Impact of anti-epileptic drug choice on discharge in acute traumatic brain injury patients.

BACKGROUND: Anti-epileptic drug (AED) prophylaxis in the first-seven days post-traumatic brain injury (TBI) is known to reduce seizure frequency acutely. AED efficacy is equivalent; therefore, choice of AED may rest with their side-effects. We hypothesise that AEDs that impair balance will prolong recovery, shown by a longer hospital stay. We compared length of hospital stay (and reported dizziness) in TBI patients receiving the commonest AEDs used in our TBI patients, Phenytoin (which may cause imbalance), and Levetiracetam (which does not affect balance). METHOD: A retrospective observational study was performed on TBI patients admitted to a Major Trauma Unit between October 2013 and June 2018. 100 of 278 patients treated with phenytoin or levetiracetam monotherapy for seizure prophylaxis were included. The inclusion criteria of admission Glasgow Coma Score of 14 or more and length of stay less than 3 weeks minimised confounding variables such as non-ambulant patients. Length of hospital stay and incidence of dizziness were assessed. RESULTS: The length of hospital stay was longer for patients on Phenytoin versus Levetiracetam, i.e., 10.74 vs. 7.58 days (p = 0.015; unpaired, two-sided t test). Dizziness reported by patients on phenytoin was 24% and levetiracetam was 8% (p = 0.018; Chi-squared test). CONCLUSION: In this cohort, using Phenytoin for acute TBI, seizure prophylaxis was associated with longer length of stay and more dizziness compared to Levetiracetam. Given their equivalent AED efficacy in acute TBI seizure prophylaxis, our data suggest that Levetiracetam is preferable to Phenytoin for early seizure prophylaxis in TBI. This requires evaluation in larger, prospective studies.

Patients with chronic dizziness following traumatic head injury typically have multiple diagnoses involving combined peripheral and central vestibular dysfunction.

OBJECTIVE: We hypothesised that chronic vestibular symptoms (CVS) of imbalance and dizziness post-traumatic head injury (THI) may relate to: (i) the occurrence of multiple simultaneous vestibular diagnoses including both peripheral and central vestibular dysfunction in individual patients increasing the chance of missed diagnoses and suboptimal treatment; (ii) an impaired response to vestibular rehabilitation since the central mechanisms that mediate rehabilitation related brain plasticity may themselves be disrupted. METHODS: We report the results of a retrospective analysis of both the comprehensive clinical and vestibular laboratory testing of 20 consecutive THI patients with prominent and persisting vestibular symptoms still present at least 6months post THI. RESULTS: Individual THI patients typically had multiple vestibular diagnoses and unique to this group of vestibular patients, often displayed both peripheral and central vestibular dysfunction. Despite expert neuro-otological management, at two years 20% of patients still had persisting vestibular symptoms. CONCLUSION: In summary, chronic vestibular dysfunction in THI could relate to: (i) the presence of multiple vestibular diagnoses, increasing the risk of 'missed' vestibular diagnoses leading to persisting symptoms; (ii) the impact of brain trauma which may impair brain plasticity mediated repair mechanisms. Apart from alerting physicians to the potential for multiple vestibular diagnoses in THI, future work to identify the specific deficits in brain function mediating poor recovery from post-THI vestibular dysfunction could provide the rationale for developing new therapy for head injury patients whose vestibular symptoms are resistant to treatment.

Functional neuroimaging of visuo-vestibular interaction.

The brain combines visual, vestibular and proprioceptive information to distinguish between self- and world motion. Often these signals are complementary and indicate that the individual is moving or stationary with respect to the surroundings. However, conflicting visual motion and vestibular cues can lead to ambiguous or false sensations of motion. In this study, we used functional magnetic resonance imaging to explore human brain activation when visual and vestibular cues were either complementary or in conflict. We combined a horizontally moving optokinetic stimulus with caloric irrigation of the right ear to produce conditions where the vestibular activation and visual motion indicated the same (congruent) or opposite directions of self-motion (incongruent). Visuo-vestibular conflict was associated with increased activation in a network of brain regions including posterior insular and transverse temporal areas, cerebellar tonsil, cingulate and medial frontal gyri. In the congruent condition, there was increased activation in primary and secondary visual cortex. These findings suggest that when sensory information regarding self-motion is contradictory, there is preferential activation of multisensory vestibular areas to resolve this ambiguity. When cues are congruent, there is a bias towards visual cortical activation. The data support the view that a network of brain areas including the posterior insular cortex may play an important role in integrating and disambiguating visual and vestibular cues.

The effect of pedunculopontine nucleus deep brain stimulation on postural sway and vestibular perception.

