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Vascular Neurology and Stroke Medicine

 

Current Research Team:

Professor Dominick J. H. McCabe PhD, FRCPI, FESO, FAHA: Consultant Neurologist / Clinical Associate Professor in Neurology, and Chairperson of the Vascular Neurology Research Foundation (VNRF), Department of Neurology/Stroke Service, AMNCH-Tallaght University Hospital (TUH)/ TCD, Ireland;
Dr Chika Offiah, BSc. Biochemistry, MUDr: Research Registrar in Vascular Neurology (PhD Student)
Dr Deirdre R. Smith MB, BCh, BAO, MICGP, DCh: Research Registrar in Vascular Neurology (MSc Student)
Dr Arun Subramanian, MD, MPH, MRCPI: Research Registrar in Vascular Neurology (MSc Student)
Dr Stephen Murphy MB, BCh (Sch), MRCPI, MRCP (UK), Dip Stat, PhD:  Research SpR in Vascular Neurology (‘Post-Doc’ MSc Student)
Dr Soon Tjin Lim, MRCPI, MRCP (UK): Research SpR in Vascular Neurology (PhD Student).

Research Group Focus on Vascular Neurology / Stroke Medicine:

Stroke is the commonest cause of acquired disability and the second to third commonest cause of death in middle-high incomes countries, including in Ireland.
The main objectives of our research are:
- To improve our understanding of the potential mechanisms causing transient ischaemic attack (TIA) or stroke, including in higher-risk subgroups;
- To identify individuals who should benefit from modified, ‘personalised’ anti-thrombotic (blood thinning) treatment to optimise their response to commonly-prescribed preventive treatments following TIA or stroke to reduce the burden of stroke on patients, care givers and society as a whole.   

Translational Platelet Science / Haemostasis and Pharmacogenetics Research in Ischaemic Cerebrovascular Disease

Prof McCabe’s Vascular Neurology Research group at AMNCH-TUH/TCD has an international reputation for conducting innovative, clinically-relevant, collaborative research studies on translational platelet science (figure 1), haemostasis and thrombosis in patients with ischaemic cerebrovascular disease (CVD) and in assessing the response to commonly-prescribed antiplatelet regimens ex vivo. They also have particular expertise in performing transcranial Doppler ultrasound imaging to detect micro-embolic signals (MES) in the cerebral circulation in vivo (figure 2), and in combining these data with other neurovascular imaging, blood and endothelial biomarkers to understand the pathogenesis of TIA/stroke and potentially improve risk-stratification of patients with moderate-severe asymptomatic and symptomatic extracranial carotid stenosis.  

Some Recent Achievements:

The service at AMNCH-TUH/TCD has facilitated clinical and academic training & education in Vascular and General Neurology, Stroke Medicine, Translational Medicine and enhanced clinical care of TIA and stroke patients, with several clinical PhD candidates having successfully defended their theses to date. Prof McCabe is currently supervising 2 further PhD students and 3 MSc students in Clinical Neurosciences/Clinical Medicine (see above), is the Principal Investigator (PI) / Co-PI in 9 local or multi-centre studies, and is collaborating in 7 national or international multi-centre research studies or trials. Prof McCabe (HRB-Stroke Clinical Trials Network Ireland [SCTNI] ‘Network Lead Investigator’; Chair of the Research and Education Committee, National Stroke Programme’s Clinical Advisory Group for the RCPI/HSE) and his team actively collaborate to support the important work of the SCTNI locally and on the international stage.

They have conducted several original pilot studies in this subspecialty area (e.g. the PACS, HEIST, TRAP & OATS studies) and have and published widely in this field.  These studies have shown that platelets may be excessively activated / hyper-reactive following a TIA or ischaemic stroke and that an important proportion of CVD patients are ‘poorly-responsive’ to antiplatelet agents with ‘high on-treatment platelet reactivity (HTPR)’ in the laboratory. These data have improved our understanding of the clinical, demographic and pharmacodynamic mechanisms influencing ex-vivo HTPR status in this patient population. They have also found an ongoing stimulus to increased platelet production and secretion, and enhanced platelet and endothelial activation and coagulation system potential after TIA/ischaemic stroke in patients with symptomatic compared with asymptomatic moderate-severe carotid stenosis, including in those who do not have micro-emboli on transcranial Doppler ultrasound. These data improve our understanding of the underlying biological mechanisms which may contribute to the disparity in the risk of TIA/stroke in subgroups of patients with recently symptomatic vs. asymptomatic carotid stenosis, and in subgroups of symptomatic patients with different plaque types and MES status.

