Neurological symptoms in a post-transplant patient: a cautionary tale

Abstract

Primary central nervous system (CNS) post-transplant lymphoproliferative disorder (PTLD) is a rare complication of organ transplantation affecting about 1 % of transplant recipients [1, 2]. The median time from transplantation to diagnosis ranges from 12.6 months to 52 months [1, 3]. We herein describe an unusual case of Epstein barr virus (EBV) positive primary CNS PTLD, presenting after a very long delay of 12 years after renal transplant. A 50-year-old woman presented with a 12-week history of gradual onset, constant, throbbing generalised headache of moderate intensity. She also reported progressive vertigo, difficulty in walking, nausea and vomiting. She was a nonsmoker and denied use of alcohol or other illicit drugs. Twelve years previously, she had a renal transplant for endstage renal disease secondary to chronic pyelonephritis. Her routine medications included cyclosporin 50 mg twice daily, azathioprine 100 mg once daily and prednisolone 5 mg once daily. Clinical examination demonstrated broken pursuit eye movements, mild appendicular ataxia and right extensor plantar response. She walked with a slightly broadbased ataxic gait. Systemic examination was unremarkable. Laboratory studies including inflammatory markers and autoimmune screen were unremarkable. Magnetic resonance imaging (MRI) of the brain with gadolinium showed scattered nodular enhancing lesions involving bilateral cerebellar hemispheres, splenium of corpus callosum and right peritrigonal white matter (Fig. 1). Cerebrospinal fluid (CSF) analysis revealed a white cell count of 7 (100 % lymphocytes), protein 0.39 g/L and normal glucose. Stains and culture results for bacteria, mycobacteria and fungi were negative. However, CSF polymerase chain reaction for EBV was positive at 1,000 copies/ml; BK and JC virus were negative. Computed tomography scan of chest, abdomen, and pelvis was unremarkable. A biopsy of the posterior fossa lesion showed a polymorphic population of lymphoid cells, in keeping with polymorphic type PTLD (Fig. 2). Azathioprine was discontinued and cyclosporin was initially reduced to 25 mg twice daily. She was also treated with 4 cycles of methotrexate (3000 mg/m on day 1) and cytarabine (1600 mg/m every 12 h on day 2 and 3) at 3 weekly intervals, with complete clinical and radiological response. The dose of cytarabine was reduced by 20 percent from the standard dose (2000 mg/m), given the reduced baseline creatinine clearance rate of 53 mL/min/ 1.73 m. She is currently on prednisolone 5 mg daily and cyclosporin 35 mg twice daily. There has been no recurrence to date over a period of 18 months. She also retains good renal graft function. Post-transplant lymphoproliferative disorders represent a spectrum ranging from EBV-driven infectious mononucleosis type polyclonal proliferations, to EBV positive or S. K. Chhetri R. Dayanandan H. C. A. Emsley (&) Department of Neurology, Royal Preston Hospital, Preston PR2 9HT, UK e-mail: h.emsley@liv.ac.uk; hedley.emsley@manchester.ac.uk