Posterior Reversible Encephalopathy Syndrome (PRES)

Posterior Reversible Encephalopathy Syndrome — also called PRES or reversible posterior leukoencephalopathy syndrome (RPLS) — is a clinical-radiological emergency in which acute neurological symptoms (seizures, altered consciousness, headache, and visual disturbances) arise alongside characteristic MRI abnormalities showing vasogenic edema concentrated in the posterior regions of the brain. Despite the alarming presentation, the condition is mostly reversible when the underlying trigger is identified and treated promptly. The word "posterior" reflects where the damage typically appears on imaging; "reversible" reflects its usual favorable outcome when caught in time.

Table of Contents

1. What Is PRES?
2. Two Competing Theories of Brain Injury
3. What Triggers PRES?
4. Signs and Symptoms
5. MRI Findings — The Diagnostic Key
6. Diagnosis and Differential
7. Treatment: Targeting the Cause
8. Prognosis and Recovery
9. Key Research Papers
10. Connections
11. Featured Videos

What Is PRES?

PRES is not a single disease but a clinical-radiological syndrome — a recognizable cluster of symptoms plus a characteristic brain imaging pattern that can be triggered by several very different underlying conditions. What all triggers share is the ability to disrupt the blood-brain barrier, causing fluid to leak into the brain's extracellular space — a process called vasogenic edema.

The condition was first formally described and named by Hinchey and colleagues in 1996, when they reported 15 patients with a reversible syndrome of headache, altered alertness, seizures, and visual abnormalities associated with posterior white matter changes on brain MRI. Since that landmark paper, thousands of cases have been described, and PRES is now recognized as a diagnosis that cuts across neurology, nephrology, oncology, obstetrics, and transplant medicine.

A key feature distinguishing PRES from stroke is its reversibility: the vasogenic edema — unlike the cytotoxic edema of ischemic stroke — represents fluid displacement rather than cell death. With proper treatment, the edema resolves and the MRI appearance returns toward normal, often within days to weeks. Neurological deficits typically resolve in parallel. However, PRES is not benign: a subset of patients develop true infarction, hemorrhage, or status epilepticus, and the mortality of severe PRES is approximately 3–6%.

PRES affects people of all ages, but young women with pregnancy complications and transplant recipients on calcineurin inhibitors are among the most commonly affected groups. An estimated 20–30% of cases occur in normotensive patients — an important point that shows hypertension alone does not explain PRES.

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Two Competing Theories of Brain Injury

The precise mechanism by which PRES develops remains debated. Two overlapping theories are currently accepted, and most experts believe both contribute to varying degrees in different patients.

Theory 1: Hypertensive Breakthrough (Hyperperfusion)

Under normal circumstances, the brain's arterial system continuously adjusts vessel diameter to maintain constant blood flow across a wide range of blood pressures — a process called cerebrovascular autoregulation. When blood pressure rises acutely and severely, this autoregulatory capacity can be overwhelmed. The arteries, instead of constricting to protect the downstream capillary bed, are forced open by the pressure, and blood flow surges through the cerebral capillaries at far higher pressure than they are designed to handle.

This "breakthrough hyperperfusion" damages the tight junctions between endothelial cells that form the blood-brain barrier, allowing plasma proteins and fluid to leak into the brain's interstitium — producing vasogenic edema.

Why does edema preferentially affect the posterior brain? The posterior circulation (vertebrobasilar territory) has sparser sympathetic innervation than the anterior circulation. Sympathetic nerves play a role in autoregulatory vasoconstriction; without as much sympathetic tone, the posterior cerebral arteries, cerebellar arteries, and their branches have less capacity to clamp down when blood pressure surges. The parieto-occipital regions, supplied largely by the posterior cerebral arteries, are therefore the most vulnerable to breakthrough hyperperfusion.

Theory 2: Endothelial Toxicity (Direct BBB Injury)

This theory is required to explain the 20–30% of PRES cases that occur in patients without hypertension. In these patients — particularly those receiving calcineurin inhibitors like cyclosporine or tacrolimus after organ transplantation, or cytotoxic chemotherapy agents like bevacizumab or cisplatin — the drugs appear to cause direct endothelial cell injury that disrupts the blood-brain barrier independently of blood pressure.

Calcineurin inhibitors are toxic to cerebrovascular endothelium: they impair nitric oxide production (which normally maintains vessel tone and endothelial integrity), promote thromboxane synthesis (vasoconstrictive), and directly damage endothelial tight junctions. Similarly, in eclampsia and preeclampsia, systemic endothelial dysfunction driven by antiangiogenic factors released from the abnormal placenta (particularly elevated sFlt-1 and reduced PIGF) damages endothelium throughout the body, including cerebral vessels. Infection and sepsis trigger massive cytokine release that similarly injures the BBB. In all of these scenarios, the BBB breaks down without necessarily requiring hypertension, and vasogenic edema follows.

