{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T13:54:20Z","timestamp":1784555660681,"version":"3.55.0"},"reference-count":56,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2022,6,9]],"date-time":"2022-06-09T00:00:00Z","timestamp":1654732800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,9,14]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>While neuropathological examinations in patients who died from COVID-19 revealed inflammatory changes in cerebral white matter, cerebral MRI frequently fails to detect abnormalities even in the presence of neurological symptoms. Application of multi-compartment diffusion microstructure imaging (DMI), that detects even small volume shifts between the compartments (intra-axonal, extra-axonal and free water\/CSF) of a white matter model, is a promising approach to overcome this discrepancy.<\/jats:p>\n               <jats:p>In this monocentric prospective study, a cohort of 20 COVID-19 inpatients (57.3\u2009\u00b1\u200917.1 years) with neurological symptoms (e.g. delirium, cranial nerve palsies) and cognitive impairments measured by the Montreal Cognitive Assessment (MoCA test; 22.4\u2009\u00b1\u20094.9; 70% below the cut-off value &amp;lt;26\/30 points) underwent DMI in the subacute stage of the disease (29.3\u2009\u00b1\u200914.8 days after positive PCR). A comparison of whole-brain white matter DMI parameters with a matched healthy control group (n\u2009=\u200935) revealed a volume shift from the intra- and extra-axonal space into the free water fraction (V-CSF). This widespread COVID-related V-CSF increase affected the entire supratentorial white matter with maxima in frontal and parietal regions. Streamline-wise comparisons between COVID-19 patients and controls further revealed a network of most affected white matter fibres connecting widespread cortical regions in all cerebral lobes. The magnitude of these white matter changes (V-CSF) was associated with cognitive impairment measured by the MoCA test (r\u2009=\u2009\u22120.64, P\u2009=\u20090.006) but not with olfactory performance (r\u2009=\u20090.29, P\u2009=\u20090.12). Furthermore, a non-significant trend for an association between V-CSF and interleukin-6 emerged (r\u2009=\u20090.48, P\u2009=\u20090.068), a prominent marker of the COVID-19 related inflammatory response. In 14\/20 patients who also received cerebral 18F-FDG PET, V-CSF increase was associated with the expression of the previously defined COVID-19-related metabolic spatial covariance pattern (r\u2009=\u20090.57; P\u2009=\u20090.039). In addition, the frontoparietal-dominant pattern of neocortical glucose hypometabolism matched well to the frontal and parietal focus of V-CSF increase.<\/jats:p>\n               <jats:p>In summary, DMI in subacute COVID-19 patients revealed widespread volume shifts compatible with vasogenic oedema, affecting various supratentorial white matter tracts. These changes were associated with cognitive impairment and COVID-19 related changes in 18F-FDG PET imaging.<\/jats:p>","DOI":"10.1093\/brain\/awac045","type":"journal-article","created":{"date-parts":[[2022,2,4]],"date-time":"2022-02-04T12:27:18Z","timestamp":1643977638000},"page":"3203-3213","source":"Crossref","is-referenced-by-count":61,"title":["Widespread white matter oedema in subacute COVID-19 patients with neurological symptoms"],"prefix":"10.1093","volume":"145","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5881-6043","authenticated-orcid":false,"given":"Alexander","family":"Rau","sequence":"first","affiliation":[{"name":"Department of Neuroradiology, Medical Center \u2013 University of Freiburg, Faculty of Medicine, University of Freiburg , Freiburg , 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