Proven Epstein–Barr encephalitis with negative EBV‐DNA load in cerebrospinal fluid after allogeneic hematopoietic stem cell transplantation in a child with acute lymphoblastic leukemia

Abstract

We report a case of EBV encephalitis in a seven-yr-old child with Ph+ ALL. Two months after an allogeneic HSCT from his HLA mismatched mother, the patient showed an altered sensorium, generalized seizures, and a left hemiparesis. Brain MRI demonstrated multiple lesions highly suggestive for viral encephalitis. Blood and CSF PCR analyses were negative for the most common viruses involved in immunocompromised patients including EBV. A cerebral biopsy was performed, which showed intense gliosis and perivascular lymphocytic cuffing. PCR analysis performed on brain tissue was positive only for the EBV genome, while extensive investigations for other viral infections were negative. The patient's neurological symptoms rapidly worsened and he died two months later. This case report suggests that in patients presenting neurological and radiological signs of encephalitis after an HSCT, an EBV involvement should be considered, even in the absence of CSF and blood PCR virus detection.

CNS infections in patients with hematological disorders (including allogeneic stem-cell transplantation)—Guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Medical Oncology (DGHO)

“…Diagnosis of EBV meningoencephalitis is based on CSF PCR [ A ] [ 2 , 73 – 75 ]. However, brain-biopsy-proven EBV meningoencephalitis in conjunction with a negative CSF EBV PCR has been reported [ 76 ].…”

Epstein–Barr virus encephalitis in a renal transplant recipient manifesting as hemorrhagic, ring‐enhancing mass lesions

“…It is interesting that the peripheral blood EBV PCR was negative in this patient. Other cases of EBV encephalitis have reported positive PCR results in both CSF and peripheral blood ; another biopsy‐proven case reported negative PCR results in both compartments . Potential explanations for the discrepancy between CSF and peripheral blood EBV PCR in our patient include the use of different PCR assays on the 2 sample types, the presence of low EBV copy number or PCR inhibitors in the peripheral blood, or localization of EBV replication to the CNS.…”

Relapsing EBV encephalitis in a renal transplant recipient

“…Neurologic sequelae of EBV infection are due to the virus-host immunity interaction, and include encephalitis, meningitis, cerebellitis, polyradiculomyelitis, transverse myelitis, and cranial and peripheral neuropathies [2] , [6] . Outside of primary EBV infection, reactivation of latent virus is a prerequisite for CNS involvement and is most likely to occur in T-cell immunosuppressed hosts [1] , [2] , [7] , [8] , [9] . In the current case, donor derived primary EBV infection is most likely, given the sero-discordance at time of transplantation.…”

“…Treatment with antivirals has no role in management of PTLD, as it does not affect latently-infected tumor cells [12] . Antivirals are not routinely recommended for primary EBV infection, including encephalitis [4] , given their lack of efficacy in IM [7] . In immunocompetent hosts however, there are case reports [6] and small case series [17] of the use of antivirals for the treatment of EBV-related neurologic complications, often with adjunct steroids [6] , [7] , [8] .…”

“…Antivirals are not routinely recommended for primary EBV infection, including encephalitis [4] , given their lack of efficacy in IM [7] . In immunocompetent hosts however, there are case reports [6] and small case series [17] of the use of antivirals for the treatment of EBV-related neurologic complications, often with adjunct steroids [6] , [7] , [8] . Based on this limited data and the experienced gained from the current case, antiviral treatment against actively proliferating, lytic virus should be considered as an adjunct to decreased immunosuppression in cases of EBV-encephalitis in immunocompromised hosts.…”