Case Report Human Herpes Virus-6 Encephalitis After Bone Marrow Transplantation: Successful Treatment with Ganciclovir

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Case report Human herpes virus-6 encephalitis after bone marrow transplantation: successful treatment with ganciclovir

BP Mookerjee and G Vogelsang

Division of Hematologic Malignancies, John Hopkins Oncology Center, Baltimore, MD, USA

Summary: Case report

Here we report a case that presented with sudden onset of neurological symptoms and was treated with gan- A 44-year-old man presented with follicular mixed, small- ciclovir. Polymerase chain reaction analysis for human cleaved and large cell type non-Hodgkins lymphoma. He herpes virus-6 (HHV-6) from his cerebrospinal fluid received three cycles of CHOP chemotherapy and had a was later found to be positive. He subsequently reco- partial response. He underwent autologous bone marrow vered with minimal residual neurological symptoms. transplantation after receiving a preparative regimen with Encephalitis secondary to this virus may be more com- cyclophosphamide and total body irradiation. His post-bone mon than previously thought in patients undergoing marrow transplant period was complicated with pneumonia bone marrow transplantation. This condition should that was successfully treated with broad-spectrum antibac- be considered in the differential diagnosis of sudden terials and amphotericin. He also had nausea and vomiting onset neurological symptoms after bone marrow refractory to multiple antiemetics. On day 56 of transplant, transplantation. he developed muscle tremors that were generalized in nat- Keywords: human herpes virus-6; encephalitis; bone ure. He was also started on acyclovir for herpes-simplex marrow transplantation virus 1 infection of the lip. Four days later he had subtle mental status changes manifesting as mild confusion and slow reponse to verbal commands. On day 63 post-trans- Human herpes virus-6 (HHV-6) is an increasingly recog- plant, he was found comatose with his eyes deviated to the nized opportunistic and a potentially life-threatening patho- right. This was attributed to a seizure episode and he was gen in recipients of bone marrow transplants.1 It can cause treated with lorazepam and phenytoin. Neurological exam- a spectrum of clinical states in the immunocompromised ination was significant for increased tone throughout, with host. The source of infection ranges from reactivation of cogwheel type rigidity. There was no demonstrable focal the latent virus, infection from a donor in a transplant set- motor, sensory, or cerebellar abnormalities. Computed tom- ting and exogenous infection.2,3 The incidence of HHV-6 ography of his head was normal. Lumbar cerebrospinal infection has been shown to occur in 38–60% of patients fluid analysis revealed five white cells per mm3, with a glu- undergoing bone marrow transplantation.2,4,5 This virus has cose level of 4.68 mmol/l and a protein level of 0.59 g/l. been reported to cause interstitital pneumonitis, sometimes Electroencephalogram showed focal temporal lobe activity with a fatal outcome.6,7 Furthermore, it has been associated suggestive of encephalitis. He also had bilateral pulmonary with marrow suppression,8 increased incidence of cytome- interstitial infiltrates on chest radiogram. He was started on galovirus and Epstein–Barr virus infection,9 and exacerbat- ganciclovir empirically within 5 days of the onset of his ing graft-versus-host disease and immunodeficiency symptoms as his neurological status continued to deterio- states.7,10 To date, there has been only one reported case rate on high-dose acyclovir. Subsequently, polymerase of HHV-6 encephalitis, post-bone marrow transplant and chain reaction analysis for HHV-6 from the cerebrospinal it proved to be fatal.11 Here we report a case of HHV-6 fluid sampled at the time of seizure was positive. Further encephalitis presenting 8 weeks after autologous bone mar- polymerase chain reaction analyses for herpes simplex row transplantation. He was treated with ganciclovir and type-1, cytomegalovirus and varicella-zoster virus were recovered with minimal neurological damage. negative. This resulted in a slow improvement of his neurological status over a period of 6 weeks. Complete recovery required extensive physical rehabilitation. Gancicloir was continued for a total of 3 weeks. Five months after com- pletion of his therapy he continues to do well without any Correspondence: BP Mookerjee, Division of Hematologic Malignancies, Johns Hopkins Oncology Center, Rm 3-121, 600 North Wolfe Street, recurrence of his neurological symptoms. Baltimore, MD 21287-8985, USA Received and accepted 14 July 1997 HHV-6 encephalitis after BMT BP Mookerjee and G Vogelsang 906 Discussion virus. Patients undergoing allogeneic bone marrow transplantation may require a longer duration of antiviral therapy The above case report demonstrates that HHV-6 is a poss- and have a higher incidence of relapse after antiviral ther- ible etiologic agent in central nervous system infections in apy is stopped compared to patients undergoing autologous patients receiving bone marrow transplants. In this case bone marrow transplantation. Future studies designed to HHV-6 infection was confirmed by cerebropsinal fluid study these issues would be important in the quest for analysis by polymerase chain reaction for HHV-6 obtained improving the management of infectious complications in at the onset of neurological symptoms. Timely institution bone marrow transplant recipients, thus improving trans- of ganciclovir resulted in a significant recovery. plant-related mortality and morbidity. The pathogenesis of HHV-6 is not yet fully delineated. In the recent past, our understanding of this virus has increased considerably along with its relation to the rel- References evance of its infection in a transplant recipient. What has not been clear is the role of HHV-6 in central nervous sys- 1 Singh N, Carrigan D. Human herpes virus-6 in transplantation: tem infection in this patient group. It is possible that cases an emerging pathogen. Ann Inter Med 1996; 124: 1065–1071. in the past have been missed, based on the fact that infec- 2 Yoshikawa T, Suga S, Asano Y et al. Human herpesvirus 6 tions may have been ascribed to more common etiology, infection in bone marrow transplantation. Blood 1991; 78: namely herpes-simplex virus encephalitis. 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