Possible Epstein-Barr virus-associated central nervous system involvement with reversible electroencephalographic...

Epstein-Barr virus (EBV)-associated central nervous system (CNS) involvement in children is uncommon and may present with nonspecific neurological symptoms. Brain magnetic resonance imaging (MRI) may remain normal, making diagnosis challenging. Cerebrospinal fluid (CSF) targeted next-generation sequencing (tNGS) has emerged as a useful diagnostic tool, although positive EBV results require careful clinical interpretation.

A previously healthy 5-year-old boy presented with fever (38.5 ℃), headache, dizziness, and nausea for 3 days without seizures, altered consciousness, focal neurological deficits, or ataxia. Laboratory tests showed leukocytosis and elevated inflammatory markers. Brain MRI was unremarkable. CSF examination revealed an opening pressure of 120 mmH₂O and mild pleocytosis (13×10⁶/L, 100% mononuclear cells), with normal glucose and protein levels. CSF tNGS detected EBV (24,002 sequence reads; estimated pathogen concentration <10³ copies/mL), while no other pathogens were identified and autoimmune encephalitis antibodies were negative. Serum EBV DNA was positive, and EBV serology demonstrated viral capsid antigen (VCA)-IgM positivity during the acute phase followed by VCA-IgG seroconversion during recovery. Electroencephalography (EEG) showed sharp and sharp-slow wave discharges in the left parietal, occipital, and posterior temporal regions despite normal MRI. The patient received intravenous ganciclovir (10 mg/kg twice daily for 2 weeks) and empirical ceftriaxone for 4 days. Clinical symptoms resolved completely, follow-up EEG normalized, and no neurological sequelae were observed at 1-month follow-up.

This case highlights that possible EBV-associated CNS involvement may occur in children despite normal brain MRI and only mild CSF abnormalities. The combination of CSF tNGS, dynamic EBV serology, EEG findings, exclusion of alternative etiologies, and clinical follow-up may facilitate diagnosis. Because EBV detected in CSF does not necessarily indicate causation, results should always be interpreted in the context of the overall clinical presentation.