Malignant Cerebral Ischemia in A COVID-19 Infected Patient: Case Review and Histopathological Findings

Abstract

Severe acute respiratory syndrome coronavirus (SARS-CoV-2) is responsible for an unprecedented worldwide pandemic that has severely impacted the United States. As the pandemic continues, a growing body of evidence suggests that infected patients may develop significant coagulopathy with resultant thromboembolic complications including deep vein thrombosis, pulmonary embolism, myocardial infarction, and ischemic stroke. However, this data is limited and comes from recent small case series and observational studies on stroke types, mechanisms, and outcomes. 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 Furthermore, evidence on the role of therapeutic anticoagulation in SARS-CoV-2 infected patients with elevated inflammatory markers, such as D-dimer, is also limited. We report the case of a middle-aged patient who presented with a large vessel ischemic stroke likely resulting from an underlying inflammatory response in the setting of known novel coronavirus infection (COVID-19). Histopathologic analysis of the patient's ischemic brain tissue revealed hypoxic neurons, significant edema from the underlying ischemic insult, fibrin thrombi in small vessels, and fibroid necrosis of the vascular wall without any signs of vasculature inflammation. Brain biopsy was negative for the presence of SARS-CoV-2 RNA (RT-PCR assay). Along with a growing body of literature, our case suggests that cerebrovascular thromboembolic events in COVID-19 infection may be related to acquired hypercoagulability and coagulation cascade activation due to the release of inflammatory markers and cytokines, rather than virus-induced vasculitis. Further studies to investigate the mechanism of cerebrovascular thromboembolic events and their prevention is warranted.

COVID-19 and Stroke: A Neurological Perspective

“…The authors suggested that the cerebrovascular thromboembolic events in COVID-19 infection may be related to acquired hypercoagulability and coagulation cascade activation due to the release of inflammatory markers and cytokines, rather than virus-induced vasculitis. Microthrombi within the vessels were more consistent with a systemic inflammatory response-mediated mechanism, probably related to elevated serum inflammatory markers such as D-dimer and fibrinogen (31,32).…”

“…Evidence suggests that infected patients may develop significant coagulopathy which leads to thromboembolic complications like stroke, peripheral artery thrombosis, deep vein thrombosis, pulmonary embolism, myocardial infarction, ischemic stroke, and venous sinus thrombosis (29,30). Histopathologic analysis of the ischemic brain of a COVID-19 patient revealed hypoxic neurons, significant edema from the underlying ischemic insult, fibrin thrombi in small vessels, and fibroid necrosis of the vascular wall without any signs of vasculature inflammation (31). The authors suggested that the cerebrovascular thromboembolic events in COVID-19 infection may be related to acquired hypercoagulability and coagulation cascade activation due to the release of inflammatory markers and cytokines, rather than virus-induced vasculitis.…”

Neurological manifestations and neuroimaging findings in patients with SARS-CoV2—a systematic review

“…Attenuation and effacement at the right hemisphere around the Sylvian fissure Case 3. Hypo-density at left basal ganglion 41 Locked-in with COVID-19 [ 47 ] MRI—brain MRA Numerous foci of restricted diffusion within the pons, (correlating with FLAIR signal abnormality) consistent with acute pontine ischemic infarcts Decreased flow in distal right vertebral artery with a patent basilar artery 42 Macrothrombosis and stroke in patients with mild COVID-19 infection [ 48 ] CT—head MRI—brain Nonocclusive thrombus in the right common carotid artery, extending into the ICA Acute stroke in the territory of the right MCA 43 Malignant cerebral ischemia in a COVID-19 infected patient: case review and histopathological findings [ 49 ] CT—head Large right MCA infarct 44 Multiple sclerosis following SARS-CoV-2 infection [ 50 ] MRI—brain Supratentorial periventricular demyelinating lesions in right occipital lobe and left temporal 45 Necessity of brain imaging in COVID-19 infected patients presenting with acute neurological deficits [ 51 ] CT—head Case 1—B/L subacute infarcts, basilar cistern effacement, a left-to-right midline shift, intraparenchymal hemorrhage, sub-falcine, and uncal herniation Case 2—Pre-op - large volume hemorrhage within the right temporal and parietal lobes, surrounding edema, midline shift, uncal herniation, and entrapment of the temporal horns. Post-op—right-sided craniectomy and anterior temporal lobectomy—improvement in overall mass effect 46 Neuralgic amyotrophy following infection with SARS-CoV-2 [ 52 ] MRI—brain Edema and inflammatory contrast enhancement of the right distal median nerve Minor right C5-C6 disk protrusion without nerve root impingement, and mild T2-signal increase of the ipsilateral C7-C8 roots, suggestive of proximal edema 47 Neurological manifestations in critically ill patients with COVID-19: a retrospective study [ 53 ] CT—head Low density lesions in the following: Case 1.…”

Decompressive hemicraniectomy for acute ischemic stroke associated with coronavirus disease 2019 infection: Case report and systematic review

“…[ 29 ] What is even more alarming are reports of stroke in COVID-19 patients younger than 50 years of age. [ 16 , 20 , 23 , 24 , 26 , 28 ] Before the COVID-19 pandemic, the average age of a patient with ischemic stroke was 66 (±12) years,[ 22 ] but the average age in this series was nearly two decades younger at 48 (±11) years.…”