R4VaD is a large, multicentre, longitudinal, inclusive study in patients presenting with stroke to UK Stroke Centres. It uses standardised proportionate ascertainment methods to assess cognition, physical function, neuropsychiatric complications and dependence to at least two years after stroke. R4VaD is a Priority Programme funded by the Stroke Association, BHF, Alzheimer’s Society, and MRC Dementia Platform UK.

R4VaD is a prospective observational, longitudinal inception cohort with central follow-up and nested sub-studies in major UK stroke centres representing geographic and socioeconomic diversity. R4VaD had recruited 1273 patients in 53 centers over 18 months to mid-March 2020.

R4VaD has approval to continue recruiting during the COVID-19 pandemic. During the early stages of the COVID-19 outbreak, R4VaD had already identified adverse impacts of COVID-19 and social distancing measures on patients up to 12 months after stroke, including high levels of anxiety and major difficulties with social support during introduction of the UK social distancing measures.

By continuing to recruit through the pandemic, using a streamlined data collection form to reduce burden on patients and researchers, R4VaD aims to compare data collected before, during and after the pandemic, using existing funded infrastructure. It will be one of the few opportunities to obtain objective data on COVID-19 and stroke, including at late stages after stroke.  COVID-19 may be a risk factor for ischaemic stroke, may influence the severity and prognosis of those who present with stroke, and together with the social distancing measures, may affect the long-term recovery and life after stroke.  These effects are unknown.

R4VaD encourages co-enrolment and uses simplified data collection processes to maximise the contribution to, while minimising the burden of, the research.

If you would like any more information about R4VaD, please contact us on r4vad@ed.ac.uk.

This service evaluation of the impact of COVID-19 on stroke is a collaboration between stroke services across the UK and we are keen for more centres to join.  Data are collected on the clinical, laboratory and imaging features of patients presenting with stroke during the pandemic, using a short case report form.  Patients with and without COVID-19 infection are included and these two groups are compared in a case-control design.  Because we have centres involved right across the UK we are able to compare centres seeing large numbers of COVID-19-positive patients with those who currently see relatively few.  The spectrum of stroke cases that we see is changing and we will use the data to disentangle the direct effects of the virus from the effects of social distancing, a sudden change in public behaviour which also appears to have an impact on stroke presentation.  The data will guide better predictions about the consequences for our stroke services as the pandemic evolves.  In addition we will learn more about the pathophysiology of stroke in the context of COVID-19 infection, including the apparent hypercoagulable state which is seen in some patients and may require a specific management strategy.  The faster we can collect data, the faster we will all be able to learn from it, so please do join our effort if you can.  Our goal is to analyse data in real time and share results with all participating centres as quickly as possible.  Approval is gained through your own stroke service leadership and your clinical governance department rather than the Health Research Authority, as the study only uses routine data collected from the clinical record.  Many centres have non-clinical staff whose normal work has been severely curtailed by the pandemic and who can support this important effort.  If you think that your centre can help, please contact us as soon as possible on uclh.seticos@nhs.net or richard.perry2@nhs.net.

Emerging information about the presentation, prognosis, prevention, and treatment of COVID-19 is constantly evolving, so you may wish to refer to collections of articles and other resources from some of the relevant journals or search for relevant articles via PubMed

The Lancet

New England Journal of Medicine

The BMJ

>BMJ Article – Covid-19: a remote assessment in primary care


Publication topics:

Click on the topic below to be directed to the relevant section of the page.


General Neurological manifestations of COVID-19

COVID-19-associated Acute Hemorrhagic Necrotizing Encephalopathy: CT and MRI FeaturesRadiology 2020 Mar 31 [Online ahead of print] Neo Poyiadji, Gassan Shahin, Daniel Noujaim, Michael Stone, Suresh Patel, Brent Griffith.

COVID-19 presenting with ophthalmoparesis from cranial nerve palsy; Marc DinkinVirginia GaoJoshua KahanSarah BobkerMarialaura SimonettoPaul WechslerJasmin HarpeChristine GreerGregory MintsGayle SalamaApostolos John TsiourisDana Leifer

Rapid implementation of virtual neurology in response to the COVID-19 pandemic; Scott N. GrossmanSteven C. HanLaura J. BalcerArielle KurzweilHarold WeinbergSteven L. GalettaNeil A. Busis

Neurologic Features in Severe SARS-CoV-2 Infection [published online ahead of print, 2020 Apr 15]. N Engl J Med. 2020;10.1056/NEJMc2008597. doi:10.1056/NEJMc2008597 Helms J, Kremer S, Merdji H, et al.

