Delirium in a Renal Transplant Recipient Associated with BK Virus in the Cerebrospinal Fluid

We present a case of delirium in a renal transplant recipient with BK virus in the cerebrospinal fluid. A 56-year-old man underwent renal transplantation in 1983 for diabetic nephropathy and was maintained on prednisone 7.5 mg per day and mycophenolate mofetil (MMF) 750 mg daily in divided doses. He was hospitalized on May 25, 2003 with congestive heart failure, oligoanuric renal failure, hypotension, and fever. Subsequent therapies included mechanical ventilation, hemodialysis, angioplasty and stenting of a common iliac artery stenosis located proximal to the transplant artery, empiric antibiotics, cessation of the MMF, and hydrocortisone 50 mg every 8 hours. By June 3, 2003, the patient was extubated and afebrile. The steroid therapy was changed to prednisone 30 mg daily, and the MMF was restarted. Subsequently, the patient developed progressive, severe lethargy and confusion. Magnetic resonance imaging of the brain demonstrated bilateral frontal and temporal encephalomalacia and gliosis. The imaging study was suggestive of progressive multifocal leukoencephalopathy (PML). Previous records revealed the patient had been evaluated on April 18, 2003 for rising creatinine at which time azathioprine was changed to MMF. Urine sent that day eventually tested positive for BK virus. Lumbar puncture yielded cerebrospinal fluid that tested positive for BK virus deoxyribonucleic acid using a polymerase chain reaction assay. No other infectious agents, including JC virus, were identified in the cerebrospinal fluid (Table 1). MMF was stopped, prednisone was tapered, and leflunomide was started. The patient recovered from the delirium and renal failure, with normalization of renal function on leflunomide 40 mg daily and prednisone 7.5 mg daily (Table 1).TABLE 1: Laboratory dataThis case demonstrates a possible association between the presence of BK virus in the cerebrospinal fluid and this patient’s neurologic deterioration, which resembled an illness similar to PML clinically as well as on imaging studies. Reactivation of BK virus is associated with various complications in kidney transplant patients, typically chronic allograft nephropathy or obstruction (1). The diagnosis of PML typically requires brain biopsy; however, imaging studies and cerebrospinal fluid analysis may allow a noninvasive presumptive diagnosis (2,3). A few studies have documented evi-dence of BK virus in the cerebrospinal fluid of patients with neurologic symptoms, but to our knowledge these reports are uncommon and this presentation has not been described in a renal transplant patient (4C). The patient’s full recovery after the immunosuppression was changed to leflunomide is of particular interest, as leflunomide is an effective immunosuppressant and possesses unique antiviral properties (5). J. Kevin Hix William E. Braun Department of Nephrology and Hypertension The Cleveland Clinic Foundation Cleveland, Ohio Carlos M.Isada Department of Infectious Disease The Cleveland Clinic Foundation Cleveland, Ohio