What are the causes of Posterior Reversible Encephalopathy Syndrome (PRES)?

Causes of Posterior Reversible Encephalopathy Syndrome (PRES)

Posterior Reversible Encephalopathy Syndrome (PRES) is primarily caused by hypertension, immunosuppressive drugs, chemotherapy agents, autoimmune disorders, renal impairment, and pre-eclampsia/eclampsia. 1, 2

Major Etiological Factors

Hypertension-Related Causes

• Severe hypertension/hypertensive emergency - Most common cause leading to disruption of cerebral autoregulation 1
• Abrupt blood pressure changes - The rate of BP increase appears more important than absolute BP value 1
• Pre-existing hypertension - Especially with poor control 1

Medication-Related Causes

• Immunosuppressive drugs:
  • Cyclosporine - Particularly high-risk 2, 3
  • Tacrolimus - Associated with PRES and potential hemorrhagic complications 4
• Chemotherapeutic agents:
  • High-dose antineoplastic therapy 1
  • Anti-angiogenic therapy 1

Transplantation-Related Causes

• Allogeneic stem-cell transplantation 1
• Solid organ transplantation with associated immunosuppression 1, 4

Other Medical Conditions

• Renal impairment/failure - Common contributing factor 1, 5
• Autoimmune diseases - Various connective tissue disorders 1, 3
• Pre-eclampsia/eclampsia - Well-established cause in pregnant women 6, 5

Pathophysiological Mechanisms

Two main hypotheses explain PRES development 7:

1. Hypertension-induced autoregulatory failure:

   • Severe hypertension exceeds cerebral autoregulation limits
   • Results in breakthrough vasogenic edema
   • Disruption of blood-brain barrier due to endothelial injury 1

2. Vasoconstriction and hypoperfusion:

   • Hypertension triggers cerebral autoregulatory vasoconstriction
   • Leads to ischemia and subsequent brain edema

Clinical Presentation

PRES typically presents with:

• Acute neurological deficits
• Altered consciousness (from impaired attention to confusion)
• Visual disturbances/blindness
• Headaches
• Seizures 1, 2

Diagnostic Features

• MRI findings: T2-weighted hyperintensities showing vasogenic edema
• Location: Predominantly in bilateral parieto-occipital lobes
• Distribution: White matter more affected than gray matter 1, 2

Risk Factors for Developing PRES

• Pre-existing hypertension
• Renal impairment
• Autoimmune diseases
• High-dose antineoplastic therapy
• Immunosuppression
• ApoE ε4 genetic status (may influence susceptibility) 1

Management Considerations

• Immediate identification and removal of triggering factors
• Discontinuation of offending medications
• Very stringent blood pressure control
• Antiepileptic treatment for seizures 2

Prognosis

PRES is typically reversible with appropriate management within 2 weeks, though delayed diagnosis and treatment may lead to permanent neurological sequelae 2, 6.

Common Pitfalls to Avoid

• Delayed recognition - Can lead to permanent neurological damage
• Failure to identify and remove triggering agents - Essential for recovery
• Overly aggressive blood pressure reduction - May cause cerebral hypoperfusion
• Misdiagnosis - PRES can mimic stroke, encephalitis, or other neurological conditions

Early recognition of risk factors and prompt management of underlying causes are crucial for favorable outcomes in patients with PRES.