Stroke Research Group

Professor Martin Brown and Dr David Werring

(E-mails: m.brown@ion.ucl.ac.uk and d.werring@ion.ucl.ac.uk)

Summary

The Stroke Research Group works in close collaboration with the Hyperacute Stroke Unit (HASU) at University College London Hospital (UCLH) and the Acute Brain Injury Unit based at Queen Square. Stroke is a priority Neuroscience theme within UCL Partners (UCLP), Europe’s largest and strongest academic health science partnership. The UCLP stroke partnership has delivered an effective and efficient clinical stroke network and consolidated hyper-acute services. We have dramatically increased thrombolysis rates and halved the door to needle times for hyper-acute stroke intervention at UCH, creating a network of shared expertise across all acute providers and working directly with community provision.

The Stroke Research Group is at the forefront of the development of innovative treatments to prevent stroke, particularly carotid angioplasty and stenting. Professor Martin Brown is the Chief Investigator on two international multicentre randomised trials of the treatment of carotid stenosis, and a member of the Steering and End-point Committees of three other multicentre trials of stroke treatments.

The group continues to be involved in research aimed at improving the acute treatment and secondary prevention of stroke - the major cause of adult physical disability in the UK. In addition, our translational research addresses the underlying mechanisms of cerebrovascular disease. We have a particular focus on cerebral microbleeds and small vessel disease, and how these relate to intracerebral haemorrhage and vascular cognitive impairment.

In addition to our own projects, the group currently collaborates in a large number of clinical trials and projects and is involved at the planning/approval stage of many others. We recruit patients for participation in studies from the Acute Brain Injury and Stroke Unit (ABIU) at the National Hospital for Neurology and Neurosurgery (NHNN) and the UCLH Trust Hyperacute Stroke Unit, and neurovascular clinics.

The Thames Stroke Research Network, based at UCLH is led by Professor Martin Brown, with Dr David Werring the Deputy Lead. The Thames Stroke Research Network has a large and active research portfolio. The network is the largest in the UK, and recruits from around 40 National Institute of Health Research (NIHR) portfolio studies across more than 30 Hospital Trusts. The Thames SRN covers a total population of around 10.5 million and has access to up to 6000 stroke patients per year at the constituent hospitals. The aims of the Thames SRN are to facilitate and develop clinical research in stroke, including randomised trials, and link well organised stroke services with primary care, tertiary care and translational science. Our vision is that we will work together to facilitate the conduct of high quality clinical research and foster the integration of research into clinical practice leading to improved treatment of stroke and its risk factors, which will prevent strokes more effectively and improve outcomes, and thus quality of life for people who have had a stroke and their families.

Selected current projects:

CAVATAS

 
In 2009, we completed follow-up and analysis of the Carotid And Vertebral Artery Transluminal Angioplasty Study (CAVATAS), funded by the British Heart Foundation, the Stroke Association and the NHS Management Executive, and have recently published two major papers in the Lancet and Lancet Neurology on the long-term (10 year) outcome of carotid angioplasty and carotid endarterectomy.
 
carotid stenosis2

ICSS

We recently completed randomisation in the International Carotid Stenting Study (ICSS), funded by the MRC and the Stroke Association. ICSS involved 50 centres in 16 countries throughout the world in three continents. An interim analysis of ICSS was published in the Lancet, exciting widespread interest in the international press and stroke academic community. The results of a sub-study using MRI as a surrogate measure of outcome was published in Lancet Neurology.

European Carotid Surgery Trial – 2 (ECST-2)

 This new multi-centre randomised trial of the treatment of carotid stenosis has recently received funding from NIHR (Research for Patient Benefit) to set up the study and conduct a pilot of the protocol over the next three years.

Carotid Stenting Trialists’ Collaboration (CSTC)

 Professor Brown has set up the CSTC with funding from the Stroke Association to bring together the trialists from the main international trials of carotid stenting and surgery, including ICSS, the French trial EVA-3S, the German trial SPACE and, in due course, the American trial, CREST. The collaboration has been successful in agreeing the pooling of data from the three European trials, and methods of analysis. The results of the first pooled meta-analysis of the data have been accepted for publication in the Lancet.

