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

Lead Research Organisation: Imperial College London
Department Name: Brain Sciences

Abstract

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.

Technical Summary

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.

Planned Impact

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.

Publications

10 25 50
 
Description Association of British Neurologists Acute Neurology Advisory Board
Geographic Reach National 
Policy Influence Type Membership of a guideline committee
Impact We are engaged in facilitating the current re-organisation of acute neurology services (and linking it to community services) in the UK.
 
Description Chair of trial steering committee
Geographic Reach National 
Policy Influence Type Membership of a guideline committee
Impact I am chair of the steering committee for the VeRMiS trial which is a multi-centre study to assess the effectiveness of vestibular rehabilitation in people with Multiple Sclerosis. The trial outcomes will have imoplications for MS patients in the UK and beyond. Trial registry: https://doi.org/10.1186/ISRCTN27374299
URL https://www.plymouth.ac.uk/research/vermis
 
Description GP referral guidelines for dizziness and imbalance for the North West region of London (population 2 million)
Geographic Reach Local/Municipal/Regional 
Policy Influence Type Implementation circular/rapid advice/letter to e.g. Ministry of Health
Impact The online document also has teaching links, including videos I have made, showing GPs how to treat certain conditions. See: https://www.healthiernorthwestlondon.nhs.uk/sites/nhsnwlondon/files/documents/dizziness_guidelines_v0_6.pdf
 
Description Royal College of Physicians - Joint Clinical Neurosciences Committee - Acute Neurology Representative.
Geographic Reach National 
Policy Influence Type Membership of a guideline committee
 
Description Automated Diagnosis of Acute Vertigo
Amount £50,000 (GBP)
Organisation Imperial Health Charity 
Sector Charity/Non Profit
Country United Kingdom
Start 08/2019 
End 07/2020
 
Description Congressionally Directed Medical Research Program (CDMRP). Title: "Advancing Rehabilitation: Physiological, Psychological and Neuroimaging Measures of Factors that Predispose, Promote, and Perpetutate Post-Traumatic Dizziness"
Amount $2,000,000 (USD)
Organisation Department of Defense 
Sector Public
Country United States
Start 09/2019 
End 08/2022
 
Description HEE/ NIHR ICA Programme Clinical Doctoral Research Fellowship
Amount £300,310 (GBP)
Funding ID ICA-CDRF-2017-03-070 
Organisation National Institute for Health Research 
Department NIHR Fellowship Programme
Sector Public
Country United Kingdom
Start 05/2018 
End 04/2021
 
Description Low-cost high tech concussion assessment and post-fall health monitoring
Amount £230,000 (GBP)
Organisation The Racing Foundation 
Sector Charity/Non Profit
Country United Kingdom
Start 04/2019 
End 07/2020
 
Description NIHR Biomedical Research Centre Grant
Amount £92,430 (GBP)
Funding ID WMCT_P64219 
Organisation National Institute for Health Research 
Department NIHR Imperial Biomedical Research Centre
Sector Public
Country United Kingdom
Start 12/2017 
End 01/2019
 
Description Spinal cord stimulation for gait dysfunction in Parkinson's disease
Amount £205,000 (GBP)
Funding ID MR/T023880/1 
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 09/2020 
End 09/2023
 
Description Trial of spinal cord stimulation to reduce imbalance and falls in Parkinson's Disease
Amount £540,000 (GBP)
Organisation J P Moulton Charitable Foundation 
Sector Charity/Non Profit
Country United Kingdom
Start 04/2020 
End 04/2023
 
Description BPPV project collaboration 
Organisation University of Plymouth
Department Faculty of Health and Human Sciences
Country United Kingdom 
Sector Hospitals 
PI Contribution Developed application for new research programme. Expert knowledge and pilot data.
Collaborator Contribution Expert knowledge.
Impact Successful grant application.
Start Year 2018
 
Description Imperial-Zurich Concussion Collaboration 
Organisation University Hospital Zürich
Country Switzerland 
Sector Hospitals 
PI Contribution I visited my our Swiss colleagues in 2017 and again in January 2018 for a Swiss concussion conference when I was accompanied by one of my research team.
Collaborator Contribution Research ideas and data exchange.
Impact We are planning a joint FENS satellite conference in July 2018 in Berlin.
Start Year 2018
 
