BK virus encephalitis without concurrent hemorrhagic cystitis in an allogeneic hematopoietic stem cell transplant recipient
A 62-year-old woman with relapsed diffuse large B cell lymphoma (DLBCL) after autologous HSCT received an allogeneic peripheral blood stem cell transplantation from a sex-mismatched and ABO- and human leukocyte antigen-matched related donor after conditioning with fludarabine (30 mg/m2/day for 6 days) and intravenous busulfan (0.8 mg/kg every 6 hr for 2 days). She had been diagnosed with DLBCL 2 years previously, and treated with autologous HSCT as salvage therapy after the first relapse of the disease. Graft versus host disease (GVHD) prophylaxis consisted of 3 mg/kg/day of intravenous cyclosporine A (CsA) and intravenous methotrexate (15 mg/m2 on day 1 and 10 mg/m2 on days 3, 6, and 11). This therapy prevented development of acute GVHD. The serum level of CsA was adjusted to maintain a target trough serum level between 200 and 300 ng/mL. No hemorrhagic cystitis occurred during the course of immunosuppression.\nOn post-transplant day 25, while the patient was still receiving CsA, memory loss, disorientation to time and place, and slurred speech were observed. Diffusion magnetic resonance imaging (MRI) showed no evidence of diffusion restriction, and only non-specific findings suggesting a subacute or chronic lacunar infarction at the right basal ganglia were found. The patient's disorientation recovered transiently over the next 24 hrs, although her neurological symptoms became progressively worse during the next 48 hrs. A repeat contrast-enhanced MRI performed 5 days after the onset of these symptoms showed no abnormal findings, with the exception of mild leukoaraiosis in the bilateral cerebral white matter, basal ganglia, and pons. A sleep and waking electroencephalogram (EEG) showed a slow, continuous generalized theta rhythm suggesting the presence of diffuse cerebral dysfunction. Based on this finding, CsA was switched to mycophenolate mofetil to exclude the possiblity of reversible posterior leukoencephalopathy syndrome, neurotoxicity caused by the immunosuppressive agent. Analysis of cerebrospinal fluid (CSF) showed normal glucose (71 mg/dL) and protein (19.5 mg/dL) levels and no evidence of pleocytosis. Microbiological examination of the CSF showed negative results for bacteria, mycobacteria, toxoplasma, herpes simplex virus type (HSV) I and II, cytomegalovirus (CMV), enterovirus, varicella-zoster virus, Epstein-Barr virus, and cryptococcus. Examination for BKV or John Cunningham (JC) viruses was not performed because there was no evidence of BKV encephalitis or progressive multifocal leukoencephalopathy on the MRI findings. The mental state of the patient deteriorated progressively with stupor without fever developing on post-transplant day 40. A follow-up sleep and waking EEG showed moderate to severe diffuse cerebral dysfunction, with evidence of progressive worsening of cerebral dysfunction. This finding led us to carry out a repeat MRI that showed the findings had changed since the initial scan. A diffusion-weighted image () identified diffusion restriction areas in the post-frontal and parietal periventricular white matter, and along the precentral and postcentral subcortical white matter, suggesting new development of encephalitis.\nBecause diffusion restriction is a common MRI finding in encephalitis cases, a follow-up CSF analysis including real-time PCR and PCR for BK virus was carried out on post-transplant day 48. Real-time PCR test and PCR were performed using a BKV quantitative real-time PCR kit (Bio-Core. Inc., Seoul, Korea) and a BKV PCR Kit (Bio-Core. Inc., Seoul, Korea), respectively, and showed positivity for the BK virus (). The viral load for BKV was 3,356 copies/mL, confirming the diagnosis of BKV encephalitis. PCR for BKV with a peripheral blood sample was also shown to be positive ().\nPCR analysis of a urine specimen yielded negative results. PCR for other viruses such as HSV I, HSV II, enterovirus, varicella-zoster virus, Epstein-Barr virus, CMV, and JC were all negative. We did not discontinue immunosuppressive therapy when the diagnosis was established because we considered it too early to stop prophylaxis for GVHD. The patient died on post-transplant day 79 owing to probable aspiration pneumonia without recovery of mental stupor.