Acute necrotizing encephalopathy with SARS-CoV-2 RNA confirmed in cerebrospinal fluid
Johan Virhammar, Eva Kumlien, David Fällmar, Robert Frithiof, Sven Jackmann, Mattias K Sköld, Mohamed Kadir, Jens Frick, Jonas Lindeberg, Henrik Olivero-Reinius, Mats Ryttlefors, Janet L Cunningham, Johan Wikström, Anna Grabowska, Kåre Bondeson, Jonas Bergquist, Henrik Zetterberg, Elham Rostami, Johan Virhammar, Eva Kumlien, David Fällmar, Robert Frithiof, Sven Jackmann, Mattias K Sköld, Mohamed Kadir, Jens Frick, Jonas Lindeberg, Henrik Olivero-Reinius, Mats Ryttlefors, Janet L Cunningham, Johan Wikström, Anna Grabowska, Kåre Bondeson, Jonas Bergquist, Henrik Zetterberg, Elham Rostami
Abstract
Here, we report a case of COVID-19-related acute necrotizing encephalopathy where SARS-CoV-2 RNA was found in CSF 19 days after symptom onset after testing negative twice. Although monocytes and protein levels in CSF were only marginally increased, and our patient never experienced a hyperinflammatory state, her neurologic function deteriorated into coma. MRI of the brain showed pathologic signal symmetrically in central thalami, subinsular regions, medial temporal lobes, and brain stem. Extremely high concentrations of the neuronal injury markers neurofilament light and tau, as well as an astrocytic activation marker, glial fibrillary acidic protein, were measured in CSF. Neuronal rescue proteins and other pathways were elevated in the in-depth proteomics analysis. The patient received IV immunoglobulins and plasma exchange. Her neurologic status improved, and she was extubated 4 weeks after symptom onset. This case report highlights the neurotropism of SARS-CoV-2 in selected patients and emphasizes the importance of repeated lumbar punctures and CSF analyses in patients with suspected COVID-19 and neurologic symptoms.
Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.
Figures
References
- Poyiadji N, Shahin G, Noujaim D, Stone M, Patel S, Griffith B. COVID-19-associated acute hemorrhagic necrotizing encephalopathy: CT and MRI features. Radiology 2020;296:E119–E120.
- Moriguchi T, Harii N, Goto J, et al. . A first case of meningitis/encephalitis associated with SARS-Coronavirus-2. Int J Infect Dis 2020;94:55–58.
- Mizuguchi M. Acute necrotizing encephalopathy of childhood: a novel form of acute encephalopathy prevalent in Japan and Taiwan. Brain Dev 1997;19:81–92.
- Murray RS, Cai GY, Hoel K, Zhang JY, Soike KF, Cabirac GF. Coronavirus infects and causes demyelination in primate central nervous system. Virology 1992;188:274–284.
- Paniz-Mondolfi A, Bryce C, Grimes Z, et al. . Central nervous system involvement by severe acute respiratory syndrome coronavirus -2 (SARS-CoV-2). J Med Virol 2020;92:699–702.
- Lau KK, Yu WC, Chu CM, Lau ST, Sheng B, Yuen KY. Possible central nervous system infection by SARS coronavirus. Emerg Infect Dis 2004;10:342–344.
- Perlman S, Jacobsen G, Afifi A. Spread of a neurotropic murine coronavirus into the CNS via the trigeminal and olfactory nerves. Virology 1989;170:556–560.
Source: PubMed