Description Spinal cord stimulation as a treatment for gait dysfunction in Parkinson's Disease 
Organisation Imperial College London
Department Division of Brain Sciences
Country United Kingdom 
Sector Academic/University 
PI Contribution Contributed in collecting pilot data and writing grant applications. My team will provide the scientific testing component needed to assess clinical outcomes as well as to explore the underlying brain mechanisms in any observed therapeutic effect of spinal cord stimulation on imbalance in Parkinson's disease.
Collaborator Contribution My partners, Dr Yen Tai and Mr Dipankar Nandi, are experts in the clinical neurology of Parkinson's disease (YT) and functional neurosurgery (DN).
Impact Mulit-disciplinary 1. Vestibular Neurology: Dr Barry M seemungal - head Brain Adn Vestibular Group, Imperial College London. 2. Movement Disorders: Dr Yen Tai. Imperial College Healthcare NHSb Trust. 3. Functional Neurosurgery: Prof Dipankar Nandi. Grants 1. MRC CARP grant: £205,000 for Dr Yen Tai, supervised by Dr Barry Seemungal. 2. Moulton Foundation Charity grant: £540,000 for Dr Yen Tai and Dr Barry Seemungal. NHS 1. A new joint clinic: BAN clinic - Balance And Neurodegeneration clinic, bringin together movement disorder and vestibular neurology expertise and the Imperial Balance Labs.
Start Year 2019
 
Description The Mechanisms of Postural Control and Spatial orientation in Dementia 
Organisation University of Cambridge
Country United Kingdom 
Sector Academic/University 
PI Contribution I am the primary supervision of a PhD student for this project.
Collaborator Contribution Professor James Rowe is co-supervising the PhD student for this project.
Impact None yet. The project started 3 months ago.
Start Year 2018
 
Description Understanding the mechanisms of chronic dizziness in mild Traumatic head injury 
Organisation Mayo Clinic Hospital
Country United States 
Sector Hospitals 
PI Contribution Collaborative approach to understanding the factors predispoing, promoting and perpetuating chronic dizziness post mild traumatic brain injury.
Collaborator Contribution We have together written a grant application submitted to the the US military. Outcome awaited.
Impact Grant application submitted to the the US military. Outcome awaited.
Start Year 2017
 
Description Understanding the mechanisms of chronic dizziness in mild Traumatic head injury 
Organisation University of Cambridge
Country United Kingdom 
Sector Academic/University 
PI Contribution Collaborative approach to understanding the factors predispoing, promoting and perpetuating chronic dizziness post mild traumatic brain injury.
Collaborator Contribution We have together written a grant application submitted to the the US military. Outcome awaited.
Impact Grant application submitted to the the US military. Outcome awaited.
Start Year 2017
 
Description Understanding the mechanisms of chronic dizziness in mild Traumatic head injury 
Organisation University of Rome Tor Vergata
Country Italy 
Sector Academic/University 
PI Contribution Collaborative approach to understanding the factors predispoing, promoting and perpetuating chronic dizziness post mild traumatic brain injury.
Collaborator Contribution We have together written a grant application submitted to the the US military. Outcome awaited.
Impact Grant application submitted to the the US military. Outcome awaited.
Start Year 2017
 
Description Neurology referral guidlines for GPs for Dizziness 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Referral guidlines to enable GPs to refer dizziness cases to the hospital. Included in the website were educational weblinks for the GPs. See URL.
Year(s) Of Engagement Activity 2019
URL https://www.healthiernorthwestlondon.nhs.uk/sites/nhsnwlondon/files/documents/dizziness_guidelines_v...
 
Description Press release concerning a trial that will look at new Parkinson's treatment for frequent falls 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact To make the target audiences aware of our initial funding to improve recruitment rates and additional funding applications (one obtained £540,000; one pending circa £100,000).
Year(s) Of Engagement Activity 2019
URL https://www.imperial.ac.uk/news/193546/trial-will-look-parkinsons-treatment-frequent/
 
Description Talk to 6 form students in a Comprehensive secondary school. 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact I enjoy motivating students, particularly those from less privileged backgrounds. I came to the UK from the West Indies aged 17, so I am able to relate to many younger people who are from imigrant families.
Year(s) Of Engagement Activity 2020
URL https://www.harriswestminstersixthform.org.uk/38/ambition-perseverance-legacy-
 
Description Talk to therapists on dizziness in mild TBI 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Professional Practitioners
Results and Impact Invited to talk on vestibular dysfunction following mild TBI at Imperial College Healthcare NHS Trust
Year(s) Of Engagement Activity 2018
 
Description Teaching therapists at Major Trauma Centres in London 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Professional Practitioners
Results and Impact Teaching ward therapists about dizziness following traumatic brain injury - how to assess and treat it.
Year(s) Of Engagement Activity 2018,2019,2020