Brain MRI Findings in Severe COVID-19: A Retrospective Observational Study

Stéphane Kremer, François Lersy, Jérome de Sèze, Jean-Christophe Ferré, Adel Maamar, Béatrice Carsin-Nicol, Olivier Collange, Fabrice Bonneville, Gilles Adam, Guillaume Martin-Blondel, Marie Rafiq, Thomas Geeraerts, Louis Delamarre, Sylvie Grand, Alexandre Krainik, Sophie Caillard, Jean Marc Constans, Serge Metanbou, Adrien Heintz, Julie Helms, Maleka Schenck, Nicolas Lefèbvre, Claire Boutet, Xavier Fabre, Géraud Forestier, Isaure de Beaurepaire, Grégoire Bornet, Audrey Lacalm, Hélène Oesterlé, Federico Bolognini, Julien Messié, Ghazi Hmeydia, Joseph Benzakoun, Catherine Oppenheim, Blanche Bapst, Imen Megdiche, Marie-Cécile Henry Feugeas, Antoine Khalil, Augustin Gaudemer, Lavinia Jager, Patrick Nesser, Yannick Talla Mba, Céline Hemmert, Philippe Feuerstein, Nathan Sebag, Sophie Carré, Manel Alleg, Claire Lecocq, Emmanuelle Schmitt, René Anxionnat, François Zhu, Pierre-Olivier Comby, Frédéric Ricolfi, Pierre Thouant, Hubert Desal, Grégoire Boulouis, Jérome Berge, Apolline Kazémi, Nadya Pyatigorskaya, Augustin Lecler, Suzana Saleme, Myriam Edjlali-Goujon, Basile Kerleroux, Pierre-Emmanuel Zorn, Muriel Matthieu, Seyyid Baloglu, François-Daniel Ardellier, Thibault Willaume, Jean Christophe Brisset, Clotilde Boulay, Véronique Mutschler, Yves Hansmann, Paul-Michel Mertes, Francis Schneider, Samira Fafi-Kremer, Mickael Ohana, Ferhat Meziani, Jean-Stéphane David, Nicolas Meyer, Mathieu Anheim, François Cotton, Stéphane Kremer, François Lersy, Jérome de Sèze, Jean-Christophe Ferré, Adel Maamar, Béatrice Carsin-Nicol, Olivier Collange, Fabrice Bonneville, Gilles Adam, Guillaume Martin-Blondel, Marie Rafiq, Thomas Geeraerts, Louis Delamarre, Sylvie Grand, Alexandre Krainik, Sophie Caillard, Jean Marc Constans, Serge Metanbou, Adrien Heintz, Julie Helms, Maleka Schenck, Nicolas Lefèbvre, Claire Boutet, Xavier Fabre, Géraud Forestier, Isaure de Beaurepaire, Grégoire Bornet, Audrey Lacalm, Hélène Oesterlé, Federico Bolognini, Julien Messié, Ghazi Hmeydia, Joseph Benzakoun, Catherine Oppenheim, Blanche Bapst, Imen Megdiche, Marie-Cécile Henry Feugeas, Antoine Khalil, Augustin Gaudemer, Lavinia Jager, Patrick Nesser, Yannick Talla Mba, Céline Hemmert, Philippe Feuerstein, Nathan Sebag, Sophie Carré, Manel Alleg, Claire Lecocq, Emmanuelle Schmitt, René Anxionnat, François Zhu, Pierre-Olivier Comby, Frédéric Ricolfi, Pierre Thouant, Hubert Desal, Grégoire Boulouis, Jérome Berge, Apolline Kazémi, Nadya Pyatigorskaya, Augustin Lecler, Suzana Saleme, Myriam Edjlali-Goujon, Basile Kerleroux, Pierre-Emmanuel Zorn, Muriel Matthieu, Seyyid Baloglu, François-Daniel Ardellier, Thibault Willaume, Jean Christophe Brisset, Clotilde Boulay, Véronique Mutschler, Yves Hansmann, Paul-Michel Mertes, Francis Schneider, Samira Fafi-Kremer, Mickael Ohana, Ferhat Meziani, Jean-Stéphane David, Nicolas Meyer, Mathieu Anheim, François Cotton

