Posterior Reversible Encephalopathy Syndrome

Introduction

Posterior reversible encephalopathy syndrome (PRES) refers to a potentially reversible neurotoxic state occurring in association with vasogenic cerebral edema. Although the reported age range varies between 4 and 90 years, most affected patients are in their fourth or fifth decade of life. There is a female predominance, partly attributed to the underlying etiology. Clinically, PRES can present with a constellation of symptoms, with altered mental status (50%–80%) and seizures (60%–75%) being the most common, followed by headaches and visual disturbances. Occasionally, patients present with focal neurologic deficits, sensorimotor symptoms, or status epilepticus. These symptoms usually develop over several hours to a few days and are gradually progressive.

PRES occurs more commonly in patients with eclampsia, organ transplantation, or hypertension. The association is perhaps strongest with eclampsia, with some authors reporting neuroimaging findings of PRES in up to 98% of these patients. Within the organ transplantation subgroup, the incidence is higher with myeloablative regimens and allogenic bone marrow transplants (7%–9%) when compared with patients receiving solid organ transplants (0.4%–6%). PRES can also accompany organ rejection or infection. Another common association is hypertension, which is seen in approximately 75% of patients and is usually moderate to severe (hypertensive encephalopathy). Other reported associations include sepsis, other infections, connective tissue disorders, autoimmune disorders, and chemotherapeutic agents such as cyclosporine, tacrolimus, and cisplatin.

Evolution: Overview

The pathogenesis of PRES remains controversial. The more widely accepted theory postulates failure of cerebral autoregulation in the setting of rapidly increasing blood pressure. Subsequent hyperperfusion and breakdown of the blood-brain barrier result in extravascular displacement of macromolecules and plasma and the appearance of vasogenic edema on neuroimaging. Because the posteriorly located regions within the brain have poor sympathetic innervation, they are more severely affected. The theory is supported by the frequent coexistence of hypertension in PRES. In addition, lowering of blood pressure results in both clinical and radiologic improvement.

However, the theory fails to explain both the absence of underlying hypertension in up to 20% to 30% of patients and lack of positive correlation between cerebral edema and severity of hypertension. In fact, patients with more severe hypertension often have less vasogenic edema and arterial spasm. In addition, perfusion studies in patients with PRES demonstrate reduced cerebral blood volumes implying hypoperfusion, contrary to the theory that suggests hyperperfusion.

Some authors therefore believe that PRES results from cerebral autoregulatory vasoconstriction precipitated by endothelial dysfunction from systemic conditions ( Fig. 3.1 ). Subsequent hypoperfusion occurs and results in involvement of watershed territories on neuroimaging. The hypertension is felt to represent a compensatory reaction to reduced brain perfusion. This theory postulates upregulation of cytokines (tumor necrosis factor-α, interleukin-1, and interferon-γ), resulting in endothelial dysfunction, vasculopathy, and increased vascular permeability. These cytokines may provide a common pathway in various systemic conditions such as eclampsia, sepsis, other infections, autoimmune disorders, and organ transplant patients while also explaining the frequent association of these entities with PRES.

Imaging Appearance

PRES most frequently appears as symmetric areas of parenchymal vasogenic edema that evolve over a period of days to weeks, becoming more prominent before eventually resolving in most cases ( Fig. 3.2 ). Cortical and subcortical white matter involvement most frequently affects the occipital and parietal regions (98%), followed by the frontal lobe (68%), inferior temporal region (40%), and cerebellum (32%) ( Fig. 3.3 ). Involvement of the deep white matter, basal ganglia, thalami, brainstem, and splenium is less common but occurs in approximately 10% to 20% of cases. Atypical patterns of involvement, with lesions predominantly localized to the brainstem ( Fig. 3.4 ), posterior fossa ( Fig. 3.5 ), or basal ganglia ( Fig. 3.6 ), occasionally occur. In addition, involvement can be asymmetric and rarely even unilateral ( Fig. 3.7 ).

The varying distribution of parenchymal involvement can be broadly divided into four patterns, each seen in approximately 20% to 30% of cases. Patients with a holohemispheric border zone pattern typically show bilateral symmetric edema in the anterior cerebral artery–middle cerebral artery (ACA-MCA) and posterior cerebral artery–middle cerebral artery (PCA-MCA) territory border zones ( Fig. 3.8 ). In the superior frontal sulcus border zone pattern, there is distinct frontal lobe involvement predominantly along the mid to posterior aspect of the superior frontal sulcus. In contrast to the holohemispheric pattern, the frontal pole is usually spared ( Fig. 3.9 ).