Posterior Reversible Encephalopathy Syndrome (PRES) in the Emergency Department
“PRES is a clinical and radiological syndrome characterized by seizure, headache, altered mental status and visual impairment…”
Case
68-year-old male with history of hypertension, chronic kidney disease presenting from home with wife at bedside for confusion and shaking movements. Per wife, the patient is independent at baseline. He walks, drives and still works. Yesterday, he complained of a mild headache and this morning she noticed he seemed more confused, described as asking repetitive questions and wandering around the house. Prior to coming into the emergency department, the patient had a one-minute episode of full body shaking. This has never happened before. He has no history of seizure activity. The shaking resolved on its own and the patient was very tired afterwards while awaiting the ambulance.
On Emergency medical services (EMS) arrival they note blood pressure (BP)200/120, heart rate (HR) 78, Temp 36 Celsius, respiratory rate (RR) 14, oxygen saturation (O2 sat) of 98% on room air, blood sugar of 145. Per wife, the patient has not had any trauma, fever, vomiting, trouble speaking or moving one side of his body or the other. He recently ran out of his blood pressure medication but has had no other medication changes. He doesn’t not drink alcohol or do any recreational drugs.
On the emergency department (ED) exam, the patient is somnolent but arousable, able to follow commands but clearly confused and answers that the year is 1999. No facial droop, pronator drift or focal neurologic deficit on examination. Physical exam is otherwise normal and nonspecific. Vitals in the emergency department are significant for a blood pressure 198/102, otherwise vitals are completely normal. Blood glucose on arrival 120. Patient underwent computer tomography angiography (CTA) brain and neck which did not show any large vessel occlusion or intracranial hemorrhage. On lab work, there is no evidence of infection or metabolic derangements. The patient’s liver function, toxin screen (including amphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine, fentanyl, methadone, opiate, phencyclidine and oxycodone) and ammonia are all normal. While in the ED the patient had witnessed generalized tonic clonic seizure which broke with 2 mg of Ativan. He was loaded with Keppra, an anti-epileptic medication. Blood pressure control was recommended by neurology and IV labetalol 10 mg was given twice lowering BP to the 160s. Patient remained somnolent but arousable and maintaining airway. No evidence of seizure activity but was placed on EEG to rule out non convulsive status. Medicine recommended lumbar puncture which was performed and unrevealing. No evidence of meningitis. Patient was admitted to neurologic service where magnetic resonance imaging (MRI) was obtained which revealed evidence of posterior reversible encephalopathy syndrome (PRES).
Diagnosis
Posterior Reversible Encephalopathy Syndrome (PRES)
Discussion
PRES is a clinical and radiological syndrome characterized by seizure, headache, altered mental status and visual impairment with radiographic findings of vasogenic edema within the posterior occipital and parietal lobes of the brain. [4]
PRES is commonly associated with acute hypertension; however, the exact pathophysiology of PRES remains unknown and controversial. The three leading hypotheses include cerebral vasoconstriction causing cerebral infarcts, failure of cerebral autoregulation resulting in cerebral vessel damage and lastly, systemic inflammation resulting in endothelial damage within the blood-brain barrier causing disruption and fluid transduction. [4]
Clinically, the symptoms of PRES vary widely. All of the commonly found symptoms of PRES do not need to be present for the diagnosis. The onset of symptoms may be acute or subacute developing between hours, days or weeks. The most common presentation is seizure (74-87%) followed by encephalopathy (28-94%), headache (50%) and lastly, visual changes (39%). [2] The severity of each presenting symptom can also vary. Seizure presentation is most commonly generalized tonic-clonic but can also present as status epilepticus, non-convulsive status epilepticus and rarely, partial seizures. Many different headache characteristics have been described in PRES ranging from the most common morphology dull and gradual, to thunderclap and debilitating. The most diverse symptom is altered mental status which can range from mild confusion to stupor, somnolence and coma. The visual changes associated with PRES can be intermittent blurred vision to complete bilateral vision loss. [3,4]
Acute hypertension is thought to trigger PRES in most cases. Approximately 70% of patients with PRES have acute hypertension, often with systolic blood pressures between 170-190 mmHG but 10% of patients have normal or only mildly elevated blood pressure. [3] The commonly associated comorbidities that can predispose a patient to PRES include chronic hypertension, kidney dysfunction, preeclampsia/eclampsia, autoimmune disorders, infection/sepsis, drugs and medical interventions such as chemotherapy and bone marrow transplantation. [2,3]
The wide variety of symptomatology and commonly associated conditions make the diagnosis of PRES increasingly difficult as it can present in many ways. The differential is broad and often the diagnosis is not made in the emergency department but, PRES should be on the differential for any patients presenting to the ED with the commonly found symptoms and risk factors as discussed above.
