emDOCs Podcast – Episode 41: Posterior Reversible Encephalopathy Syndrome (PRES)
- Nov 8th, 2021
- Brit Long
Today on the emDOCs cast with Brit Long, MD (@long_brit), we cover Posterior Reversible Encephalopathy Syndrome, or PRES.
- Patients with PRES will often present with encephalopathy manifesting on a spectrum from mild confusion to obtundation. Focal neurological deficits may occur. Headache is common, as are visual disturbances, including decreased visual acuity, visual field deficits and cortical blindness. Seizures occur in a majority of patients with PRES and are often the presenting symptom.
- In a 1996 case series, the entity most commonly known as PRES was first presented as a clinical syndrome. Its recognition has become more widespread as advanced neuroimaging modalities, in particular MRI, have become increasingly available.
- The exact incidence of PRES is not known, in part to etiologic heterogeneity, overlap with other disease processes, and a lack of standardized diagnostic criteria and nomenclature.
- PRES is perhaps the most widely recognized name for this syndrome, but it has also been called reversible posterior leukoencephalopathy syndrome (RPLS) and a handful of less commonly used names.
- Findings are not always posterior or reversible.
- The pathophysiology is not completely understood, but proposed mechanisms involve cerebral endothelial dysfunction and impaired cerebral autoregulation resulting from acutely elevated blood pressure. In both mechanisms, the final common pathway is reduced integrity of the cerebral endothelium and blood brain barrier with resultant vasogenic cerebral edema.
- If PRES is recognized and treated appropriately, a majority of patients recover without neurologic sequelae.
What causes PRES?
- There are several notable theories regarding the pathophysiology of PRES, but the final common pathway in each is endothelial dysfunction, disruption of the blood-brain barrier, and vasogenic edema.
- Hyperperfusion theory: blood pressure elevations exceed the autoregulatory mechanism of cerebral blood flow and lead to increased vascular leakage. The posterior circulation may be particularly susceptible to these changes, owing to the relative paucity of sympathetic innervation in the posterior fossa. However, up to 30% of patients may present without significantly elevated (or normal) blood pressure.
- Cytotoxic and immunologic theories: circulating exogenous or endogenous chemokines and vasoactive neuropeptides lead to endothelial injury and vascular instability, blood-brain barrier disruption and cerebral edema.
Who’s at risk?
- There are many conditions associated with PRES: hypertension, renal disease, organ transplantation, autoimmune disease, preeclampsia/eclampsia, malignancy, sepsis, immunosuppressive therapy, and cytotoxic medications (Table 1).
- Renal disease and hypertension are present in over half of patients with PRES, and autoimmune disorders are present in about 40%.
- Among immunosuppressive and cytotoxic drugs, corticosteroids and calcineurin inhibitors, such as cyclosporine and tacrolimus, are particularly associated with PRES.
- PRES is also common in eclampsia.
- Variable presentation, but there is some degree of encephalopathy and altered mental status in most.
- Seizures are often the presenting symptom and occur in a majority of patients.
- Blood pressure is often elevated on presentation but commonly does not exceed the upper autoregulatory limit. Blood pressure may also be normal on presentation.
- Other focal deficits may also occur (Table 2).
- Critical considerations include ischemic stroke, intracranial hemorrhage, HTN emergency, meningoencephalitis, malignancy, eclampsia, and toxic/metabolic encephalopathy.
- Diagnosis of PRES is often made after exclusion of other emergent conditions and may not be definitively recognized until an MRI is obtained and demonstrates radiographic findings characteristic of the disease.
- There are no laboratory findings that are specific to PRES. Cerebrospinal fluid, if obtained, may demonstrate increased protein with normal cell counts.
- Non-contrast CT is commonly the initial neuroimaging study obtained in the ED and may demonstrate findings of vasogenic edema, though it may be normal or non-specific. In one series, the initial head CT was non-specific or normal in over half of patients who were ultimately found to have MRI findings characteristic of PRES.
- Intracranial hemorrhage can occur in up to 25% of patients with PRES, though in most instances the area of hemorrhage is small and localized to the areas adjacent to visualized edema.
- MRI is imaging modality most likely to identify abnormalities consistent with PRES, though there is no true gold standard. The characteristic findings include subcortical and cortical vasogenic edema seen on T2 weighted sequences, such as fluid-attenuated inversion recovery (FLAIR). Edema is often seen in the occipital and parietal lobes, though edema is quite commonly seen in other cerebral regions as well. Clinical features may be discordant with the degree of edema seen on imaging.
- ED management of PRES involves management and prevention of seizures and management of blood pressure, though there exist no randomized trials to define the efficacy of specific treatment modalities.
- Potential offending drugs should be discontinued if possible.
- Seizures are treated in the same manner as in other disorders, with benzodiazepines as first-line agents. There is no data to suggest one anti-epileptic drug over another in this condition.
- Control of blood pressure is an essential component of treatment of PRES, but specific treatment parameters are not clearly defined in the literature. Target blood pressure reduction of 20-30% within the first hour of treatment is reasonable. Nicardipine, clevidipine, and labetalol may be used for initial blood pressure management of PRES.
- With prompt recognition and treatment of PRES, many patients will recover fully, though persistent neurologic deficits can occur in 10-44%, with delay in initiation of treatment associated with unfavorable outcomes.
- Recurrent episodes of PRES can occur, and overall mortality is reported to be in the range of 3-6%.
Take Home Points:
- Emergency physicians should consider PRES in patients presenting with altered mental status, seizures, and neurologic deficits who have risk factors for PRES. Heightened suspicion should be raised in those patients who are on immune-suppressive medications, those with renal disease and acutely elevated blood pressure.
- While non-contrast CT scan may show signs of vasogenic edema, MRI is the imaging modality of choice.
- Seizures are often the presenting symptom of PRES and occur in a majority of cases.
- Treatment is focused on seizure management, blood pressure control, and removal of offending agents.
- PRES and eclampsia have significant overlap, and management principles are similar, though magnesium is the preferred agent for treatment of seizures in eclampsia.