The emerging spectrum of COVID-19 neurology: clinical, radiological and laboratory findings

Author:

Paterson Ross W123,Brown Rachel L14,Benjamin Laura56,Nortley Ross17,Wiethoff Sarah18,Bharucha Tehmina91011ORCID,Jayaseelan Dipa L112,Kumar Guru2,Raftopoulos Rhian E13,Zambreanu Laura112,Vivekanandam Vinojini9,Khoo Anthony9ORCID,Geraldes Ruth714,Chinthapalli Krishna17,Boyd Elena7,Tuzlali Hatice7ORCID,Price Gary9,Christofi Gerry9,Morrow Jasper19,McNamara Patricia9,McLoughlin Benjamin9,Lim Soon Tjin9ORCID,Mehta Puja R9,Levee Viva9,Keddie Stephen1,Yong Wisdom15,Trip S Anand115,Foulkes Alexander J M112,Hotton Gary9,Miller Thomas D16ORCID,Everitt Alex D17,Carswell Christopher1718,Davies Nicholas W S18,Yoong Michael19,Attwell David20,Sreedharan Jemeen13,Silber Eli13,Schott Jonathan M1ORCID,Chandratheva Arvind5,Perry Richard J5,Simister Robert5,Checkley Anna21,Longley Nicky21,Farmer Simon F9,Carletti Francesco22ORCID,Houlihan Catherine923,Thom Maria1,Lunn Michael P1,Spillane Jennifer924,Howard Robin924,Vincent Angela114ORCID,Werring David J5,Hoskote Chandrashekar22,Jäger Hans Rolf122,Manji Hadi19,Zandi Michael S19ORCID

Affiliation:

1. University College London, Queen Square Institute of Neurology, London, UK

2. Darent Valley Hospital, Dartford, Kent, UK

3. UK Dementia Research Institute, London, UK

4. UCL Institute of Immunity and Transplantation, London, UK

5. Stroke Research Centre, UCL Queen Square Institute of Neurology, London, UK

6. University of Liverpool, Brain Infections Group, Liverpool, Merseyside, UK

7. Wexham Park Hospital, Frimley Health NHS Foundation Trust, Berkshire, UK

8. Center for Neurology and Hertie Institute for Clinical Brain Research, Eberhard-Karls-University, Tübingen, Germany

9. National Hospital for Neurology and Neurosurgery, University College London Hospitals NHS Foundation Trust, Queen Square, London, UK

10. Department of Biochemistry, University of Oxford, Oxford, UK

11. Lao-Oxford-Mahosot Hospital-Wellcome Trust-Research Unit, Mahosot Hospital, Vientiane, Laos

12. Watford General Hospital, Watford, Hertfordshire, UK

13. King’s College Hospital, Denmark Hill, London, UK

14. University of Oxford, Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, Oxford, UK

15. Northwick Park Hospital, Harrow, London, UK

16. Lister Hospital, Stevenage, Hertfordshire, UK

17. Imperial College Healthcare NHS Trust, London, UK

18. Chelsea and Westminster Hospital, London, UK

19. Barts and The London NHS Trust, London, UK

20. UCL, Department of Neuroscience, Physiology and Pharmacology, London, UK

21. Hospital for Tropical Diseases, University College London Hospitals NHS Foundation Trust, London, UK

22. Lysholm Department of Neuroradiology, National Hospital for Neurology and Neurosurgery, University College London Hospitals NHS Foundation Trust, Queen Square, London, UK

23. UCL Division of Infection and Immunity, London, UK

24. Guy's and St Thomas’ NHS Foundation Trust, London, UK

Abstract

Abstract Preliminary clinical data indicate that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with neurological and neuropsychiatric illness. Responding to this, a weekly virtual coronavirus disease 19 (COVID-19) neurology multi-disciplinary meeting was established at the National Hospital, Queen Square, in early March 2020 in order to discuss and begin to understand neurological presentations in patients with suspected COVID-19-related neurological disorders. Detailed clinical and paraclinical data were collected from cases where the diagnosis of COVID-19 was confirmed through RNA PCR, or where the diagnosis was probable/possible according to World Health Organization criteria. Of 43 patients, 29 were SARS-CoV-2 PCR positive and definite, eight probable and six possible. Five major categories emerged: (i) encephalopathies (n = 10) with delirium/psychosis and no distinct MRI or CSF abnormalities, and with 9/10 making a full or partial recovery with supportive care only; (ii) inflammatory CNS syndromes (n = 12) including encephalitis (n = 2, para- or post-infectious), acute disseminated encephalomyelitis (n = 9), with haemorrhage in five, necrosis in one, and myelitis in two, and isolated myelitis (n = 1). Of these, 10 were treated with corticosteroids, and three of these patients also received intravenous immunoglobulin; one made a full recovery, 10 of 12 made a partial recovery, and one patient died; (iii) ischaemic strokes (n = 8) associated with a pro-thrombotic state (four with pulmonary thromboembolism), one of whom died; (iv) peripheral neurological disorders (n = 8), seven with Guillain-Barré syndrome, one with brachial plexopathy, six of eight making a partial and ongoing recovery; and (v) five patients with miscellaneous central disorders who did not fit these categories. SARS-CoV-2 infection is associated with a wide spectrum of neurological syndromes affecting the whole neuraxis, including the cerebral vasculature and, in some cases, responding to immunotherapies. The high incidence of acute disseminated encephalomyelitis, particularly with haemorrhagic change, is striking. This complication was not related to the severity of the respiratory COVID-19 disease. Early recognition, investigation and management of COVID-19-related neurological disease is challenging. Further clinical, neuroradiological, biomarker and neuropathological studies are essential to determine the underlying pathobiological mechanisms that will guide treatment. Longitudinal follow-up studies will be necessary to ascertain the long-term neurological and neuropsychological consequences of this pandemic.

Funder

Alzheimer's Association Clinician Scientist Fellowship

UK Dementia Research Institute

Medical Research Council Clinical Research Training Fellowship

Ministry of Science, Research and the Arts of Baden-Württemberg and the European Social Fund of Baden-Württemberg

Guarantors of Brain and Association of British Neurologists

European Research Council Advanced Investigator

Wellcome Trust

NIHR

Stroke Investigation in North and Central London

UCLH Biomedical Research Centre

Publisher

Oxford University Press (OUP)

Subject

Clinical Neurology

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