Posterior Reversible Encephalopathy Syndrome (PRES)

What Causes PRES?

Scientists don’t know precisely what causes PRES, but it is likely linked to conditions that cause increased blood pressure in the brain.

PRES may be associated with several underlying medical conditions, including:

• High blood pressure
• Kidney disease
• Systemic infections (sepsis)
• Eclampsia
• Cancer

People undergoing immunosuppressive therapies as part of treatment for another disorder are at an increased risk for PRES. Conditions associated with PRES in this way include:

• Organ transplants
• Bone marrow or stem cell transplants
• Cancer
• Autoimmune disorders

PRES has been identified as a side effect of medications commonly used to treat cancer and autoimmune disorders. Some of the drugs linked to PRES include:

• Tacrolimus
• Ciclosporin
• Bevacizumab
• Sunitinib
• Sorafenib
• Interferon alpha
• Intravenous immunoglobulins
• Cisplatin
• Cytarabine
• Fludarabine
• Rituximab
• Infliximab
• Alemtuzumab
• Corticosteroids
• Bortezomib

Is PRES Hereditary?

PRES typically has an identifiable underlying medical cause. Therefore, it is not an inherited disorder.

How Is PRES Detected?

Early diagnosis of PRES and treatment of its underlying cause is crucial. Missed diagnosis and delayed treatment can increase the risk of life-threatening symptoms and long-term complications.

Diagnosis of PRES can be challenging because its symptoms resemble those of several other brain-related disorders. Other conditions that may be confused with PRES include:

• Encephalitis
• Brain tumor
• Stroke
• Vasculitis
• Reversible cerebral vasoconstriction syndrome
• Progressive multifocal leukoencephalopathy

How Is PRES Diagnosed?

A doctor may suspect PRES if a patient exhibits rapid onset of the disorder’s neurological symptoms in conjunction with one of the known risk factors for the syndrome. To confirm a diagnosis of PRES and rule out other possible causes for the symptoms, a doctor will perform diagnostic steps that may include:

• Magnetic resonance imaging (MRI) or other imaging scans to look for brain abnormalities characteristic of PRES.
• Blood tests may be used to help identify the underlying cause of PRES.
• Examination of cerebrospinal fluid (lumbar puncture). This test may show elevated levels of protein in the spinal fluid.
• Electroencephalogram (EEG). This measure of the brain’s electrical activity may help determine the nature of the patient’s seizures.

PLEASE CONSULT A PHYSICIAN FOR MORE INFORMATION.

How Is PRES Treated?

No treatment will directly stop PRES. Instead, treatment is based on the underlying condition, and successful treatment of the underlying cause will usually relieve PRES symptoms within a matter of hours or days.

Common treatment options include:

• Blood pressure medications in cases where high blood pressure (hypertension) is the cause of PRES
• Anticonvulsant drugs to treat seizures that occur in association with PRES
• Discontinuation of treatment with immunosuppressive medications

How Does PRES Progress?

Most people with PRES recover completely when the syndrome’s underlying cause is successfully treated. However, PRES symptoms are sometimes severe enough to cause life-threatening complications, especially if treatment is delayed. Potentially fatal complications include brain hemorrhage and stroke.

In a small number of cases, PRES can recur. This is most common when uncontrolled high blood pressure is the underlying cause.

Permanent, long-term neurological effects occur in 10-20% of PRES cases. Risk factors for long-term complications include:

• Age of the patient
• Diabetes
• Some specific patterns of abnormal brain activity
• Delayed treatment

How Is PRES Prevented?

Early diagnosis and treatment of the conditions that can cause PRES is the best way to prevent the development of the syndrome. Prompt treatment of the underlying cause after PRES symptoms appear is the most effective way to avoid potentially life-threatening or permanent complications.

PRES Caregiver Tips

Some people with PRES also suffer from other brain-related issues, a condition called co-morbidity. Here are a few of the disorders commonly associated with PRES:

• Eclampsia is a common trigger of PRES.
• A small number of people who have had PRES will experience recurrent seizures or epilepsy.
• Brain disorders that may be mistaken for PRES include stroke and encephalitis.

PRES Brain Science

Scientists don’t know precisely what causes PRES. The disorder results from the accumulation of excess fluid in brain tissue resulting from proteins and fluids leaking from blood vessels. This condition is called vasogenic edema.

