Developmental Clinical Studies - Does Repeated Vestibular Stimulation Induce Lasting Recovery From Hemi-Spatial Neglect?

Lead Research Organisation: University of Kent
Department Name: Research Services

Abstract

The research will pilot a new treatment for hemi-spatial neglect. This is an attentional disorder that commonly arises after stroke, causing sufferers to act as if one half of their visual world is missing. Symptoms include bumping into objects, leaving food on one side of the plate, and failing to notice people on the affected side. Aside from these debilitating effects, the condition strongly predicts the rate at which individuals recover from the other symptoms of stroke. Many individuals who show hemi-spatial neglect at hospital admission still struggle with daily routine years later. The current treatment provides little relief.
Our new approach involves passing tiny electrical currents through the part of the scalp that lies just behind the ears. The currents are too small to cause discomfort, but stimulate nerve pathways that project from the inner ear to those parts of the brain that are damaged. Unlike the current treatment which requires specialist staff and space, stimulation can be applied by a nurse at bedside with no technical expertise and at whatever time is convenient for the patient. More so, the apparatus can be cheaply miniaturised for personal use at home, reducing hospital stay and saving on the need to travel to clinic.
A major drawback of our treatment is that the beneficial effects disappear as soon as stimulation is stopped. We need to find a way of triggering effects that last for much longer. Other kinds of neuro-stimulation are most effective when repeatedly applied across 5-10 days, inducing gains in stroke survivors that last for many weeks. Our own pilot data, albeit very preliminary, suggests that the same pattern holds for the new technique described here. A larger, properly controlled study is now needed to confirm this observation. Compellingly, other types of neuro-disability including aspects of dementia also recede during vestibular stimulation, so if lasting recovery is shown here then other types of patient might also be expected to benefit.
We plan to recruit 60 individuals with hemi-spatial neglect from the East Kent Neuro-Rehabilitation Service to receive both 10 days of stimulation and then several follow-up sessions a few weeks later. These follow-ups will tell us whether lasting improvement has occurred, enabling us to determine if the technique might be relevant to rehabilitative practice. If so, then we will begin further trials with a miniature device that is currently undergoing validation by a downstream commerical collaborator.

Technical Summary

Hemi-spatial neglect is a debilitating, attentional disorder that is difficult to treat. Sufferers behave as if one side of their visual world (usually the left) is missing, often colliding with obstacles and failing to acknowledge people on their affected side. The condition significantly lengthens hospital stay and is the strongest predictor of general functional recovery from stroke. We need funds to pilot a potentially more effective and cost-saving treatment based on painless, non-invasive stimulation of the vestibular nerves. These nerves convey information from the balance organs to parts of the brain involved in spatial attention. While a single session of stimulation provides immediate relief from the symptoms of neglect, these resurface shortly after stimulation is stopped. The present study will tell us whether repeated, daily sessions induce longer-lasting relief that could have relevance to rehabilitative practice. 60 individuals with hemi-spatial neglect will receive either 1, 5 or 10 sessions of stimulation and then undergo testing several weeks later to establish whether lasting remission has occurred. We need to show ?proof of carry-over? before a more controlled investigation of efficacy can proceed, and further development can occur on an inexpensive, portable device that is suitable for self-administration.
 
Description Citation in Annual Parliamentary Report on RandD in Assistive Technology
Geographic Reach National 
Policy Influence Type Citation in other policy documents
 
Description Director, NIHR Research Design Service South East
Geographic Reach National 
Policy Influence Type Citation in other policy documents
Impact The NIHR research design service provides methodological and other forms of preparatory support for healthcare and social care funding applications to the NIHR, MRC and other relevant funding bodies with a view to improving longterm national outcomes.
URL http://www.rds-se.nihr.ac.uk
 
Description Member of working group to formulate RandD strategy for East Kent Hospitals University NHS Foundation Trust
Geographic Reach Local/Municipal/Regional 
Policy Influence Type Participation in advisory committee
Impact Increases in the frequency and quality (as measured by external funding and journal outputs) of clinical research within the hospital trust; More stream-lined and effective monitoring and facilitation of trust research
 
