What is the management approach for Posterior Reversible Encephalopathy Syndrome (PRES)?

Management of Posterior Reversible Encephalopathy Syndrome (PRES)

Immediately discontinue any offending agent (immunosuppressants, chemotherapy, or other triggering medications) and implement stringent blood pressure control with gradual reduction to avoid cerebral hypoperfusion—these are the two cornerstone interventions for PRES management. 1

Step 1: Identify and Remove Triggering Factors

• Discontinue the causative agent immediately upon suspicion of PRES, including anticancer therapy, immunosuppressants (particularly cyclosporine), or other implicated medications 1, 2, 3
• Common triggers include pre-existing hypertension, renal impairment, autoimmune diseases (especially systemic lupus erythematosus), high-dose chemotherapy, stem-cell or solid organ transplantation, and immunosuppression 1, 2
• For immunotherapy-related PRES, follow Society for Immunotherapy of Cancer guidelines for immune-related adverse events 1

Clinical pitfall: Failure to identify and stop the triggering agent leads to prolonged illness and increased risk of permanent brain injury 1. Even in normotensive patients with active autoimmune disease, PRES can occur, so do not rely solely on blood pressure elevation for diagnosis 2.

Step 2: Blood Pressure Management

• Implement very stringent blood pressure control as the primary therapeutic intervention, targeting gradual reduction rather than rapid normalization to prevent cerebral hypoperfusion 1, 4, 3
• The European Society of Cardiology emphasizes gradual reduction when blood pressure is markedly elevated and cerebral autoregulation has failed 1
• Monitor blood pressure frequently during the acute phase to maintain safe ranges 1

Important nuance: While hypertension is typically present, approximately one-third of PRES cases occur without severe hypertension, particularly in patients with active autoimmune disease 2. The goal is controlled reduction, not aggressive lowering, as overly rapid correction can worsen cerebral ischemia 3.

Step 3: Seizure Management

• Administer antiepileptic treatment for patients who develop seizures, which are present in the majority of PRES cases 1, 4, 2
• Consider prophylactic anticonvulsants in high-risk patients with significant neurological deficits 1
• Use benzodiazepines for symptomatic treatment of acute seizures, but monitor carefully to avoid CNS depression 1, 5

Step 4: Supportive Care Measures

• Position patients with head elevated at 30 degrees to reduce intracranial pressure 6
• Implement aspiration precautions and provide intravenous hydration for patients with altered consciousness 1
• Avoid medications that cause CNS depression in patients with encephalopathy 1
• Correct electrolyte imbalances if present and monitor renal function closely 1

For severe cases (Grade III-IV encephalopathy): Patients with declining consciousness require urgent ICU assessment for airway protection and ventilatory support 6. Consider intubation for airway protection in patients with severe somnolence or coma 6.

Step 5: Adjunctive Therapies for Cerebral Edema

• Administer dexamethasone and furosemide for reduction of cerebral edema in patients with significant mass effect or clinical deterioration 5
• Midazolam may be used for seizure control and sedation when needed 5

Diagnostic Confirmation

• MRI is the gold standard, showing increased signal intensity on T2-weighted or FLAIR imaging in posterior brain regions (bilateral parietal-occipital lobes), predominantly affecting white matter 1
• CT scan can be useful to exclude intracranial hemorrhage when MRI is not immediately feasible 1
• Obtain neuroimaging within 24 hours and ensure access to neurophysiology (EEG) for patients with seizures 6

Atypical presentations: Approximately 30% of cases show involvement of anterior brain regions or brainstem, and some cases demonstrate coexisting ischemia or hemorrhage 4. Do not exclude PRES based solely on atypical imaging distribution.

Monitoring and Follow-Up

• Perform frequent neurological assessments (every 4-6 hours) until complete resolution 7
• Obtain repeat neuroimaging to document resolution of vasogenic edema 3
• Most patients experience complete spontaneous remission without sequelae, typically within 5-14 days after trigger removal 5, 8

Special Considerations by Underlying Cause

For methotrexate-induced PRES: Leukoencephalopathy typically develops within 5-14 days after intrathecal administration and resolves within one week with supportive management 5

For cyclosporine-related PRES: Immediate cessation of the calcineurin inhibitor is essential, as continuation leads to risk of cerebral infarction 2

For SLE-associated PRES: Treatment with IV cyclophosphamide or plasmapheresis for active lupus disease, in addition to standard PRES management, leads to resolution of both radiologic and neurologic findings 2

Prognosis

• Complete recovery occurs in most cases when early detection and prompt management are implemented 1, 8
• Delayed diagnosis and improper management may result in permanent brain injury, including cerebral infarction 5, 2
• Residual neurological sequelae occur in a minority of patients, particularly when treatment is delayed 4

Critical success factor: Early detection through high clinical suspicion and prompt neuroimaging, combined with immediate removal of triggering agents and controlled blood pressure reduction, are key determinants of rapid recovery and excellent outcomes 8.