2 pressing issues which need be resolved within this subspecialty field:

  •  We need to determine whether monitoring ‘antiplatelet-HTPR status’ with platelet function/reactivity assays, in combination with pharmacogenetic testing via a Genome-Wide Association Study (GWAS) approach, definitively predicts the risk of recurrent vascular events in CVD patients on antiplatelet therapy. Such information would facilitate ‘personalised antiplatelet therapy’ to optimise secondary prevention following TIA/ischaemic stroke. To address this issue, we have designed the adequately-sized Optimal Antiplatelet Therapy in TIA and Ischaemic Stroke-International (OATS-I) multicentre observational study.
  • We need to collate established and innovative blood, endothelial and neurovascular imaging biomarker data to aid risk-stratification of patients with symptomatic and asymptomatic carotid stenosis to identify patients who may benefit most from early surgical or endovascular intervention or optimised medical therapy alone.

 

Collaborators:

Dr Sinead Murphy, Dr Allan McCarthy, Dr Richard Walsh and Dr Sean O’Dowd, Consultant Neurologists, Dept of Neurology and Stroke Service, AMNCH-TUH;
Prof Ronan Collins, Dr Tara Coughlan, Dr Dan Ryan and Professor Des O’Neill, Consultants in Older Adult Medicine, Age Related Health Care and Stroke Service, AMNCH-TUH;
Professor Sean Tierney, Ms Emily Boyle and Ms Bridget Egan, Consultant Vascular Surgeons, Department of Vascular Surgery, AMNCH-TUH;
Professor Joseph Harbison, Consultant Geriatrician and Stroke Physician, SJH;
Mr Prakash Madhavan, Mr Sean O Neill and Dr Mary-Paula Colgan, Department of Vascular Surgery, SJH;
Professor Colin Doherty, Dr Janice Redmond, Dr David Bradley and Dr Siobhan Hutchinson, Consultant Neurologists, Department of Neurology, SJH;
Prof. Dermot Cox BSc, PhD, Associate Professor in Molecular and Cellular Therapeutics, Dept. of Molecular & Cellular Therapeutics, Irish Centre for Vascular Biology, RCSI;
Prof James O'Donnell, Professor of Vascular Biology and Consultant Haematologist, Director, Irish Centre for Vascular Biology, RCSI and Director, Haemostasis Research Group, SJH;
Prof Joan Montaner, Neurovascular Research Laboratory, Vall d'Hebron Institute of Research (VHIR), Barcelona, Spain; Institute de Biomedicine of Seville, IBiS/Hospital Universitario Virgen del Rocío/CSIC/University of Seville & Department of Neurology, Hospital Universitario Virgen Macarena, Seville;
Dr Israel Fernandez-Cadenas, Institut de Recerca Hospital de la Santa Creu i Sant Pau, Barcelona, Spain;
Prof Vincent Thijs, Dept. of Neurology, Austin Health and Florey Institute of Neuroscience and Mental Health, University of Melbourne, Heidelberg, Victoria, Australia / Department of Neurology, Austin Health, Heidelberg, Victoria, Australia;
Prof Jesse Dawson, Division of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK / Institute of Neuroscience and Psychology, University of Glasgow, Glasgow, UK;
Prof. Keith Muir, Institute of Neuroscience and Psychology, University of Glasgow, Glasgow, UK;
Dr Richard Perry and Prof David Werring, Stroke Research Centre, Department of Brain Repair and Rehabilitation, UCL Queen Square Institute of Neurology, London, UK;
Prof David JP Williams, School of Medicine, Royal College of Surgeons in Ireland, Dublin, Ireland / Department of Geriatric and Stroke Medicine, Beaumont Hospital, Dublin, Ireland / Irish Centre for Vascular Biology, Dublin, Ireland
Prof Peter J Kelly, Stroke Service / Neurovascular Clinical Science Unit, Mater University Hospital / University College Dublin; Stroke Clinical Trials Network Ireland;
Prof Sean Murphy, Stroke Service / Neurovascular Clinical Science Unit, Mater University Hospital / University College Dublin; 
Prof Martin O’Donnell, Department of Medicine and Health Research Board Clinical Research Facility, National University of Ireland Galway, Galway, Ireland;
Dr Lina Zgaga, Department of Public Health and Primary Care, Trinity College Dublin, Ireland;
Mr Chris Macey, Head of Patient Advocacy, Irish Heart Foundation (IHF), Dublin Ireland, and Dr Gary Randall, European Research Manager for Stroke Alliance for Europe (SAFE), London, U.K.;
Prof Calin Prodan, Dept. of Neurology, University of Oklahoma Health Sciences Center and VA Medical Center, Oklahoma, USA;
Prof Phil Barber, Dept. of Clinical Neurosciences, University of Calgary, Canada;
Prof Lars Marquardt, Dept. of Neurology, Asklepios Klinik Wandsbek, Hamburg, Germany;
Prof Philip M. Bath, Stroke Trials Unit, University of Nottingham, U.K.; 
Prof Gary A Ford, University of Oxford / Oxford University Hospital NHS Foundation Trust, Oxford, UK;
Prof Bo Norrving, Department of Clinical Sciences Lund, Neurology, Lund University, Lund, Sweden.