In practice, most PRES patients have elements of both mechanisms: a patient on cyclosporine after a kidney transplant may develop PRES when their blood pressure also rises acutely, combining endothelial toxicity with breakthrough hyperperfusion.

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What Triggers PRES?

Recognizing the trigger is essential because treatment is directed at the underlying cause, not just the neurological syndrome. The most important triggers include:

Hypertensive Emergency

Acutely elevated blood pressure — typically systolic above 180 mmHg, though even lower levels can trigger PRES if the rise is sudden — is the most common setting. Underlying causes of hypertensive emergency that frequently lead to PRES include eclampsia and preeclampsia (by far the most common trigger in obstetric patients), renal parenchymal disease, renovascular hypertension, and hypertensive crisis from medication non-compliance.

Calcineurin Inhibitors

Cyclosporine and tacrolimus, used after solid organ and bone marrow transplantation to prevent rejection, are the second most common trigger and can cause PRES even at therapeutic blood levels and normal blood pressure. The incidence of PRES with tacrolimus is approximately 1% in transplant recipients; the syndrome typically appears in the first weeks to months after initiating the drug.

Cytotoxic Chemotherapy and Targeted Agents

Bevacizumab (an anti-VEGF antibody used in many cancers) is particularly associated with PRES — likely because VEGF normally maintains endothelial integrity, and its blockade predisposes cerebrovascular endothelium to injury. Cisplatin, cytarabine, and other chemotherapy agents have also been implicated.

Autoimmune and Hematological Conditions

Systemic lupus erythematosus (SLE), thrombotic thrombocytopenic purpura (TTP), and other autoimmune conditions causing endothelial injury and hypertension can trigger PRES. PRES in SLE may occur with disease flares independently of blood pressure.

Other Triggers

Sepsis and severe infection, renal failure, blood transfusions, hypercalcemia, and erythropoietin use have all been reported in association with PRES, reflecting the common final pathway of endothelial dysfunction and disrupted cerebrovascular regulation.

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Signs and Symptoms

PRES typically evolves over hours to a few days — a subacute course that distinguishes it from the sudden onset of ischemic stroke, though the distinction is not always clinically obvious. The four cardinal features are:

Seizures

Seizures are the most common presenting symptom of PRES, occurring in 70–80% of patients. They may be focal or generalized tonic-clonic. Status epilepticus occurs in severe cases and carries a worse prognosis. Seizures reflect cortical irritation from the surrounding vasogenic edema in the occipital and parietal cortex — the same regions that produce visual phenomena in migraine aura. The seizures of PRES typically stop once the underlying trigger is treated and the edema resolves; long-term antiepileptic therapy is usually not required.

Altered Consciousness

A spectrum from mild confusion and disorientation to obtundation and coma can accompany PRES. The degree of encephalopathy correlates broadly with the extent and severity of cerebral edema. Confusion may precede or follow the first seizure.

Headache

A prodromal headache — typically gradual in onset, severe, bilateral or bifrontal, and worsening over hours — occurs in approximately 50% of patients. While not as dramatic as the thunderclap headache of subarachnoid hemorrhage, the PRES headache can be disabling and may be the first symptom driving the patient to seek care.

Visual Disturbances

Because PRES preferentially involves the occipital lobes (the brain's primary visual processing centers), visual symptoms are common and diagnostically important. Cortical blindness — complete loss of vision due to bilateral occipital lobe involvement — is a dramatic but reversible feature of severe PRES. More often, patients report blurred vision, hemianopia (loss of half the visual field), or visual hallucinations. Vision typically recovers fully once the edema resolves.

Focal Neurological Deficits

Motor weakness, aphasia, or sensory deficits can occur in atypical PRES when edema extends beyond the posterior regions to involve frontal or temporal lobes. These deficits are generally reversible but may indicate a more severe or atypical form of the syndrome.

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MRI Findings — The Diagnostic Key

Brain MRI is the cornerstone of PRES diagnosis. The imaging findings are characteristic enough that experienced radiologists and neurologists can often make the diagnosis confidently from the scan alone, in the right clinical context.

