Stroke Research Themes Across UCL

Our research strengths include:

• observational studies in stroke prevention, advanced neuroimaging, carotid artery disease, small vessel disease and intracerebral haemorrhage, and neurorehabilitation
• links between infection and inflammation and stroke, including the consequences of  COVID-19, HIV, varicella and other viruses
• assessment and understanding of the cognitive and psychological consequences of stroke
• complex modelling
• randomised controlled trials in acute stroke and stroke prevention including carotid artery disease, small vessel disease and intracerebral haemorrhage, and anticoagulation
• neuroscience-based mechanistic and applied studies of neurorehabilitation in cognitive and motor domains
• innovative clinical stroke pathways for diagnosis, treatment and follow-up
• vascular neurosurgical research with a focus on intracranial and subarachnoid haemorrhage

Basic Neuroscience

Professor David Attwell - Attwell lab - UCL Dept of Neuroscience, Physiology & Pharmacology

The Attwell lab studies neuron-glial interactions and brain energy supply. A major focus of current work is how pericytes control cerebral blood flow at the capillary level. On this topic, the lab have shown that:

(1) pericytes regulate capillary diameter in the retina and brain (Peppiatt et al. (2006);

(2) different signalling pathways regulate control of blood flow by pericytes and by arteriolar smooth muscle (Mishra et al. 2016);

(3) after stroke, CNS pericytes constrict and die in rigor, producing a long-lasting decrease of cerebral blood flow (the no-reflow phenomenon phenomenon: Hall et al., 2014);

(4) a similar no-reflow phenomenon mediated by pericytes occurs after cardiac ischaemia (O’Farrell et al., 2017);

(5) in human subjects developing Alzheimer’s disease, brain capillaries become constricted by pericytes, apparently as a result of amyloid beta evoking the release of endothelin-1 (Nortley et al., 2019).

For other areas of the lab’s work, please see the website above.

Work in the lab is supported by Investigator Awards from the Wellcome Trust and European Research Council, and a grant from the Rosetrees Trust.

References

Hall, C.N., Reynell, C., Gesslein, B., Hamilton, N.B., Mishra, A., Sutherland, B., O’Farrell, F.M., Buchan, A.M., Lauritzen, M. & Attwell, D. (2014) Capillary pericytes regulate cerebral blood flow in health and disease. Nature 508, 55-60.

Mishra, A., Reynolds, J., Chen, Y., Gourine, A., Rusakov, D. & Attwell, D. (2016) Astrocytes mediate neurovascular signalling to capillary pericytes but not to arterioles. Nature Neuroscience 19, 1619-1627.

Nortley R, Korte N, Izquierdo P, Hirunpattarasilp C, Mishra A, Jaunmuktane Z, Kyrargyri V, Pfeiffer T, Khennouf L, Madry C, Gong H, Richard-Loendt A, Huang W, Saito T, Saido TC, Brandner S, Sethi H, Attwell D. (2019) Amyloid oligomers constrict human capillaries in Alzheimer’s disease via signaling to pericytes. Science 365, 250 DOI: 10.1126/science.aav9518.

O’Farrell, F.M., Mastitskaya, S., Hammond-Haley, M., Freitas, F., Wah, W.R. & Attwell, D. (2017)  Capillary pericytes mediate coronary no-reflow after myocardial ischaemia. Elife. 2017 Nov 9;6. pii: e29280. doi: 10.7554/eLife.29280.

Peppiatt, C.M., Howarth, C., Mobbs, P. & Attwell, D. (2006) Bidirectional control of CNS capillary diameter by pericytes Nature 443, 700-704. News and Views on this paper: http://www.nature.com/nature/journal/v443/n7112/full/443642a.html

Neuroimaging (Neuroradiology)

Professor Mark Lythgoe

Professor Mark Lythgoe is the Founder and Director of the Centre for Advanced Biomedical Imaging (CABI) at UCL, which is a new multidisciplinary research centre for experimental imaging. The Centre now hosts 10 state-of-the-art imaging modalities and 50 researchers. Mark is also Director of Biomedical Imaging Research at the Francis Crick Institute.

Centre for Advanced Biomedical Imaging:   http://www.ucl.ac.uk/cabi/

collaborates with stroke researchers at UCL and internationally, utilising state-of-the-art imaging techniques to advance research into stroke mechanisms.  For specific details of stroke neuroradiology see the relevant sections below. 

For detailed information on stroke imaging, see the below section ‘Carotid and Large Artery Disease’.

Carotid and Large Artery Disease

Carotid and large artery research is led at UCL by Martin Brown and Leo Bonati.  

