A Rush of Blood to the Head: Tacrolimus Related Reversible Cerebral Vasoconstriction Syndrome After Pediatric Heart Transplantation

Abstract

<h3>Introduction</h3> Posterior reversible encephalopathy syndrome (PRES) is a known complication associated with calcineurin inhibitor (CNI) therapy after solid organ transplant. A pathophysiologically related but clinically distinct diagnosis, reversible cerebral vasoconstriction syndrome (RCVS), is rarely reported in pediatric patients. RCVS is characterized by segmental constrictions of the cerebral arteries versus edema seen in PRES. Here we present RCVS related to tacrolimus in two adolescents after heart transplantation. <h3>Case Report</h3> A 10-year-old female with a history of tricuspid atresia status post Hemi-Fontan palliation and progressive ventricular dysfunction underwent heart transplantation. Her post-transplant course was complicated by graft diastolic dysfunction and early donor specific antibody production, treated with intravenous immunoglobulin and rituximab. Her immunosuppression was prednisone, tacrolimus, and mycophenolate mofetil. Seven weeks after transplantation she developed a thunderclap headache, acute severe hypertension and mental status changes and was found to have a multifocal subarachnoid hemorrhage (SAH) without identifiable aneurysm, most consistent with RCVS. Her tacrolimus trough was therapeutic. She was transitioned from tacrolimus to cyclosporine and symptoms resolved after 2 days. She successfully transitioned back to tacrolimus at one year post transplant without RCVS recurrence. A 14-year-old-male with a history of dilated cardiomyopathy status post left ventricular assist device underwent heart transplantation. His immunosuppression was prednisone, tacrolimus, and mycophenolate mofetil. His post-transplant course was uncomplicated until one week after transplant he developed a thunderclap headache and acute severe hypertension, and was found to have a SAH, with mild multisegmental narrowing of the circle of Willis, consistent with RCVS. His tacrolimus trough was subtherapeutic. He was transitioned from tacrolimus to cyclosporine with no recurrence of RCVS symptoms. <h3>Summary</h3> This is the first reported case series of tacrolimus related RCVS in pediatric heart transplant patients without elevated tacrolimus levels. CNI related RCVS should be considered if acute SAH occurs and may be managed with switching CNI to another immunosuppression agent.