Posterior Reversible Encephalopathy Syndrome, Part 2: Controversies Surrounding Pathophysiology of Vasogenic Edema

Abstract

SUMMARY:Posterior reversible encephalopathy syndrome (PRES) is a neurotoxic state accompanied by a unique brain imaging pattern typically associated with a number of complex clinical conditions including: preeclampsia/eclampsia, allogeneic bone marrow transplantation, solid organ transplantation, autoimmune diseases and high dose cancer chemotherapy. The mechanism behind the developing vasogenic edema and CT or MR imaging appearance of PRES is not known. Two theories have historically been proposed: 1) Severe hypertension leads to failed auto-regulation, subsequent hyperperfusion, with endothelial injury/vasogenic edema and; 2) vasoconstriction and hypoperfusion leads to brain ischemia and subsequent vasogenic edema. The strengths/weaknesses of these hypotheses are reviewed in a translational fashion including supporting evidence and current available imaging/clinical data related to the conditions that develop PRES. While the hypertension/hyperperfusion theory has been most popular, the conditions associated with PRES have a similar immune challenge present and develop a similar state of T-cell/endothelial cell activation that may be the basis of leukocyte trafficking and systemic/cerebral vasoconstriction. These systemic features along with current vascular and perfusion imaging features in PRES appear to render strong support for the older theory of vasoconstriction coupled with hypoperfusion as the mechanism.T he mechanism of posterior reversible encephalopathy syndrome (PRES) is not known. Two opposing hypotheses are commonly cited, but the issue is controversial: 1) The current more popular theory suggests that severe hypertension exceeds the limits of autoregulation, leading to breakthrough brain edema; 2) the earlier original theory suggests that hypertension leads to cerebral autoregulatory vasoconstriction, ischemia, and subsequent brain edema. The issues surrounding these theories are reviewed to summarize the potential values of each mechanism. Current Popular Theory: Hypertension, Failed Autoregulation, HyperperfusionSevere hypertension with failed autoregulation, injury to the capillary bed, and hyperperfusion remains the most popular theory for the brain edema that develops in PRES. [1][2][3][4] This concept is naturally intuitive, due to the frequent presence of hypertension at toxicity, and was originally embraced as the cause of eclampsia, historically labeled as a "hypertensive disorder of pregnancy." The hypertension/hyperperfusion theory is primarily based on blood pressure exceeding the autoregulation limits of the brain. AutoregulationAutoregulation is an intrinsic function of the vasculature of the brain, designed to maintain a stable blood flow in the face of fluctuating blood pressure. 5,6 Under normal circumstances, brain vessels possess intrinsic vascular tone.7 With autoregulation, vasodilation occurs as blood pressure drops and vasoconstriction occurs as blood pressure increases. [5][6][7] This function is regulated by the endothelium with release of relaxing factors (endothelium-de...

The effect of presymptomatic hypertension in posterior reversible encephalopathy syndrome

“…Clinical symptoms are headache, visual disturbance, mental alteration, and seizure. The characteristic radiologic finding is the vasogenic edema in the posterior part of the brain (Bartynski, 2008a,2008b). Diverse brain imaging patterns are currently reported with the advances of the imaging techniques (McKinney, Jagadeesan, & Truwit, 2013).…”

“…The mechanism behind the brain edema development is controversial. The failure of auto‐regulation caused by severe hypertension or direct toxic insult to endothelium is the most popular theory for pathophysiology (Bartynski, 2008b; Dinsdale, 1983; Schwartz et al., 1995; Strandgaard, Olesen, Skinhoj, & Lassen, 1973). One of the unsettled questions about PRES is the correlation between the brain lesion distribution patterns and blood pressure (BP).…”

Posterior reversible encephalopathy syndrome (PRES) after bevacizumab therapy for metastatic colorectal cancer

“…The mechanism by which bevacizumab causes PRES is not fully understood, although it is hypothesized that it disrupts the blood-brain barrier through endothelial dysregulation resulting in hyperperfusion and vasogenic edema leading to failure of autoregulation. Bevacizumab-induced hypertension might also play some role, although cases of bevacizumab-induced PRES have been reported in normotensive patients [15,16]. The incidence of PRES with bevacizumab is <0.5% according to the package insert.…”

Involvement of the cervical cord and medulla in posterior reversible encephalopathy syndrome

“…However, in 25% of patients with PRES, hypertension is absent or mild, and autoregulatory failure cannot explain the findings 8. The alternative theory holds that there is endothelial dysfunction (e.g., in sepsis, organ transplantation, pre-eclampsia) with subsequent vasoconstriction or leukocyte trafficking or both.…”

“…This leads to vasculopathy and hypoperfusion, explaining the watershed appearance of PRES lesions on CT/MR imaging. According to this theory, autoregulatory vasoconstriction superimposed on toxicity vasoconstriction/hypoperfusion with borderzone ischemia could be responsible for beneficial effect of antihypertensive/magnesium management 89…”