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COVID-19–associated acute necrotising encephalopathy successfully treated with steroids and polyvalent immunoglobulin with unusual IgG targeting the cerebral fibre network
  1. Louis Delamarre1,
  2. Cédric Gollion2,
  3. Gaspard Grouteau3,
  4. David Rousset1,
  5. Guillaume Jimena1,
  6. Jérôme Roustan4,
  7. François Gaussiat4,
  8. Etienne Aldigé1,
  9. Charlène Gaffard1,
  10. Julien Duplantier5,
  11. Charlotte Martin1,
  12. Olivier Fourcade1,
  13. Chloé Bost6,7,
  14. Françoise Fortenfant6,
  15. Pierre Delobel3,
  16. Guillaume Martin-Blondel3,
  17. Jérémie Pariente2,
  18. Fabrice Bonneville5,
  19. Thomas Geeraerts1
  20. NeuroICU Research Group
    1. 1 Anesthesiology and Intensive Care, Centre Hospitalier Universitaire de Toulouse, Toulouse, France
    2. 2 Neurology, Centre Hospitalier Universitaire de Toulouse, Toulouse, France
    3. 3 Infectious and Tropical Diseases, Centre Hospitalier Universitaire de Toulouse, Toulouse, France
    4. 4 Intensive Care, Centre Hospitalier de Montauban, Montauban, Midi-Pyrénées, France
    5. 5 Neuroradiology, Centre Hospitalier Universitaire de Toulouse, Toulouse, Midi-Pyrénées, France
    6. 6 Immunology, Centre Hospitalier Universitaire de Toulouse, Toulouse, Midi-Pyrénées, France
    7. 7 INSERM U1043—CNRS UMR 5282, Centre de Physiopathologie de Toulouse Purpan, Toulouse, Midi-Pyrénées, France
    1. Correspondence to Dr Louis Delamarre, Anesthesiology and Intensive Care, Centre Hospitalier Universitaire de Toulouse, 31300 Toulouse, France; delamarre.l{at}

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    A recent case report described the radiological features of a suspected COVID-19 necrotising haemorrhagic encephalopathy.1 We present here a description of clinical, biological, radiological and immunological features of a COVID-19 patient case, evocative of virus-associated acute necrotising encephalopathy (ANE) possibly mediated by antibodies. Patient’s representative consent has been obtained in agreement with the journal’s policy.

    A 51-year-old man without personal or family history of neurological disease was hospitalised after 10 days of fever and cough. COVID-19 was diagnosed by reverse-transcriptase PCR on nasal swab and bilateral ground-glass opacities on thoracic CT scan. At day 12, he was admitted in intensive care unit (ICU) for non-invasive ventilation. The result of the neurological examination was normal. At day 21, while the patient had been weaned off oxygen, he became unresponsive and rapidly comatose (Glasgow Coma Scale 6: E1, V1, M4) with a disconjugated gaze. The patient was groaning and showing rhythmic movements of the right upper limb. An urgent brain MRI, including diffusion-weighted imaging (DWI) and MR angiogram, ruled out vertebrobasilar ischaemic stroke; gradient echo T2*-weighted images excluded haemorrhage and thrombus in the venous system. It revealed only subtle hyperintensities in bilateral thalami on FLAIR sequence (figure 1). Consciousness impairment required tracheal intubation. He was hyperthermic (39°C) without shock. Blood and cerebrospinal fluid (CSF) samples revealed thrombopenia and lymphopenia, mild inflammatory response (C reactive protein, ferritin and fibrinogen), CSF albumin-cytological dissociation with increased CSF IgG antibodies (91.9 mg/L, normal 10–30 mg/L) and altered blood–brain barrier integrity (CSF/serum albumin index=17.3, normal <6.5) (online supplementary material). An electroencephalogram revealed symmetrical background activity of low-voltage delta waves without spatial organisation, triphasic waves or paroxysmal activity. He showed unresponsive coma (Glasgow Coma Scale=3), pyramidal syndrome, right-sided sixth nerve palsy and no corneal reflex. A second brain contrast-enhanced MRI at day 22 revealed progressing lesions with diffuse hyperintense …

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    • Collaborators The members of the NeuroICU Research Group are Diane Osinski, MD; Ségolène Mrozek, MD, PhD; Edouard Naboulsi, MD; Maxime Pommier, MD; Maud Prezman-Pietri, MD; Maxime Beilvert, MD; Vincent Minville, MD, PhD; and Samuel Groyer, MD.

    • Contributors LD, CGo, FG, GJ, CGa and EA wrote the first draft. JD and FB ensured neuroradiological analysis and editing. GG, PD and GM-B wrote the infectiology section, analysis of literature and corrections. CB and FF performed and analysed the immunological assays. CGo and JP supervised the diagnostic process and patient neurological expert assessment. TG and LD supervised the manuscript writing and edited the final version. Other authors ensured corrections and literature analysis.

    • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

    • Competing interests None declared.

    • Patient consent for publication Parental/guardian consent obtained.

    • Provenance and peer review Not commissioned; externally peer reviewed.