Abstract

Background Brain MRI parenchymal signal abnormalities have been associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Purpose To describe the neuroimaging findings (excluding ischemic infarcts) in patients with severe coronavirus disease 2019 (COVID-19) infection. Materials and Methods This was a retrospective study of patients evaluated from March 23, 2020, to April 27, 2020, at 16 hospitals. Inclusion criteria were (a) positive nasopharyngeal or lower respiratory tract reverse transcriptase polymerase chain reaction assays, (b) severe COVID-19 infection defined as a requirement for hospitalization and oxygen therapy, (c) neurologic manifestations, and (d) abnormal brain MRI findings. Exclusion criteria were patients with missing or noncontributory data regarding brain MRI or brain MRI showing ischemic infarcts, cerebral venous thrombosis, or chronic lesions unrelated to the current event. Categorical data were compared using the Fisher exact test. Quantitative data were compared using the Student t test or Wilcoxon test. P < .05 represented a significant difference. Results Thirty men (81%) and seven women (19%) met the inclusion criteria, with a mean age of 61 years ± 12 (standard deviation) (age range, 8-78 years). The most common neurologic manifestations were alteration of consciousness (27 of 37, 73%), abnormal wakefulness when sedation was stopped (15 of 37, 41%), confusion (12 of 37, 32%), and agitation (seven of 37, 19%). The most frequent MRI findings were signal abnormalities located in the medial temporal lobe in 16 of 37 patients (43%; 95% confidence interval [CI]: 27%, 59%), nonconfluent multifocal white matter hyperintense lesions seen with fluid-attenuated inversion recovery and diffusion-weighted sequences with variable enhancement, with associated hemorrhagic lesions in 11 of 37 patients (30%; 95% CI: 15%, 45%), and extensive and isolated white matter microhemorrhages in nine of 37 patients (24%; 95% CI: 10%, 38%). A majority of patients (20 of 37, 54%) had intracerebral hemorrhagic lesions with a more severe clinical presentation and a higher admission rate in intensive care units (20 of 20 patients [100%] vs 12 of 17 patients without hemorrhage [71%], P = .01) and development of the acute respiratory distress syndrome (20 of 20 patients [100%] vs 11 of 17 patients [65%], P = .005). Only one patient had SARS-CoV-2 RNA in the cerebrospinal fluid. Conclusion Patients with severe coronavirus disease 2019 and without ischemic infarcts had a wide range of neurologic manifestations that were associated with abnormal brain MRI scans. Eight distinctive neuroradiologic patterns were described. © RSNA, 2020.

Figures

Figure 1.
Figure 1.
Flowchart of patient inclusion and exclusion
Figure 2.
Figure 2.
Axial FLAIR in four different COVID-19 patients. A) 58-year old man with impaired consciousness: FLAIR hyperintensities located in the left medial temporal lobe. B) 66-year old man with impaired consciousness: FLAIR ovoid hyperintense lesion located in the central part of the splenium of the corpus callosum. C) 71-year old woman with pathological wakefulness after sedation: extensive and confluent supratentorial white matter FLAIR hyperintensities (arrows). Association with leptomeningeal enhancement (stars) D) 61-year old man with confusion: hyperintense lesions involving both middle cerebellar peduncles.
Figure 3.
Figure 3.
65-year old man with pathological wakefulness after sedation. Non-confluent multifocal white matter hyperintense lesions on FLAIR and diffusion, with variable enhancement, and hemorrhagic lesions. Axial Diffusion (A, B), Apparent Diffusion Coefficient (ADC) map (C), axial FLAIR (D, E), sagittal FLAIR (F), axial Susceptibility weighted imaging (SWI) (G), and postcontrast T1 weighted MR images (H). Multiple nodular hyperintense Diffusion and FLAIR lesions localized in the white matter including the corpus callosum (F). Some of them (white arrow) are associated with reduced ADC corresponding to cytotoxic edema (C). Other lesions are located next to the lenticular nucleus (cross) (E, G, H), with hemorrhagic changes (G), and enhancement after contrast administration.
Figure 4.
Figure 4.
57-year old man with pathological wakefulness after sedation. Extensive and isolated white matter microhemorrhages. Axial Susceptibility weighted imaging (SWI) (A, B, C, D): multiple microhemorrhages mainly affecting the subcortical white matter, corpus callosum, internal capsule, and cerebellar peduncles.
Figure 5.
Figure 5.
54-year old man with pathological wakefulness after sedation. Non-confluent multifocal white matter hyperintense lesions on FLAIR and diffusion, with variable enhancement. Axial Diffusion (A, B), Apparent Diffusion Coefficient (ADC) map (C, D), axial postcontrast FLAIR (E, F), and postcontrast T1 weighted MR images (G, H). Multiple nodular hyperintense Diffusion and FLAIR subcortical and corticospinal tracts lesions, with very mild mass effect on adjacent structures. The lesions present a center with an elevation of ADC corresponding to vasogenic edema and a peripheral ring of reduced ADC corresponding to cytotoxic edema (C, D). After contrast administration, small areas of very mild enhancement are detected (G, H).
Figure 6.
Figure 6.
51-year old man with impaired consciousness. Acute necrotizing encephalopathy. Axial FLAIR (A, C, D), and coronal FLAIR (B): bilateral FLAIR hyperintensity (cross) in both thalami (A, B), associated with involvement of the cerebellar (C), and cerebral (D) white matter (arrows).