BACKGROUND AND PURPOSE: Deep brain stimulation (DBS) of the pedunculopontine nucleus (PPN) reduces the number of falls in patients with Parkinson's disease (PD). It was hypothesized that enhanced sensory processing contributes to this PPN-mediated gait improvement. METHODS: Four PD patients (and eight matched controls) with implanted bilateral PPN and subthalamic nucleus DBS electrodes were assessed on postural (with/without vision) and vestibular perceptual threshold tasks. RESULTS: Pedunculopontine nucleus ON stimulation (compared to OFF) lowered vestibular perceptual thresholds but there was a disproportionate increase in the normal sway increase on going from light to dark. CONCLUSIONS: The disproportionate increased sway with PPN stimulation in the dark may paradoxically improve balance function since mechanoreceptor signals rapidly adapt to continuous pressure stimulation from postural akinesia. Additionally, the PPN-mediated vestibular signal enhancement also improves the monitoring of postural sway. Overall, PPN stimulation may improve sensory feedback and hence balance performance.

How imagery changes self-motion perception.

Imagery and perception are thought to be tightly linked, however, little is known about the interaction between imagery and the vestibular sense, in particular, self-motion perception. In this study, the observers were seated in the dark on a motorized chair that could rotate either to the right or to the left. Prior to the physical rotation, observers were asked to imagine themselves rotating leftward or rightward. We found that if the direction of imagined rotation was different to the physical rotation of the chair (incongruent trials), the velocity of the chair needed to be higher for observers to experience themselves rotating relative to when the imagined and the physical rotation matched (on congruent trials). Accordingly, the vividness of imagined rotations was reduced on incongruent relative to congruent trials. Notably, we found that similar effects of imagery were found at the earliest stages of vestibular processing, namely, the onset of the vestibular-ocular reflex was modulated by the congruency between physical and imagined rotations. Together, the results demonstrate that mental imagery influences self-motion perception by exerting top-down influences over the earliest vestibular response and subsequent perceptual decision-making.

Effects of prochlorperazine on normal vestibular ocular and perceptual responses: a randomised, double-blind, crossover, placebo-controlled study.

BACKGROUND: The present study investigated whether prochlorperazine affects vestibulo-ocular reflex (VOR) and vestibulo-perceptual function. METHODS: We studied 12 healthy naïve subjects 3 h after a single dose of oral prochlorperazine 5 mg in a randomised, placebo-controlled, double-blind, crossover study in healthy young subjects. Two rotational tests in yaw were used: (1) a threshold task investigating perceptual motion detection and nystagmic thresholds (acceleration steps of 0.5°/s(2)) and (2) suprathreshold responses to velocity steps of 90°/s in which vestibulo-ocular and vestibuloperceptual time constants of decay, as well as VOR gain, were measured. RESULTS: Prochlorperazine had no effect upon any measure of nystagmic or perceptual vestibular function compared to placebo. This lack of effects on vestibular-mediated motion perception suggests that the drug is likely to act more as an anti-emetic than as an antivertiginous agent.

A new device to quantify ocular counterroll using retinal afterimages.

BACKGROUND: The integrity of vertical semicircular canal and otolith function remains difficult to assess in the clinical setting, partly due to difficulties in recording ocular counterroll. Here, we quantify static ocular counterroll from head tilt using a new head-mounted device. METHODS: The device consists of an LED positioned 42 cm in front of one eye and a striated lens which produces a streak of light on the retina. The LED is illuminated at full intensity (80 cd) to generate a retinal afterimage. Subsequently, in darkness, the subject's head is tilted in the roll plane. Finally, the LED is illuminated dimly (0.2 cd) and the subject rotates the striated lens to superimpose the dim light streak onto the afterimage. An angular scale indicates the angle through which the lens is rotated, giving a measure of the ocular counterroll. To validate the device, we recorded binocular counterroll simultaneously with 3D computerised video-oculography of the other eye in 16 normal subjects; 2 patients with acquired bilateral loss of vestibular function were also tested. RESULTS: In the normal subjects, there was no significant difference between the two techniques (p=0.24) when recording ocular counterroll and the correlation between the two techniques was R2=0.78. The 2 avestibular patients essentially showed no ocular counterroll with both techniques. CONCLUSIONS: We have devised a non-invasive, quick and reliable test of ocular counterroll. The lack of response in the 2 avestibular patients indicates that this device is clinically applicable to assess otolith function.

Visual motion adaptation increases the susceptibility of area V5/MT to phosphene induction by transcranial magnetic stimulation.

