Critical illness-associated cerebral microbleeds for patients with severe COVID-19: etiologic hypotheses
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Critical illness‑associated cerebral microbleeds for patients with severe COVID‑19: etiologic hypotheses François Lersy1 · Thibault Willaume1 · Jean‑Christophe Brisset2 · Olivier Collange3 · Julie Helms4,5 · Francis Schneider6 · Agathe Chammas1 · Alexandre Willaume7 · Nicolas Meyer8 · Mathieu Anheim9,10 · François Cotton11,12 · Stéphane Kremer1,13 Received: 8 October 2020 / Revised: 2 November 2020 / Accepted: 8 November 2020 © Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract Background and purpose During the COVID-19 outbreak, the presence of extensive white matter microhemorrhages was detected by brain MRIs. The goal of this study was to investigate the origin of this atypical hemorrhagic complication. Methods Between March 17 and May 18, 2020, 80 patients with severe COVID-19 infections were admitted for acute respiratory distress syndrome to intensive care units at the University Hospitals of Strasbourg for whom a brain MRI for neurologic manifestations was performed. 19 patients (24%) with diffuse microhemorrhages were compared to 18 control patients with COVID-19 and normal brain MRI. Results The first hypothesis was hypoxemia. The latter seemed very likely since respiratory failure was longer and more pronounced in patients with microhemorrhages (prolonged endotracheal intubation (p = 0.0002), higher FiO2 (p = 0.03), increased use of extracorporeal membrane oxygenation (p = 0.04)). A relevant hypothesis, the role of microangiopathy, was also considered, since patients with microhemorrhages presented a higher increase of the D-Dimers (p = 0.01) and a tendency to more frequent thrombotic events (p = 0.12). Another hypothesis tested was the role of kidney failure, which was more severe in the group with diffuse microhemorrhages (higher creatinine level [median of 293 µmol/L versus 112 µmol/L, p = 0.04] and more dialysis were introduced in this group during ICU stay [12 versus 5 patients, p = 0.04]). Conclusions Blood–brain barrier dysfunction secondary to hypoxemia and high concentration of uremic toxins seems to be the main mechanism leading to critical illness-associated cerebral microbleeds, and this complication remains to be frequently described in severe COVID-19 patients. Keywords COVID-19 · Microhemorrhages · MRI · Hypoxemia · Kidney failure Abbreviations ARDS Acute respiratory distress syndrome CIAM Critical illness-associated cerebral microbleeds CSF Cerebrospinal fluid ECMO Extracorporeal Membrane Oxygenation ICU Intensive care unit RT-PCR Reverse transcriptase–polymerase chain reaction WM White matter
François Lersy and Thibault Willaume authors contributed equally to the work and are considered as co-first authors. * Stéphane Kremer stephane.kremer@chru‑strasbourg.fr
Introduction Recently, some cerebral complications related to COVID-19 were depicted on brain MRIs. Diffuse microbleeds, located in the white matter (WM) with an atypical distribution affecting, in particular, the corpus callosum, has recently been described in critically ill
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