PRES
Posterior Reversible Encephalopathy Syndrome. Vasogenic edema predominantly in the posterior circulation. Classic presentation: seizures + headache + visual changes + hypertension. MRI is the diagnostic study of choice. Usually reversible if treated promptly.
🔍 Overview
Overview
Posterior Reversible Encephalopathy Syndrome (PRES) is a clinico-radiographic syndrome characterized by vasogenic edema predominantly in the posterior (occipital/parietal) white matter. Pathophysiology: failure of cerebral autoregulation leads to blood-brain barrier breakdown and vasogenic edema.
Common Causes
- Severe hypertension -most common trigger. Exceeds upper limit of autoregulation.
- Eclampsia / pre-eclampsia -one of the most important causes in young women
- Immunosuppressants -tacrolimus, cyclosporine (calcineurin inhibitors) -common in transplant patients
- Chemotherapy -especially VEGF inhibitors (bevacizumab)
- Autoimmune disease -SLE, TTP, thrombotic microangiopathy
- Renal failure -especially with fluid overload and hypertension
Clinical Presentation
Classic features: seizures (most common presenting symptom, 60-75%), headache (50%), visual disturbances (cortical blindness, blurry vision, visual field defects -33%), altered mental status (28%), and hypertension (often severe). Typically acute/subacute onset over hours to days.
🚨 Management
Management Principles
- TREAT THE CAUSE -this is the most important step:
- Hypertensive emergency: lower BP gradually (IV antihypertensives -nicardipine, labetalol)
- Eclampsia: magnesium sulfate + delivery
- Drug-induced: discontinue offending agent (tacrolimus, cyclosporine, chemotherapy)
- Seizure management: Benzodiazepines for acute seizures. Levetiracetam (Keppra) for prophylaxis/maintenance (fewer drug interactions than phenytoin in transplant patients).
- BP control: Target 25% reduction in MAP over first few hours. Avoid precipitous drops (risk of ischemia). IV nicardipine or labetalol preferred.
- Usually REVERSIBLE if treated promptly -clinical and radiographic improvement typically within days to weeks. Delayed treatment can lead to permanent infarction, hemorrhage, and death.
PRES is a clinical-radiographic diagnosis. MRI is key -CT may miss early changes. Despite the name, PRES is not always posterior (can involve frontal lobes, brainstem, cerebellum) and not always reversible (delayed treatment can cause permanent ischemic injury, hemorrhage, or death).
🧪 Workup
Diagnostic Workup
- MRI brain (with FLAIR) -study of choice. Shows bilateral, symmetric white matter edema in posterior regions (occipital/parietal lobes). FLAIR and T2 sequences show hyperintense signal. DWI helps distinguish vasogenic (PRES) from cytotoxic (stroke) edema.
- CT head -less sensitive, may appear normal early. Can show low-density areas in posterior regions. Rule out hemorrhage.
- BP -often severely elevated (but PRES can occur at normal BPs, especially drug-induced)
- BMP -renal function, electrolytes
- CBC, LDH, peripheral smear, haptoglobin -rule out TTP/HUS if thrombocytopenia present
- Urine protein/Cr ratio -if pregnant or postpartum (pre-eclampsia workup)
- Drug levels -tacrolimus, cyclosporine trough levels if applicable
- LP -typically not needed. CSF may show mild protein elevation. Mainly to rule out meningitis/encephalitis if diagnosis uncertain.
💊 Medications
Medications
| Drug | Indication | Dose | Notes |
|---|---|---|---|
| Nicardipine BP CONTROL | Hypertensive PRES | 5 mg/hr IV, titrate by 2.5 mg/hr q5-15 min (max 15 mg/hr) | Preferred -titratable, consistent effect. No cerebral vasoconstriction. |
| Labetalol | Hypertensive PRES | 10-20 mg IV bolus, double q10 min (max 300 mg) or 1-2 mg/min drip | Alternative to nicardipine. Avoid in severe bradycardia, asthma, heart block. |
| Levetiracetam (Keppra) | Seizure prophylaxis | 500-1000 mg IV/PO BID | Preferred in transplant patients (no CYP interactions -does not affect tacrolimus/cyclosporine levels). |
| Lorazepam (Ativan) | Acute seizures | 2-4 mg IV PRN | First-line for acute seizure control. |
| Magnesium sulfate | Eclampsia-related PRES | 4-6 g IV load, then 1-2 g/hr | Standard of care for eclamptic seizures. Also has antihypertensive effect. |
🏥 Rounds
Pimp Questions
❓ Why is the posterior circulation preferentially affected in PRES?
