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. 2020 Dec;51(12):3719-3722.
doi: 10.1161/STROKEAHA.120.031224. Epub 2020 Oct 15.

Large and Small Cerebral Vessel Involvement in Severe COVID-19: Detailed Clinical Workup of a Case Series

Emanuela Keller  1 , Giovanna Brandi  2 , Sebastian Winklhofer  3 , Lukas L Imbach  4 , Daniel Kirschenbaum  5 , Karl Frontzek  5 , Peter Steiger  2 , Sabeth Dietler  2 , Marcellina Haeberlin  4 , Jan Willms  2 , Francesca Porta  6 , Adrian Waeckerlin  6 , Michael Huber  7 , Irene A Abela  8 , Andreas Lutterotti  9 , Christoph Stippich  3 , Christoph Globas  10 , Zsuzsanna Varga  11 , Ilijas Jelcic  9
Affiliations

Large and Small Cerebral Vessel Involvement in Severe COVID-19: Detailed Clinical Workup of a Case Series

Emanuela Keller et al. Stroke. 2020 Dec.

Abstract

Background and purpose: Case series indicating cerebrovascular disorders in coronavirus disease 2019 (COVID-19) have been published. Comprehensive workups, including clinical characteristics, laboratory, electroencephalography, neuroimaging, and cerebrospinal fluid findings, are needed to understand the mechanisms.

Methods: We evaluated 32 consecutive critically ill patients with COVID-19 treated at a tertiary care center from March 9 to April 3, 2020, for concomitant severe central nervous system involvement. Patients identified underwent computed tomography, magnetic resonance imaging, electroencephalography, cerebrospinal fluid analysis, and autopsy in case of death.

Results: Of 32 critically ill patients with COVID-19, 8 (25%) had severe central nervous system involvement. Two presented with lacunar ischemic stroke in the early phase and 6 with prolonged impaired consciousness after termination of analgosedation. In all but one with delayed wake-up, neuroimaging or autopsy showed multiple cerebral microbleeds, in 3 with additional subarachnoid hemorrhage and in 2 with additional small ischemic lesions. In 3 patients, intracranial vessel wall sequence magnetic resonance imaging was performed for the first time to our knowledge. All showed contrast enhancement of vessel walls in large cerebral arteries, suggesting vascular wall pathologies with an inflammatory component. Reverse transcription-polymerase chain reactions for SARS-CoV-2 in cerebrospinal fluid were all negative. No intrathecal SARS-CoV-2-specific IgG synthesis was detectable.

Conclusions: Different mechanisms of cerebrovascular disorders might be involved in COVID-19. Acute ischemic stroke might occur early. In a later phase, microinfarctions and vessel wall contrast enhancement occur, indicating small and large cerebral vessels involvement. Central nervous system disorders associated with COVID-19 may lead to long-term disabilities. Mechanisms should be urgently investigated to develop neuroprotective strategies.

Keywords: central nervous system; cerebrospinal fluid; cerebrovascular disorders; coronavirus disease; neuroimaging.

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Conflict of interest statement

Dr Frontzek received an unrestricted research grant from Ono Pharmaceuticals outside of the submitted work. The other authors report no conflicts.

Figures

Figure 1.
Figure 1.
Magnetic resonance imaging (MRI) findings in patient 2. Susceptibility-weighted imaging (SWI) shows subarachnoid hemorrhage (A). Intracranial vessel wall imaging (VWI) demonstrates vessel wall contrast enhancement of the left middle cerebral artery (MCA; B) and right posterior cerebral artery (PCA; C).
Figure 2.
Figure 2.
Magnetic resonance imaging (MRI) findings in patient 6. Diffusion-weighted imaging (DWI) shows multiple subacute ischemic lesions in different territories (A) and ubiquitous microbleeds in susceptibility-weighted imaging (SWI; B). Intracranial vessel wall imaging (VWI) demonstrates vessel wall contrast enhancement of the left middle cerebral artery (MCA; C).
See this image and copyright information in PMC

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