Search

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.

Calzolari et al. show that acute traumatic brain injury may cause a ‘vestibular agnosia’. This mediates imbalance both directly via white matter tract damage in the right temporal lobe, and indirectly by reducing clinician recognition of common, treatable vestibular diagnoses., 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.

Vestibular migraine is amongst the commonest causes of vertigo, but the regions underlying the development of symptoms including enhanced self-motion sensitivity and visually induced dizziness remain unknown. Bednarczuk et al. provide evidence for an abnormal interaction between visual and vestibular cortical regions in vestibular migraine., 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.

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.

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.

Classic experiments over several decades examined the physiology and pathophysiology of a critical brainstem function called vestibulo-ocular reflex. These studies provided a wealth of information on how the brain, particularly the cerebellum and brainstem, computes the representation of our own motion in order to generate compensatory movements. Contemporary literature over last two decades started focusing on an equally important aspects of vestibular function – the motion perception and spatial orientation. From both physiological and computational standpoints, these studies further extended the application of cerebellar principles (for the control of vestibulo-ocular reflex) to thalamic and cortical function, emphasising on cerebello-cerebral connections. This chapter provides a concise review of the physiology and pathophysiology of vestibular perception and discusses seminal work from our laboratories.

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.

A 31-year-old woman (figure) with relapsing-remitting multiple sclerosis (MS) (first symptoms February 1994, first diagnosis August 1994, Expanded Disability Status Scale [EDSS] 3.0) was diagnosed with breast cancer in January 2014. The last relapse had occurred in August 2007. Under treatment with natalizumab from August 2007 to June 2013, the patient was clinically stable and the brain MRI showed no signs of disease activity. Because of a positive JC virus antibody test, the immunomodulatory therapy was changed to fingolimod in July 2013. The patient remained clinically stable during the switching period and thereafter. In January 2014, a brain MRI showed 2 new lesions without contrast enhancement. After diagnosis of breast cancer in January 2014 and subsequent surgery in February 2014, adjuvant chemotherapy with cyclophosphamide, doxorubicin, and docetaxel was started (March–July 2014). Fingolimod was stopped in March 2014 considering the strong immunosuppressive effect of cyclophosphamide. The patient received granulocyte colony-stimulating factor (G-CSF; pegfilgrastim) 6 mg subcutaneously at each of the 6 cycles of chemotherapy to reduce the risk of infection during the phase of chemotherapy-induced neutropenia. In July 2014, the patient experienced a numbness and tingling in her right leg, which progressed to a severe hemiparesis (EDSS 7.0) leading to hospitalization. The MRI scan of the brain revealed several new lesions including a lesion with contrast enhancement. An IV steroid pulse therapy was administered. She recovered partially (EDSS 6.5). Fingolimod was started again in August 2014. Subsequently the patient developed another relapse with a worsening of the atactic hemiparesis on the left side, resulting in an inability to walk (EDSS 7.5). Again an IV steroid pulse therapy was administered. The patient recovered partially until the end of August 2014, when she was discharged from rehabilitation. At that time, she was able to walk for 50 meters without aid (EDSS 6.0). Another brain MRI in September 2014 revealed confluent progressive lesions in the white matter with partial contrast enhancement. The patient was referred to our inpatient clinic, where again a steroid pulse therapy was administered. In the following months, the patient recovered to a clinical condition similar to that before the start of the chemotherapy (as of August 2015, EDSS 3.0). An MRI scan of the brain in September 2015 did not show new lesions or contrast enhancement compared to the preceding MRI examination in September 2014.

Background Patients with multiple sclerosis (MS) suffer from diminished balance control due to slowed sensory conduction and possibly delayed central processing. Vibrotactile biofeedback of trunk sway has been shown to improve balance control in patients with peripheral and central vestibular disorders. Here, the effects of vibrotactile feedback training on trunk sway and a possible carry-over effect was measured in MS patients during stance and gait. Methods Ten MS patients (mean age 46.8±7.7 years, 40% male) participated in a crossover study in which 7 different stance and gait tasks were trained with and without angle feedback for stance and angular velocity feedback for gait. An assessment sequence of 12 tasks was performed once before and twice after the training sequence. Trunk sway was measured with body-worn gyroscopes. Head mounted vibrotactile biofeedback of trunk sway was provided during one crossover training arm and the following second assessment sequence. Results Biofeedback generally leads to a decrease in sway but an increase in sway angular velocities during some stance tasks compared to training without biofeedback. Biofeedback while walking eyes open resulted in a decreased sway angular velocity. The greatest changes were found in the pitch direction of trunk sway. Effects diminished after biofeedback was removed. Conclusions This study showed that vibrotactile biofeedback of trunk sway beneficially effects stance and provides significant improvement in gait compared to training without biofeedback in MS patients.