The presence of leukoencephalopathy and/or cerebral microbleeds is associated with critical illness, increased mortality, and worse functional outcome in patients with coronavirus disease 2019 (COVID-19).
Shashank Agarwal, Department of Neurology, NYU Langone Health, New York, NY, and colleagues said that their findings, published in the journal Stroke, could shed light on the pathophysiology of brain damage and encephalopathy observed in COVID-19, and may be helpful for neuroprognostication, although they cautioned that more follow-up studies are needed.
Researchers performed a retrospective chart review of COVID-19-positive adult patients admitted to 3 tertiary care hospitals of an academic medical center in New York City from March 1 to May 10, 2020, who had magnetic resonance imaging (MRI) of the brain. They found 115 patients, 35 (30.4%) of whom had leukoencephalopathy and/or cerebral microbleeds. Out of the remaining 80 patients, 47 (40.9%) had acute/chronic infarcts, hemorrhages, or other chronic findings, while 33 (28.7%) had normal MRI of the brain.
Patients with leukoencephalopathy and/or cerebral microbleeds had neuroimaging performed later during the hospitalization course (27 versus 10.6 days; P<0.001) and were clinically sicker at the time of brain MRI (median Glasgow Coma Scale [GCS] 6 versus 14; P<0.001), when compared to patients without these findings. They also had higher peak D-dimer levels (8018±6677 versus 3183±3482; P<0.001), lower nadir platelet count (116.9±62.2 versus 158.3±76.2; P=0.03), and higher peak international normalized ratio (2.2 versus 1.57; P<0.001) values.
Patients with cerebral leukoencephalopathy and/or cerebral microbleeds on neuroimaging were also typically younger (median age 61 versus 69; P=0.003) and predominantly males (82.8% versus 66.3%; P=0.078).
Results showed they required longer ventilator support (34.6 versus 9.1 days; P<0.001) and were more likely to have a moderate-to-severe acute respiratory distress syndrome (ARDS) score (88.6% versus 23.8%, P<0.001). These patients also had longer hospitalizations (42.1 versus 20.9 days; P<0.001), overall worse functional status on discharge (modified Rankin Scale [mRS] 5 versus 4; P=0.001), and higher mortality (20% versus 9%; P=0.144).
The authors noted that in their study, the majority of cerebral microbleeds were located in subcortical white matter and the corpus callosum, similar to the patterns described with high-altitude cerebral edema and ARDS, and none of the patients demonstrated superficial siderosis. “Hypoxemia is common to these disease processes, and hypoxia-induced hydrostatic or chemical effects on the blood-brain barrier could potentially account for extravasation of erythrocytes and lead to cerebral microbleeds,” they said, adding that “microscopic disruption of the endothelium in brain tissue may also be responsible for these small cerebral microbleeds.”
In addition, researchers noted that since the majority of patients with leukoencephalopathy in the study required multiple days in the intensive care unit on a ventilator and had moderate-severe ARDS scores, they possibly suffered cerebral hypoxia and ischemic injury due to prolonged shock and refractory hypoxia. “This could also result in a diffuse leukoencephalopathy similar to delayed post hypoxic leukoencephalopathy,” they said.
“Although the mechanism of leukoencephalopathy and cerebral microbleeds, its relationship to SARS-CoV-2, as compared with critical illness in general, is uncertain, possibilities include endotheliitis with thrombotic microangiopathy and prolonged respiratory failure and hypoxemia,” the authors said.