S2489 Tacrolimus-Induced Posterior Reversible Encephalopathy Syndrome With Seizures: A Rare Clinical Combination

Abstract

INTRODUCTION: Tacrolimus, a calcineurin inhibitor, is a backbone of many liver transplant anti-rejection regimens. Posterior Reversible Encephalopathy Syndrome (PRES) is a rare clinical entity, with acute neurological symptoms and a classic MRI pattern. This case presents a recent liver transplant patient who developed PRES while on tacrolimus (TAC). CASE DESCRIPTION/METHODS: A 47-year-old woman s/p deceased donor liver transplant presented with 2 generalized tonic-clonic seizures. Her OLT 7 weeks prior for NASH with MELDNa 28 required retransplant day 2 for primary nonfunction. Immunosuppression included Basiliximab day 1 and day 4 induction, Mycophenolate Mofetil 1gm BID, Prednisone taper, and TAC with goal levels maintained 8–10 ng/mL. One week before presentation, she had progressive headaches, unsteady gait, hypertension, and hyperglycemia. Medications included unchanged doses of TAC 3 mg BID, prednisone 15 mg daily, TMP/SMX, 81mg ASA, and 20 mg omeprazole. She had 2 witnessed brief tonic- clonic seizures, which responded to lorazepam and leviteracetam, and was empirically treated with antimicrobials. Neurology evaluation revealed BP 176/86 mmHg and a postictal state without focal findings, and an encephalopathic EEG without seizure. CT head was negative for hemorrhage. Labs earlier that day showed normal CBC, INR, chemistry panel including renal and liver function except a glucose of 465mg/dL. Negative studies included: full respiratory viral panel including COVID-19, serum cryptococcus antigen and CMV PCR, UA, a LP with normal opening pressure and cell counts, and broad encephalitis PCR panels. TAC trough was 13.7 ng/mL. MRI revealed patchy focal T2-hyperintensities in bilateral cerebellar hemispheres and occipital lobes, consistent with PRES. DISCUSSION: PRES occurs in <1% of liver transplants, characterized by a typical brain edema pattern. Hypertension, encephalopathy, and seizures are frequent often without a seizure history. Of the few reports associating PRES with TAC, trough levels were not supratherapeutic. Presentation ranges days to months after drug initiation, with a more delayed PRES from TAC than cyclosporine at 26 vs. 12 days. MRI findings do not correlate with severity. The pathophysiology is unknown but may include blood-brain barrier damage and abnormal vascular autoregulation. Early recognition is key as management includes TAC discontinuation and aggressive blood pressure management. Most patients, including ours, have no major neurological sequelae if diagnosed and treated quickly.Figure 1.: MRI FLAIR images of Tacrolimus associated PRES. Multiple relatively symmetric patchy juxtacortical white matter abnormality in occipital lobes (A). Multiple patchy regions of abnormal focal T2-hyperintensity in the bilateral cerebellar hemispheres, right thalamus, centrum semiovale bilaterally (B). No evidence of acute infarction, hemorrhage, mass effect, hydrocephalus, vascular abnormality, nor any pathologic intracranial enhancement.