Large Vessel Occlusion Secondary to COVID-19 Hypercoagulability in a Young Patient: A Case Report and Literature Review.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) initially most appreciated for its pulmonary symptoms, is now increasingly recognized for causing multi-organ disease and stroke in the setting of a hypercoagulable state. We report a case of 33-year-old African American woman with COVID-19 who developed acute malignant middle cerebral artery infarction due to thromboembolic occlusion of the left terminal internal carotid artery and middle cerebral artery stem. Mechanical thrombectomy was challenging and ultimately unsuccessful resulting in limited reperfusion of <67% of the affected vascular territory, and thrombectomized clot was over 50 mm in length, at least three times the average clot length. The final stroke size was estimated at 224 cubic centimeters. On admission her D-dimer level was 94,589 ng/mL (normal 0-500 ng/ml). Throughout the hospitalization D-dimer decreased but never reached normal values while fibrinogen trended upward. Hypercoagulability panel was remarkable for mildly elevated anticardiolipin IgM of 16.3 MPL/mL (normal: 0-11.0 MPL/mL). With respect to remaining stroke workup, there was no evidence of clinically significant stenosis or dissection in the proximal internal carotid artery or significant cardioembolic source including cardiomyopathy, atrial fibrillation, cardiac thrombus, cardiac tumor, valvular abnormality, aortic arch atheroma, or patent foramen ovale. She developed malignant cytotoxic cerebral edema and succumbed to complications. This case underscores the importance of recognizing hypercoagulability as a cause of severe stroke and poor outcome in young patients with COVID-19 and highlights the need for further studies to define correlation between markers of coagulopathy in patients with COVID-19 infection and outcome post stroke.

Mutation of sec63 in zebrafish causes defects in myelinated axons and liver pathology.

Mutations in SEC63 cause polycystic liver disease in humans. Sec63 is a member of the endoplasmic reticulum (ER) translocon machinery, although it is unclear how mutations in SEC63 lead to liver cyst formation in humans. Here, we report the identification and characterization of a zebrafish sec63 mutant, which was discovered in a screen for mutations that affect the development of myelinated axons. Accordingly, we show that disruption of sec63 in zebrafish leads to abnormalities in myelinating glia in both the central and peripheral nervous systems. In the vertebrate nervous system, segments of myelin are separated by the nodes of Ranvier, which are unmyelinated regions of axonal membrane containing a high density of voltage-gated sodium channels. We show that sec63 mutants have morphologically abnormal and reduced numbers of clusters of voltage-gated sodium channels in the spinal cord and along peripheral nerves. Additionally, we observed reduced myelination in both the central and peripheral nervous systems, as well as swollen ER in myelinating glia. Markers of ER stress are upregulated in sec63 mutants. Finally, we show that sec63 mutants develop liver pathology. As in glia, the primary defect, detectable at 5 dpf, is fragmentation and swelling of the ER, indicative of accumulation of proteins in the lumen. At 8 dpf, ER swelling is severe; other pathological features include disrupted bile canaliculi, altered cytoplasmic matrix and accumulation of large lysosomes. Together, our analyses of sec63 mutant zebrafish highlight the possible role of ER stress in polycystic liver disease and suggest that these mutants will serve as a model for understanding the pathophysiology of this disease and other abnormalities involving ER stress.