Posterior Reversible Encephalopathy Syndrome

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Continuing Education Activity

Posterior reversible encephalopathy syndrome (PRES) is a neurologic disorder in which a person presents with visual disturbance, seizure, headaches, and altered mentation. This activity reviews the clinical presentation, etiology, epidemiology, pathophysiology, evaluation, differential diagnosis, treatment and management, prognosis, and complications of PRES. This article also highlights the role of the interprofessional team in recognizing and treating PRES promptly to improve patient safety, quality of care, and outcomes.


  • Describe the symptoms and risk factors of PRES to initiate prompt evaluation and treatment.
  • Summarize potential emergent conditions that emulate PRES, and outline the evaluation of such diseases to improve patient outcomes.
  • Outline a few treatment considerations for people with PRES.
  • Explain the importance of education and communication among the interprofessional team to enhance the care, safety, and outcomes of patients with PRES.


Posterior reversible encephalopathy syndrome (PRES) is an illness in which a person can present with acutely altered mentation, drowsiness or sometimes stupor, visual impairment (e.g., visual hallucinations, cortical blindness, hemianopia, quadrantanopia, and diplopia), seizures (focal or general tonic-clonic), and sudden or constant, non-localized headaches.[1] PRES can unfold acutely or subacutely, with symptoms developing within hours to days. Often, the presentation occurs in the context of acute uncontrolled hypertension, with systolic blood pressures ranging between 160 to 190 mmHg.[2] The name designated to this clinical and radiographic syndrome is inspired from (1) radiographic findings of white matter edema (i.e., hyperintense T2 signal or hypointense T1 signal on magnetic resonance imaging (MRI)), typically found in the posterior cerebrum in a symmetric fashion (although asymmetric presentations are possible); and (2) the fact that symptoms are reversible, provided that the syndrome is recognized and treated promptly. However, the name used to describe the syndrome is misleading because the edema is not localized necessarily to the posterior cerebrum white matter and can appear in watershed zones other than parietal-occipital regions thalamus, and sometimes in the anterior circulation.[2][3][4] Moreover, the syndrome is not always reversible. Some individuals can develop life-threatening complications, such as transforaminal cerebellar herniation and focal neurologic deficits, especially if prompt treatment is not initiated.[5][3]


People who are at risk for developing PRES tend to have one or more of the following risk factors, triggers, or etiologies: hypertension; preeclampsia; kidney disease (such as nephrotic syndrome, which can lead to hypovolemia and secondary hypertension via activation of the renin-angiotensin system; renal failure; liver disease; exposure to cytotoxic medications or immunosuppressants; autoimmune disorders (such as thrombotic thrombocytopenic purpura, eosinophilic granulomatosis with polyangiitis, and systemic lupus erythematosus); or sepsis.[2][6] Of these etiologies or triggers, uncontrolled hypertension is the most common.[4] However, having acute hypertension does not suggest that an individual will develop PRES, and it is difficult to determine which hypertensive individuals will develop PRES.[2][7]


PRES has been a syndrome that has been underdiagnosed, perhaps due to limited awareness; however, given the increasing availability and improvement in the quality of imaging, awareness of PRES has improved, and an understanding of the epidemiology of PRES has been emerging. Based on several reports and studies, PRES affects people of all ages but mostly middle-aged females.[1][8][1]

In a retrospective study involving the review of demographics, risk factors, and clinical presentation of 113 patients with PRES, Fugate and colleagues found that 51 individuals (45%) had an autoimmune disease.[4] Most of the individuals in the study presented with seizures (74%), followed by encephalopathy (28%), headache (26%), and visual disturbance (20%).[4] Having an epileptic seizure at presentation was found to be the best predictor for PRES, and encephalopathy was the second-best predictor. Per Laetitia della Faille and colleagues, having exposure to chemotherapy and having renal failure were also crucial predictors of PRES.[9]