Neurologic Manifestations of Hospitalized Patients With Coronavirus Disease 2019 in Wuhan, ChinaMao L, Jin H, Wang M, et al. JAMA Neurol. Published online April 10, 2020. doi:10.1001/jamaneurol.2020.1127

Neurologic complications of coronavirus infections; Nath A.; Neurology May 2020, 94 (19) 809-810; DOI: 10.1212/WNL.0000000000009455

The Neurology and Neuropsychiatry of COVID-19; Matt Butler, Cameron Watson, Mark Ellul, Tom Pollak, Benedict Michael and Tim Nicholson; Journal of Neurology, Neuroscience and Psychiatry.

Clinical characteristics and outcomes of inpatients with neurologic disease and COVID-19 in Brescia, Lombardy, Italy; Alberto Benussi, Andrea Pilotto, Enrico Premi, Ilenia Libri, Marcello Giunta, Chiara Agosti, Antonella Alberici, Enrico Baldelli, Matteo Benini, Sonia Bonacina, Laura Brambilla, Salvatore Caratozzolo, Matteo Cortinovis, Angelo Costa, Stefano Cotti Piccinelli, Elisabetta Cottini, Viviana Cristillo, Ilenia Delrio, Massimiliano Filosto, Massimo Gamba, Stefano Gazzina, Nicola Gilberti, Stefano Gipponi, Alberto Imarisio, Paolo Invernizzi, Ugo Leggio, Matilde Leonardi, Paolo Liberini, Martina Locatelli, Stefano Masciocchi, Loris Poli, Renata Rao, Barbara Risi, Luca Rozzini, Andrea Scalvini, Francesca Schiano di Cola, Raffaella Spezi, Veronica Vergani, Irene Volonghi, Nicola Zoppi, Barbara Borroni, Mauro Magoni, Alessandro Pezzini, Alessandro Padovani

Generalized myoclonus in COVID-19; Pablo Rábano-SuárezLaura Bermejo-GuerreroAntonio Méndez-GuerreroJavier Parra-SerranoDaniel Toledo-AlfoceaDaniel Sánchez-TejerinaTeresa Santos-FernándezMaría Dolores Folgueira-LópezJudit Gutiérrez-GutiérrezBlanca Ayuso-GarcíaJesús González de la AlejaJulián Benito-León

Bilateral transient olfactory bulbs edema during COVID-19-related anosmia; Thomas LaurendonThomas RadulescoJustine Mugnier, Mélanie GéraultChristophe Chagnaud, Ahmed-Ali El Ahmadi, Arthur Varoquaux

Pearls and Oy-sters: Facial nerve palsy as a neurological manifestation of Covid-19 infection; Yihui GohDarius L.L. BehAndrew MakmurJyoti SomaniAmanda C.Y. Chan


Thrombectomy

Endovascular Therapy for Patients With Acute Ischemic Stroke During the COVID-19 Pandemic: A Proposed Algorithm; Matthew S. Smith, MD; Jordan Bonomo, MD; William A. Knight IV, MD; Charles J. Prestigiacomo, MD; Christopher T. Richards, MD, MS; Evan Ramser, DO; Opeolu Adeoye, MD; Stuart Bertsch, MD; Peyman Shirani, MD; Achala Vagal, MD; Carl J. Fichtenbaum, MD; Anne Housholder, MD, MPH; Pooja Khatri, MD; Dawn O. Kleindorfer, MD; Joseph P. Broderick, MD; Aaron W. Grossman , MD, PhD
American Heart Association Journal, 2020; pg1-8; doi:10.1161/STROKEAHA.120.029863

Mechanical Thrombectomy in the Era of the COVID-19 Pandemic: Emergency Preparedness for Neuroscience Teams A Guidance Statement From the Society of Vascular and Interventional Neurology; Thanh N. Nguyen , MD, FRCPc; Mohamad Abdalkader, MD; Tudor G. Jovin, MD; Raul G. Nogueira, MD; Ashutosh P. Jadhav, MD; Diogo C. Haussen, MD; Ameer E. Hassan, DO; Roberta Novakovic, MD; Sunil A. Sheth, MD; Santiago Ortega-Gutierrez, MD, MSc; Peter D. Panagos, MD; Steve M. Cordina, MD; Italo Linfante, MD; Ossama Yassin Mansour, MD, PhD; Amer M. Malik, MD, MBA; Sandra Narayanan, MD; Hesham E. Masoud, MD;
Sherry Hsiang-Yi Chou, MD; Rakesh Khatri, MD; Vallabh Janardhan, MD; Dileep R. Yavagal, MD; Osama O. Zaidat, MD; David M. Greer, MD; David S. Liebeskind, MD
American Heart Association Journal, 2020; pg1-6;doi:10.1161/STROKEAHA.120.030100

