Why does posterior reversible encephalopathy syndrome (PRES) cause vasogenic edema?

Why PRES Causes Vasogenic Edema

PRES causes vasogenic edema through disruption of the blood-brain barrier, resulting from either severe hypertension exceeding autoregulatory limits (breakthrough edema) or direct endothelial injury from cytotoxic agents, inflammatory mediators, or metabolic derangements. 1

Primary Pathophysiological Mechanisms

The development of vasogenic edema in PRES involves two competing but not mutually exclusive mechanisms:

Hypertension-Induced Autoregulatory Failure (Breakthrough Edema Theory)

• Severe hypertension exceeds the upper limits of cerebral autoregulation, forcing hyperperfusion through cerebral vessels and causing breakdown of the blood-brain barrier. 2 This is currently the more popular theory explaining PRES pathophysiology. 2

• The rate of blood pressure rise matters more than absolute values—patients with chronic hypertension may tolerate higher pressures than previously normotensive individuals. 1

• When blood pressure rises acutely and markedly, cerebral autoregulation fails, leading to cerebral edema particularly in posterior brain areas. 3

Direct Endothelial Injury Theory

• Direct endothelial damage from cytotoxic agents, inflammatory mediators, or metabolic derangements compromises blood-brain barrier integrity independent of blood pressure elevation. 1

• This mechanism explains why PRES can occur without severe hypertension, particularly in patients receiving immunosuppressive therapy (especially calcineurin inhibitors like cyclosporine), chemotherapy, or those with autoimmune conditions. 3, 1

• Endothelial activation triggers tight junction protein disruption and increased vascular permeability, ultimately resulting in vasogenic edema formation. 1

Cellular-Level Mechanism of Vasogenic Edema

• At the cellular level, vasogenic edema represents an increase in extracellular fluid volume due to increased permeability of brain capillary endothelial cells to serum proteins. 4

• This contrasts fundamentally with cytotoxic edema, which involves increased intracellular fluid related to high intracellular osmolality from cellular damage (such as failure to maintain homeostatic Na/K gradients in acute infarction). 4

• The increased MR signal on FLAIR sequences is usually transient and not associated with restricted diffusion, tissue necrosis, or other sequelae of cytotoxic edema. 4

Anatomical Vulnerability: Why the Posterior Circulation?

• The posterior circulation (vertebrobasilar system) has less sympathetic innervation compared to anterior circulation, making it less capable of autoregulatory vasoconstriction and more vulnerable to vasogenic edema accumulation. 1

• This reduced sympathetic innervation explains the characteristic posterior distribution of edema in PRES, predominantly affecting the parietal and occipital lobes. 3, 1

• The posterior circulation's vulnerability to autoregulatory failure makes these regions more susceptible when blood-brain barrier integrity is compromised. 1

Multifactorial Nature: A Critical Clinical Pitfall

• Most PRES cases involve multiple simultaneous insults creating additive endothelial stress—overlooking this multifactorial nature can lead to delayed diagnosis and treatment. 1

• Common combinations include pre-existing hypertension plus immunosuppressive drugs, or renal impairment plus cytotoxic chemotherapy. 3

• In eclampsia specifically, shallow cytotrophoblast invasion of maternal spiral arteries causes placental hypoxia and ischemia, leading to systemic endothelial dysfunction and impaired cerebral autoregulation. 1

Imaging Characteristics of Vasogenic Edema in PRES

• Vasogenic edema appears as hypodense, frond-like regions on CT that follow white-matter tracts in a "finger-like" pattern and typically spare cortical gray matter. 5

• On MRI, increased signal intensity appears on T2-weighted or FLAIR sequences in posterior brain regions, predominantly affecting white matter in the parietal, occipital, and frontal lobes. 3

• The edema shows no restricted diffusion on diffusion-weighted imaging, distinguishing it from cytotoxic edema seen in acute ischemic stroke. 5

Clinical Implications of the Vasogenic Nature

• Because the edema is vasogenic rather than cytotoxic, it is potentially reversible with prompt blood pressure control and removal of the offending agent. 3, 2

• Vasogenic edema responds to corticosteroid therapy, whereas cytotoxic edema does not—making this distinction therapeutically critical. 5

• Complete spontaneous remission occurs in most cases without sequelae when the underlying cause is addressed promptly. 3