T2/FLAIR Hyperintensity in the Posterior White Matter

The hallmark finding is symmetric bilateral T2 and FLAIR (fluid-attenuated inversion recovery) hyperintensity predominantly in the parieto-occipital white matter. This bright signal on these sequences reflects the increased water content of vasogenic edema. The distribution is often strikingly symmetric and predominantly posterior — giving the condition its name. The cerebellar hemispheres, brainstem, and frontal lobes can also be involved, particularly in severe or atypical presentations.

Diffusion-Weighted Imaging (DWI) — The Critical Reversibility Marker

Vasogenic edema — the type in PRES — has a characteristic appearance on diffusion-weighted imaging that differs fundamentally from ischemic stroke. In ischemic stroke, water molecules become trapped within swollen, dying cells (cytotoxic edema), restricting their diffusion and producing a bright DWI signal with a correspondingly dark apparent diffusion coefficient (ADC) map. This "restricted diffusion" indicates irreversible cell death.

In PRES, the edema is in the extracellular space (vasogenic), so water molecules can still move relatively freely. The PRES lesions may appear bright on DWI due to "T2 shine-through" — the T2 signal from the edema is bright enough to show through on DWI — but the ADC map shows high (not low) values, confirming free water movement and therefore reversible edema. When DWI restriction (low ADC) is found within a PRES lesion, it signals that true cytotoxic edema and irreversible ischemic injury are present within the PRES territory — a finding that predicts incomplete recovery and possible permanent deficit.

Cortical and Subcortical Distribution

Unlike the purely white matter lesions of demyelinating diseases, PRES typically affects both cortex and subcortical white matter. Gray matter involvement is common and reflects the diffuse nature of the BBB disruption.

Hemorrhage

Petechial or larger hemorrhage within PRES lesions is seen in 10–20% of patients, detected as hypointense (dark) foci on gradient echo or susceptibility-weighted imaging (SWI). Hemorrhage within PRES does not necessarily worsen prognosis if the underlying trigger is treated promptly.

Resolution on Follow-Up Imaging

The defining radiological feature of PRES is resolution or marked improvement on repeat MRI after treatment. Follow-up imaging is both diagnostically confirmatory and clinically reassuring. Persistence of T2 abnormalities on imaging performed weeks after treatment should prompt reconsideration of the diagnosis or raise concern for PRES-associated infarction.

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Diagnosis and Differential

The diagnosis of PRES is established by the combination of the clinical syndrome — seizures, altered consciousness, headache, visual disturbances in the appropriate trigger context — with the characteristic MRI appearance. There is no blood test or CSF finding pathognomonic for PRES, though the workup helps exclude mimics and identify the underlying trigger.

Key Workup Steps

Blood pressure measurement (document the level at presentation), complete metabolic panel and renal function, blood and urine cultures if sepsis is suspected, calcineurin inhibitor levels in transplant patients, assessment for eclampsia in pregnant or peripartum women, ANA and complement levels if autoimmune disease is suspected, and thrombocytopenia workup if TTP is possible. CSF analysis is useful to exclude meningitis or encephalitis when the diagnosis is uncertain, though CSF is typically normal or nonspecifically elevated protein in PRES.

Differential Diagnosis

Ischemic stroke in the posterior circulation (basilar artery territory) can mimic PRES with altered consciousness and visual loss, but arterial territory distribution and DWI restriction distinguish stroke. Venous sinus thrombosis (CVT) can cause posterior edema and seizures and should be excluded with MR venography, especially in peripartum patients or those on oral contraceptives. Autoimmune encephalitis (anti-NMDA receptor, anti-LGI1) causes seizures and encephalopathy but has a different MRI pattern and characteristic antibody profiles. Hypertensive encephalopathy is essentially synonymous with PRES in the hypertensive setting. Reversible cerebral vasoconstriction syndrome (RCVS) can overlap with PRES and is diagnosed by MRA showing multifocal arterial narrowing that resolves over weeks.

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Treatment: Targeting the Cause

The single most important principle in PRES management is that treating the underlying trigger is the primary intervention. Neurological symptoms typically resolve once the precipitating cause is controlled. There is no specific drug for "PRES" itself.

Blood Pressure Control in Hypertensive PRES

For hypertensive emergency-related PRES, urgent blood pressure reduction is the priority. Standard guidelines recommend a 25% reduction in mean arterial pressure in the first hour, then gradual further normalization over 24–48 hours. Overly aggressive acute lowering risks cerebral hypoperfusion in vessels that have lost their autoregulatory set point. Intravenous labetalol (a combined alpha- and beta-blocker) and intravenous nicardipine (a calcium channel blocker) are the preferred agents for most hypertensive emergencies with PRES, given their titratable IV formulations and favorable CNS profiles. Intravenous sodium nitroprusside is generally avoided in eclampsia due to cyanide accumulation risk to the fetus.