Description Presentation of study data about mild traumatic brain injury in military veterans to the All Party Parliamentary Group on Acquired Brain Injury
Geographic Reach National 
Policy Influence Type Gave evidence to a government review
Impact Our study highlights the lifetime prevalence of mild traumatic brain injury in UK military veterans and its longterm effect on mental well-being
 
Description Regional HEI/ NHS Health and social care research strategy
Geographic Reach Local/Municipal/Regional 
Policy Influence Type Membership of a guideline committee
Impact Change in NHS and HEI health/social care research strategy
 
Description Research conduct instruction to new hospital consultant physicians
Geographic Reach Local/Municipal/Regional 
Policy Influence Type Influenced training of practitioners or researchers
 
Description Collaboration between Planned Parkinson's Centre and Kent Multiple Sclerosis Therapy Centre 
Organisation Multiple Sclerosis Society
Country United Kingdom 
Sector Charity/Non Profit 
PI Contribution Initial talks to locate our planned clinical, research and education centre for Parkinson's disease in the purpose built MS Therapy Centre
Collaborator Contribution Work towards an MoU
Impact n/a
Start Year 2022
 
Description East Kent Hospitals University NHS Foundation Trust 
Organisation East Kent Hospitals University NHS Foundation Trust
Department Neuro-rehabilitation Service
Country United Kingdom 
Sector Hospitals 
PI Contribution (1) Given talks to clinical staff to raise understanding about the cause, diagnosis, and management of certain stroke disorders. (2) Patient assessment (3) Patient rehabilitation
Collaborator Contribution (1) Provision of patients for our research (2) Clinical oversight for our research (3) Payment of NHS treatment costs (£10,500)
Impact (1) PMID: 22483722 (Multi-disciplinary: Medicine/Neuroscience/Psychology/Rehabilitation) (2) PMID: 21991592 (Multi-disciplinary: Medicine/Neuroscience/Psychology) (3) PMID: 21447917 (Multi-disciplinary: Medicine/Neuroscience/Psychology/Rehabilitation) (4) PMID: 19697173 (Multi-disciplinary: Medicine/Neuroscience/Psychology/Rehabilitation) (6) PMID: 19706224 (Multi-disciplinary: Medicine/Neuroscience/Psychology/Rehabilitation) (7) Various international conference presentations including: (i) Sakel M, Wilkinson DT (2012). Patients with hemi-spatial neglect are more prone to limb spasticity, but this does not prolong their hospital stay. American Congress of Rehabilitation Medicine 2012 Annual Meeting, Vancouver, Canada. (ii) Wilkinson DT, Sakel M. (2009). 'Safety of Super-Sensory Galvanic Vestibular Stimulation Following Stroke: A Single-Case Study'. 2009 World Neurology Congress, Thailand.
Start Year 2007
 
Description GVS development 
Organisation Rogue Resolutions Ltd
Country United Kingdom 
Sector Private 
PI Contribution downstream development planning to gain regulatory compliance for their mobile GVS device
Collaborator Contribution downstream development planning to gain regulatory compliance for their mobile GVS device
Impact Front Integr Neurosci. 2014 Jan 29;8:4. doi: 10.3389/fnint.2014.00004. eCollection 2014. Galvanic vestibular stimulation in hemi-spatial neglect. Wilkinson D1, Zubko O1, Sakel M2, Coulton S3, Higgins T3, Pullicino P2. Author information Abstract Hemi-spatial neglect is an attentional disorder in which the sufferer fails to acknowledge or respond to stimuli appearing in contralesional space. In recent years, it has become clear that a measurable reduction in contralesional neglect can occur during galvanic vestibular stimulation, a technique by which transmastoid, small amplitude current induces lateral, attentional shifts via asymmetric modulation of the left and right vestibular nerves. However, it remains unclear whether this reduction persists after stimulation is stopped. To estimate longevity of effect, we therefore conducted a double-blind, randomized, dose-response trial involving a group of stroke patients suffering from left-sided neglect (n = 52, mean age = 66 years). To determine whether repeated sessions of galvanic vestibular stimulation more effectively induce lasting relief than a single session, participants received 1, 5, or 10 sessions, each lasting 25 min, of sub-sensory, left-anodal right-cathodal noisy direct current (mean amplitude = 1 mA). Ninety five percent confidence intervals indicated that all three treatment arms showed a statistically significant improvement between the pre-stimulation baseline and the final day of stimulation on the primary outcome measure, the conventional tests of the Behavioral Inattention Test. More remarkably, this change (mean change = 28%, SD = 18) was still evident 1 month later. Secondary analyses indicated an allied increase of 20% in median Barthel Index (BI) score, a measure of functional capacity, in the absence of any adverse events or instances of participant non-compliance. Together these data suggest that galvanic vestibular stimulation, a simple, cheap technique suitable for home-based administration, may produce lasting reductions in neglect that are clinically important. Further protocol optimization is now needed ahead of a larger effectiveness study.
Start Year 2010
 
