Fig. 5

Strokes and concurrent subacute inflammatory necrotizing response. An 84-year-old SARS-CoV-2-positive female presented solely with rapidly progressive encephalopathy and neurological decline associated with mild left sided hemiparesis and left sided-visuospatial neglect. There were no concurrent respiratory or any other systemic symptoms. Serological findings were remarkable for CRP of 5.89 mg/dl, ferritin of 383 ng/dl, and D-Dimer of 852 ng/dl, and positive anticardiolipin IgM antibodies of 32.CSF analysis revealed elevated protein (153 mg/dl), normal glucose, and a cell count of three nucleated cells. Computed tomography (CT) scan (1, 2) shows prominent vasogenic edema nearly involving the entire right temporal lobe (green arrow), watershed subacute-chronic ischemic infarction of the right anterior frontal (red arrow), and old cystic encephalomalacia of the left parietal (blue arrow). 3D CT angiogram (3) shows normal flow through the right middle cerebral artery without evidence of large vessel occlusion or high grade stenosis. Axial T1-(4) and T1-weighted post-gadolinium [axial (5) and sagittal (6)] MR images show diffuse gyral cortical enhancement with subcortical areas of necrosis involving right temporal lobe (green arrow). Axial FLAIR (7) and axial T2W (8) MR images reveal signal hyperintensities with gyral swelling nearly involving the entire right temporal lobe and insula (green arrow) associated with petechial hemorrhage, best seen on the gradient echo image (9). In addition, there are subacute-chronic infarct of the right anterior lateral frontal lobe (red arrow) and a wedge-shaped old cystic encephalomalacia of the left parietal lobe (blue arrow). Following treatment with tocilizumab 560 mg (4 mg/kg), the patient exhibited significant improvement of the mental status and left hemiparesis and was subsequently discharged home. Hypercoagulopathy is the likely etiology of the right frontal and left parietal strokes. The appearance of the concurrent right temporal lobe and insula abnormalities is highly suggestive of an independent subacute inflammatory-necrotizing, rather than ischemic, process. This is supported by the findings of completely patent right middle cerebral artery, diffuse gyral swelling and enhancement with concurrent prominent subcortical vasogenic edema and necrosis, and significantly elevated CSF protein. Although the precise mechanisms underlying vasogenic edema and necrosis remain unclear, we suggest that localized hyper-inflammation provoked by exuberant innate immune response (CNS cytokine response) might be pathogenetically relevant. Direct viral neuroinvasion and involvement of the neurovascular endothelial cells were subsequently excluded by the brain biopsy from the right temporal necrotizing lesion