Emeritus Professor Martin Brown made a major contribution to this area of research.  Carotid artery stenosis is an important cause of stroke. Professor Brown led the Carotid and Vertebral Artery Transluminal Angioplasty Study (CAVATAS) and the International Carotid Stenting Study (ICSS). These were multicentre randomised controlled trials comparing carotid endarterectomy with endovascular treatment (angioplasty with or without stenting) for recently symptomatic carotid stenosis. CAVATAS showed that endovascular treatment had similar major risks and effectiveness at prevention of stroke during 3 years compared with surgery with the advantage of avoiding minor complications such as cranial neuropathy. This research programme on carotid artery surgery and stenting has had substantial influence on practice and service delivery and the prevention of stroke from carotid artery atherosclerosis The results informed the National Clinical Guidelines for Stroke and the NICE recommendations on Carotid Stenting. ICSS was a follow on study from CAVATAS, comparing primary stenting with carotid surgery. ICSS has promoted the prudent development of optimal carotid stenting in the UK and incorporates arrangements for training radiologists in carotid stenting.  

Dr Leo Bonati is a stroke researcher and neurologist at the University Hospital in Basel, Switzerland.

Small Vessel Disease and Intracerebral Haemorrhage (including cerebral amyloid angiopathy)

Professor David Werring leads research into small vessel disease (SVD) and intracerebral haemorrhage (ICH).

Professor Werring explains his work on brain haemorrhages in this video.  

Hyperacute Stroke

Professor Rolf Jager and Dr Richard Perry lead this area of research.  Rolf Jager is a member of the UCL Queen Square Institute of Neurology Department of Brain Repair and Rehabilitation, Neuroradiology area, and Richard Perry is a Consultant Neurologist and research lead on the Hyper-acute Stroke Unit at the National Hospital for Neurology and Neurosurgery in Queen Square (NHNN).  Currently they are leading the PISTE Trial at the NHNN which is showing the value of thrombectomy in the UK.

For details of Hyperacute trials, please visit: Hyperacute Trials

SIGNaL

The Stroke Investigation Group in North and Central London (SIGNaL) is a large stroke registry study that follows patients from hyperacute care to follow-up in the community.  It is capturing routine clinical data, adverse events, neuroimaging at baseline and uses detailed functional outcome measures at 6 months and beyond.  The lead investigator is Dr Rob Simister.

High-Dimensional Neurology

Led by Professor Parachkev Nachev, this group’s research goals are:

(1)  To apply to neurological research innovative inferential approaches that do not assume that causal relations in biology are sufficiently stereotyped across individuals to be adequately characterised by conventional methods.  (2) To use large-scale, high-dimensional analysis of rich clinical datasets to identify non-intuitive patterns within the data that are individually clinically predictive and illuminative of the highly complex casual mechanisms we believe are likely to obtain in reality.  

Funded Research Projects:  Automatic anomaly detection for brain imaging triage and classification (Wellcome Trust/DoH Health Innovation Challenge Fund).

Upper Limb Rehabilitation

Professor Nick Ward leads a team researching upper limb rehabilitation:

In 2020 COVID-19 restrictions prevented in-person therapy, and this gave rise to remote therapy under the name NROL (Neurorehabilitation online), supported by SameYou.  See full information and videos about the project here.

Aphasia/Cognition

Professor Alex Leff leads the Neurotherapeutics lab where his team are developing online and digital therapies to support recovery.

Therapy Apps. Eye-Search. Eye-Search is a free online therapy for patients with visual search problems caused by brain injury. It is a clinically proven, behavioural therapy designed to improve patients’ speed and accuracy when finding objects. Read-Right.

https://www.ucl.ac.uk/aphasialab/alex/home.html

Prof Alex Leff’s current research and interests:

Brain imaging studies of aphasia and alexia. Web-based therapies for patients with visual impairment or language impairment.

Lasting language dysfunction is among the most feared and disabling symptoms complicating stroke, yet there is little in the way of an evidence base for its treatment. This is because the mechanisms underpinning recovery from language disorders are not understood and trial interventions are generally not tested within rigorously designed studies. My work is aimed at filling in both these knowledge gaps simultaneously by combining modern trial-based methodology with functional imaging techniques so that the neural correlates of therapy driven recovery can be identified. My work is split between two common post-stroke syndromes: generalized language dysfunction (aphasia) and isolated reading dysfunction (alexia).

1. Acquired generalized language disorders (aphasia)
I have published several papers on the cortical regions involved in supporting speech perception in both normal subjects and patients with post-stroke aphasia. Supported by a Wellcome Trust Fellowship in Clinical Science, I am Chief Investigator on a trial of both a behavioural and drug (cholinergic) therapy in a group of patients with aphasia caused by stroke: Imaging the neural correlates of cholinergic and behaviour driven rehabilitation in patients with Wernickeâ??s aphasia. The aim of this project is to identify neural regions that correlate with therapy induced improvements in language function using functional Magnetic Resonance Imaging and Magnetoencephalography. The design is longitudinal, randomized, cross-over and double-blind (for the drug therapy).