GOSH (Genetics Of Subarachnoid Haemorrhage)

 This is a multi-centre study of genetic polymorphisms in aneurysmal subarachnoid haemorrhage co-ordinated from UCL. Its aim is to investigate whether specific susceptibility loci are associated with ruptured intracranial aneurysms, and the interaction between genetic factors and aneurysm location. Dr David Werring is leading this genome-wide association study on the genetics of ruptured intracranial aneurysms, including detailed clinical phenotyping, in collaboration with Professor John Hardy and Dr Henry Houlden.

PrOMBiS (Predicting Outcome and Measuring Benefit from Botulinum toxin in Stroke)

 Dr David Werring has commenced a randomized controlled trial of botulinum toxin for the improvement of active upper limb function after stroke; this is the first trial of its kind to address this specific question. This is a phase IV randomised, placebo, controlled, double-blind, single centre out-patient Trial to investigate the functional benefit of botulinum toxin injections combined with physiotherapy treatment for spasticity of the upper limb after stroke (collaboration with Prof John Rothwell).

CROMIS Study (Clinical Relevance of Microbleeds in Stroke)

Dr David Werring and collaborators have successfully completed recruitment to a preliminary study of the clinical relevance of microbleeds in stroke (CROMIS), which has led to a number of papers in high quality journals. Follow up is in process. A new anatomical rating scale for microbleeds has been validated. The first data showing that hypertension is a risk factor for new microbleeds in the brain over 5 years has been published. We have also reported an association between microbleeds and intracerebral haemorrhage related to aspirin, in our own cohort and in collaboration with other centres around the world. New studies are investigating the impact of microbleeds and other imaging abnormalities on vascular cognitive impairment in a large cohort of stroke patients.

A 5-year programme grant from the British Hearth Foundation and The Stroke Association has been awarded (CI Dr David Werring) (2010) to continue this work, investigating the role of microbleeds and genetic factors in predicting the risk of intrwcerebral haemorrhage in patients prescribed anticoagulants after ischaemic stroke.

Cerebral amyloid angiopathy (CAA)

This disorder is an important cause of intracerebral haemorrhage and cognitive impairment, yet is under-recognized in clinical practice. As part of the CROMIS program, we are developing an increasing interest in this area, as microbleeds seem to be a key imaging marker for this condition. We aim to establish a large prospective cohort of CAA patients to characterize the natural history and establish biomarkers relevant to prognosis. 
Cerebral Amyloid Angiopathy2

Stroke Genetics

Dr David Werring, in collaboration with Prof J Hardy and Dr Henry Houlden is contributing to an international stroke genetics collaboration, the International Stroke Genetics Consortium.
Acute Lacunar Infarction2

International Stroke Trial 3 (IST-3)

We are participating in this international multi-centre, randomised, controlled trial to investigate the safety and efficacy of treatment with intravenous recombinant tissue plasminogen activator (rt-PA) within six hours of onset of acute ischaemic stroke.
CTAngiogramInAcuteStroke (2.JPG

Stroke-INF

This is a cluster randomised trial of different strategies of antibiotic use to reduce the incidence and consequences of chest infection in acute stroke patients with swallowing problems. The main hypothesis for the study is that prophylactic use of antibiotics (an "act first" approach) in acute stroke patients with swallowing problems on a bedside clinical assessment will be better than the current practice of monitoring for infection and treatment if necessary (a "wait and watch" approach) in reducing chest infections and their consequences in stroke patients.

IRIS

This is a randomized, placebo-controlled trial of pioglitazone, compared with placebo, for prevention of stroke and myocardial infarction after ischemic stroke and transient ischemic attack. The study will test the hypothesis that reducing insulin resistance and its sequelae with thiazolidinedione therapy will prevent stroke and myocardial infarction (MI) among patients with a recent ischemic stroke or transient ischemic attack (TIA).

