Posterior Reversible Encephalopathy Syndrome (PRES) after Pediatric Heart Transplantation: A Multicenter Study

Purpose PRES is an uncommon complication of organ transplantation. Little is known about its clinical course and risk factors. We sought to examine the natural history and risk factors for PRES in pediatric heart transplant (HTx) recipients. Methods 14-center international retrospective study of 46 pediatric PRES cases between 2000-2018, compared with 1372 HTx recipients without PRES between 2000-2018. Demographic and clinical data were entered into a central database. PRES diagnosis was based on a combination of seizures, headache, altered mental status or focal neurological deficits, and required confirmation, either by MRI or resolution of neurological symptoms after CNI withdrawal. Factors associated with PRES were identified by Cox Proportional Hazard multivariable analysis. Results Median onset of symptoms was 16 days (R, 2-2468 d) after HTx; 23 (50%) developed PRES in the first 2 weeks, 32 (70%) in the first month, and 40 (87%) within the first year after HTx. Symptoms at presentation included seizures (40/46, 87%), altered mental status (27/46, 59%), headache (18/46, 39%), focal neurological deficits (16/46), and lasted for median of 4 days (R 1-1772d), with almost all recipients (44/46, 96%) making a full recovery. MRI was obtained in 43/46, showing a vasogenic pattern of edema characteristic of PRES in 37 recipients (80%). Recipients with PRES tended to be older (9.1 y vs 5.9 y, p=0.06). Hypertension (SBP>95%ile) was present in 40/44 (91%) recipients with PRES at presentation, with severe hypertension (SBP>99%ile plus 5mmHG) in 37 (85%). Though all cases occurred in the setting of CNI use (TAC 40, CSA 6), levels were supratherapeutic in only 13/42 (31%). Cox analysis revealed a 5.3x increased hazard for PRES with Glenn (CI 1.54,18.01; p=0.008) and a 3.8x increased hazard with Fontan (1.08,13.00; p=0.038), while age, underlying cardiac diagnosis, BMI, ischemic time and type of CNI did not appear to contribute significantly. Conclusion 2/3 of pediatric PRES cases occurred in the first month after HTx with seizures as the most common presenting symptom. An overwhelming majority of patients were severely hypertensive, whereas less than a third had supratherapeutic CNI levels. Almost all recipients recovered fully within days. Recipients with pre-existing Glenn or Fontan have a higher rate of developing PRES after HTx.