Literature on radiological worsening following treatment and clinical resolution in pediatric Herpes Simplex Virus Encephalitis (HSVE) is non-existent. While radiological decline following clinical relapse in HSVE patients during treatment has been reported and is unsurprising, radiological decline despite clinical resolution is a rarely reported phenomenon in adults and has never been reported in children. This highlights a disconnect between clinical status and imaging outcomes and implies a secondary inflammatory disease process beyond direct infection in HSVE.

A term male presented at two weeks of age with fever and focal left hemibody motor seizures. Initial cerebrospinal fluid (CSF) testing was positive for HSV-2 and his magnetic resonance imaging (MRI) showed diffuse right hemisphere involvement. He received six months of acyclovir with clinical improvement, although he continued to have left hemibody seizures and left hemibody weakness and spasticity. Despite no clinical deterioration, his repeat MRI over one year later revealed radiological deterioration throughout the previously unaffected left cerebral hemisphere, raising concern for HSV relapse; however, a thorough work-up including CSF was negative. This raises critical questions regarding the type of treatment required in HSV and the need for regular MRI to track evolution in patients who receive standard of care therapy.

NA

NA

We propose a hypothesis suggesting that the observed decline in MRI may not indicate primary (infectious) disease progression. Rather, it could reflect an underlying etiology characterized by immune and inflammatory sequelae, which may exhibit a temporal delay before manifesting as radiological changes. If so, immune-modulatory therapy with anti-viral therapy may be needed, using regular MRI assessments to track response to therapy. This case highlights the necessity for more frequent radiological assessments in HSVE and invites further investigation into the relationship between clinical symptoms and imaging findings in pediatric populations.