COVID-19 and stroke: from the cases to the causes

Abstract

During COVID-19 pandemic, a wide variety of stroke typologies have been described in patients affected by SARS-CoV-2. Investigating the case reports of acute stroke in COVID-19 patients, published since the beginning of the pandemic, we tried to trace the pathogenic mechanisms of stroke during SARS-CoV-2 infection. We conducted a systematic review analyzing demographic data, cerebrovascular risk factors, NIHSS score, vascular territory involvement and laboratory findings of 168 patients described in 89 studies, from a pool of 1243 records. Based on our results, we have identified different stroke profiles: (1) cerebral large vessel disease (CLVD) profile with a low disability, simultaneous onset of COVID-19 and stroke symptoms, good outcome and low serum levels of D-dimer and CRP; (2) intracranial bleeding (IB) profile with high disability, poor outcome and low levels of serum markers of inflammation and coagulopathy; (3) CLVD profile with a short time-lapse between COVID-19 symptoms and stroke onset, high neurological disability and very high systemic inflammatory markers; (4) multiple thrombo-embolic disease (MTED) profile with older patients, many comorbidities, disabling stroke, poor outcome, evident alteration of coagulation tests and high serum levels of both D-dimer and CRP. We therefore summarized these different profiles in a spectrum similar to that of visible light, where the violet–blue band included IB and CSVD with low inflammation and prothrombotic activity, the green–yellow band included CLVD with high inflammation and moderate prothrombotic activity and the orange–red band for MTED with moderate-high levels of inflammation and very high prothrombotic activity.

A Case of Bilateral Thalamic Infarcts Involving the Artery of Percheron in the Setting of COVID-19

“…Frisullo et al identified a cerebral small vessel profile of patients who developed acute stroke with COVID-19 symptoms simultaneously [9]. This group was found to have a low degree of disability with low serum markers for systemic inflammation and coagulopathy [9]. Interestingly, our patient fits this stroke profile as he developed an acute stroke simultaneously with COVID-19 symptoms.…”

“…Serum markers of systemic inflammation and coagulopathy were likely to be normal in this group [9]. Direct viral damage via ACE2 receptors on vascular endothelium and arterial smooth muscle cells in intracranial arteries leading to vessel wall rupture could explain such phenomenon [9][10][11][12]. Poyiadji et al reported a rare case of a woman with COVID-19 who presented with a three-day history of cough, fever, and altered mental status who was found to have hemorrhagic rim-enhancing lesions within the bilateral thalami and medial temporal lobes [14].…”

“…In a recent systematic review of COVID-19 and cerebrovascular events, Frisullo et al reported different stroke profiles based on serum markers for systemic inflammation and coagulopathy, stroke type, and vascular territory [9]. Frisullo et al identified a cerebral small vessel profile of patients who developed acute stroke with COVID-19 symptoms simultaneously [9]. This group was found to have a low degree of disability with low serum markers for systemic inflammation and coagulopathy [9].…”

“…SARS-CoV-2 infection is mediated by angiotensin-converting enzyme 2 (ACE2) receptors, which are expressed on the epithelium of the small intestine, kidney, and lung. ACE2 receptors are also abundant on vascular endothelium and arterial smooth muscle cells [9][10][11][12]. The direct local effect of SARS-CoV-2 on ACE2 receptors in the vascular endothelium has been reported to induce an inflammatory response that has been postulated to be a constituent of thrombotic events associated with infection [10][11][12].…”

“…In the systematic review described by Frisullo et al, an intracranial bleeding profile was identified, characterized by a high disability and poor outcome in patients with few cerebrovascular risk factors. Serum markers of systemic inflammation and coagulopathy were likely to be normal in this group [9]. Direct viral damage via ACE2 receptors on vascular endothelium and arterial smooth muscle cells in intracranial arteries leading to vessel wall rupture could explain such phenomenon [9][10][11][12].…”