Description Parkinson's Care and Support UK 
Organisation Parkinsons Care and Support UK
Country United Kingdom 
Sector Charity/Non Profit 
PI Contribution new collaboration to launch a new clinical, education and research centre for Parkinson's disease
Collaborator Contribution financial, strategic and operational
Impact n/a
Start Year 2020
 
Description Scion Neurostim 
Organisation Scion NeuroStim
Country United States 
Sector Private 
PI Contribution Scion Neurostim have provided free vestibular stimulation equipment and a potable EEG unit for studies post-MRC funding and also provided methodological and conceptual advice for my group's on-going studies. They have also funded an RCT that assesses the effect of vestibular stimulation on episodic migraine
Collaborator Contribution Data sharing with Scion and its other academic collaborators
Impact Wilkinson DT, Morris R, Milberg W et al. (2013). Caloric vestibular stimulation in aphasic syndrome. Frontiers in Integrative Neuroscience, 7 (99). pp. 1-9. Wilkinson, D., Podlewska, A., & Sakel, M. (2016). A durable gain in motor and non-motor symptoms of Parkinson's Disease following repeated caloric vestibular stimulation: A single-case study. Neurorehabilitation, 1-4. doi:10.3233/NRE-161308
Start Year 2012
 
Title Does repeated vestibular stimulation induce lasting recovery from hemi-spatial neglect? 
Description The intervention involves the novel application of galvanic vestibular stimulation to the neurological condition of hemi-spatial neglect, a post-stroke visual attentional impairment. Our double-blind RCT sought initial proof-of-effect (n=52) for the procedure, comparing the safety and efficacy of different treatment doses at 4 weeks post-intervention. We are now preparing a new funding application to the MRC to support a second round of protocol optimisation prior to a much larger effectiveness study. 
Type Therapeutic Intervention - Medical Devices
Current Stage Of Development Early clinical assessment
Year Development Stage Completed 2012
Development Status Actively seeking support
Clinical Trial? Yes
Impact Ninety five percent confidence intervals (n=52) indicated that all three treatment arms showed a statistically significant improvement between the pre-stimulation baseline and the final day of stimulation on the primary outcome measure, the conventional tests of the Behavioural Inattention Test. This change (mean change=28%, SD=18) was still evident 1month later. Secondary analyses indicated an allied increase of 20% in median Barthel Index score, a measure of functional capacity, in the absence of any adverse events or instances of participant non-compliance. Together these data suggest that galvanic vestibular stimulation, a simple, cheap technique suitable for home-based administration, may produce lasting reductions in neglect that are clinically important. Further protocol optimization is now needed ahead of a larger effectiveness study. 
URL http://public.ukcrn.org.uk/Search/StudyDetail.aspx?StudyID=10505
 