CSC Expert Consensus on Principles of Clinical Management of Patients with Severe Emergent Cardiovascular Diseases during the COVID-19 Epidemic; Running Title: Han et al.; Consensus on Managing CVD during COVID-19 Epidemic; Yaling Han, MD, FACC, FAHA, Chair; Hesong Zeng, MD, co-chair; Hong Jiang, MD, FACC,
co-chair; Yuejin Yang, MD, FACC, co-chair; Zuyi Yuan, MD, FACC, co-chair; Xiang Cheng,
MD, FACC; Zhicheng Jing, MD; Bin Liu, MD, FACC; Jiyan Chen, MD, FACC; Shaoping
Nie, MD, FACC; Jianhua Zhu, MD, FACC; Fei Li, BN; Changsheng Ma, MD, FACC
American Heart Association Journal, 2020; pg1-21; doi:10.1161/CIRCULATIONAHA.120.047011

Society of Neuro Interventional Surgery recommendations for the care of emergent neurointerventional patients in the setting of covid-19; Justin F Fraser, Adam S Arthur, Michael Chen, Michael Levitt, J Mocco,
Felipe C Albuquerque, Sameer A Ansari, Guilherme Dabus, Mahesh V Jayaraman,
William J Mack, James Milburn, Maxim Mokin , Sandra Narayanan,
Ajit S Puri, Adnan H Siddiqui , Jenny P Tsai, Richard P Klucznik

Fraser JF, et al. J NeuroIntervent Surg 2020; pg1–3. doi:10.1136/neurintsurg-2020-016098

Neurointervention for emergent large vessel occlusion during the covid-19 pandemic; David Fiorella , Kyle M Fargen , Thabele M Leslie-Mazwi, Michael Levitt, Stephen Probst, Sergio Bergese, Joshua A Hirsch , Felipe C Albuquerque

Fiorella D, et al. J NeuroIntervent Surg; 2020 Vol 0; pg 1-3

Anesthetic Management of Endovascular Treatment of Acute Ischemic Stroke During COVID-19 Pandemic: Consensus Statement from Society for Neuroscience in Anesthesiology & Critical Care (SNACC)

Journal of Neurosurgical Anesthesiology; Publish Ahead of Print; DOI:10.1097/ANA.0000000000000688

European Society of Minimally Invasive Neurological Therapy (ESMINT) recommendations for optimal interventional neurovascular management in the covid-19 era. Aggour M, White P, Kulcsar Z, Fiehler J, Brouwer P.  JNIS 2020.


Mechanisms of disease

Severe Acute Respiratory Syndrome Coronavirus 2 Infection and Ischemic Stroke; Eduard Valdes Valderrama; Kelley Humbert; Aaron Lord; Jennifer Frontera; Shadi Yaghi

American Heart Association Journal, 2020;
DOI: 10.1161/STROKEAHA.120.030153

Evidence of the COVID-19 Virus Targeting the CNS: Tissue Distribution, Host–Virus Interaction, and Proposed Neurotropic MechanismsACS Chemical Neuroscience 2020 11 (7), 995-998 Abdul Mannan Baig, Areeba Khaleeq, Usman Ali, and Hira Syeda.


Practice guidelines and recommendations

Consensus for prevention and management of coronavirus disease 2019 (COVID-19) for neurologists. Stroke & Vascular Neurology 2020;0. doi:10.1136/svn-2020-000382 Jin H, Hong C, Chen S, et al.

Challenges and Potential Solutions of Stroke Care During the Coronavirus Disease 2019 (COVID-19) Outbreak. Stroke; 51(5):1356-1357 Zhao J, Rudd A, Liu R.

Protected Code Stroke: Hyperacute Stroke Management During the Coronavirus Disease 2019 (COVID-19) Pandemic.Khosravani H, Rajendram P, Notario L, Chapman MG, Menon BK.  Stroke 2020 Apr 1:STROKEAHA120029838.

Temporary Emergency Guidance to US Stroke Centers During the COVID-19 Pandemic On Behalf of the AHA/ASA Stroke Council Leadership.

