UMEM Educational Pearls

 

Emergency physicians are familiar with posterior reversible [leuko]encephalopathy syndrome as an entity associated with untreated hypertension. It also happens to be a well-documented entity amongst solid organ transplant patients.  

While the exact pathophysiology remains unclear, PRES is characterized by posterior subcortical vasogenic edema due to blood-brain barrier disruption, usually in the setting of elevated blood pressure with loss of cerebral autoregulation and/or endothelial dysfunction.

The immunosuppressants used in this population, namely calcineurin inhibitors (CNI) such as tacrolimus and cyclosporine, are thought to contribute most to this endothelial dysfunction and development of PRES in transplant patients, although high-dose corticosteroids, ischemia-reperfusion injury during surgery, and antibiotics have also been implicated. 

Presentation of PRES post-transplant:

Clinical symptoms:

• Seizures (75-85%)
• AMS - confusion/somnolence (30-40%)
• Headache (25-50%)
• Vision disturbance (20-40%)

Time course:

• Within weeks to a year posttransplant, rarely after a year
• Rapid onset once it starts, can develop over hours to days

Diagnostics:

• Labs nonspecific, although supratherapeutic CNI levels are often associated with:
  • Acute renal injury
  • Hyperchloremic metabolic acidosis
  • Hyperkalemia
  • Hypomagnesemia
  • Hypercalciuria
• Thoughts on checking FK506 (tacrolimus) levels
  • For transplant patients, usually advise only checking troughs (~12 hrs after last dose)
  • A low random level may rule out CNI toxicity but not PRES
  • A high random level isn't really helpful
• MRI is diagnostic modality of choice >> subcortical edema, usually bilateral, symmetric, in parieto-occipital regions

Management:

1. Stabilization via supportive care – seizure, cerebral edema, BP management as applicable, etc.
2. Withdrawal/holding of offending agent – will require consultation with transplant physician and pharmacist usually by inpatient team
   • Mixed data re: use of CYP-inducers to lower CNI levels in CNI toxicity

Bottom Line: 

Patients with a history of solid organ transplant are at risk for PRES. While ED stabilization of these patients remains the same, recognition of PRES as a potential etiology for a transplant patient's presentation is crucial to proceed with important testing and necessary changes to their immunosuppressive regimen. 

References

1. Jeelani H, Sharma A, Halawa AM. Posterior Reversible Encephalopathy Syndrome in Organ Transplantation. Exp Clin Transplant. 2022 Jul;20(7):642-648. doi: 10.6002/ect.2021.0268. PMID: 35924741.
2. Farouk SS, Rein JL. The Many Faces of Calcineurin Inhibitor Toxicity-What the FK? Adv Chronic Kidney Dis. 2020 Jan;27(1):56-66. doi: 10.1053/j.ackd.2019.08.006. PMID: 32147003; PMCID: PMC7080294.
3. Hinchey J, Chaves C, Appignani B, Breen J, Pao L, Wang A, Pessin MS, Lamy C, Mas JL, Caplan LR. A reversible posterior leukoencephalopathy syndrome. N Engl J Med. 1996 Feb 22;334(8):494-500. doi: 10.1056/NEJM199602223340803. PMID: 8559202.