The pathophysiology of PRES remains unclear, but some proposed mechanisms center around the dysregulation of cerebral autoregulation, the brain’s ability to maintain constant cerebral blood flow over a range of blood pressures via the constriction or dilation of the cerebral blood vessels.[2] When blood pressures are high, typically above a systolic pressure of 160 mmHg for most people, the amount of vasoconstriction to achieve constant cerebral blood flow is maximized, and blood flow begins to rise with increasing blood pressure. Increased hydrostatic pressure can contribute to the breakdown of the blood-brain barrier, causing intravascular fluid to extravasate to the surrounding brain tissue, leading to edema. There is the belief that the posterior circulation is mostly affected in cases of PRES because it has less adaptive mechanisms to regulate the extent of extravasation and the breakdown of the blood-brain barrier in the context of high blood pressures, compared to the anterior circulation.[10] Such speculation is perhaps inspired by findings of a formaldehyde histofluorescence study conducted by Edvinsson and colleagues that revealed a more significant number of adrenergic perivascular fibers innervating the anterior cerebral circulation compared to the vertebral circulation.[11] The amount of sympathetic nerve involvement is thought to be proportional to the effectiveness of autoregulation.[10]

One critique of the hypertensive-hyperperfusion hypothesis above is that there have been cases where individuals exhibited PRES. Still, their blood pressures were not high enough to surpass the autoregulative capability of the brain.[1][12] Not all cases of PRES occur in the context of hypertension. For instance, there have been some case reports that revealed the presence of PRES in normotensive individuals who have been taking cytotoxic therapies, such as tacrolimus in the context of liver transplantation, lending credence to the idea that endothelial dysfunction plays a crucial role in the pathophysiology of the disease.[1][3] Although not yet fully understood, tacrolimus, cyclosporine, cisplatin, and other immunosuppressants can have direct toxic effects on the endothelium, compromising the blood-brain barrier.[3][10]

Not only can immunosuppressants affect the blood-brain barrier, but also neuroinflammation, such as in the context of sepsis and autoimmune disorders. Astrogliosis, microgliosis, and endothelial activation occurring in sepsis or endothelial injury in anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitides can enhance blood-brain barrier permeability, allowing for extravasation of intravascular fluid and potential for developing PRES.[6][13][14]

History and Physical

PRES is a clinical and radiographic diagnosis. Performing a thorough history and physical examination are indispensable. While obtaining a history, asking about the presence of headache, visual impairment (e.g., binocular diplopia, vision loss, no light perception vision, hemianopia, or quadrantanopia), seizure and seizure history, and medications taken are crucial.[15] Sometimes the affected individual may have changes in mental status and not provide a reliable history; therefore, obtaining collateral information from relatives, friends, or acquaintances is valuable. When conducting a physical examination, attention to the following should be noted: hemianopia, quadrantanopia, visual neglect, cortical blindness, horizontal gaze palsy with intact vestibulo-ocular reflex, papilledema, oral trauma (tongue biting seen during a seizure), brisk reflexes, active convulsions, and urinary and fecal incontinence.[16][17]


Obtaining imaging is essential since the assessment of radiographs is the gold standard for the diagnosis of PRES.[18] A head CT is critical to assess for neurologic emergencies that can explain an acute onset of altered mentation, headache, and seizures, such as intracranial hemorrhage. An MRI of the brain without intravenous (IV) contrast is the imaging modality of choice, looking for vasogenic edema as a hyperintense signal on T2, most commonly in the parieto-occipital lobes—although other areas can be involved, such as the temporal lobe, frontal lobe, brainstem, and deep white matter.[4] The MRI will also help in the evaluation of other potential diagnoses, such as hypoxic-ischemic encephalopathy, posterior circulation infarct, and primary central nervous system vasculitis.[2] A magnetic resonance angiography (MRA) of the brain, which is typically normal in PRES, can show focal vasoconstriction or vasodilation patterns present in CNS vasculitis; and magnetic resonance venography (MRV), which is also typically normal in PRES, can help exclude sagittal sinus thrombosis as a possible diagnosis.[19]

Part of the work-up for PRES also includes evaluation of potential etiologies since their identification will be crucial for management. Obtaining blood work can help evaluate electrolyte imbalances, hypoalbuminemia, protein deficiency, an underlying infection (for example, herpes simplex virus type 1 or 2, which can cause herpes simplex encephalitis), and autoimmune etiologies. Blood work can also help exclude severe hypoglycemia as a potential diagnosis. A lumbar puncture is sometimes done in immunocompromised individuals to assess for encephalitis.