 

Fig. 1: Whole Blood Flow Cytometric Assessment of Platelet Activation Status:
The percentages of neutrophil-platelet complexes (green), monocyte-platelet complexes (blue) and lymphocyte-platelet complexes (purple) in fresh whole blood can be quantified with this sensitive and specific technique as a marker of platelet activation status ex vivo in an individual CVD patient.  

 

Fig. 2: Spectral waveform display from a transcranial Doppler ultrasound recording of the middle cerebral artery:  Micro-embolus in the left middle cerebral artery in vivo in a patient with > 50% extracranial left internal carotid artery stenosis (bold white arrow)

Recent Peer-Reviewed Publications 2017-2019

  • Huber R, Grittner U, Weidemann F, Thijs VN, Tanislav C, Enzinger C, Fazekas F, Wolf M, Hennerici M, McCabe DJH, Putaala J, Tatlisumak T, Kessler C, von Sarnowski B, Martus P, Kolodny E, Norrving B, and Rolfs A. Patent Foramen Ovale and cryptogenic strokes in the Stroke in Young Fabry Patients Study. Stroke 2017; 48: 30-35.
  • Walsh ME, Galvin R, Boland F, Williams D, Harbison JA, Murphy S, Collins DR, McCabe DJH, Crowe M, Horgan NF. Validation of two risk prediction models for recurrent falls in the first year after stroke: A prospective cohort study. Age and Ageing 2017; 46: 642-648.
  • O’Connell K, Williams L, Jones J, McCabe DJH, Killeen R, Hutchinson M, Tubridy N, O’Riordan S, McGuigan C. Neurosarcoidosis: Clinical presentation and changing treatment patterns in an Irish Caucasian population. Ir J Med Sci 2017; 186: 759-766.
  • Tobin WO, Kinsella JA, Kavanagh GF, O’Donnell JS, McGrath R, Tierney S, Egan B, Feeley TM, Coughlan T, Collins DR, O’Neill D, Murphy SJX, Lim SJ, Murphy RP, McCabe DJH. Profile of von Willebrand factor antigen and von Willebrand factor propeptide in an overall TIA and ischaemic stroke population and amongst subtypes. J Neurol Sci 2017; 375: 404-410.
  • Kinsella JA, Tobin WO, Tierney S, Feeley TM, Egan B, Coughlan T, Collins DR, O’Neill D, Harbison JA, Doherty CP, Madhavan P, Moore DJ, O’Neill SM, Colgan M-P, Saqqur M, Murphy RP, Moran N, Hamilton G, McCabe DJH. Assessment of ‘on-treatment platelet reactivity’ and relationship with cerebral microembolic signals in asymptomatic and symptomatic carotid stenosis. J Neurol Sci 2017; 376: 133-139.
  • McElwaine P, McCormack J, McCormick M, Rudd A, Brennan C, Coetzee H, Cotter PE, Doyle R, Hickey A, Horgan F, Loughnane C, Macey C, Marsden P, McCabe D, Mulcahy R, Noone I, Shelley E, Stapleton T, Williams D, Kelly P, Harbison J. A comparison of service organization and guideline compliance between two adjacent European health services. European Stroke Journal 2017; 2: 238-243.
  • Lim ST, Murphy SJX, Smith DR, Williams J, Gil Navarro S,  McCabe J, Moore DP, McHugh J, McCabe DJH.  Long-term outcome in TIA or ischaemic stroke patients with a patent foramen ovale +/- an inter-atrial septal aneurysm in conjunction with comprehensive arterial and venous thrombophilia screening. J Neurol Sci 2017; 377: 227-233.
  • Brett FM, Flavin R, Chen D, Loftus T, Looby S, McCarthy A, de Gascun C, Jaffe ES, Nor N, Javadpour M, McCabe D. EBV-driven natural killer cell disease of the central nervous system presenting as subacute cognitive decline. Human Pathology: Case Reports 2017; 10: 64-68.