More information about current research

For information on studies, research staff and sites within the Thames Stroke Research network please see: http://thames.uksrn.ac.uk/

For information on carotid intervention studies (CAVATAS/ICSS): www.cavatas.com

Carotid Stenting Trialists Collaboration Website: www.carotid-trialists.com

UCL Neuroscience: http://www.ucl.ac.uk/neuroscience/

UCL Partners : http://www.uclpartners.com/

Stroke@UCL is a network of scientists and clinicians working on Stroke related topics within UCL and its NHS Partners Institutions (CULPartners), including UCL Hospitals, Royal Free Hospital, Great Ormond Street Hospital and Moorfields NHS Trusts. Please see:

http://www.ucl.ac.uk/silva/stroke for more information.

Information for patients

The Stroke Association: http://www.stroke.org.uk/information/

Different strokes – support for younger stroke survivors:

http://www.differentstrokes.co.uk/

Information for stroke professionals

British Association of Stroke Physicians: http://www.basp.ac.uk/

NHS Evidence – Stroke: http://www.library.nhs.uk/stroke/

Research Team

Martin Brown, Professor of Stroke Medicine

(See Lancet profile: http://www.thelancet.com/journals/laneur/article/PIIS1474442209702522/fulltext?rss=yes)

Dr David Werring, Clinical Senior Lecturer in Neurology

Dr Roland Featherstone, Clinical Trials Manager

Jennifer Godwin, Network Manager, Thames Stroke Research Network

Dr Richard Perry, Consultant Neurologist and Hyperacute Stroke Research Lead

Dr Rob Simister, Clinical Lead, Hyperacute Stroke Unit

Dr Richard Greenwood, Clinical Lead, Acute Brain Injury and Stroke Service

Dr Nick Losseff, Clinical Lead, UCH Stroke Service

Dr Charlie Davie, Stroke Lead, UCL Partners

Research Fellows

Dr Simone Gregoire

Dr Varinder Alg

Dr David Doig

Stroke Research PA

Helen Tindall

Research Practitioners based at UCH

Christopher Hille, Lead Research Practitioner, Thames Stroke Research Network

Ms Vanessa Bassan, Research Practitioner, Thames Stroke Research Network

Mr Phillip Rayson , research

Teaching activity

Members of the group are active in undergraduate and postgraduate education. A weekly stroke teaching seminar is held on the Hyperacute Stroke Unit (HASU) at University College Hospital. Educational programmes for stroke clinical staff also take place on the HASU and Queen Square Acute Brain Injury and Stroke Unit. Members of the group lecture on MSc. courses in Clincial Neuroscience, Clinical Neurology and Advanced Neuroimaging at the Institute of Neurology. Professor Brown organizes a regular undergraduate half-day stroke training session, and Dr Werring organizes the Stroke day at the Queen Square Short Courses.

MD/PhD Supervision

Professor Brown and Dr Werring both supervise PhD and MD students. Dr Werring offers supervision for MSc research projects. If you are interested in clinical stroke research please contact Dr Werring or Professor Brown. 

Information about a career in Stroke Medicine

http://careers.bmj.com/careers/advice/view-article.html?id=20001084

Selected recent publications

Ederle J, Bonati LH, Dobson J, Featherstone RL, Gaines PA, Beard JD, Venables GS, Markus HS, Clifton A, Sandercock P, Brown MM; CAVATAS Investigators. Endovascular treatment with angioplasty or stenting versus endarterectomy in patients with carotid artery stenosis in the Carotid and Vertebral Artery Transluminal Angioplasty Study (CAVATAS): long-term follow-up of a randomised trial. Lancet Neurol. 2009 Oct;8(10):898-907. Epub 2009 Aug 28.

