COVID‐19 encephalopathy: Clinical and neurobiological features

Abstract

Severe acute respiratory coronavirus 2 (SARS-CoV-2) has been associated with neurological complications, including acute encephalopathy. To better understand the neuropathogenesis of this acute encephalopathy, we describe a series of patients with coronavirus disease 2019 (COVID-19) encephalopathy, highlighting its phenomenology and its neurobiological features. On May 10, 2020, 707 patients infected by SARS-CoV-2 were hospitalized at the Geneva University Hospitals; 31 (4.4%) consecutive patients with an acute encephalopathy (64.6 ± 12.1 years; 6.5% female) were included in this series, after exclusion of comorbid neurological conditions, such as stroke or meningitis. The severity of the COVID-19 encephalopathy was divided into severe and mild based on the Richmond Agitation Sedation Scale (RASS): severe cases (n = 14, 45.2%) were defined on a RASS < −3 at worst presentation. The severe form of this so-called COVID-19 encephalopathy presented more often a headache. The severity of the pneumonia was not associated with the severity of the COVID-19 encephalopathy: 28 of 31 (90%) patients did develop an acute respiratory distress syndrome, without any difference between groups (p = .665). Magnetic resonance imaging abnormalities were found in 92.0% (23 of 25 patients) with an intracranial vessel gadolinium enhancement in 85.0% (17 of 20 patients), while an increased cerebrospinal fluid/serum quotient of albumin suggestive of blood-brain barrier disruption was reported in 85.7% (6 of 7 patients). Reverse transcription-polymerase chain reaction for SARS-CoV-2 was negative for all patients in the cerebrospinal fluid. Although different pathophysiological mechanisms may contribute to this acute encephalopathy, our findings suggest the hypothesis of disturbed brain homeostasis and vascular dysfunction consistent with a SARS-CoV-2-induced endotheliitis.

Intermittent Frontal Rhythmic Discharges as an Electroencephalogram Biomarker of Acute SARS-CoV-2 Infection-Associated Encephalopathy in Children

“…Background slowing is the most dominant EEG signature in various reports. In a cohort of 23 adult patients with COVID-19 encephalopathy, 17 had diffuse background slowing but none had any ictal discharges [10]. Pasiti et al reported a group of 13 adult patients, all of them had mixed theta and delta 4-8 Hz slowing, among them four had consistent bifrontal slowing [16].…”

“…Full understanding of the pathophysiological process behind pediatric COVID-19 attributed encephalopathy is lacking, but hematogenous dissemination, direct brain invasion, secondary hypoxic brain injury, angiotensin-converting enzyme dysfunction, autoimmune-mediated neurotoxicity, and inflammatory cascade pathways activation are presumed contributing mechanisms [9]. Interestingly, the majority of patients have elevated CSF protein indicating some degree of blood-brain barrier disruption, but SARS-CoV-2 cannot usually be isolated from CSF [10]. The commonest brain neuroimaging findings are acute and subacute infarcts, leptomeningeal enhancement, microbleeds, and hyperintense signal abnormalities [11].…”

Neurological consequences of COVID-19 and brain related pathogenic mechanisms: A new challenge for neuroscience

“…Besides, EEG studies were also performed in 41.3% of these patients, indicating alterations in 61.9% of them ( Abenza Abildúa et al, 2021 ). However, other smallest studies pointed encephalopathies in lower frequencies, as for example in a retrospective study developed in Geneva, it is reported 4,4% ( Uginet et al, 2021 ). The Spanish registry cited before found viral RNA of SARS-CoV-2 in cerebrospinal fluid (CSF) of patients with encephalitis in only one case ( Abenza Abildúa et al, 2021 ) and the study from Geneve did not find in any of the patient ( Uginet et al, 2021 ).…”

COVID-19: neurologische Manifestationen – Update

“…Als Enzephalopathie wird ein klinisches Erkrankungsbild verstanden, welches sich meist mit einer Kombination aus akuten Aufmerksamkeits‑, Bewusstseins- und Kognitionsstörungen, mit Delir oder Psychose manifestiert [ 47 ]. Bereits erste retrospektive Studien aus der Stadt Wuhan vermerkten Bewusstseinsstörungen (7,5 %) und Verwirrtheit (9 %) zu den häufigen neurologischen Komplikationen bei hospitalisierten COVD-19-Patienten [ 8 ].…”