Cerebral Microbleeds Assessment and Quantification in COVID-19 Patients With Neurological Manifestations

Abstract

It is increasingly acknowledged that Coronavirus Disease 2019 (COVID-19) can have neurological manifestations, and cerebral microbleeds (CMBs) have been observed in this setting. The aim of this study was to characterize CMBs patterns on susceptibility-weighted imaging (SWI) in hospitalized patients with COVID-19 with neurological manifestations. CMBs volume was quantified and correlated with clinical and laboratory parameters. The study included patients who were hospitalized due to COVID-19, exhibited neurological manifestations, and underwent a brain MRI between March and May 2020. Neurological, clinical, and biochemical variables were reported. The MRI was acquired using a 3T scanner, with a standardized protocol including SWI. Patients were divided based on radiological evidence of CMBs or their absence. The CMBs burden was also assessed with a semi-automatic SWI processing procedure specifically developed for the purpose of this study. Odds ratios (OR) for CMBs were calculated using age, sex, clinical, and laboratory data by logistic regression analysis. Of the 1,760 patients with COVID-19 admitted to the ASST Papa Giovanni XXIII Hospital between 1 March and 31 May 2020, 116 exhibited neurological symptoms requiring neuroimaging evaluation. Of these, 63 patients underwent brain MRI and were therefore included in the study. A total of 14 patients had radiological evidence of CMBs (CMBs+ group). CMBs+ patients had a higher prevalence of CSF inflammation (p = 0.020), a higher white blood cell count (p = 0.020), and lower lymphocytes (p = 0.010); the D-dimer (p = 0.026), LDH (p = 0.004), procalcitonin (p = 0.002), and CRP concentration (p < 0.001) were higher than in the CMBs- group. In multivariable logistic regression analysis, CRP (OR = 1.16, p = 0.011) indicated an association with CMBs. Estimated CMBs volume was higher in females than in males and decreased with age (Rho = −0.38; p = 0.18); it was positively associated with CRP (Rho = 0.36; p = 0.22), and negatively associated with lymphocytes (Rho = −0.52; p = 0.07). CMBs are a frequent imaging finding in hospitalized patients with COVID-19 with neurological manifestations and seem to be related to pro-inflammatory status.

Cerebral small vessel disease pathology in COVID-19 patients: A systematic review

“…At 6 months 5/12 patients who underwent second PET had persisting hypometabolism. ( Napolitano et. al., 2022 ) Retrospective Fourteen MB + and 49 MB – patients age and sex matched COVID-19 patients with no difference in acute symptom presentation.…”

“…COVID-19 patients with WMH and/or MB were associated with longer hospital stay, longer duration of mechanical ventilation and worse Glasgow Coma Scale compared to COVID-19 patients without neuropathology ( Agarwal et al, 2020 , Lersy et al, 2021 ). COVID-19 patients with MB had an increased burden of WMH compared to age, sex, past medical history, and acute symptom-matched COVID-19 patients with no MB ( Napolitano et al, 2022 ). When comparing COVID-19 positive to COVID-19 negative patients, Mendez et al examined 481 brain MRIs and found MB in 26/481 scans, 23.07% COVID-19 positive patients compared to 4.15% COVID-19 negative patients ( Mendez Elizondo et al, 2021 ).…”

Neurointensivmedizin und COVID-19

“…Als Subgruppe der hämorrhagischen Schlaganfälle werden „microbleeds“ in MRT-Studien berichtet. Dabei war das Verteilungsmuster gemischt (lobär und tief) und zeigte passend zu der bereits beschriebenen Entität der „critical illness-associated cerebral microbleeds“ (CIAMs) eine Häufung im Bereich des Corpus callosum sowie juxtakortikal [ 33 , 38 ]. Ähnlich wie für sonstige Intensivkohorten mit „microbleeds“ ergaben sich Korrelationen mit Hypoxämie, Invasivität der Beatmung und Schweregrad der Erkrankung, sodass eine SARS-CoV-2-spezifische Pathophysiologie auch hier unwahrscheinlich erscheint [ 1 , 33 , 38 ].…”

COVID-19-associated cerebral microbleeds in the general population

“… 4 From an imaging point of view, COVID-19 has been associated with a multitude of findings, which also include CMB on MRI. 3 , 5-12 Most CMB-related studies have focused on critically ill cohorts, without a non-COVID-19 control group, 7-11 , 13 leaving it impossible to identify whether CMB are preexisting phenomena, arise due to critical illness, or are a direct consequence of COVID-19 itself. 14 To date, only one study comprised of a mainly non-hospitalized population, and a non-COVID-19 control group with matched controls exists 15 where cases and controls had similar numbers of CMB.…”