Cytomegalovirus Ventriculoencephalitis in a Peripheral Blood Stem Cell Transplant Recipient

Abstract

Cytomegalovirus encephalitis occurs rarely in transplant recipients. We describe a patient with cytomegalovirus ventriculoencephalitis who had a very high CSF viral load but a low peripheral blood viral load. No resistance mutations were present in cerebrospinal fluid viral DNA, whereas DNA from blood showed a resistance mutation in the UL54 gene but not in the UL97 gene. Viral replication was intense in the brain ependyma and periventricular areas without evidence of peripheral cytomegalovirus disease. The data provide evidence for compartmentalization of cytomegalovirus infection. Levels of ganciclovir and foscarnet in the cerebrospinal fluid may be inadequate for treatment, even for some drug-susceptible strains, and, together with periventricular replication, may explain the disparity between cerebrospinal fluid viral load and peripheral blood viral load.

CMV encephalitis in BMT recipients

“…In fact, a second patient was noted to have localization of CMV to the CNS while systemic disease was improving. 2 At the time of his CNS disease, one of our patients had active pulmonary CMV infection, similar but not restricted to the pattern that is seen in advanced HIV patients. Both patients' magnetic resonance imaging showed typical but subtle findings, with ependymal enhancement and non-enhancing periventricular white matter lesions consistent with the 'owl's eye' pattern of CMV ventriculitis.…”

A fatal case of cytomegalovirus ventriculoencephalitis in a mycosis fungoides patient who received multiple umbilical cord blood cell transplantations

“…Fourteen cases of CMV-induced central nervous system (CNS) disease have been reported (Table 1) [ [5][6][7][8][9][10][11][12][13][14][15][16][17]. Of published cases including ours, the median time of onset of CMV CNS disease was 185 days (range 107-285 days).…”

Temporal and Spatial Compartmentalization of Drug-Resistant Cytomegalovirus (CMV) in a Child with CMV Meningoencephalitis: Implications for Sampling in Molecular Diagnosis

“…Whatever the hypothesis, our results show that blood samples may not be representative of the resistance status of the virus isolated in the CNS compartment. Interestingly, previous reports of CMV CNS diseases which compared the CMV genotypic resistance profiles in concomitant CSF and blood samples described similar profiles in the two compartments (6,11) or viral compartmentalization, with wild-type CMV in CSF samples and resistant CMV in blood and other sites (5,8,9,13). The authors suggested that decreased CMV fitness due to drug resistance mutations located in UL97 and/or UL54 genes could explain the predominance of wild-type strains in the CSF, even in cases of previous selection of resistant mutants in blood (17).…”

“…CMV infection of the central nervous system (CNS) is rare in HSCT recipients. Fifteen well-documented cases have been reported (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13). In most of them, the authors described a high viral load in the CSF contrasting with low peripheral blood viral load (2, 9, 13) or low antigenemia (3,4), suggesting a high level of viral replication in the CNS.…”