OBJECTIVES: The effects of visual cortical transcranial magnetic stimulation (TMS) depends upon the initial state of the stimulated region. Thus TMS perceptually facilitates the attributes encoded by adapted neuronal populations. These reports however, relied upon subjects' description of phosphene qualia and were not quantified. We aimed to: (1) quantify the effect of visual motion adaptation on cortical excitability; (2) assess whether the effect on neuronal excitability was limited to the neuronal population undergoing adaptation or whether there was a generalised modulation of visual cortical excitability. METHODS: Visual motion adaptation was induced using a random dot kinematogram display. The frequency of induced phosphenes, using baseline threshold TMS intensity, was used to probe visual cortical excitability. RESULTS: Adaptation to visual motion increased the frequency of V5/MT-stimulated phosphene reports. The effect was only observed when the adapting stimulus and the phosphene spatially overlapped. CONCLUSIONS: Neuronal adaptation increases the susceptibility to threshold intensity TMS-induced facilitation of neuronal activation. SIGNIFICANCE: Our data imply that the process of neuronal adaption is not synonymous with down-modulation of neuronal excitability depends upon the relative intensity of the stimulus probing neuronal function.

Chronic dizziness: a practical approach.

Patients with chronic dizziness pose a particular challenge to the clinician, partly because their symptoms correlate poorly with standard vestibular tests; so a 'test and think later' approach is likely to lead to diagnostic confusion rather than clarity. Rather, a meticulous clinical assessment is required. Here our approach to the chronic dizzy patient is described with an emphasis on treating the patient's symptoms.

Perceptual and nystagmic thresholds of vestibular function in yaw.

A technique for simultaneous measurement of conscious (perceptual) and reflex (nystagmus) thresholds of vestibular function is described. We used an automated modified binary search algorithm with simultaneous infrared oculography in determining perceptual and VOR nystagmic thresholds respectively, during discrete whole body rotations in the dark. In a young group of 14 normal subjects (mean age 23 years) angular acceleration thresholds were significantly higher for perceptual detection (1.18 deg/s/s) than for nystagmus generation (0.51 deg/s/s). Only nystagmic thresholds were slightly raised (0.87 deg/s/s) in an older group of 9 normal subjects (mean age 63 years). The finding that nystagmic thresholds are lower than perceptual ones indicates a higher sensitivity of brainstem than cortical vestibular mechanisms. This technique would be of particular value in clinical situations where a dissociation between reflex and conscious vestibular mechanisms is expected, e.g. in patients with cortical lesions or in elderly patients with falls.

The endocrine system, vertigo and balance.

Steroid, amine and peptide hormones affect the peripheral vestibular system. Vasopressin hypersensitivity of the endolymphatic sac may be implicated in the pathogenesis of Meniere's disease. Specific vasopressin antagonists will help define the role of vasopressin in Meniere's disease. The modulation of central vestibular pathways by neuroactive steroids may involve effects on gamma-aminobutyric acid-ergic and glutaminergic pathways. The vestibular nuclei also express enzymes that are important in the synthesis of steroids and the modulation of their activity. Steroids mediate both facilitatory and deleterious effects of stress on vestibular compensation. The quality and quantity of stressor that determines the pattern of hormonal output, may be important. Clinical observation suggests that episodic ataxia type 2, a P/Q calcium channelopathy, may be phenotypically modulated by endocrine fluctuations. Steroid hormones may affect the episodic ataxia type 2 phenotype by modulation of voltage-gated calcium channel activity via second messenger systems and ion channel subunit expression. Despite evidence to support the link, the role of the endocrine system in vestibular function and disease is as yet virtually unexplored.

Antagonism of the effects of 5-hydroxytryptamine on the rabbit isolated vagus nerve by BRL 43694 and metoclopramide.

Depolarization and reduction in the C fibre compound action potential (C spike) in response to 5-HT were recorded simultaneously from rabbit isolated vagus nerve. 5-HT (0.1-100 mumol/l) was applied cumulatively and EC50 and IC50 values measured from individual concentration-response curves. Blockade of 5-HT responses by the 3-indazole carboxamide, BRL 43694, was investigated and compared with the blocking action of metoclopramide. BRL 43694 was a selective antagonist of 5-HT responses. A concentration of 10 nmol/l BRL 43694, which nearly abolished the depolarization and reduction of the C spike evoked by 5-HT (100 mumol/l), had no effect on similar responses evoked by DMPP (100 mumol/l) or GABA (100 mumol/l). Blockade of 5-HT responses by BRL 43694 (0.3 nmol/l) was slow in onset, a plateau blockade occurring after equilibrium of tissue with antagonist for 2 to 3 h. Metoclopramide induced a blockade of rapid onset. The maximal blockade was apparent within 30 min of application. Full recovery in the responsiveness of the tissue to 5-HT was observed within 30 min of washing out metoclopramide. BRL 43694 at concentrations of 0.3, 1, 3 and 10 nmol/l caused a progressive rightward shift of the concentration-response curves to 5-HT. At the highest concentration of antagonist, there was some depression of the maximal 5-HT response. The apparent pA2 estimated from the Schild equation was 10.03 +/- 0.09 (mean +/- SEM, n = 20) against 5-HT depolarization and 10.31 +/- 0.1 against C spike reduction. Schild plots had slopes not significantly different from 1.0.(ABSTRACT TRUNCATED AT 250 WORDS)