The posterior (vertebrobasilar) circulation has less sympathetic innervation than the anterior (carotid) circulation. Sympathetic innervation helps maintain cerebral autoregulation during acute hypertension. Because the posterior circulation lacks this protective mechanism, it is more susceptible to breakthrough hyperperfusion and blood-brain barrier breakdown when BP exceeds the autoregulatory threshold.
❓ How do you differentiate PRES from ischemic stroke on MRI?
Key is DWI (diffusion-weighted imaging). PRES shows vasogenic edema -T2/FLAIR bright, but DWI normal or dark (no restricted diffusion). Ischemic stroke shows cytotoxic edema -DWI bright with corresponding ADC dark (restricted diffusion). If PRES shows restricted diffusion, it suggests progression to infarction (poor prognostic sign).
❓ Why use levetiracetam over phenytoin in transplant patients with PRES?
Phenytoin is metabolized via CYP3A4 and also induces CYP3A4, which metabolizes tacrolimus and cyclosporine. Using phenytoin in transplant patients would dramatically lower immunosuppressant levels, risking acute rejection. Levetiracetam is renally cleared with no CYP interactions, making it the preferred anticonvulsant in this population.
Sample Presentation
Mrs. Kim is a 45-year-old woman who is 6 months post-renal transplant on tacrolimus, presenting with sudden-onset severe headache, blurry vision, and a witnessed generalized tonic-clonic seizure. BP on arrival: 210/115. Neuro exam: confused, bilateral visual field deficits. Tacrolimus trough elevated at 18 (target 5-8). MRI brain: bilateral symmetric T2/FLAIR hyperintensity in the occipital and parietal white matter consistent with vasogenic edema. No restricted diffusion. No hemorrhage.
Key Points: Classic PRES -transplant patient on tacrolimus with HTN emergency + seizure + visual changes + posterior white matter edema on MRI. Management: (1) nicardipine drip for BP control, (2) levetiracetam for seizure management (no CYP interactions with tacrolimus), (3) HOLD tacrolimus (supratherapeutic level likely contributing). Expect clinical improvement within days if treated promptly.
Monitoring
- Blood pressure -continuous arterial line or frequent NIBP. Target 25% MAP reduction over first hours, then gradually normalize.
- Neurologic exam -serial neuro checks q1-2h. Document mental status, vision, motor function.
- Repeat MRI -in 1-2 weeks to confirm radiographic resolution. If not improving, reconsider diagnosis.
- Seizure monitoring -consider continuous EEG if altered mental status persists or recurrent seizures.
- Drug levels -if calcineurin inhibitor-related, check trough levels and hold/reduce dose until resolution.
- Urine output and renal function -especially if pre-eclampsia or renal failure is the trigger.
📋 Summary
Summary
Recognize the Syndrome
Seizures, headache, visual disturbance and altered mental status, usually with hypertension. Seizure is the commonest presenting feature, and the visual symptoms range from blurring and hemianopia to cortical blindness. Onset is over hours to days rather than the seconds of a stroke.
The Name Is Misleading Twice Over
It is not always posterior: frontal lobes, brainstem, cerebellum and basal ganglia can all be involved. And it is not always reversible: delayed recognition and treatment lead to infarction, hemorrhage and permanent deficit. Treat the fact that the syndrome is potentially reversible as a reason to act fast, not as reassurance.
MRI Is the Test
MRI with FLAIR shows symmetric vasogenic edema in the parieto-occipital white matter. CT may miss early changes entirely, so a normal CT does not exclude it. Diffusion-weighted imaging separates vasogenic edema (no restriction) from infarction (restriction), and that distinction is what stops PRES being treated as a stroke.
