Recovery from vestibular dysfunction following Traumatic Brain Injury: A prospective behavioural and neuro-imaging study

Traumatic Brain Injury (TBI) is the commonest cause of chronic disability in young adults. We found that 86% of acute TBI patients have problems with their balance. The problem of imbalance is important for this young working age group since previous studies have shown that following a mild TBI, at 6 months, 66% of TBI patients with balance problems will still be unemployed versus only 25% of those without balance dysfunction. A key step in treating TBI imbalance is to understand the underlying pathophysiology, however previous studies could not identify a clear-cut cause in 25% of TBI patients with chronic imbalance.

Our acute TBI data show that most patients have a type of imbalance that is typical for patients with a loss of function of the inner ear balance organ - the vestibular organ. When we tested acute TBI patients with normal inner ear function we still found the same type of vestibular gait impairment, implying that the problem lay with the brain's processing of the vestibular organ's signals. Whilst screening acute TBI patients we also observed that acute TBI patients appeared to lose the perception of vertigo (the sensation of bodily self-motion) despite overt vestibular activation (vestibular nystagmus, nausea and vomiting). This again implies a failure by the brain to adequately process the inner ear vestibular signals. Taken together, TBI impairs the brain processing of vestibular signals with a major impact upon balance function. But what is the mechanism underlying this impairment of vestibular processing?

Our previous work (Nigmatullina 2015) showed that vertigo perception is mediated by a cerebral cortical network. Congruent with this notion and using a test to quantify the vestibular perception of self-motion, we found that focal cortical damage from stroke did not affect vestibular perception of self-motion (Kaski 2015). In contrast, in our pilot data, we quantitatively show that acute TBI does indeed impair this vestibular perception of self-motion (which we call 'Vestibular Agnosia').

We thus hypothesise that TBI causes a disruption of a cerebral cortical network that processes vestibular signals important for perceiving our sense of bodily motion. We additionally hypothesise that impairment of this vestibular cortical network will also compromise balance, particularly in the dark, since excessive sway (normally indicated by vestibular signals of head motion) will not be detected, leading to falls.

Hence in our study we propose to:
(i) prospectively assess if our vestibular perceptual test (of vestibular agnosia) predicts functional outcome;
(ii) test our hypothesis that vestibular agnosia is a marker of brain network dysfunction;
(iii) develop models linking pathophysiology and symptoms and hence enable us to explain why the persistence of symptoms post-TBI correlates poorly with TBI severity.

The output of this study will thus enable us to:
(i): predict which patients will be at risk of imbalance and falls post-TBI;
(ii) objectively monitor the improvement in brain network dysfunction and hence provide an objective indicator of response to treatment;
(iii) provide a clinical framework to progress the research and treatment of TBI including sports concussion.

CLINICAL NEED: Traumatic Brain Injury (TBI) is the commonest cause of chronic disability in young adults. We found in 111 consecutive head injury patients (Fig.1), 86% had symptoms and/or signs of imbalance.

IMPACT OF TBI-RELATED VESTIBLAR DYSFUNCTION: Post-TBI imbalance is an independent predictor of failure to return to work but the cause of imbalance in chronic TBI patients is unknown in 25%.

TBI IMPAIRS THE BRAIN'S PROCESSING OF THE VESTIBULAR SIGNAL: Patients without inner ear vestibular function display a complete loss of vestibular responsivity, from loss of the vestibular reflexes, to a particular type of gait dysfunction ('vestibular ataxia') as well as an absence of any perception of vertigo during stimuli that would ordinarily provoke this sensation. In the 84% of acute TBI patients with NORMAL INNER EAR FUNCTION, we found a normal vestibular reflex responsivity (e.g. vestibular nystagmus) however we found a vestibular ataxia and an impaired perception of vertigo. The combination of preserved vestibular reflexes and impaired perception and balance indicate an impaired brain processing of the inner ear vestibular signals. The loss of vestibular sensation of self-motion could itself lead to falls since there is no indication of excessive sway, especially in the dark.

WHAT WE WILL DO: We will prospectively recruit acute TBI patients (and matched controls) and prospectively acquire data on functional outcome, falls, laboratory measures of vestibular function (of reflex, perceptual and balance function) and structural and functional neuro-imaging. We will assess which of the behavioral and neuroimaging factors predict functional outcome and falls at 6 months.

EXPECTED OUTPUTS: We hope to reveal the mechanisms mediating TBI-imbalance enabling a prediction of patients at high risk of imbalance, providing putative mechanisms for developing new treatments as well as objective measures to monitor the response to these treatments.

PATIENTS
Patients' lives are severely disrupted by TBI-related imbalance. An understanding of the causes and treatment that we hope to bring for this condition, will help to ensure patients return to a fulfilling life.

ATHELETES AND SPORTS PHYSICIANS
Concussion is common in some sports. How do you diagnoses a concussion? Am I ready to play again? Objectifying concussion with some of the approaches we will use will hopefully make the approach to concussion in sport more clear-cut.

HEALTHCARE ORGANISATIONS
Is this head inured patient safe to go home? How can we tell? We believe that some of the techniques we will use to interrogate brain health post-TBI may allow a rapid triaging of patients into those requiring discharge versus those requiring admission.

PHARMACEUTICAL COMPANIES
Our study aims to produce a biomarker for brain injury recovery. Such a biomarker will allow Pharma companies to monitor the impact of their therapy in head trauma patients.
Insurance companies. If we can provide a sensitive and specific marker of head injury then such a technique could be sued in the court to assess whether there is persisting brain injury in a chronic symptomatic patient.