2. Acquired isolated reading disorders (alexia)
The commonest type of alexia is hemianopic alexia (HA). It is caused by a right-sided homonymous hemianopia that interferes with text reading (in left-to-right readers); patients cannot plan their reading eye-movements efficiently across a line of text. My work to date has been on: a) characterizing the reading deficit in these patients (both in terms of behaviour and brain function); and, b) developing a community based behavioural therapy that produces a clinically meaningful, statistically significant improvement in text reading speed in the context of a controlled clinical trial. I have now made this therapy available for free on a website Read-Right: http://www.readright.ucl.ac.uk/ and have received a grant to further extend the diagnostic, therapeutic and research potential of this resource (Project grant from The Stroke Association: Web-based rehabilitation of hemianopic alexia). I am also supporting a trial of behavioural therapy for one of the other, rarer forms of peripheral alexia, pure alexia: Investigation of the rehabilitation of pure alexia using MEG.

Fatigue, NeuroFAST

 https://the-effort-lab.wixsite.com/fatigue  

Transcranial Magnetic Stimulation

Professor John Rothwell has researched transcranial magnetic stimulation extensively as a tool in neurorehabilitation after stroke.  See his full list of publications in his UCL IRIS entry here.

Transcranial magnetic stimulation has also been studied by Professor Nick Ward and Professor Nick Wood.

Neuropsychology, Vascular Cognitive Impairment

Cognitive impairment following stroke is a major form of disability.  The Neuropsychology area has collected data on executive function, attention, speed of information processing, and memory deficits in acute and chronic stroke patients.  Research focuses on cognitive screening and characterisation of cognitive impairments resulting from stroke and microbleeds, and their progression, investigating early detection of domain-specific impairments, their time course to recovery, and detection of reliable markers predicting cognitive outcomes. 

Professor Lisa Cipolotti heads the UCLH Neuropsychology Department, and leads research under UCL. 

For research into vascular dementia, see the UCL ION Dementia Centre website.

PLORAS

PLORAS (Predicting Language Outcome and Recovery After Stroke) is led by Professor Cathy Price, and aims to give future stroke survivors a prediction about their speech and language recovery.  The project is based at the Wellcome Centre for Human Neuroimaging, UCL Queen Square Institute of Neurology.  

For more information on this research project, see the PLORAS website

Stroke Prevention, including atrial fibrillation

To improve the care of patients with stroke, we are looking at one of the key challenges in stroke medicine: what is the optimal timing of anticoagulation in acute ischaemic stroke associated with atrial fibrillation?   The OPTIMAS trial, funded by the British Heart Foundation, aims to answer this clinical challenge.  See more on this trial (Optimal Timing of Anticoagulation after Stroke) on the OPTIMAS website

Symptomatic Treatments

Treatments for symptomatic conditions are being developed at the UCL Institute of Neurology and made available through services at the National Hospital for Neurology and Neurosurgery.

Dr Rachel Farrell  researches and has led trials in spasticity management.  Dr Farrell, Dr Valerie Stevenson, and Dr Stefania de Trane specialise in this area and offer a Spasticity Management Service.  Information on spasticity treatment can be found here.

Dr Jalesh Panicker leads a Uroneurology research group investigating urinary, bowel and sexual dysfunction after stroke and other neurological conditions, and a comprehensive clinical service.

Vascular Neurosurgery

Advances in vascular neurosurgery are let by Mr Ahmed Toma, at the National Hospital for Neurology and Neurosurgery.

Neurorehabilitation

Researchers at the National Hospital for Neurology and Neurosurgery and the UCL Institute of Neurology are advancing the science of neurorehabilitation.  

Neurorehabilitation services are offered at the National Hospital for Neurology and Neurosurgery Therapies and Rehabilitation Department.

The UCLP Centre for Neurorehabilitation, a virtual centre housed under the UCL Department of Brain Repair and Rehabilitation, offers research information and resources for those working in neurorehabilitation.

Superficial Siderosis of the Central Nervous System

Classical (type 1) infratentorial superficial siderosis (iSS, also known as superficial siderosis of the CNS) is a rare but often disabling neurodegenerative condition that results from long-term (chronic) low volume and low pressure bleeding into cerebro-spinal fluid (CSF) and deposition of iron-degradation products (haemosiderin) in the subpial layers of the CNS structures.

Superficial siderosis is most often associated with a dural defect from previous CNS trauma or surgery or connective tissue that forms dura, or less frequently a CNS lesion such as certain types of tumour that are prone to bleeding.

The most commonly involved structures are cerebellum (especially the superior vermis), vestibulo-cochlear nerves, brainstem and spinal cord. This results in a clinical presentation (a triad) of hearing impairment, ataxia and myelopathy. However, other symptoms such as cognitive impairment, anosmia, bladder and bowel sphincter dysfunction, visual disturbances and dysphagia also occur.

