Medications That Cause Posterior Reversible Encephalopathy Syndrome (PRES)
The medications most commonly implicated in causing PRES are antineoplastic agents (particularly high-dose chemotherapy and VEGF inhibitors like bevacizumab), immunosuppressants (especially ciclosporin and tacrolimus), and glucocorticoids. 1, 2
Primary Drug Categories
Antineoplastic Agents
The chemotherapy drugs most frequently associated with PRES include:
- High-dose antineoplastic therapy - particularly in the context of stem cell transplantation 1
- VEGF inhibitors - bevacizumab is specifically highlighted as a common culprit 3, 4
- Ifosfamide - explicitly mentioned in treatment guidelines 1
- Cytarabine, platinum agents, gemcitabine, topotecan, paclitaxel 5, 4
- Targeted therapies - including tyrosine kinase inhibitors 6
- Immunotherapies - anti-CD19 CAR T-cell therapies and checkpoint inhibitors like atezolizumab 7, 6
Immunosuppressants
Ciclosporin (cyclosporine) is the prototypical immunosuppressant causing PRES and is specifically cited in guidelines 1. This class is particularly relevant in:
- Solid organ transplantation
- Allogeneic stem cell transplantation
- Autoimmune disease management
Glucocorticoids
High-dose corticosteroid therapy is identified as a significant risk factor 2.
Clinical Context and Risk Factors
PRES occurs most commonly in patients with:
- Pre-existing arterial hypertension 1
- Renal impairment 1
- Autoimmune diseases 1
- Cancer - particularly those receiving high-dose chemotherapy 2, 4
- Post-transplantation status (organ or stem cell) 1, 2
Important caveat: PRES is 24.77% more likely to occur in females than males 2, which should heighten clinical suspicion in women receiving these medications.
Mechanism and Pathophysiology
The syndrome results from endothelial dysfunction and blood-brain barrier disruption due to abrupt blood pressure changes, leading to vasogenic edema predominantly affecting bilateral parietal-occipital lobes 1. The white matter is affected more than grey matter 1.
Critical Management Points
When PRES is suspected, immediately discontinue the offending anticancer therapy or immunosuppressant and implement very stringent blood pressure control 1. This is the cornerstone of management and directly impacts morbidity and mortality.
Additional management includes:
- Antiepileptic treatment if seizures occur 1
- Correction of electrolyte imbalances 1
- Symptomatic treatment (e.g., benzodiazepines for seizures) 1
Prognosis: PRES is usually reversible with appropriate supportive management within 2 weeks, with spontaneous full remission in almost all cases without sequelae 1. However, reported mortality ranges from 10-19%, and 40-44% may experience persistent neurological deficits 8, making early recognition critical.
Diagnostic Considerations
MRI is far more sensitive than CT - 37% of patients with both imaging modalities had normal CT concurrent with PRES visible on MRI 4. T2-weighted MRI demonstrates characteristic hyperintensities in bilateral parietal-occipital regions 1.
Rechallenge Considerations
Reintroduction of the prior anticancer therapy must be decided on an individual basis 1. However, successful chemotherapy rechallenge without recurrent PRES was achieved in 41% of cancer patients in one series 4, suggesting it may be possible in selected cases after careful risk-benefit assessment.