  • Thijs V, Grittner U, Fazekas F, McCabe DJH, Giese A-K, Kessler C, Martus P, Norrving B, Ringelstein EB, Schmidt R, Tanislav C, Putaala J, Tatlisumak T, von Sarnowski B, Rolfs A, Enzinger C, on behalf of the Stroke in Fabry (SIFAP 1) Investigators. Dolichoectasia and small vessel disease in young patients with TIA and stroke. Stroke 2017; 48: 2361-2367.
  • McElwaine P, McCormack J, Brennan C, Coetzee H, Cotter P, Doyle R, Hickey A, Horgan F, Loughnane C, Macey C, Marsden P, McCabe D, Mulcahy R, Noone I, Shelley E, Stapleton T, Williams D, Kelly P, Harbison J. Thrombolysis for stroke in Ireland: increasing access and maintaining safety in a challenging environment. Ir J Med Sci 2018; 187: 275-280.
  • Naylor AR, Ricco JB, de Borst GJ, Debus S, de Haro J, Halliday A, Hamilton G, Kakisis J, Kakkos S, Lepidi S, Markus HS, McCabe DJ, Roy J, Sillesen H, van den Berg JC, Vermassen F; ESVS Guidelines Committee: Kolh P, Chakfe N, Hinchliffe RJ, Koncar I, Lindholt JS, Vega de Ceniga M, Verzini F; ESVS Guideline Reviewers: Archie J, Bellmunt S, Chaudhuri A, Koelemay M, Lindahl AK, Padberg F, Venermo M. Management of Atherosclerotic Carotid and Vertebral Artery Disease: 2017 Clinical Practice Guidelines of the European Society for Vascular Surgery (ESVS). Eur J Vasc Endovasc Surg 2018; 55: 3-81.
  • Bogdanova-Mihaylova P, Burke D, O’Dwyer JP, Bradley D, Williams J, Cronin SJ, Smyth S, Murphy RP, Murphy SM, Wall C, McCabe DJH. Aciclovir-induced acute kidney injury in patients with ‘suspected viral encephalitis’ encountered on a liaison neurology service. Ir J Med Sci 2018; 187: 777-780.
  • Holodinsky J, Patel AB, Thornton J, Kamal N, Jewett LR, Kelly PJ, Murphy S, Collins R, Walsh T, Cronin S, Power S, Brennan P, O'Hare A, McCabe DJ; Moynihan B, Looby S, Wyse G, McCormack J, Marsden P, Harbison J, Hill MD; Williams D. Drip 'N Ship Versus Direct to Endovascular Thrombectomy Centre (Mothership):  The Impact of Treatment Times on the Future Design of Thrombectomy Services. Eur Stroke Journal 2018; 3: 126–135.
  • Murphy SJX, Lim ST, Kinsella JA, Murphy D, Enright HM, McCabe DJH, for the HEIST study group. Increased platelet count and reticulated platelets in recently symptomatic versus asymptomatic carotid artery stenosis and in cerebral microembolic signal-negative patient subgroups: Results from the HaEmostasis In carotid STenosis (HEIST) Study. J Neurol 2018; 265: 1037–1049.
  • Walsh ME, Galvin R, Williams DJP, Harbison JA, Murphy S, Collins R, McCabe DJH, Crowe M, Horgan NF. Falls-Related EvEnts in the first year after StrokE in Ireland: Results of the multi-centre prospective FREESE cohort study. Eur Stroke Journal 2018; 3: 246–253.
  • Walsh ME, Sorensen J, Galvin R, Williams DJP, Harbison JA, Murphy S, Collins R, McCabe DJH, Crowe M, Horgan NF. First year post-stroke healthcare costs and fall-status among those discharged to the community. Eur Stroke Journal 2018; 3: 254–262.
  • Kidd DP, McCabe DJ, Wilhelm T, Galloway M. Carotid arteritis causing amaurosis fugax and ischaemic cerebrovascular events in Neurosarcoidosis. Clinical Neurology and Neurosurgery 2018; 169: 103-106.