The main modern way to diagnose iSS is magnetic resonance imaging (MRI) with blood-sensitive scanning methods, as it allows haemosiderin to be visualised along the surfaces of the CNS structures. Radiological diagnostic criteria have been proposed by the group of clinicians and researchers at UCL Institute of Neurology, Department of Brain Repair and Rehabilitation, and the National Hospital for Neurology and Neurosurgery at Queen Square, London 1.

ISS is associated with deposition of haemosiderin along the surfaces of the infratentorial structures. Two subtypes have been identified 1. Type 1 (classical) iSS results, as discussed, from chronic intermittent or continuous bleeding into CSF, gradual deposition of haemosiderin and disease progression, whereas Type 2 (secondary) iSS seems to be due to an acute intracranial haemorrhagic event, with resultant deposition of haemosiderin following clearance of extravasated blood, and is not considered progressive.

Due to complexity of iSS (type 1, classical), multidisciplinary approach to management of this condition is essential and it is patient- and needs-specific. Input from several specialties allows optimisation of patient care and may involve neurology, neurosurgery, and neuro-radiology. Involvement of haematology team is necessary if medical treatment with an iron chelating agent such as deferiprone is considered because such patients require regular follow-up to monitor for agranulocytosis 2.

Neuro-otological, neuro-psychological and uro-neurological input is preferable to address the associated deficits in hearing, impaired balance and cognitive function, as well as and bladder involvement, thus optimising patient care and their quality of life.

Raising awareness and dissemination of information among clinicians, as well as further research into this rare condition is necessary due to our currently limited clinical and scientific knowledge of iSS.

We aim to offer research participation to patients with siderosis wherever possible.

For details of our recent research publications, please see the links below.

Health-Related Quality of Life in Adults With Classical Infratentorial Superficial Siderosis: A Cross-sectional Study. Kharytaniuk N, Mazaheri AA, Pavlou M, Werring D, Bamiou DE. Neurology. 2022 Aug 25;99(19):e2201-11. doi: 10.1212/WNL.0000000000201115. Link

Olfactory dysfunction is common in classical infratentorial superficial siderosis of the central nervous system. Kharytaniuk N, Lim EA, Chan E, Pavlou M, Werring DJ, Bamiou DE. J Neurol. 2022 Dec;269(12):6582-6588. doi: 10.1007/s00415-022-11329-y. Epub 2022 Aug 23. Link

Classical infratentorial superficial siderosis of the central nervous system: pathophysiology, clinical features and management. Kharytaniuk N, Cowley P, Sayal P, Eleftheriou P, Farmer SF, Chan E, Bamiou DE, Werring DJ. Pract Neurol. 2022 Jul 11:practneurol-2021-003324. doi: 10.1136/practneurol-2021-003324. Link

Targeted detection and repair of a spinal dural defect associated with successful biochemical resolution of subarachnoid bleeding in classical infratentorial superficial siderosis. Lobo R, Batbayar B, Kharytaniuk N, Cowley P, Sayal P, Farmer S, Werring DJ. Neurol Sci. 2022 Sep;43(9):5643-5646. doi: 10.1007/s10072-022-06181-x. Epub 2022 Jun 13. Link

Neuropsychological and neuroimaging characteristics of classical superficial siderosis. Chan E, Sammaraiee Y, Banerjee G, Martin AF, Farmer S, Cowley P, Sayal P, Kharytaniuk N, Eleftheriou P, Porter J, van Harskamp N, Cipolotti L, Werring DJ. J Neurol. 2021 Nov;268(11):4238-4247. doi: 10.1007/s00415-021-10548-z. Epub 2021 Apr 17. PMID: 33866413 Link

Case Report: Auditory Neuropathy and Central Auditory Processing Deficits in a Neuro-Otological Case-Study of Infratentorial Superficial Siderosis. Kharytaniuk N, Cowley P, Werring DJ, Bamiou DE. Front Neurol. 2021 Jan 14;11:610819. doi: 10.3389/fneur.2020.610819. eCollection 2020. Link

References:

1. Infratentorial superficial siderosis: Classification, diagnostic criteria, and rational investigation pathway. Wilson D, Chatterjee F, Farmer SF, Rudge P, McCarron MO, Cowley P, Werring DJ. Ann Neurol 2017;81(3):333-43. doi: 10.1002/ana.24850 [published Online First: 2016/12/27] Link

2. Risks associated with oral deferiprone in the treatment of infratentorial superficial siderosis. Sammaraiee Y, Banerjee G, Farmer S, Hylton B, Cowley P, Eleftheriou P, Porter J, Werring DJ. J Neurol 2020;267(1):239-43. doi: 10.1007/s00415-019-09577-6 [published Online First: 2019/10/18] Link