As emergency physicians it is important to consider and rule out life threatening etiologies in patients who present with the symptoms found in PRES such as stroke, intracranial hemorrhage, encephalitis, meningitis, sinus venous thrombosis as well as, infection, metabolic derangements, and toxins. [3] In pursuit of a diagnosis, patients often undergo broad workup in the ED with Computer tomography (CT) scan and extensive lab work. If labs and imaging are unrevealing, patients often undergo lumbar puncture to rule out meningitis. CT imaging and cerebrospinal fluid analysis (CSF) studies in PRES are usually normal. MRI inpatient often is what confirms the diagnosis. The common MRI findings include bilateral white-matter abnormalities in vascular watershed areas in the posterior regions of occipital and parietal lobes. [4]
Management of patients presenting with symptoms of PRES are supportive. There have been no randomized trials on the various interventions used to treat PRES and treatments are by consensus opinion. [5] The mainstay of treatment in the ED are the ABCs (airway, breathing, circulation.) If the patient is seizing or in status, treatment should be aimed to stop seizure activity with benzodiazepines, anti-epileptics, and neurology consultation. If persistently somnolent, patients will require EEG to rule out non-convulsive status. [2]
Ultimately, the main objective is to treat the offending cause or associated “trigger” to PRES. [2,3] As previously discussed, the most common inciting cause of PRES is acute hypertension. Therefore, the most common treatment of PRES is to lower the blood pressure. Keep in mind, blood pressure management is only recommended if ischemic stroke is not evident on imaging or the leading diagnosis on the differential. The goal of blood pressure management is to reduce the mean arterial blood pressure by 20-25% within the first 1-2 hours, then to 160/100 over the next 2-6 hours and then normal approximately systolic of 120 over 2 days. The recommended agent is short acting and easily titratable. Commonly used agents include IV beta blockers and IV calcium channel blockers. [1]
Other less common triggers include eclampsia, chemotherapy agents, end stage renal disease, autoimmune crisis. The treatments in these specific instances are delivery, removal of offending agents, hemodialysis and, high dose steroids respectively. These instances are less common and typically, acute hypertension is the inciting cause. It is important to remember, regardless of the inciting cause the treatment goal is to mitigate the trigger while doing appropriate supportive care. [2,3]
Patients with PRES on the differential are often admitted to the hospital. The level of care is based on the degree of altered mental status, ongoing seizure activity and blood pressure management. If a patient is intubated, in status or on continuous anti-hypertensive infusion they should be admitted to intensive care. While inpatient, patients will receive ongoing treatment for any seizure activity and blood pressure control. MRI imaging is often obtained inpatient and will reveal the diagnosis.
The prognosis for patients with PRES has historically been thought to be favorable. As more studies are coming out that notion is being challenged. The mortality of PRES is approximately 19% in some studies, with 44% of patients with varying functional impairments. Most patients will make full neurologic recovery in a matter of weeks, with symptoms improving rapidly with correction of blood pressure. [2,5]
Case resolution
On the inpatient neurologic service, the patient had ongoing blood pressure control and was restarted on his home medication. MRI was obtained inpatient which revealed areas of hyperintensity in bilateral parietal and occipital lobes consistent with PRES. He returned to baseline on day three of hospitalization. He was discharged with primary care follow up for blood pressure checks and neurologic follow up. On his three-month visit with neurology, the patient had no residual neurologic deficits or recurrent seizures.
TAKEAWAYS
PRES is a neurotoxic syndrome characterized by clinical symptoms and radiographic findings.
Most common symptoms are seizure, altered mental status, headache and visual changes.
Symptom onset may be over hours, days or weeks and doesn’t follow one particular course.
Diagnosis is made by MRI with evidence of vasogenic edema in posterior parietal and occipital lobes.
Common risk factors for PRES include chronic hypertension, CKD, autoimmune disorders and drugs such as chemotherapy agents.
Treatment is supportive with the goal to remove inciting agents. Common management includes ABCs, seizure management, blood pressure control.
Author: Katie Miller, MD is a fourth year emergency medicine resident at Brown University/Rhode Island Hospital.
Faculty Reviewer: Kristina McAteer, MD is an attending physician and Rhode Island Hospital and Newport Hospital.
REFERENCES
[1] Alley WD, Schick MA. Hypertensive Emergency. [Updated 2022 Jul 25]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK470371/
[2] Hinduja, Archana. “Posterior Reversible Encephalopathy Syndrome: Clinical Features and Outcome.” Frontiers, Frontiers, 21 Jan. 2020, https://www.frontiersin.org/articles/10.3389/fneur.2020.00071/full.
[3] Hobson, E. V., Craven, I., & Blank, S. C. (2012). Posterior reversible encephalopathy syndrome: a truly treatable neurologic illness. Peritoneal dialysis international: journal of the International Society for Peritoneal Dialysis, 32(6), 590–594. https://doi.org/10.3747/pdi.2012.00152
[4] Sudulagunta, S. R., Sodalagunta, M. B., Kumbhat, M., & Settikere Nataraju, A. (2017). Posterior reversible encephalopathy syndrome (PRES). Oxford medical case reports, 2017(4), omx011. https://doi.org/10.1093/omcr/omx011
[5] Triplett JD, Kutlubaev MA, Kermode AG, et al. Posterior reversible encephalopathy syndrome (PRES): diagnosis and management. Practical Neurology 2022; 22:183-189.