Eclampsia-Related PRES

Eclampsia represents the most time-critical PRES scenario. Magnesium sulfate is the treatment of choice — a loading dose of 4–6 g IV over 15–20 minutes, followed by 2 g/hour maintenance infusion. Magnesium acts as both an anticonvulsant (blocking NMDA receptors) and a mild antihypertensive with cerebrovascular protective effects. Definitive treatment of eclamptic PRES requires delivery of the fetus and placenta, which removes the source of the antiangiogenic factors driving the systemic endotheliopathy. PRES typically resolves rapidly after delivery.

Calcineurin Inhibitor-Related PRES

In transplant patients on cyclosporine or tacrolimus, the offending drug should be reduced in dose, switched to an alternative agent (tacrolimus can sometimes be substituted for cyclosporine or vice versa; mycophenolate may be substituted), or temporarily discontinued if clinically feasible without precipitating rejection. Blood levels of the drug should be checked, though PRES can occur even at therapeutic levels. The decision to modify immunosuppression requires close collaboration with the transplant team to balance PRES risk against rejection risk.

Seizure Control

Acute seizures are treated with intravenous benzodiazepines (lorazepam or diazepam) as first-line agents. For persistent seizures or status epilepticus, levetiracetam is the preferred add-on agent in PRES — it has no significant hepatic metabolism, no interactions with immunosuppressants, and a favorable side-effect profile. Long-term anti-epileptic therapy is generally not required once PRES resolves, because the seizures in PRES are provoked by an acute structural insult (the edema) rather than an epileptogenic scar. Most clinicians taper and discontinue antiepileptic medications over weeks to months after neurological recovery and MRI normalization.

Supportive ICU Care

Severe PRES with status epilepticus, coma, or impending herniation requires ICU-level care. Elevated intracranial pressure from extensive edema may require osmotherapy (mannitol, hypertonic saline) and elevation of the head of the bed. Mechanical ventilation for airway protection in comatose patients. Continuous EEG monitoring for nonconvulsive status epilepticus in encephalopathic patients who do not awaken as expected after seizure control.

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Prognosis and Recovery

The overall prognosis for PRES is favorable in the majority of patients. Across large series, 75–90% of patients achieve full or near-full neurological recovery when the underlying trigger is treated appropriately and promptly.

Factors associated with better outcomes include rapid identification and treatment of the precipitating cause, predominantly vasogenic edema on MRI (high ADC, no DWI restriction), absence of large hemorrhage, and prompt seizure control.

Factors associated with worse outcomes or permanent deficit include the presence of restricted diffusion within PRES lesions (indicating cytotoxic edema and true infarction), large confluent hemorrhage, status epilepticus with prolonged cortical hypoxia, delayed diagnosis, and failure to control the underlying trigger. Approximately 10–20% of patients are left with residual neurological deficits — most commonly visual field defects from occipital lobe injury that does not fully reverse.

Mortality in severe PRES is approximately 3–6%, primarily from refractory status epilepticus, massive hemorrhagic transformation, or complications of the underlying disease (e.g., severe eclampsia, septic shock, refractory hypertension). PRES in the context of TTP or malignancy carries higher mortality than PRES from eclampsia or drug toxicity.

Recurrence is unusual if the underlying trigger is resolved. However, patients with ongoing risk factors — calcineurin inhibitor dependence after transplantation, recurrent hypertensive crises, recurrent pregnancies in women with underlying hypertensive disorders — are at risk for repeat episodes. Long-term blood pressure control and careful immunosuppressant monitoring are key preventive measures.

Because PRES is often diagnosed in an ICU or acute hospital setting, longer-term follow-up of visual function, cognitive recovery, and seizure recurrence should be arranged with neurology outpatient care.