Bonati LH, Ederle J, McCabe DJ, Dobson J, Featherstone RL, Gaines PA, Beard JD, Venables GS, Markus HS, Clifton A, Sandercock P, Brown MM; CAVATAS Investigators. Long-term risk of carotid restenosis in patients randomly assigned to endovascular treatment or endarterectomy in the Carotid and Vertebral Artery Transluminal Angioplasty Study (CAVATAS): long-term follow-up of a randomised trial. Lancet Neurol. 2009 Oct;8(10):908-17. Epub 2009 Aug 28.

International Carotid Stenting Study investigators, Ederle J, Dobson J, Featherstone RL, Bonati LH, van der Worp HB, de Borst GJ, Lo TH, Gaines P, Dorman PJ, Macdonald S, Lyrer PA, Hendriks JM, McCollum C, Nederkoorn PJ, Brown MM.Carotid artery stenting compared with endarterectomy in patients with symptomatic carotid stenosis (International Carotid Stenting Study): an interim analysis of a randomised controlled trial. Lancet 2010 Mar 20;375(9719):985-97. Epub 2010 Feb 25.

Bonati LH, Jongen LM, Haller S, Flach HZ, Dobson J, Nederkoorn PJ, Macdonald S, Gaines PA, Waaijer A, Stierli P, Jäger HR, Lyrer PA, Kappelle LJ, Wetzel SG, van der Lugt A, Mali WP, Brown MM, van der Worp HB, Engelter ST; ICSS-MRI study group.New ischaemic brain lesions on MRI after stenting or endarterectomy for symptomatic carotid stenosis: a substudy of the International Carotid Stenting Study (ICSS). Lancet Neurol. 2010 Apr;9(4):353-62. Epub 2010 Feb 25

Gregoire SM, Jäger HR, Yousry TA, Kallis C, Brown MM, Werring DJ. Brain microbleeds as a potential risk factor for antiplatelet-related intracerebral haemorrhage: hospital-based, case-control study. J Neurol Neurosurg Psychiatry. 2010 Jun;81(6):679-84. PubMed PMID: 20522874. This was selected as Editors Choice, and a Podcast was recorded

Lovelock CE, Cordonnier C, Naka H, Al-Shahi Salman R, Sudlow CL; Edinburgh Stroke Study Group, Sorimachi T, Werring DJ, Gregoire SM, Imaizumi T, Lee SH, Briley D, Rothwell PM. Antithrombotic drug use, cerebral microbleeds, and intracerebral hemorrhage: a systematic review of published and unpublished studies. Stroke. 2010 Jun;41(6):1222-8. Epub 2010 Apr 29. PubMed PMID:20431083.

Gregoire SM, Werring DJ, Chaudhary UJ, Thornton JS, Brown MM, Yousry TA, Jäger HR. Choice of echo time on GRE T2*-weighted MRI influences the classification of brain microbleeds. Clin Radiol. 2010 May;65(5):391-4. Epub 2010 Feb 13. PubMed PMID: 20380939.

Gregoire SM, Chaudhary UJ, Brown MM, Yousry TA, Kallis C, Jäger HR, Werring DJ. The Microbleed Anatomical Rating Scale (MARS): reliability of a tool to map brain microbleeds. Neurology. 2009 Nov 24;73(21):1759-66. PubMed PMID: 19933977.

Gregoire SM, Brown MM, Collas DM, Jacob P, Lachmann RH, Werring DJ. Posterior circulation strokes without systemic involvement as the presenting feature of Fabry disease. J Neurol Neurosurg Psychiatry. 2009 Dec;80(12):1414-6. PubMed PMID: 19917829.

Gregoire SM, Brown MM, Kallis C, Jäger HR, Yousry TA, Werring DJ. MRI detection of new microbleeds in patients with ischemic stroke: five-year cohort follow-up study. Stroke. 2010 Jan;41(1):184-6. Epub 2009 Nov 5. PubMed PMID: 19892991.

Werring DJ. Reversible cerebral vasoconstriction and intracerebral haemorrhage: some answers, many questions. Stroke 2010 (in press).

Page last modified on 28 oct 10 16:02