Clinical Pearls & Morning Reports
Posterior reversible encephalopathy syndrome (PRES) derives its name from the altered mental status and reversible white-matter signal changes in posterior brain regions that characterize the syndrome. Read the latest NEJM Clinical Problem-Solving here.
Q: What causes PRES?
A: The pathophysiological mechanism of PRES remains poorly understood but is thought to relate to cerebral autoregulatory and endothelial dysfunction leading to a breakdown of the blood–brain barrier, transudation of fluid and proteinaceous material, and petechial hemorrhages. In the clinical context of rapidly progressive hypertension, blood pressure exceeds the autoregulatory capacities of cerebral vasculature. In contrast to the autoregulatory failure associated with hypertension, sepsis and eclampsia are thought to induce PRES through endothelial dysfunction driven by systemic inflammatory factors (in the case of sepsis) and placental factors (in the case of eclampsia).
Q: What are some of the risk factors, other than hypertension, sepsis, and eclampsia, for PRES?
A: Cytotoxic and immunosuppressive medications, such as tacrolimus, cyclosporine, and bevacizumab, are known risk factors for PRES, but the mechanism of this relationship remains poorly understood. Tacrolimus and cyclosporine need not be at supratherapeutic levels or recently introduced to cause symptoms. Autoimmunity has also been associated with PRES, although the mechanism is also poorly understood.
A: The neurologic symptoms of PRES vary across case series. Encephalopathy occurs in 50 to 80% of patients; hypoactive symptoms may alternate with periods of agitation, and coma may occur in advanced cases. Visual disturbances ranging from blurred vision to hemianopia and cortical blindness occur in roughly a third of cases. A total of 60 to 75% of patients present with seizures, which may be preceded by vision loss; in 5 to 15% of these patients, the seizures become generalized or progress to status epilepticus. Constant holocephalic headache is reported in 50% of cases. Deep-tendon reflexes are often diffusely brisk, and the Babinski sign may be positive. Other than these findings, the neurologic examination is typically unrevealing, unless ischemia or hemorrhage gives rise to focal deficits, which occur in 10 to 15% of cases. The parietal and occipital lobes are the most commonly affected regions of the brain, although edema can extend into the cerebellum and brainstem. T2-weighted fluid-attenuated inversion recovery sequences on MRI are the most sensitive method for detecting PRES and can help to differentiate this syndrome from other pathologic processes. Diffusion-weighted imaging is useful in distinguishing vasogenic edema from tissue infarction. Extensive vasogenic edema, tissue infarction, or hemorrhage (either intraparenchymal or subarachnoid) may occur in PRES and predicts poorer outcomes.
A: Although most patients recover within 1 week after the initiation of treatment, a small number of cases require several weeks of treatment for a full recovery. A total of 3 to 6% of PRES cases are fatal, and 10 to 20% of patients have persistent neurologic sequelae. A retrospective study showed that poorer outcomes were significantly more likely to occur among patients who were older, had undergone previous intracranial radiation, had sepsis, or had a history of autoimmune disease, diabetes, or smoking.