Consensus for prevention and management of coronavirus disease 2019 (COVID-19) for neurologists. Jin H, Hong C, Chen S, et al. Stroke & Vascular Neurology 2020;0. doi:10.1136/

Early Lessons From World War COVID; Sunil A. Sheth, Tzu-Ching Wu, Anjail Sharrief, Christy Ankrom, James C. Grotta, Marc Fisher, Sean I. Savitz;

Prehospital Triage of Acute Stroke Patients During the COVID-19 Pandemic; Mayank GoyalJohanna M. OspelAndrew M. SoutherlandCharles WiraSepideh Amin-HanjaniJustin F. FraserPeter Panagosand on behalf of the AHA/ASA Stroke Council Science Subcommittees: Emergency Neurovascular Care (ENCC), the Telestroke and the Neurovascular Intervention Committees


Clinical stroke manifestations and characteristics

Neurologic Manifestations of Hospitalized Patients With Coronavirus Disease 2019 in Wuhan, China. JAMA Neurol Published online April 10, 2020. doi:10.1001/jamaneurol.2020.1127 Mao L, Jin H, Wang M, et al.

Cerebrovascular disease is associated with an increased disease severity in patients with Coronavirus Disease 2019 (COVID-19): A pooled analysis of published literature. International Journal of Stroke. Aggarwal, G., Lippi, G., & Michael Henry, B. (2020).

Coagulopathy and Antiphospholipid Antibodies in Patients with Covid-19. N Engl J Med 2020;382(17):e38. doi: 10.1056/NEJMc2007575 Zhang Y, Xiao M, Zhang S, Xia P, Cao W, Jiang W, Chen H, Ding X, Zhao H, Zhang H, Wang C, Zhao J, Sun X, Tian R, Wu W, Wu D, Ma J, Chen Y, Zhang D, Xie J, Yan X, Zhou X, Liu Z, Wang J, Du B, Qin Y, Gao P, Qin X, Xu Y, Zhang W, Li T, Zhang F, Zhao Y, Li Y, Zhang S.

Large-Vessel Stroke as a Presenting Feature of Covid-19 in the Young. N Engl J Med 2020 Apr 28. doi: 10.1056/NEJMc2009787 Oxley TJ et al.

Characteristics of ischaemic stroke associated with COVID-19 Rahma Beyrouti, Matthew E Adams,Laura Benjamin, Hannah Cohen,Simon F Farmer,Yee Yen Goh,Fiona Humphries,Hans Rolf Jäger, Nicholas A Losseff, Richard J Perry,Sachit Shah,Robert J Simister,David Turner, Arvind Chandratheva,David J Werring

Acute Cerebrovascular Disease Following COVID-19: A Single Center, Retrospective, Observational Study. Yanan Li, Mengdie Wang, Yifan Zhou, Jiang Chang, Ying Xian, Ling Mao, Candong Hong, Shengcai Chen, Yong Wang, Hailing Wang, Man Li, Huijuan Jin, Bo Hu.

SARS2-CoV-2 and Stroke in a New York Healthcare System; Shadi Yaghi, Koto Ishida, Jose Torres, Brian Mac Grory, Eytan Raz, Kelley Humbert, Nils Henninger, Tushar Trivedi, Kaitlyn Lillemoe, Shazia Alam, Matthew Sanger, Sun Kim, Erica Scher, Seena Dehkharghani, Michael Wachs, Omar Tanweer, Frank Volpicelli, Brian Bosworth, Aaron Lord, Jennifer Frontera

Improving Stroke Care in Times of the COVID-19 Pandemic Through Simulation; Martin W. Kurz, Johanna Maria Ospel, Kathinka Daehli Kurz, Mayank Goyal


Impact on stroke services

Impact of the COVID-19 Epidemic on Stroke Care and Potential Solutions; Jing Zhao, Hang L, David Kung, Marc Fisher, Ying Shen, Renyu Liu

Delays in Stroke Onset to Hospital Arrival Time During COVID-19; Kay-Cheong Teo, William C.Y. Leung, Yuen-Kwun Wong, Roxanna K.C. Liu, Anna H.Y. Chan, Olivia M.Y. Choi, Wing-Man Kwok, Kung-Ki Leung, Man-Yu Tse, Raymond T.F. Cheung, Anderson Chun-On Tsang, Kui Kai Lau

Initial experiences of US neurologists in practice during the COVID-19 pandemic via survey; Akanksha SharmaChristina R. MaxwellJill FarmerDiana Greene-ChandosKathrin LaFaver, Karima Benameur