  • Bonati LH, Gregson J, Dobson J, McCabe DJH, Nederkoorn PJ, van der Worp HB, de Borst GJ, Richards T, Cleveland T,. Müller MD, Wolff T, Engelter ST, Lyrer PA, Brown MM; for the International Carotid Stenting Study investigators. Restenosis and risk of stroke after stenting or endarterectomy for symptomatic carotid stenosis in the International Carotid Stenting Study (ICSS): secondary analysis of a randomised trial. Lancet Neurol 2018; 17: 587 – 596.
  • Safouris A, Katsanos A, Kerasnoudis A, Krogias C, Kinsella J, Sztajzel R, Lambadiari V, Deftereos S, Kargiotis O, Sharma VK, Demchuk AM,  Saqqur M, McCabe DJH, Tsivgoulis G. Statin pre-treatment and micro-embolic signals in large artery atherosclerosis: A systematic review and meta-analysis. Stroke 2018; 49: 1992-1995.
  • D'Alton M, Coughlan T, Cogan N, Greene S, McCabe DJH, McCarthy A, Murphy S, Walsh R, O’Neill D, Kennelly S, Ryan D, Collins R. Patterns of mortality in modern stroke care. Ir Med J 2018; 111: 750.
  • Walsh ME, Galvin R, Williams DJP, Harbison JA, Murphy S, Collins R, McCabe DJH, Crowe M, Horgan NF. The experience of recurrent fallers in the first year after stroke. Disabil Rehabil 2019; 41: 142-149.
  • Murphy SJX, Naylor AR, Ricco J-B, Sillesen H, Kakkos S, Hamilton G, McCabe DJH. Optimal antiplatelet therapy in moderate to severe asymptomatic and symptomatic carotid stenosis: A comprehensive review of the literature. Eur J Vasc Endovasc Surg 2019; 57: 199 – 211.
  • Delaney S, O’Connor G, Reardon W, Murphy SJX, Tierney S, Ryan BM, Delaney H, Doherty CP, Guiney M, Brennan P, Tobin WO, McCabe DJH. Extracranial and intracranial vasculopathy with ‘moyamoya phenomenon’ in association with Alagille Syndrome. Frontiers in Neurology 29 January 2019; https://doi.org/10.3389/fneur.2018.01194.
  • Murphy SJX, Lim ST, Kinsella JA, Tierney S, Egan B, Feeley TM, Murphy SM, Walsh RA, Collins DR, Coughlan T, O’Neill D, Harbison JA, Madhavan P, O’Neill SM, Colgan MP, Cox D, Moran N, Hamilton G, McCabe DJH. Increased leucocyte-platelet complex formation in recently symptomatic versus asymptomatic carotid stenosis patients and in micro-emboli negative subgroups. Thromb Haemost 2019; 119: 821-833.
  • Muller MD, Gregson J, McCabe DJH, Nederkoorn PJ, van der Worp HB, de Borst GJ, Cleveland T, Wolff T, Engelter ST, Lyrer P, Brown M, Bonati LH, For the International Carotid Stenting Study investigators. Stent design, restenosis and recurrent stroke after carotid artery stenting in the International Carotid Stenting Study. Stroke 2019; 50: 3013-3020.
  • Murphy SJX, Lim ST, Kinsella JA, Tierney S, Egan B, Feeley TM, Dooley C, Kelly J, Murphy SM, Walsh RA, Collins DR, Coughlan T, O’Neill D, Harbison JA, Madhavan P, O’Neill SM, Colgan MP, Meaney JF, Hamilton G, McCabe DJH. Simultaneous assessment of plaque morphology, cerebral micro-embolic signal status and platelet biomarkers in patients with recently symptomatic and asymptomatic carotid stenosis. Journal of Cerebral Blood Flow and Metabolism 2019 (in press).
  • Murphy SJX, Lim ST, Kinsella JA, Tierney S, Egan B, Feeley TM, Murphy SM, Walsh RA, Collins DR, Coughlan T, O’Neill D, Harbison JA, Madhavan P, O’Neill SM, Colgan MP, Cox D, Moran N, Hamilton G, Meaney JF, McCabe DJH. Relationship between ‘on-treatment platelet reactivity’, shear stress and cerebral micro-embolic signals in asymptomatic and symptomatic carotid stenosis. J Neurol 2019 (in press).

Manuscripts in which Prof McCabe was a Named Collaborator on Authors’ List since 2017: