Posterior reversible encephalopathy syndrome

Background

• Clinical-radiographic syndrome characterized by headache, seizures, visual disturbances, and altered mental status with vasogenic edema predominantly in posterior brain regions
• Previously known as reversible posterior leukoencephalopathy syndrome (RPLS)
• Usually reversible with prompt treatment of underlying cause, but can be irreversible if untreated (cytotoxic edema, hemorrhage)
• Pathophysiology (two proposed mechanisms):
  • Hypertensive theory: severe hypertension exceeds cerebral autoregulation → hyperperfusion → vasogenic edema (posterior brain more vulnerable due to less sympathetic innervation)
  • Endothelial dysfunction theory: direct endothelial injury from toxins, medications, or autoimmune activation → blood-brain barrier disruption → vasogenic edema

Common Causes

• Hypertensive emergency (most common; including eclampsia/preeclampsia)
• Immunosuppressive/cytotoxic medications: cyclosporine, tacrolimus, cisplatin, bevacizumab, methotrexate
• Autoimmune conditions: SLE, thrombotic thrombocytopenic purpura, hemolytic uremic syndrome
• Renal failure (especially with fluid overload)
• Eclampsia/preeclampsia (most common cause in young women)
• Sepsis, shock, organ transplantation

Clinical Features

• Headache (most common presenting symptom)
• Seizures (60-75% of cases; may be the presenting feature)
• Visual disturbances: blurred vision, cortical blindness, visual neglect, homonymous hemianopia
• Altered mental status: confusion, obtundation, decreased alertness
• Focal neurologic deficits (less common but can occur)
• Hypertension (present in 70-80% but PRES can occur with normal BP in 20-30% of cases)
• Nausea, vomiting

Differential Diagnosis

• Ischemic stroke (especially posterior circulation)
• Cerebral venous sinus thrombosis
• Encephalitis
• CNS vasculitis
• Toxic leukoencephalopathy
• Demyelinating disease (ADEM)
• Subarachnoid hemorrhage
• Status epilepticus
• CNS metastatic disease

Evaluation

MRI (Diagnostic Study of Choice)

• MRI with FLAIR and DWI is the gold standard
• Classic pattern: bilateral, symmetric vasogenic edema in parieto-occipital white matter
• FLAIR/T2: hyperintense signal in affected regions
• DWI/ADC: elevated ADC (vasogenic edema) vs restricted diffusion (cytotoxic edema → worse prognosis)
• Atypical patterns (30-40%): frontal lobe, temporal lobe, cerebellum, brainstem, unilateral, hemorrhagic
• Hemorrhage occurs in 5-15% of cases (petechial or frank hemorrhage)

CT Head

• May show hypodensity in posterior regions but sensitivity is low
• Useful to rule out hemorrhage or ischemic stroke initially
• If MRI unavailable, CT findings may be suggestive but are often subtle

Labs

• BMP (renal function, electrolytes)
• CBC with smear (evaluate for TMA — schistocytes if TTP/HUS)
• LFTs, LDH, haptoglobin (hemolysis workup)
• Urinalysis (proteinuria if eclampsia)
• Magnesium level
• Drug levels (cyclosporine, tacrolimus)
• Pregnancy test in reproductive-age women

Management

Blood Pressure Control (If Hypertensive)

• Gradual reduction — target 25% reduction in MAP in first few hours
• Avoid precipitous drops (risk of posterior circulation ischemia)
• Preferred agents:
  • Nicardipine infusion 5-15 mg/hr (easily titratable)
  • Labetalol 10-20 mg IV q10-20min
• If eclampsia: magnesium sulfate is first-line for seizure prevention (see eclampsia)

Seizure Management

• Benzodiazepines for acute seizures (lorazepam 2-4 mg IV)
• AEDs for ongoing seizure prophylaxis (levetiracetam preferred)
• If eclampsia: magnesium sulfate (primary treatment)
• Most seizures resolve with BP control and treatment of underlying cause

Treat Underlying Cause

• Discontinue or reduce offending medication (cyclosporine, tacrolimus, chemotherapy)
• Delivery for eclampsia/preeclampsia with severe features
• Treat sepsis, renal failure, autoimmune flare as indicated
• Dialysis for uremic patients

Monitoring

• ICU admission for most patients
• Continuous BP monitoring (arterial line preferred)
• Serial neurologic exams
• Repeat MRI at 1-2 weeks to confirm resolution of edema

Prognosis

• Majority of cases are fully reversible within days to weeks with appropriate treatment
• Risk factors for poor outcome:
  • Restricted diffusion on DWI (cytotoxic edema → infarction)
  • Hemorrhage
  • Delayed diagnosis and treatment
  • Untreated PRES can progress to permanent brain injury

Disposition

• Admit to ICU for BP monitoring, seizure management, and neurologic observation
• Neurology consultation
• Nephrology if drug-related (immunosuppressant dose adjustment)
• OB consultation if eclampsia/preeclampsia

See Also

• Eclampsia
• Preeclampsia
• Hypertensive emergency
• Status epilepticus
• Ischemic stroke
• Cerebral venous sinus thrombosis

References

• Fugate JE, Rabinstein AA. Posterior reversible encephalopathy syndrome: clinical and radiological manifestations, pathophysiology, and outstanding questions. Lancet Neurol. 2015;14(9):914-925. PMID 26184985
• Bartynski WS. Posterior reversible encephalopathy syndrome, part 2: controversies surrounding pathophysiology of vasogenic edema. AJNR Am J Neuroradiol. 2008;29(6):1043-1049. PMID 18403560
• Hinchey J, et al. A reversible posterior leukoencephalopathy syndrome. N Engl J Med. 1996;334(8):494-500. PMID 8559202
• Liman TG, et al. Clinical and radiological differences in posterior reversible encephalopathy syndrome between patients with preeclampsia-eclampsia and other predisposing diseases. Eur J Neurol. 2012;19(7):935-943. PMID 22248339