Obtaining an electroencephalogram (EEG) in people with PRES can be helpful. For instance, if there is persistently altered mentation in the absence of tonic, clonic, or tonic-clonic movements, an individual may have subclinical seizure activity that can be captured on EEG. EEG patterns, however, are generally non-specific.[20]

Treatment / Management

Identifying, treating, and managing the underlying etiology, in addition to careful treatment of hypertension, is crucial for the management of PRES. There is no specific, established antihypertensive regimen for the treatment of acute hypertension in people with PRES.[21] Treatment is recommended when the blood pressure exceeds 160 mmHg/110 mmHg, with a goal of 130 to 150 mmHg/80 to 100 mmHg.[17] [Level 5] A sudden or drastic reduction of blood pressure can lead to cerebral hypoperfusion and increase the risk of developing ischemia; thus, blood pressure should not be reduced for more than 10 to 20 mmHg every 10 to 20 minutes.[17] Such careful acute blood pressure management may warrant a need for admission to the intensive care unit until a stable blood pressure goal is reached. Thereafter, maintaining target blood pressure on the medical floors and in the outpatient setting is recommended. The exact duration for treatment post-acutely with antihypertensives is unclear and will vary among individuals.

Sometimes individuals with PRES develop life-threatening complications, such as status epilepticus or coma, and treatment and management of such complications at an intensive care unit (ICU) should follow.[22] At this time, there is no established antiepileptic treatment for seizures in people with PRES, and studies aimed to identify a specific antiseizure regimen are lacking.[21] Some antiepileptic treatment is given during the acute phase of PRES and discontinued once PRES resolves.[23] In certain circumstances, complications such as epilepsy emerge, and treatment with antiepileptic drugs will be long-term.[1]

If PRES is attributed to an immunosuppressant, reduction of the dose or substitution of the agent is recommended.[24]

Differential Diagnosis

The differential diagnosis of PRES is broad and includes the following:[2]

  • Intracranial hemorrhage
  • Subdural hemorrhage
  • Subarachnoid hemorrhage
  • Cerebral sinus venous thrombosis
  • Posterior circulation ischemic or hemorrhagic stroke
  • thrombosis of the basilar artery
  • Vasculitis of the central nervous system
  • Herpes simplex encephalitis
  • Autoimmune encephalitis
  • Uremic encephalopathy
  • Hypoglycemia


The prognosis of PRES is typically favorable if recognized and treated early, with symptom improvement or resolution in a few days to several weeks.[2][8] Visual symptoms often completely resolve, especially with early treatment of PRES, although there are some reported cases where residual visual deficits can remain (albeit improved) at 3 to 4 months after onset.[15] It is unclear which individuals are at risk of having prolonged visual deficits. PRES symptom irreversibility can ensue if treatment is delayed. If the amount of cerebral vasogenic edema is large, the prognosis can worsen, as the increased pressure to surrounding blood vessels can compromise blood flow and result in ischemia.[10] In certain situations, if there is the involvement of the brainstem, the prognosis can also worsen.[10] Recurrence of PRES is possible and has been reported in individuals undergoing dialysis.[2]


Complications of PRES develop if the disease is not treated promptly. Complications include focal neurologic deficits from ischemic injury, epilepsy, and life-threatening conditions, such as transforaminal cerebellar herniation, as reported in children.[5]

Deterrence and Patient Education

Early recognition and treatment of PRES can help reduce the incidence of complications and improve patient outcomes. Awareness and education are instrumental for the proper management of PRES and its risk factors and etiologies. For instance, educating patients about blood pressure management can decrease the likelihood of cerebral autoregulation dysfunction, leading to PRES and other complications. Knowledge about the effects of cytotoxic immunosuppressants on the blood-brain barrier, even in non-hypertensive patients, can help care providers become more mindful about the development of PRES in patients taking these medicines.

Enhancing Healthcare Team Outcomes

Enhancement of healthcare team outcomes for PRES rests on education and effective communication among physicians, nurses, technicians, therapists, and every member involved in patient care, especially patients themselves. With effective communication, awareness and recognition of PRES improve, and prompt team action can ensue, preventing lethal complications and enhancing patient safety, quality of care, and outcomes.