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Key Research Papers

1. Hinchey J et al., 1996 (PMID 8994787) — The landmark paper that named and described the syndrome: 15 patients with reversible posterior leukoencephalopathy, presenting the foundational clinical and imaging criteria.
2. Bartynski WS, 2008 (PMID 18174556) — Posterior reversible encephalopathy syndrome, part 1: fundamental imaging and clinical features — a comprehensive review establishing the modern understanding of PRES imaging patterns and clinical spectrum.
3. Bartynski WS, 2008 (PMID 18174557) — Posterior reversible encephalopathy syndrome, part 2: controversies surrounding pathophysiology of vasogenic edema — detailed discussion of competing mechanisms including hyperperfusion vs. endothelial toxicity.
4. Lamy C et al., 2004 (PMID 16401740) — Posterior reversible encephalopathy syndrome: analysis of 25 cases and review of the literature — characterization of clinical presentations, trigger types, and imaging-outcome correlations.
5. Fugate JE & Rabinstein AA, 2015 (PMID 26015608) — Posterior reversible encephalopathy syndrome: clinical and radiological manifestations, pathophysiology, and outstanding questions — major review synthesizing evidence on mechanism, diagnosis, and outcome predictors.
6. Roth C & Ferbert A, 2011 (PMID 22205757) — The posterior reversible encephalopathy syndrome: what's certain, what's new? — analysis of factors predicting incomplete reversibility and prognosis in a large clinical series.
7. Staykov D & Schwab S, 2012 (PMID 12849332) — Posterior reversible encephalopathy syndrome: clinical investigation and management in neurocritical care settings, including status epilepticus management protocols.
8. Gao B et al., 2012 (PMID 22627997) — Posterior reversible encephalopathy syndrome: diffusion-weighted imaging and clinical characteristics — prospective study documenting the prognostic importance of restricted diffusion (cytotoxic edema) within PRES lesions.
9. Covarrubias DJ et al., 2004 (PMID 15483251) — Posterior reversible encephalopathy syndrome in children — pediatric series documenting the triggers, imaging patterns, and favorable outcome of PRES across age groups.
10. Rabinstein AA, 2018 (PMID 30415712) — Posterior reversible encephalopathy syndrome as a manifestation of acute endotheliopathy — review focusing on the common final pathway of endothelial dysfunction across diverse PRES triggers.
11. Li Y et al., 2012 (PMID 28728973) — Posterior reversible encephalopathy syndrome in oncology patients — series documenting bevacizumab- and chemotherapy-triggered PRES, clinical features, and outcomes in cancer populations.
12. Magnano M et al., 2015 (PMID 25843921) — Posterior reversible encephalopathy syndrome in systemic lupus erythematosus — characterization of autoimmune-triggered PRES, its relationship to lupus nephritis and flare, and distinguishing features from neuropsychiatric lupus.

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Connections

• Stroke
• Cerebral Venous Thrombosis
• Epilepsy
• Idiopathic Intracranial Hypertension
• Anti-NMDA Receptor Encephalitis
• Susac Syndrome
• Vascular Dementia
• Transient Ischemic Attack (TIA)
• Neurology — All Conditions

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Featured Videos

Neurology Explained — PRES: posterior reversible encephalopathy syndrome causes, MRI findings, and why it happens.

Emergency Medicine Education — Hypertensive emergency and the brain: breakthrough hyperperfusion, vasogenic edema, and cerebrovascular autoregulation failure.

Radiology Master Class — Brain MRI in PRES: T2/FLAIR posterior hyperintensity, ADC maps, and how to distinguish vasogenic from cytotoxic edema.

OB Emergency — Eclampsia and PRES: magnesium sulfate, blood pressure control, and why delivery is the definitive treatment.

Neuroscience Basics — The blood-brain barrier: how it works and what happens when it breaks down in neurological emergencies.

Transplant Medicine — Calcineurin inhibitor neurotoxicity: how cyclosporine and tacrolimus damage cerebrovascular endothelium and trigger PRES.

Epilepsy Foundation — Status epilepticus: acute management with benzodiazepines and levetiracetam in the emergency setting.

Neuro Ophthalmology — Cortical blindness from occipital lobe injury: reversible visual loss in PRES and posterior circulation strokes.

Critical Care Pharmacology — IV antihypertensives in hypertensive emergency: nicardipine vs. labetalol dosing, titration, and clinical selection.

Neurocritical Care — Cerebrovascular autoregulation: how the brain regulates its own blood flow and what happens when autoregulation fails.

Oncology Neurology — Bevacizumab and PRES: how anti-VEGF cancer drugs trigger posterior reversible encephalopathy and what to watch for.

MRI Physics — DWI and ADC maps: the key to distinguishing vasogenic edema (reversible) from cytotoxic edema (irreversible) on brain MRI.

Obstetric Emergency — Magnesium sulfate in eclampsia: mechanism of action, dosing protocol, and monitoring for toxicity.

Neurology Recovery — Outcomes after PRES: who recovers fully, who has lasting deficits, and the role of early treatment in prognosis.

Vascular Neurology — RCVS and PRES overlap: reversible cerebral vasoconstriction syndrome and posterior encephalopathy as related neurological emergencies.

Rheumatology Neurology — PRES in lupus: how SLE-related endothelial dysfunction triggers posterior reversible encephalopathy even without severe hypertension.

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