However, it is not yet clear what causes the edema in the first place. Current theories include:

• High blood pressure (hypertension) may disrupt the brain’s ability to control fluid buildup by constricting and dilating blood vessels. However, blood pressure is not high in all cases of PRES, and the severity of hypertension is not consistently correlated with the severity of edema.
• Inflammation may interfere with the normal constriction or dilation of blood vessels in the brain, leading to edema. PRES is often associated with conditions that cause systemic inflammation, such as eclampsia, autoimmune diseases, transplants, and infections. However, this theory does not explain those cases of PRES in which there is no source of inflammation.

PRES Research

Title: Eclampsia and Posterior Reversible Encephalopathy Syndrome (PRES): (PRESIDEX)

Stage: Completed

Principal investigator: James Martin, MD

University of Mississippi Medical Center

Jackson, MS

This is a double-blinded, placebo-controlled trial to determine if IV dexamethasone more quickly than placebo assists resolution of Posterior Reversible Encephalopathy Syndrome (PRES) encountered in eclamptic patients. Regardless of assignment to placebo or steroid, all patients will receive standard therapy to include magnesium sulfate, blood pressure medications, and diuretics. Researchers hypothesize that adding dexamethasone to standard therapy will accelerate CNS recovery more quickly than traditional management without dexamethasone.

Thirty eclamptic patients who do not require steroids for fetal lung maturation purposes will be randomized to placebo or steroid. This includes patients with eclampsia who encountered antepartum prior to 23 weeks gestation, postpartum eclampsia, undelivered patients encountered after 33 weeks gestation who would not be candidates for fetal lung maturation steroids, or patients not eligible for repeat steroid administration in the 23-34 week gestational window. Planned enrollment in this pilot study is up to 30 patients with at least 12 in each group.

Title: Copeptin Kinetics in Critically Ill Patients With Posterior Reversible Encephalopathy Syndrome (XPRESSE)

Stage: Not Yet Recruiting

Contact: Charlotte Salmon Gandonniere, MD, PhD

University Hospital

Nantes, France

Posterior reversible encephalopathy syndrome (PRES) is a clinical and radiological entity associating various neurological manifestations (e.g., encephalopathy, seizures) with typical subcortical brain edema. While the pathophysiology of PRES remains elusive, the involvement of the arginine vasopressin (AVP) axis has recently been suggested by its stimulation in almost all etiologies of PRES as well as by its pathogenesis in the generation of brain edema that has been established in different preclinical models (e.g., traumatic brain injury, intracerebral hemorrhage) (Largeau et al., Mol Neurobiol 2019 – PMID: 30924075). Copeptin, a stable peptide derived from the same precursor as AVP and released in an equimolar ratio to AVP, is used mainly in vivo to monitor AVP secretion. In a series of 225 critically ill patients free from PRES, the median copeptin admission level was 50 pmol/L (Krychtiuk et al., PLOS ONE 2017- PMID: 28118414). By analogy to copeptin kinetics in patients with traumatic brain injury (Dong et al., J Trauma 2011 – PMID: 21502880), copeptin could attain peak level during the first week of PRES.

Blocking vasopressin receptors with vaptan appears to be a promising approach for PRES treatment. This study aims to investigate the relationship between copeptin and PRES to establish the optimal therapeutic time window for vaptan treatment against PRES.

XPRESSE is a multicenter observational prospective biomarker study in which critically ill patients in 4 French ICUs with MRI-based PRES diagnosis will have copeptin kinetics from a daily blood sample for six days and a 3-month follow-up.

Data collection using an eCRF will include demographic data, medical history, and data related to PRES: onset modalities and date of symptoms control, radiological features of PRES, biological investigations, results of etiological investigations, and therapeutic management (e.g., anticonvulsants, antihypertensive drugs, supportive treatments). Outcomes will include modified Rankin scale score and Glasgow Outcome Scale score at ICU discharge, 3-month modified Rankin Scale score, and 3-month mortality.

Title: The Clinical and Prognostic Features of PRES

Stage: Recruiting

Contact:  Dunjin Chen  

Guangzhou Medical University

 Guangzhou, China

The purpose of this study is to determine the features of clinical imaging, disease severity, and pregnancy outcomes in posterior reversible encephalopathy syndrome with preeclampsia or eclampsia.

The investigators retrospectively collected data (General information, clinical data, biochemical indicators, imaging features, and pregnancy outcome) from pregnant women diagnosed with PRES with preeclampsia or eclampsia to analyze features of clinical imaging, disease severity, and pregnancy outcomes from 2012 to 2021. Then, the investigators grouped all the patients into an early-onset group and a late-onset PE group according to gestational weeks to analyze differences in clinical imaging. Finally, the investigators grouped all the patients into a good pregnancy outcomes group and a poor pregnancy outcomes group according to diagnostic criteria, including the incidence of stillbirth and premature birth, to analyze differences in clinical imaging.