Lama Al-Khoury


5/1/2022 8:37:17 AM



Fischer M, Schmutzhard E. Posterior reversible encephalopathy syndrome. Journal of neurology. 2017 Aug:264(8):1608-1616. doi: 10.1007/s00415-016-8377-8. Epub 2017 Jan 4     [PubMed PMID: 28054130]


Hobson EV, Craven I, Blank SC. Posterior reversible encephalopathy syndrome: a truly treatable neurologic illness. Peritoneal dialysis international : journal of the International Society for Peritoneal Dialysis. 2012 Nov-Dec:32(6):590-4. doi: 10.3747/pdi.2012.00152. Epub     [PubMed PMID: 23212858]


Hinchey J, Chaves C, Appignani B, Breen J, Pao L, Wang A, Pessin MS, Lamy C, Mas JL, Caplan LR. A reversible posterior leukoencephalopathy syndrome. The New England journal of medicine. 1996 Feb 22:334(8):494-500     [PubMed PMID: 8559202]


Fugate JE, Claassen DO, Cloft HJ, Kallmes DF, Kozak OS, Rabinstein AA. Posterior reversible encephalopathy syndrome: associated clinical and radiologic findings. Mayo Clinic proceedings. 2010 May:85(5):427-32. doi: 10.4065/mcp.2009.0590. Epub     [PubMed PMID: 20435835]


Cordelli DM, Masetti R, Ricci E, Toni F, Zama D, Maffei M, Gentili A, Parmeggiani A, Pession A, Franzoni E. Life-threatening complications of posterior reversible encephalopathy syndrome in children. European journal of paediatric neurology : EJPN : official journal of the European Paediatric Neurology Society. 2014 Sep:18(5):632-40. doi: 10.1016/j.ejpn.2014.04.014. Epub 2014 Apr 25     [PubMed PMID: 24814477]


Garner O, Ramirez A, Iardino A. A case of posterior reversible encephalopathy syndrome associated with sepsis. BMJ case reports. 2018 Jul 10:2018():. pii: bcr-2018-225128. doi: 10.1136/bcr-2018-225128. Epub 2018 Jul 10     [PubMed PMID: 29991547]

Level 3 (low-level) evidence


Chowdhary M, Kabbani AA, Tobey D, Hope TD. Posterior reversible encephalopathy syndrome in a woman with focal segmental glomerulosclerosis. Neuropsychiatric disease and treatment. 2015:11():1111-4. doi: 10.2147/NDT.S84010. Epub 2015 Apr 21     [PubMed PMID: 25960654]


Sundin CS, Johnson ML. Posterior Reversible Encephalopathy Syndrome. MCN. The American journal of maternal child nursing. 2018 Mar/Apr:43(2):77-82. doi: 10.1097/NMC.0000000000000409. Epub     [PubMed PMID: 29470266]


Faille LD, Fieuws S, Van Paesschen W. Clinical predictors and differential diagnosis of posterior reversible encephalopathy syndrome. Acta neurologica Belgica. 2017 Jun:117(2):469-475. doi: 10.1007/s13760-017-0750-6. Epub 2017 Jan 31     [PubMed PMID: 28144796]


Covarrubias DJ, Luetmer PH, Campeau NG. Posterior reversible encephalopathy syndrome: prognostic utility of quantitative diffusion-weighted MR images. AJNR. American journal of neuroradiology. 2002 Jun-Jul:23(6):1038-48     [PubMed PMID: 12063238]


Edvinsson L, Owman C, Sjöberg NO. Autonomic nerves, mast cells, and amine receptors in human brain vessels. A histochemical and pharmacological study. Brain research. 1976 Oct 22:115(3):377-93     [PubMed PMID: 184880]


Bartynski WS. Posterior reversible encephalopathy syndrome, part 1: fundamental imaging and clinical features. AJNR. American journal of neuroradiology. 2008 Jun:29(6):1036-42. doi: 10.3174/ajnr.A0928. Epub 2008 Mar 20     [PubMed PMID: 18356474]


Nwafor DC, Brichacek AL, Mohammad AS, Griffith J, Lucke-Wold BP, Benkovic SA, Geldenhuys WJ, Lockman PR, Brown CM. Targeting the Blood-Brain Barrier to Prevent Sepsis-Associated Cognitive Impairment. Journal of central nervous system disease. 2019:11():1179573519840652. doi: 10.1177/1179573519840652. Epub 2019 Apr 9     [PubMed PMID: 31007531]