Know the Causes You Can Reverse
Severe hypertension and hypertensive emergency; preeclampsia and eclampsia; calcineurin inhibitors (tacrolimus, cyclosporine) and other cytotoxic agents; renal failure; sepsis; autoimmune disease. In a transplant patient, suspect the calcineurin inhibitor even when the level is therapeutic, since PRES is idiosyncratic rather than dose-dependent.
Lower the Blood Pressure, But Not Too Fast
Reduce mean arterial pressure by no more than about 25% in the first hours. Overshooting causes cerebral hypoperfusion and watershed infarction in a brain whose autoregulation is already deranged. Nicardipine 5 mg/h titrated by 2.5 mg/h every 5 to 15 min is preferred: titratable, predictable, and without the cerebral vasoconstriction of some alternatives. Labetalol is the alternative, avoiding it in asthma, bradycardia and heart block.
Remove the Trigger
Stop or reduce the offending drug, and deliver the baby in eclampsia. No amount of blood pressure control fixes PRES while the precipitant is still acting, and in eclampsia delivery is the definitive treatment.
Treat Seizures, Do Not Anticoagulate the Brain
Lorazepam 2 to 4 mg IV for an acute seizure, then levetiracetam 500 to 1,000 mg BID. Levetiracetam is preferred in transplant patients because it has no CYP interactions and does not alter calcineurin inhibitor levels the way phenytoin does. Antiepileptics can usually be stopped after a few weeks to months once imaging resolves, since this is a provoked seizure, not epilepsy.
Expect Recovery, but Follow the Imaging
Most patients improve clinically within days and radiographically within weeks. Repeat MRI to confirm resolution, because persistent change suggests infarction or hemorrhage and predicts residual deficit. Recurrence happens if the trigger returns, so document the cause clearly and flag the offending drug in the record.
📄 One Pager
Text version
Neurology · One Pager
PRES
Posterior Reversible Encephalopathy Syndrome: vasogenic edema from failed cerebral autoregulation, and it reverses only if you find and fix the trigger fast.
Triggers (Find One, Because Treating It Is the Treatment)
- Severe hypertension: most common trigger, BP exceeds the upper limit of cerebral autoregulation
- Eclampsia / pre-eclampsia: one of the most important causes in young women
- Immunosuppressants: tacrolimus, cyclosporine (calcineurin inhibitors), common in transplant patients
- Chemotherapy: especially VEGF inhibitors (bevacizumab)
- Autoimmune disease: SLE, TTP, thrombotic microangiopathy
- Renal failure: especially with fluid overload plus hypertension
- Note: PRES can occur at normal BP, especially drug-induced, so a normal blood pressure does not exclude it
Presentation and Diagnosis
- Seizures (60 to 75%), the most common presenting symptom, then headache (50%), visual disturbance (cortical blindness, blurry vision, field defects, 33%), altered mental status (28%), and often severe hypertension. Acute to subacute over hours to days
- MRI brain with FLAIR is the study of choice: bilateral, symmetric white matter edema in the posterior (occipital/parietal) regions, hyperintense on FLAIR and T2
- DWI is what separates PRES from stroke: vasogenic edema is DWI normal or dark (no restricted diffusion); cytotoxic stroke edema is DWI bright with ADC dark. Restricted diffusion in PRES means progression to infarction, a poor prognostic sign
- CT head is less sensitive and may be normal early. Use it to rule out hemorrhage, not to rule out PRES
- Labs: BMP for renal function and electrolytes; CBC, LDH, smear, haptoglobin to exclude TTP/HUS if thrombocytopenic; urine protein/Cr if pregnant or postpartum; tacrolimus or cyclosporine trough if applicable
- LP is typically not needed (CSF may show mild protein elevation), mainly to exclude meningitis or encephalitis if the diagnosis is uncertain
Management, Step by Step
1
TREAT THE CAUSE: this is the most important step and the reason the syndrome is reversible at all. Hypertensive emergency gets IV antihypertensives, eclampsia gets magnesium sulfate plus delivery, drug-induced gets the offending agent discontinued (tacrolimus, cyclosporine, chemotherapy)
2
