Fulminant multisystem adenovirus-associated illness with cerebrospinal fluid PCR positivity and minimal pleocytosis in previously healthy toddlers: a case series

Central nervous system manifestations of human adenovirus infection are uncommon in immunocompetent children and may be difficult to recognize when routine cerebrospinal fluid (CSF) indices are normal or only minimally abnormal. We report a severe pediatric case series characterized by concurrent adenovirus detection in CSF and respiratory specimens, marked systemic inflammation, and multiorgan illness. We retrospectively reviewed four consecutive, previously healthy toddlers aged 13–26 months who met the study case definition during admission to Vietnam National Children’s Hospital between June and December 2022. Eligibility required acute neurological dysfunction together with adenovirus detected by real-time PCR in both CSF and a nasopharyngeal specimen. CSF leukocyte counts ranged from 1 to 3 cells/µL and protein concentrations from 0.38 to 0.62 g/L. Brain MRI was performed in two children: one showed bilateral frontoparietal cortical lesions compatible with encephalitic involvement and the other showed nonspecific widening of the frontoparietal subarachnoid spaces. All four required invasive mechanical ventilation; one additionally required extracorporeal membrane oxygenation and renal replacement therapy. Marked hyperferritinemia and other features of systemic hyperinflammation were present, and three children died. Two children had a clinical diagnosis of macrophage activation syndrome recorded during admission, although a complete HLH-2004 evaluation was not performed. Near-normal CSF indices do not exclude clinically important adenovirus-associated CNS disease. CSF adenovirus PCR may contribute to etiological assessment when neurological dysfunction accompanies systemic adenoviral illness, but escalation of respiratory, circulatory, renal, or extracorporeal support should be guided by physiological deterioration and objective organ dysfunction rather than by CSF PCR positivity alone.