Unusual evolution of posterior reversible encephalopathy syndrome (PRES) one year after liver transplantation

Abstract

Thirteen months after liver transplantation for endstage liver disease due to heptatitis C, a 65-year-old patient without a previous history of neurological problems suddenly developed left hemianopsia with hemiparesis of the left upper limb. On admission the patient was conscious, afebrile with a blood pressure of 170/90 mmHg (which returned to baseline a few hours later). Cyclosporine level was 260 ng/mL. Computerized tomography revealed right temporal hypodensities, and brain magnetic resonance imaging showed a right temporal hyperintense lesion on FLAIR and T2-weighted images (Fig. 1). The lumbal puncture was unremarkable. The clinical evolution was spontaneously resolutive in a few days, and the patient was allowed to be discharged on day 24 of hospitalization. Three days later the patient was readmitted due to a sudden onset of a tonic rigidity, confusion, and blurred vision. The patient was disoriented in time and space, and his systolic blood pressure peaked to 207 mmHg. The clinical examination again revealed a slight paresis of the left upper limb. In spite of a reduction of the doses, the cyclosporine levels remained elevated. A follow-up magnetic resonance imaging (MRI) on admission revealed a significant progression of the right parieto-temporal T2-hypersignal with local mass-effect (Fig. 2). An electroencephalography performed on the same day found a right temporal irritative focus. During the course of hospitalization a partial epilepsy was observed with tonic-clonical movements of the left upper limb with secondary temporary paresis. A therapy with 400 mg/d gabapentin was started. The query of an embolic etiology remained negative. A stereotactic biopsy of the right parieto-temporal lesion found signs neither of an infection nor of a neoplastic process, and it showed an unspecific reactive aspect with numerous astrocytes without inflammatory cells or signs of fresh necrosis. The immunohistochemical examination revealed a reactive gliosis with perivascular macrophages (Fig. 3). In consideration of possible cyclosporine toxicity, the immunosuppressive therapy was switched to sirolimus. The neurological deficit disappeared completely within 6 to 8 days. Ten days after switching the therapy (20 days after the last follow-up) a new MRI control showed no progression of the principal lesion. Under sirolimus the patient developed a thrombocytopenia and was then placed on tacrolimus; since then there has been no recurrence of the neurological manifestations. Posterior reversible encephalopathy syndrome (PRES) is a radiological/clinical entity.1 Clinically, it includes headache, vomiting, confusion, altered mental functioning, hemiplegia or hemiparesis, seizure,2 cortical blindness,3 and other visual disturbances such as homonymous hemianopsia, blurred vision, and visual neglect. Under cyclosporine patients frequently (in about 53% of reported cases) present with arterial hypertension. The magnetic resonance radiological findings4,5 typically show an abnormal high signal in the subcortical white matter, mainly in the occipitalparietal regions.6,7 PRES can derive from several conditions, but it is a significant complication of therapy with calcineurin inhibitors. Among 50 cases published in the literature,8 31 occurred in liver, 8 in renal, 6 in lung, and 5 in heart recipients with a median time of onset of 28 days. In most cases PRES is reversible on removal or reduction in dosage of the offending agent (clinical improvement after 5 to 30 days and radiological improvement after a median delay of 21 days). The case we presented is a complete radiological/ clinical illustration of PRES. Unusual were the long delay between liver transplantation and the onset of the first symptoms (13 months) and the spontaneous clinical resolution during the first hospitalization in spite of progression of the radiological findings. A case of PRES Abbreviations: MRI, magnetic resonance imaging; PRES, posterior reversible encephalopathy syndrome. From the Department of Clinical Pharmacology, and Department of Pathology, Inselspital, Bern, Switzerland. Address reprint requests to Jean-Francois Dufour, Institute for Clinical Pharmacology, University of Bern, 35 Murtenstrasse, 3010 Bern, Switzerland. Telephone: 41 31-632-31-91; FAX: 41 31-632-49-97; E-mail: jf.dufour@ikp.unibe.ch Copyright © 2005 by the American Association for the Study of Liver Diseases Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/lt.20425