Marra AM, Barilaro G, Villella V, Granata M. Eosinophilic granulomatosis with polyangiitis (EGPA) and PRES: a case-based review of literature in ANCA-associated vasculitides. Rheumatology international. 2015 Sep:35(9):1591-5. doi: 10.1007/s00296-015-3261-x. Epub 2015 Apr 3     [PubMed PMID: 25836767]

Level 3 (low-level) evidence


Lifson N, Pasquale A, Salloum G, Alpert S. Ophthalmic Manifestations of Posterior Reversible Encephalopathy Syndrome. Neuro-ophthalmology (Aeolus Press). 2019 Jun:43(3):180-184. doi: 10.1080/01658107.2018.1506938. Epub 2018 Aug 17     [PubMed PMID: 31312242]


Hawatmeh A, Studyvin S, Al-Halawani M, Amireh S, Thawabi M. Posterior reversible encephalopathy syndrome associated with left horizontal gaze palsy. Annals of translational medicine. 2017 Mar:5(5):104. doi: 10.21037/atm.2017.03.09. Epub     [PubMed PMID: 28361069]


Vandenbossche G, Maquet J, Vroonen P, Lambert G, Nisolle M, Kridelka F, Emonts E. A reversible posterior leucoencephalopathy syndrome including blindness caused by preeclampsia. Facts, views & vision in ObGyn. 2016 Sep:8(3):173-177     [PubMed PMID: 28003872]


Zou LP, Liu LY, Li H, Wang YY, Liu Y, Chen J, Hu LY, Liu MJ, Zhang MN, Lu Q, Ma SF. Establishment and utility assessment of posterior reversible encephalopathy syndrome early warning scoring (PEWS) scale establishment and utility assessment of PEWS scale. BMC neurology. 2019 Feb 21:19(1):30. doi: 10.1186/s12883-019-1247-0. Epub 2019 Feb 21     [PubMed PMID: 30791893]


Bartynski WS, Boardman JF. Catheter angiography, MR angiography, and MR perfusion in posterior reversible encephalopathy syndrome. AJNR. American journal of neuroradiology. 2008 Mar:29(3):447-55     [PubMed PMID: 18079186]


Murray K, Amin U, Maciver S, Benbadis SR. EEG Findings in Posterior Reversible Encephalopathy Syndrome. Clinical EEG and neuroscience. 2019 Sep:50(5):366-369. doi: 10.1177/1550059419856968. Epub 2019 Jun 19     [PubMed PMID: 31215229]


Strother R, Wong H, Miller NE. Posterior Reversible Encephalopathy Syndrome Secondary to Hypertensive Encephalopathy Brought on by a MAO Inhibitor: A Case Report. Journal of primary care & community health. 2019 Jan-Dec:10():2150132719869539. doi: 10.1177/2150132719869539. Epub     [PubMed PMID: 31423884]

Level 3 (low-level) evidence


Gokhale A, Kimona A, Kantor S, Prakash S, Manhas Y. Posterior Reversible Leukoencephalopathy Syndrome (PRES) in Intensive Care Unit - Case series. Indian journal of critical care medicine : peer-reviewed, official publication of Indian Society of Critical Care Medicine. 2017 Nov:21(11):772-778. doi: 10.4103/ijccm.IJCCM_235_17. Epub     [PubMed PMID: 29279639]


Spencer D. PRES-ing for Answers About Long-Term Seizure Risk in Patients With Posterior Reversible Encephalopathy Syndrome. Epilepsy currents. 2015 Nov-Dec:15(6):317-8. doi: 10.5698/1535-7511-15.6.317. Epub     [PubMed PMID: 26633947]


Gijtenbeek JM, van den Bent MJ, Vecht CJ. Cyclosporine neurotoxicity: a review. Journal of neurology. 1999 May:246(5):339-46     [PubMed PMID: 10399863]


Atça AÖ, Erok B, Aydoğdu S. Neuroimaging findings of posterior reversible encephalopathy syndrome (PRES) following haematopoietic stem cell transplantation in paediatric recipients. BMC pediatrics. 2021 Oct 11:21(1):445. doi: 10.1186/s12887-021-02890-y. Epub 2021 Oct 11     [PubMed PMID: 34629063]


Gewirtz AN,Gao V,Parauda SC,Robbins MS, Posterior Reversible Encephalopathy Syndrome. Current pain and headache reports. 2021 Feb 25;     [PubMed PMID: 33630183]