Viral meningoencephalitis in pediatric solid organ or hematopoietic cell transplant recipients: a diagnostic and therapeutic approach

Abstract

Neurologic complications, both infectious and non-infectious, are frequent among hematopoietic cell transplant (HCT) and solid organ transplant (SOT) recipients. Up to 46% of HCT and 50% of SOT recipients experience a neurological complication, including cerebrovascular accidents, drug toxicities, as well as infections. Defects in innate, adaptive, and humoral immune function among transplant recipients predispose to opportunistic infections, including central nervous system (CNS) disease. CNS infections remain uncommon overall amongst HCT and SOT recipients, compromising approximately 1% of total cases among adult patients. Given the relatively lower number of pediatric transplant recipients, the incidence of CNS disease amongst in this population remains unknown. Although infections comprise a small percentage of the neurological complications that occur post-transplant, the associated morbidity and mortality in an immunosuppressed state makes it imperative to promptly evaluate and aggressively treat a pediatric transplant patient with suspicion for viral meningoencephalitis. This manuscript guides the reader through a broad infectious and non-infectious diagnostic differential in a transplant recipient presenting with altered mentation and fever and thereafter, elaborates on diagnostics and management of viral meningoencephalitis. Hypothetical SOT and HCT patient cases have also been constructed to illustrate the diagnostic and management process in select viral etiologies. Given the unique risk for various opportunistic viral infections resulting in CNS disease among transplant recipients, the manuscript will provide a contemporary review of the epidemiology, risk factors, diagnosis, and management of viral meningoencephalitis in these patients.

Keywords: encephalitis; immunocompromised; pediatric; transplantation; viral.

Figure 1

Suggested diagnostic and therapeutic approach to meningoencephalitis among HCT and SOT recipients. CMV, cytomegalovirus; CNS, central nervous system; CSF, cerebrospinal fluid; CT, computed tomography; EBV, Epstein-Barr Virus; EEG, electroencephalography; HCT, hematopoietic cell transplant; HHV-6, human herpesvirus-6; HSV, herpes simplex virus; IVIG, intravenous immunoglobulin; JCpvV, JC polyomavirus; MRI, magnetic resonance imaging; PCR, Polymerase chain reaction; PML, progressive multifocal leukoencephalopathy; PTLD, post-transplant lymphoproliferative disease; SOT, solid organ transplant; VZV, varicella zoster virus. ^aSee text for diagnostic recommendations, expected findings and empiric treatment recommendations for viral etiologies. Remainder of pathogen specific testing recommendations have been discussed by Venkatesan et al. (22). ^bBased on diagnostic considerations, ensure adequate cerebrospinal fluid volume is requested for all anticipated tests.