Title iPad app for improved diagnosis of hemi-spatial neglect 
Description This project aims to develop and evaluate a mobile application for diagnosing hemi-spatial neglect (HSN). HSN is a debilitating, neurological disorder in which the sufferer fails to perceive stimuli on one side of space. Common symptoms involve failing to notice people on the affected side, becoming lost, bumping into objects, and failing to groom or wash parts of the body. The condition is estimated to affect one half of all stroke survivors, and is the strongest predictor of long-term disability post-stroke, significantly prolonging length of inpatient stay and increasing the need for assisted living after discharge. The established method of diagnosing HSN is the Behavioural Inattention Test, a paper and pencil test. Unfortunately, this is time-consuming, requires technical expertise to administer, is open to subjective interpretation, and must be conducted within a dedicated quiet room. Clinicians and hospital managers tell us that a quicker and cheaper means of diagnosis is needed that can be more easily integrated into standard, routine assessment. Our proposed Apple iPad application will meet this need. A working prototype has already been constructed and is now ready to undergo clinical validation. 
Type Diagnostic Tool - Non-Imaging
Current Stage Of Development Early clinical assessment
Year Development Stage Completed 2014
Development Status Under active development/distribution
Impact still under validation 
 
Title thermo-neuromodulation device 
Description The device is currently under going FDA/MHRA CE approval for use as a neuro-stimulation treatment for various neurological diseases 
Type Therapeutic Intervention - Medical Devices
Current Stage Of Development Initial development
Year Development Stage Completed 2012
Development Status Under active development/distribution
Impact currently under-going FDA/MHRA CE marking trial in UK and USA double-blind efficacy RCT just completed and shown 50% reduction in the frequency of episodic migraine 
URL http://www.companyname.com
 
Description BBC Radio Kent 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Type Of Presentation Keynote/Invited Speaker
Geographic Reach Regional
Primary Audience Media (as a channel to the public)
Results and Impact BBC Radio Kent (25/8/2011) featured Dr Olga Zubko (study assistant employed by MRC grant) and Dr Mo Sakel (consultant physician in neuro-rehabilitation) describing the phenomenon of hemi-spatial neglect, its impact on families, and ways in which it might potentially be overcome.

Increased patient referrals for the study
Year(s) Of Engagement Activity 2011
 
Description Hospital Trust magazine 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Type Of Presentation Keynote/Invited Speaker
Geographic Reach Regional
Primary Audience Participants in your research and patient groups
Results and Impact Full-page spread (on page 1) in the quarterly magazine of the local hospital trust (April/May 2011) magazine. The article highlights Dr Wilkinson's brain stimulation work with hemi-spatial neglect patients and, given the general impact on functional recovery from stroke, aims to encourage physicians and carers to prioritize the diagnosis and treatment of the condition. The magazine is distributed widely across East Kent to employees, visitors and patients of the hospital trust.

My MRC study was featured in the local hospital trust's published celebration of its 75th Anniversary, under the headline, 'The Medicine of the Future' (half-page spread), with the intention of raising public awareness about certain post-stroke conditions.

Invited to present my stimulation research to the hospital trust's annual R&D symposium for clinicians and other healthcare professionals
Year(s) Of Engagement Activity 2011,2012
 
Description Invited talks to healthcare professionals, academics and clinical academics + chair of international research symposiums 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Media (as a channel to the public)
Results and Impact -----
2017-2020:
'Caloric Vestibular Stimulation in Parkinson's disease', Parkinson's UK research conference: accelerating research and improving care, Imperial College London, UK.

*'Vestibular Stimulation as a tool for neurorehabilitation', American Congress of Rehabilitation Medicine 2019 Annual Conference, Chicago, USA
*At the same meeting, co-chair of the 'Vestibular Cognition' symposium.

'The effects of Brainstem Modulation Therapy on Cognition Impairment in Parkinson's Disease'. International Parkinson and Movement Disorder Society, Nice, France.

'Neuromodulation: A key rehabilitation tool?' 9th Brain Injury Multi-disciplinary conference, Kent & Canterbury Hospital, Kent, UK.

'Vestibular Stimulation: an adjuvant therapy for cognitive and psychiatric impairment', British Neuroscience Association 2019 Annual Meeting, Dublin, Ireland*.
*At the same meeting, co-chair of the 'Vestibular Cognition' symposium.

'Vestibular Stimulation in Parkinson's Disease', World Parkinson's Day, King's College Parkinson's National Centre, London, UK.

'Vestibular Stimulation: an adjuvant therapy for cognitive and psychiatric impairment', Kent Clinical Neuropsychology Service, St Martin's Hospital, Canterbury, UK

'Caloric Vestibular Stimulation for the management of motor and non-motor symptoms in Parkinson's Disease', East Kent Hospitals Brain Injury Multi-disciplinary conference.