Lower BP gradually, target a 25% reduction in MAP over the first few hours. Avoid precipitous drops because of the risk of ischemia. IV nicardipine or labetalol preferred
3
Seizure control: benzodiazepines for acute seizures, then levetiracetam for prophylaxis and maintenance because it has fewer drug interactions than phenytoin in transplant patients
4
Expect reversal: clinical and radiographic improvement typically within days to weeks if treated promptly. If it is not improving, reconsider the diagnosis
5
Understand the cost of delay: delayed treatment can lead to permanent infarction, hemorrhage, and death. The reversibility is conditional, not automatic
Key Drugs
Nicardipine (BP control, preferred)5 mg/hr IV, titrate by 2.5 mg/hr q5 to 15 min, max 15 mg/hr
Labetalol (alternative)10 to 20 mg IV bolus, double q10 min to max 300 mg, or 1 to 2 mg/min drip
Lorazepam (Ativan), acute seizures2 to 4 mg IV PRN
Levetiracetam (Keppra), prophylaxis500 to 1000 mg IV/PO BID
Magnesium sulfate, eclamptic PRES4 to 6 g IV load, then 1 to 2 g/hr
Monitoring
- BP continuously (arterial line or frequent NIBP): target 25% MAP reduction over the first hours, then normalize gradually, because overshooting risks ischemia
- Serial neuro checks q1 to 2h, documenting mental status, vision, and motor function, since these are what tell you the edema is resolving
- Repeat MRI in 1 to 2 weeks to confirm radiographic resolution. If it is not improving, reconsider the diagnosis
- Continuous EEG if altered mental status persists or seizures recur, to catch nonconvulsive activity
- Calcineurin inhibitor trough levels if drug-related, and hold or reduce the dose until resolution
- Urine output and renal function, especially when pre-eclampsia or renal failure is the trigger
Pitfalls
- Dropping the BP precipitously. The target is a 25% MAP reduction over hours, not normalization in minutes, because a fast drop causes ischemia
- Trusting a normal CT. CT is less sensitive and may be normal early; MRI with FLAIR is what makes the diagnosis
- Assuming the name is literal. PRES is not always posterior (frontal lobes, brainstem, cerebellum can be involved) and not always reversible
- Excluding PRES because the BP is normal. Drug-induced PRES can occur at normal blood pressures
- Reaching for phenytoin in a transplant patient. It induces CYP3A4, which metabolizes tacrolimus and cyclosporine, so immunosuppressant levels crash and the graft is at risk of rejection. Levetiracetam is renally cleared with no CYP interactions
- Calling restricted diffusion "still PRES" and relaxing. It signals progression to infarction
Escalate / Act Immediately When
- Seizure plus visual change plus severe hypertension: get the MRI, do not sit on it, because the window in which this is reversible is short
- Transplant patient with a supratherapeutic calcineurin inhibitor trough: hold the drug, that is the trigger and removing it is the treatment
- Pregnant or postpartum: eclampsia pathway, magnesium sulfate plus delivery, involve obstetrics immediately
- Thrombocytopenia on the CBC: send LDH, smear, and haptoglobin to exclude TTP/HUS, which is a different emergency with a different treatment
- Restricted diffusion, hemorrhage, or no improvement on repeat imaging: reconsider the diagnosis and escalate, this is no longer simple reversible PRES
The Core Concepts
- Pathophysiology: failure of cerebral autoregulation leads to blood-brain barrier breakdown and vasogenic edema
- Why posterior: the posterior (vertebrobasilar) circulation has less sympathetic innervation than the anterior (carotid) circulation, and sympathetic tone is what maintains autoregulation during acute hypertension, so the posterior circulation breaks through into hyperperfusion first
- Why levetiracetam over phenytoin: phenytoin is metabolized by and induces CYP3A4, dramatically lowering tacrolimus and cyclosporine levels and risking acute rejection
- The one-line takeaway: PRES is a clinical-radiographic diagnosis, and treating the trigger is what drives recovery
Related Topics
Altered Mental Status & DeliriumGuillain-Barré SyndromeHeadache & MigraineHeat StrokeIntracerebral HemorrhageMyasthenic Crisis