Posterior Reversible Encephalopathy Syndrome and brain haemorrhage as COVID-19 complication: a review of the available literature

Abstract

Background: SARS-CoV-2 infection has been associated with various neurological manifestations. Since patients affected by SARS-CoV-2 infection present coagulation and immune system dysregulation, ischemic or haemorragic stroke is not uncommon, irrespective of respiratory distress. However, the occurrence of focal neurological deficits together with other symptoms like headache, cortical blindness, seizure and altered mental status should prompt the diagnosis of Posterior Reversible Encephalopathy Syndrome (PRES). Antithrombotic treatment, the alteration of endothelial function, and coagulopathy due to COVID-19 and PRES leading to the breakdown of blood-brain barrier may then contribute to the occurrence of a brain haemorrhage.

Methods: We describe the case of a COVID-19 patient who developed bilateral occipital lobe haemorrhages suggestive of haemorrhagic PRES. We then reviewed the available literature about haemorrhagic evolution of PRES in COVID-19.

Results: We describe the clinical and radiological features of five COVID-19 patients who developed haemorrhagic PRES.

Conclusions: Coagulopathy and endothelial dysfunction resulting from the massive release of cytokines during the host immune response may be key factors in the pathogenesis of COVID-19-related PRES. Antithrombotic therapy and the leakage of the blood-brain barrier can subsequently increase the risk of haemorrhagic transformation of the lesioned brain tissue. A prompt diagnosis of PRES is mandatory, since the timely interruption/reversal of antithrombotic therapy may be a key determinant for a good prognosis.

Keywords: COVID-19; Haemorrhage; PRES; Posterior Reversible Encephalopathy Syndrome; SARS-CoV-2.

Fig. 1

Intraparenchymal hemorrhage with occipital pattern in our patient, at the onset (A), after 4 h (B), after 2 days (C), after 7 days (D), and after 20 days (E). Axial CT scan (A) demonstrates bilateral occipital lobes hematomas with surrounding vasogenic edema. Vascular malformations were not detected on CT angiography (not shown). After 4 h (B) and 2 days (C), axial CT scans show an increase of hematomas volume, especially in the right occipital lobe with a slight mass effect on the right lateral ventricle. After 7 days (D) and 20 days (E) axial CT scans show a progressive decrease in the density and size of hematomas, as for the physiological evolution

Fig. 2

Different factors contribute to the hemorrhagic evolution of PRES in COVID-19 patients. The reduction in cerebral blood perfusion may be due to the release of vasoactive and proinflammatory molecules in response to COVID-19-related immune activation (round panel). The hypoperfusion determines the breakdown of blood–brain barrier (panel A) that together with antithrombotic treatment (panel B)—a mainstay of SARS-CoV-2 infection therapy—endothelial dysfunction (panel C) and coagulopathy (panel D)—both related to the immune response—contribute to the development of hemorrhage