References

    1. Na Zhu, Dingyu Zhang, Wenling Wang, et al. . A Novel Coronavirus From Patients With Pneumonia in China, 2019.N Engl J Med. 2020 Feb 20;382(8):727-733. doi: 10.1056/NEJMoa2001017.
    1. Bohmwald K, Gálvez NMS, Ríos M, Kalergis AM. Neurologic Alterations Due to Respiratory Virus Infections. Front Cell Neurosci. 2018;12:386 Published 2018 Oct 26. doi:10.3389/fncel.2018.00386
    1. Desforges M, Le Coupanec A, Stodola JK, Meessen-Pinard M, Talbot PJ. Human coronaviruses: viral and cellular factors involved in neuroinvasiveness and neuropathogenesis. Virus Res. 2014 Dec 19;194:145-58. doi: 10.1016/j.virusres.2014.09.011.
    1. Desforges M, Le Coupanec A, Dubeau P, et al. . Human Coronaviruses and Other Respiratory Viruses: Underestimated Opportunistic Pathogens of the Central Nervous System? Viruses. 2019 Dec 20;12(1). pii: E14. doi: 10.3390/v12010014.
    1. Li Y, Li H, Fan R, et al. . Coronavirus Infections in the Central Nervous System and Respiratory Tract Show Distinct Features in Hospitalized Children. Intervirology. 2016;59(3):163-169. doi: 10.1159/000453066.
    1. Arabi YM, Harthi A, Hussein J, et al. . Severe neurologic syndrome associated with Middle East respiratory syndrome corona virus (MERS-CoV). Infection. 2015 Aug;43(4):495-501. doi: 10.1007/s15010-015-0720-y.
    1. Kim JE, Heo JH, Kim HO, et al. . Neurological Complications during Treatment of Middle East Respiratory Syndrome. J Clin Neurol. 2017 Jul;13(3):227-233. doi: 10.3988/jcn.2017.13.3.227.
    1. Yeh EA, Collins A, Cohen ME, Duffner PK, Faden H. Detection of coronavirus in the central nervous system of a child with acute disseminated encephalomyelitis. Pediatrics. 2004 Jan;113(1 Pt 1):e73-6.
    1. 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 Mar 31:201187. doi: 10.1148/radiol.2020201187.
    1. Moriguchi T, Harii N, Goto J, et al. . A first Case of Meningitis/Encephalitis associated with SARS-Coronavirus-2. Int J Infect Dis. 2020 Apr 3. pii: S1201-9712(20)30195-8. doi: 10.1016/j.ijid.2020.03.062.
    1. Kandemirli SG, Dogan L, Sarikaya ZT, et al. . Brain MRI Findings in Patients in the Intensive Care Unit with COVID-19 Infection. Radiology. 2020 May 8:201697. doi: 10.1148/radiol.2020201697.
    1. Radmanesh A, Derman A, Lui YW, et al. . COVID-19 -associated Diffuse Leukoencephalopathy and Microhemorrhages [published online ahead of print, 2020 May 21]. Radiology. 2020;202040. doi:10.1148/radiol.2020202040.
    1. Franceschi AM, Ahmed O, Giliberto L, Castillo M. Hemorrhagic Posterior Reversible Encephalopathy Syndrome as a Manifestation of COVID-19 Infection [published online ahead of print, 2020 May 21]. AJNR Am J Neuroradiol. 2020;10.3174/ajnr.A6595. doi:10.3174/ajnr.A6595
    1. Mao L, Jin H, Wang M, et al. . Neurologic Manifestations of Hospitalized Patients With Coronavirus Disease 2019 in Wuhan, China. JAMA Neurol. 2020 Apr 10. doi: 10.1001/jamaneurol.2020.1127.
    1. Mahammedi A, Saba L, Vagal A, et al. . Imaging in Neurological Disease of Hospitalized COVID-19 Patients: An Italian Multicenter Retrospective Observational Study [published online ahead of print, 2020 May 21]. Radiology. 2020;201933. doi:10.1148/radiol.2020201933.
