C-reactive protein and white matter microstructural changes in COVID-19 patients with encephalopathy

Abstract

Encephalopathy is a neurological complication of COVID-19. The objective of this exploratory study is to investigate the link between systemic inflammation and brain microstructural changes (measured by diffusion-weighted imaging) in patients with COVID-19 encephalopathy. 20 patients with COVID-19 encephalopathy (age: 67.3 $$\pm$$ ± 10.0 years; 90% men) hospitalized in the Geneva University Hospitals for a SARS-CoV-2 infection between March and May 2020 were included in this retrospective cohort study. COVID-19 encephalopathy was diagnosed following a comprehensive neurobiological evaluation, excluding common causes of delirium, such as hypoxemic or metabolic encephalopathy. We investigated the correlation between systemic inflammation (measured by systemic C-reactive protein (CRP)) and brain microstructural changes in radiologically normal white matter (measured by apparent diffusion coefficient (ADC)) in nine spatially widespread regions of the white matter previously associated with delirium. Systemic inflammation (CRP = 60.8 ± 50.0 mg/L) was positively correlated with ADC values in the anterior corona radiata (p = 0.0089), genu of the corpus callosum (p = 0.0064) and external capsule (p = 0.0086) after adjusting for patients’ age. No statistically significant association between CRP and ADC was found in the other six white matter regions. Our findings indicate high risk of white matter abnormalities in COVID-19 encephalopathy patients with high peripheral inflammatory markers, suggesting aggressive imaging monitoring may be warranted in these patients. Future studies should clarify a possible specificity of the spatial patterns of CRP–white matter microstructure association in COVID-19 encephalopathy patients and disentangle the role of individual cytokines on brain inflammatory mechanisms.

Brain Imaging Changes in Patients Recovered From COVID-19: A Narrative Review

“…This indicates that severe patients still have some brain diffuse dysfunction 3 months after recovery, and the changes in the brain microstructure of severe patients are closely related to the CBF of the insula and negatively correlated with the levels of PCT and IL-6 in serum (Qin et al, 2021). Another study also found that microstructural changes in white matter were closely associated with systemic inflammatory responses and concluded that in patients with COVID-19 encephalopathy, the average apparent diffusion coefficient (ADC) in the white matter region of the genu of the corpus callosum, ATR, and EC was increased with local CRP levels, consistent with the delirium associated with the frontal-subcortical syndrome (Rhally et al, 2021).…”

Brain diffusion alterations in patients with COVID-19 pathology and neurological manifestations

“…Most of the previous studies assessing brain DWI alterations in COVID-19 patients were limited to case reports or case series ( Parsons et al, 2021 ) or focused on specific neurological complications such as encephalopathy, where white matter abnormalities were associated with high peripheral inflammatory markers ( Rhally et al, 2021 ).…”

“…Previous DWI studies reported alterations in brain diffusivity in COVID-19 patients ( Parsons et al, 2021 , Chougar et al, 2020 , Kremer et al, 2020 , Kandemirli et al, 2020 , Douaud et al, 2022 , Rhally et al, 2021 , Zhang et al, 2011 , Huang et al, 2021 ), as assessed by morphologic evaluation of brain DWI scans only. The diffusion tensor imaging (DTI) studies published so far confirmed significant alterations in mean diffusivity in COVID-19 survivors ( Newcombe et al, 2021 , Lu et al, 2020 , Benedetti et al, 2021 , Díez-Cirarda et al, 2022 ).…”

The prevention of major neurocognitive disorders in the next phase of COVID-19 pandemic: On being proactive

“…Thus, we suggest that the risk of incident MNCD has greatly increased in older people, especially among those with minor neurocognitive disorders, regardless of their COVID-19 status. Furthermore, those who have been infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) require particular attention because of potential neurological damage [7] , [8] . The prevalence of neurological symptoms like loss of smell and taste was high in infected patients, especially older ones, at around 30–40% [7] .…”

“…Both cytokine storms and hypoxemia caused by pneumonia can provoke brain damage and alterations of the blood-CSF barrier that may increase risk of neurodegenerative diseases like Alzheimer's disease [8] . Furthermore, COVID-19-related encephalopathy and an increased prevalence of strokes have been described in patients with severe SARS-CoV-2 infections, especially in older patients [6] , [8] . Both of these neurological complications may be associated with an increased incidence of MNCD.…”