'Neurostimulation for the rehabilitation of brain Injury', Tonbridge Acquired Brain Injury group, UK.

'Caloric Vestibular Stimulation for the management of motor and non-motor symptoms in Parkinson's Disease', Aix-Marseille Université, Marseille, France.

'Bringing Balance to the Brain - harnessing the vestibular system for neuro-rehabilitation', Brain Injury Group, London.

'Caloric Vestibular Stimulation in Parkinson's Disease', Parkinson's UK, UK.

'Neuropsychiatric outcomes in UK military veterans with mild traumatic brain injury and vestibular dysfunction', Translational Centre for Traumatic Brain Injury and Stress Related Disorders, VA Boston Healthcare system and Harvard Medical School, Boston, USA.

'Neuropsychiatric outcomes in UK military veterans with mild traumatic brain injury and vestibular dysfunction', 8th Brain Injury Multi-disciplinary conference, Kent & Canterbury Hospital, Kent, UK.

'Caloric vestibular stimulation in the management of episodic migraine', 11th Word Congress on Neurology & Therapeutics, Spain.

'Cross-modal interactions between the vestibular system and visual short-term memory', Experimental Psychology Society, London, UK

-----

'Stimulating the vestibular system in health and disease', Beth Israel Deaconess Cognitive Neurology Grand Round Seminar Series, Boston, USA, 2016.

'A durable gain in motor and non-motor symptoms of Parkinson's Disease following repeated caloric vestibular stimulation: A single-case study', 10th Word Congress of International Physical and Rehabilitation Medicine, Kuala Lumpar, Malaysia, 2016.

'Cognitive and psychiatric comorbidities in patients with vestibular disorder', The British Neuropsychiatry Association Annual Meeting, UK, 2016. Also accepted at The American Academy of Neurology 68th Annual Meeting, Vancouver, Canada, 2016.

'Vestibular Stimulation in Acquired Brain Injury', Annual Meeting of the Association of Chartered Physiotherapists Interested in Neurology, Northampton, UK, 2015.

'Incidence and co-occurrence of neglect and spasticity, a prospective multi-centre study', American Congress of Rehabilitation Medicine Meeting, Dallas, USA, 2015.

'Caloric Vestibular Stimulation Modulates High Level Face Processing', European Conference on Visual Perception (ECVP), Liverpool, UK. 2015.

'Caloric Vestibular Stimulation in Low Awareness States', 11th Conference of the Neuropsychological Rehabilitation Special Interest Group of the World Federation of NeuroRehabilitation (WFNR), Cyprus, 2014.

'Vestibular Stimulation Therapy for Prosopagnosia', Experimental Psychology Society London Meeting, UK, 2014.

'Can Galvanic Vestibular Stimulation Induce Lasting Relief from Spatial Neglect?', American Congress of Rehabilitation Medicine Meeting, Toronto, Canada, 2014.

'Caloric Vestibular Stimulation in Traumatic Brain Injury?', BPS Division of Neuropsychology Annual Conference, UK, 2014.

'Vestibular Stimulation in brain disorder - is there a role for improving arousal and vigilance in acquired brain injury?', Symposium on sleep and fatigue after brain injury, Raphael Medical Centre, UK, 2014.

'Galvanic Vestibular Stimulation in Limb Spasticity', Spasticity Research in East Kent Symposium, Kent & Canterbury Hospital, Kent, UK, 2014.
'Neuro-modulation for post-stroke hemi-spatial neglect', 5th Brain Injury Multi-disciplinary conference, Kent & Canterbury Hospital, Kent, UK, 2014.

'The effects of vestibular stimulation on acquired brain injury', Experimental Psychology Society Workshop on Vestibular Cognition, UCL, 2014.
'Vestibular stimulation as a therapy for patients in persistent vegetative state', Annual Christmas Lecture of the Association of Chartered Physiotherapists Interested in Neurology (ACPIN), 2013.

'Caloric Vestibular Stimulation (CVS) may improve aphasia and mobility, a novel study', American Congress of Rehabilitation Medicine Meeting, Florida, USA, 2013.

