COVID-19–related encephalopathy responsive to high-dose glucocorticoids

Abstract

One hundred twenty patients with coronavirus disease 2019 were hospitalized in our intensive care unit, Geneva, Switzerland, between March 9 and April 16, 2020. We report the clinical evolution of 5 consecutive patients intubated because of COVID-19related acute respiratory distress syndrome, presenting with a pathologic recovery of consciousness, which was responsive to high-dose glucocorticoids. These patients all presented with angio-MRI signs of inflammation of CNS arteries, consistent with an endothelialitis rather than a vasculitis. The median time between COVID-19 first symptoms and intubation was 10 days (IQR 10-11 days).After at least 2 weeks of mechanical ventilation, all 5 patients presented with delayed awakening (Glasgow Coma Scale [GCS] score 4-9). Sedation/agitation Confusion assessment method for the intensive care unit or Richmond agitation sedation scale scores were not measured due to the severity of the impaired consciousness. Other causes of impaired consciousness classically found in such patients were assessed. Metabolic disorders including renal or hepatic insufficiency, dysnatremia, persistence of sedatives effects, or hypoxemia were not present in these patients and could therefore not explain their clinical status (tables S1-S3, available from Dryad, doi.org/10.5061/dryad.dv41ns1vq). An EEG was performed in all patients, ruling out epilepsy showing only nonspecific changes.

Intravenous immunoglobulin therapy in COVID-19-related encephalopathy

“…Correspondingly, our patients showed a prompt and dramatic improvement of neurological manifestations following IVIg. Similar results have been achieved in six other patients with COVID-19-related encephalopathy treated with high-dose corticosteroids [5,11]. In our third case, steroid pulse therapy was ineffective, where subsequent IVIg was concomitant with clinical recovery.…”

COVID‐19: A Global Threat to the Nervous System

“…These findings suggest that an endothelialitis rather than a vasculitis was responsible for the encephalopathy. 18 Direct infection of endothelial cells by SARS-CoV-2 and associated endothelial inflammation has been demonstrated histologically in postmortem specimens from a variety of organs, which did not include the brain. 19 However, in an autopsy series, including examination of the brain, of 20 patients with COVID-19, six had microthrombi and acute infarctions and two focal parenchymal infiltrates of T-lymphocytes, whereas the others mainly had minimal inflammation and slight neuronal loss without acute hypoxic-ischemic changes in most cases.…”

Encephalopathy in COVID-19 Presenting With Acute Aphasia Mimicking Stroke

“…Encephalopathy in the contest of potentially neurotropic virus infection, such as SARS-CoV-2, may raise suspicion of a viral encephalitis; however, CSF and MRI findings in our patient were inconsistent with this hypothesis, in line with the vast majority of COVID-19 patients presenting with central neurological manifestations (1,5,6). Accordingly, clinical responses observed to various immunomodulatory treatments, such as corticosteroids (13,14) and plasmapheresis (15), suggest an immune-mediated pathogenesis, at least for a subgroup of patients. Recently, cytokine-mediated neuroinflammation has been proposed as the underlying pathogenesis of COVID-19-related encephalopathy/encephalitis (7,13,16), a peculiar pathogenic mechanism also responsible for immune effector cell-associated neurotoxicity syndrome (ICANS) (17)(18)(19)(20).…”