    1. Helms J, Kremer S, Merdji H, et al. . Neurologic Features in Severe SARS-CoV-2 Infection. N Engl J Med. 2020 Apr 15. doi: 10.1056/NEJMc2008597.
    1. Romero-Sánchez CM, Díaz-Maroto I, Fernández-Díaz E, et al. . Neurologic manifestations in hospitalized patients with COVID-19: The ALBACOVID registry [published online ahead of print, 2020 Jun 1]. Neurology. 2020;10.1212/WNL.0000000000009937. doi:10.1212/WNL.0000000000009937
    1. World Health Organization . Protocol: Real-time RT-PCR assays for the detection of SARS-CoV-2 Institut Pasteur, Paris.
    1. Budhram A, Leung A, Nicolle MW, Burneo JG. Diagnosing autoimmune limbic encephalitis. CMAJ. 2019 May 13;191(19):E529-E534. doi: 10.1503/cmaj.181548.
    1. Parsons T, Banks S, Bae C, Gelber J, Alahmadi H, Tichauer M. COVID-19-associated acute disseminated encephalomyelitis (ADEM) [published online ahead of print, 2020 May 30]. J Neurol. 2020;1‐4. doi:10.1007/s00415-020-09951-9
    1. Pohl D, Alper G, Van Haren K, et al. . Acute disseminated encephalomyelitis: Updates on an inflammatory CNS syndrome. Neurology. 2016 Aug 30;87(9 Suppl 2):S38-45. doi: 10.1212/WNL.0000000000002825.
    1. Nabi S, Badshah M, Ahmed S, Nomani AZ. Weston-Hurst syndrome: a rare fulminant form of acute disseminated encephalomyelitis (ADEM). BMJ Case Rep. 2016 Oct 19;2016. pii: bcr2016217215. doi: 10.1136/bcr-2016-217215.
    1. Needham EJ, Chou SH, Coles AJ, Menon DK. Neurological Implications of COVID-19 Infections [published online ahead of print, 2020 Apr 28]. Neurocrit Care. 2020;1‐5. doi:10.1007/s12028-020-00978-4
    1. Reichard RR, Kashani KB, Boire NA, Constantopoulos E, Guo Y, Lucchinetti CF. Neuropathology of COVID-19: a spectrum of vascular and acute disseminated encephalomyelitis (ADEM)-like pathology [published online ahead of print, 2020 May 24]. Acta Neuropathol. 2020;10.1007/s00401-020-02166-2. doi:10.1007/s00401-020-02166-2
    1. Radmanesh F, Rodriguez-Pla A, Pincus MD, Burns JD. Severe cerebral involvement in adult-onset hemophagocytic lymphohistiocytosis. J Clin Neurosci. 2020 Apr 16. pii: S0967-5868(20)30681-0. doi: 10.1016/j.jocn.2020.04.054
    1. Taylor FB, Toh CH, Hoots WK, Wada H, Levi M. Scientific Subcommittee on Disseminated Intravascular Coagulation (DIC) of the International Society on Thrombosis and Haemostasis (ISTH). Towards definition, clinical and laboratory criteria, and a scoring system for disseminated intravascular coagulation. Thromb Haemost. 2001;86(5):1327–1330.
    1. Katyal N, Narula N, George P, Nattanamai P, Newey CR, Beary JM. Delayed Post-hypoxic Leukoencephalopathy: A Case Series and Review of the Literature. Cureus. 2018;10(4):e2481. Published 2018 Apr 15. doi:10.7759/cureus.2481
    1. Kishfy L, Casasola M, Banankhah P, et al. . Posterior reversible encephalopathy syndrome (PRES) as a neurological association in severe Covid-19 [published online ahead of print, 2020 May 23]. J Neurol Sci. 2020;414:116943. doi:10.1016/j.jns.2020.116943

Source: PubMed

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