dysfunction in acute traumatic brain injury.

Traumatic brain injury (TBI) is the commonest cause of disability in under-40-year-olds. Vestibular features of dizziness (illusory self-motion) or imbalance which affects 50% of TBI patients at 5 years, increases unemployment threefold in TBI survivors. Unfortunately, vestibular diagnoses are cryptogenic in 25% of chronic TBI cases, impeding therapy. We hypothesized that chronic adaptive brain mechanisms uncouple vestibular symptoms from signs. This predicts a masking of vestibular diagnoses chronically but not acutely. Hence, defining the spectrum of vestibular diagnoses in acute TBI should clarify vestibular diagnoses in chronic TBI. There are, however, no relevant acute TBI data. Of 111 Major Trauma Ward adult admissions screened (median 38-years-old), 96 patients (87%) had subjective dizziness (illusory self-motion) and/or objective imbalance were referred to the senior author (BMS). Symptoms included: feeling unbalanced (58%), headache (50%) and dizziness (40%). In the 47 cases assessed by BMS, gait ataxia was the commonest sign (62%) with half of these cases denying imbalance when asked. Diagnoses included BPPV (38%), acute peripheral unilateral vestibular loss (19%), and migraine phenotype headache (34%), another potential source of vestibular symptoms. In acute TBI, vestibular signs are common, with gait ataxia being the most frequent one. However, patients underreport symptoms. The uncoupling of symptoms from signs likely arises from TBI affecting perceptual mechanisms. Hence, the cryptogenic nature of vestibular symptoms in TBI (acute or chronic) relates to a complex interaction between injury (to peripheral and central vestibular structures and perceptual mechanisms) and brain-adaptation, emphasizing the need for acute prospective, mechanistic studies.

Balance Changes in Patients With Relapsing-Remitting Multiple Sclerosis: A Pilot Study Comparing the Dynamics of the Relapse and Remitting Phases.

Aims: To compare balance changes over time during the relapse phase of relapsing-remitting multiple sclerosis (RRMS) with balance control during the remitting phase. Methods: Balance control during stance and gait tasks of 24 remitting-phase patients (mean age 43.7 ± 10.5, 15 women, mean EDSS at baseline 2.45 ± 1.01) was examined every 3 months over 9 months and compared to that of nine relapsing patients (age 42.0 ± 12.7, all women, mean EDSS at relapse onset 3.11 ± 0.96) examined at relapse onset and 3 months later. Balance was also compared to that of 40 healthy controls (HCs) (age 39.7 ± 12.6, 25 women). Balance control was measured as lower-trunk sway angles with body-worn gyroscopes. Expanded Disability Status Scale scores (EDSS) were used to monitor, clinically, disease progression. Results: Remitting-phase patients showed more unstable stance balance control than HCs (p < 0.04) with no worsening over the observation period of 9 months. Gait balance control was normal (p > 0.06). Relapsing patients had stance balance control significantly worse at onset compared to remitting-phase patients and HCs (p < 0.04). Gait tasks showed a significant decrease of gait speed and trunk sway in relapsing patients (p = 0.018) compatible with having increased gait instability at normal speeds. Improvement to levels of remitting patients generally took longer than 3 months. Balance and EDSS scores were correlated for remitting but not for relapse patients. Conclusions: Balance in remitting RRMS patients does not change significantly over 9 months and correlated well with EDSS scores. Our results indicate that balance control is a useful measure to assess recovery after a relapse, particularly in patients with unchanged EDSS scores. Based on our results, balance could be considered as additional measurement to assess recovery after a relapse, particularly in patients with unchanged EDSS.

Prefrontal gamma-band activity distinguishes between sound durations.

The present study used magnetoencephalography to assess the cortical representation of brief sound durations during a short-term memory task. Twelve subjects were instructed to memorize sounds S1 with durations of either 100 or 200 ms during an 800-ms delay phase. Subsequently, they had to judge whether the duration of a probe sound S2 matched the memorized stimulus. Statistical probability mapping of oscillatory signals revealed several components of gamma-band activity (GBA) over prefrontal cortex. A first component with a center frequency of 40 Hz responded more strongly to longer than shorter sounds during the encoding of S1. During the subsequent delay phase, shorter and longer durations were associated with topographically and spectrally distinct GBA enhancements at 71 and 80 Hz, respectively. S2 was again associated with stronger oscillatory activation for longer than shorter sounds at approximately 72 Hz. Non matching compared with matching S1-S2 pairs elicited an additional approximately 66 Hz GBA component peaking at approximately 200 ms after the offset of S2. The analysis of magnetoencephalographic GBA thus served to identify prefrontal network components underlying the representation of different sound durations during the various phases of a delayed matching-to-sample task.

Dizziness in the emergency department: an update on diagnosis.

This review aims to assist emergency physicians in finding the underlying aetiology when a patient presents with dizziness to the emergency department. After reading this review, the emergency physician will be able to consider the most relevant differential diagnoses and have an idea about dangerous aetiologies that require immediate action. The emergency physician will also know what diagnostic steps need to be taken at what time, such as the three-component HINTS Test (Head Impulse, Nystagmus, and Test-of-Skew), which helps with distinguishing central from peripheral causes of the acute vestibular syndrome. Furthermore, episodic vestibular syndromes and chronic vestibular syndromes are discussed in detail. The five most frequent categories of dizziness are vasovagal syncope / orthostatic hypotension (22.3%), vestibular causes (19.9%), fluid and electrolyte disorders (17.5%), circulatory/pulmonary causes (14.8%) and central vascular causes (6.4%). Given that it would neither be economical nor practical to send all patients to specialists from the start, we present general guidelines for the diagnostic workup of patients presenting with dizziness to the emergency department. This review will focus on epidemiology, aetiologies, differential diagnoses and diagnostics. Treatment is described in a separate article.

Treatment of dizziness: an interdisciplinary update.

This review provides an update on interdisciplinary treatment for dizziness. Dizziness can have various causes and the treatment offered should depend on the cause. After reading this article, the clinician will have an overview of current treatment recommendations. Recommendations are made for the most prevalent causes of dizziness including acute and chronic vestibular syndromes, vestibular neuritis, benign paroxysmal positional vertigo, endolymphatic hydrops and Menière's disease, vestibular paroxysmia and vestibular migraine, cardiac causes, transient ischaemic attacks and strokes, episodic ataxia type 2, persistent postural-perceptual dizziness, bilateral vestibulopathy, degenerative, autoimmune and neoplastic diseases, upbeat- and downbeat nystagmus. Recommendations include clinical approaches (repositioning manoeuvres), medication (adding, removing or changing current medication depending on aetiology), vestibular physiotherapy, ergotherapy and rehabilitation, treatment of chest pain or stroke units and surgical interventions. If symptoms are acute and severe, medication with antivertigo agents is recommended as a first step, for a maximum period of 3 days. Following initial symptom control, treatment is tailored depending on aetiology. To assist the clinician in obtaining a useful overview, the level of evidence and number needed to treat are reported whenever possible based on study characteristics. In addition, warnings about possible arrhythmias due to medication are issued, and precautions to enable these to be avoided are discussed.