Neuroanatomical substrates of generalized brain dysfunction in COVID-19
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LETTER
Neuroanatomical substrates of generalized brain dysfunction in COVID‑19 Virginia F. J. Newcombe1,2* , Lennart R. B. Spindler1,3, Tilak Das4, Stefan Winzeck1,5, Kieren Allinson6, Emmanuel A. Stamatakis1,2,3 and David K. Menon1,2* on behalf of the Cambridge NeuroCovid Imaging Collaborators © 2020 Springer-Verlag GmbH Germany, part of Springer Nature
Dear Editor, Central nervous system involvement is common in coronavirus disease 2019 (COVID-19), and may be driven by many mechanisms [1]. Reports of brain X-ray computed tomography [2] or magnetic resonance imaging (MRI) [3] findings in individual patients or small case series have generally focused on discrete pathologies such as stroke or focal abnormalities. However, these reports do not elucidate more generalized abnormalities of central nervous function, such as the alteration of mental status in a third of patients [4], or quantitative imaging correlates of reported brainstem pathology [5]. We report MRI findings in six patients with severe COVID-19-related respiratory failure (WHO Ordinal Scale 7), imaged 19 days (range 16–26) post admission, using conventional MRI and diffusion tensor imaging (DTI, Supplementary Table 1). The scans were performed for clinical reasons while the patients were in the intensive care unit with data prospectively collected. Indications included: persistent unresponsiveness after washout of sedative agents (n = 4); severe delirium (n = 1); or generalized myoclonus (n = 1). Three patients had small acute ischemic lesions in the frontal deep white matter and two of these also had subarachnoid, intraventricular, or small parenchymal hemorrhage. However, none of the patients had abnormalities on conventional *Correspondence: [email protected]; [email protected] 1 Division of Anaesthesia, Department of Medicine, University of Cambridge, Cambridge, United Kingdom Full author information is available at the end of the article
The Cambridge NeuroCovid Imaging Collaboratos are listed in the Acknowledgements section.
MRI that explained their clinical presentation or indicated hypoxic-ischemic injury. DTI characterizes the diffusion of water molecules in tissue environments which are influenced by the microstructural organization of tissues. The diffusion tensor can be used to represent the magnitude of water diffusion (quantified as mean diffusivity (MD), which quantifies overall diffusion of water in tissue compartments), describe whether such diffusion is directionally nonuniform (fractional anisotropy, which classically changes with white matter pathology), and characterize the orientation of that direction (eigenvectors/eigenvalues, used for tractography; a modeling technique was used to map out white matter tracts, see Supplementary Tables 3, 4 and 5 for tract names). All of the COVID-19 patients showed pervasive abnormalities on quantitative DTI compared to controls (Fig. 1A–B, Supplementary Tables 2–5), with increased mean diffusivity (MD) in frontal, temporal, parietal, and occipital cortices and hippocampi, consistent with
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