'Can Galvanic Vestibular Stimulation promote recovery from cerebellar dysfunction? 11th Word Congress of the International Neuromodulation Society, Berlin, 2013.

'Are we neglecting neglect?', Second World Conference on Medical Rehabilitation in Rural and Developing Regions, International Rehabilitation Forum, Dhaka, 2012.

'Do repeated sessions of galvanic vestibular stimulation induce lasting relief from hemi-spatial neglect?' Mid-Year Meeting of the International Neuropsychological Society, Oslo, Norway, 2012.

'Patients with hemi-spatial neglect are more prone to limb spasticity but this does not prolong their hospital stay'. American Congress of Rehabilitation Medicine Meeting, Vancouver, Canada, 2012.

'Galvanic vestibular stimulation in hemi-spatial neglect', British Psychological Society Cognitive Psychology Section Annual Conference, Glasgow, Scotland, 2012.

'Improving the visual perception of stroke sufferers via stimulation of the inner ear', 15th Annual Conference of Recent Advances in Brain Injury Rehabilitation, Homerton University Hospital, London, 2011.



A new collaboration with clinicians from a hospital in Dhaka has been initiated to develop our stimulation therapy in Bangladesh.

A new collaboration with a medical device company in the USA has been initiated to develop the delivery system for our stimulation method. The company recently awarded us £92K to help broaden the range of neurological conditions studied.

Pilot study completed (article under review ) assessing the effects of vestibular stimulation on other types of disorders of c
Year(s) Of Engagement Activity 2008,2009,2010,2011,2012,2013,2014,2015,2016,2017,2018,2019,2020
 
Description Keynotes speeches, invited presentations, conference platform talks 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Dissemination of research / trials data
Increasing public awareness of neurological disease and neurorehabilitation
Year(s) Of Engagement Activity 2014,2015,2016,2017,2018,2019,2020
 
Description National newspaper coverage 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Type Of Presentation Keynote/Invited Speaker
Geographic Reach International
Primary Audience Media (as a channel to the public)
Results and Impact Examples include: (1) Three-quarter page spread in Daily Mail newspaper entitled, 'Help at least for stroke victims who are left with only half a life (p34, 23/8/2011), highlighting the need for healthcare workers and patients' families to devote greater effort to the diagnosis and management of cognitive impairment post-stroke. The potential merit of our MRC trial was also outlined.

(2) A similar half page spread was featured in the local newspaper (KM Gazette, 16/6/2011).

Patients (and their carers) got in touch to say that they found the article useful because it helped them to describe their experiences to relatives/friends.
Year(s) Of Engagement Activity 2011,2015,2016,2017
 
Description TV Interviews (BBC South East, ITV Meridian) 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Type Of Presentation Keynote/Invited Speaker
Geographic Reach Regional
Primary Audience Media (as a channel to the public)
Results and Impact ITV Meridian 6 O'clock News (2mins 14s, 9/5/2011) featured Dr Wilkinson and the director of the East Kent Neuro-rehabilitation Service talking to a stroke patient about how she felt she had benefited from our vestibular stimulation treatment. Aside from raising understanding about the potential merit of neuro-stimulation post-stroke, the news-piece also informed the public about the types of less observable, but nevertheless debilitating, cognitive deficit that can accompany stroke.

As above, the BBC TV South East Today evening news (2mins 41s, 24/08/2011) featured a patient along with Dr Olga Zubko (a post-doctoral researcher from Dr. Wilkinson's group) describing how he felt he had benefited from our stimulation treatment.

Subsequent reports of this coverage have been reproduced on many scientific and medical websites.

Increased number of patient referrals to our study

Full-page article in Stroke Watch, the quarterly magazine of East Kent Strokes, a stroke charity run by stroke survivors for stroke survivors. The article was aimed at increasing patients' and carers' awareness of hemi-spatial neglect, underlining the dramatic effect it has on functional independence, and the need for effective management.

The TV footage prompted East Kent Hospitals Trust to feature our research study as one of the two patient
Year(s) Of Engagement Activity 2011,2012,2013,2014,2016