Chronic granulomatous herpes simplex encephalitis in a child with digeorge syndrome- expanding the spectrum of herpes-associated neurological disease.

Abstract

Background: Herpes simplex virus(HSV) encephalitis is typically an acute, monophasic illness but can rarely present as a chronic granulomatous encephalitis, especially among immunocompromised individuals. The diagnosis of chronic HSV encephalitis is challenging due to its prolonged latency period, atypical imaging findings, and potential false-negative cerebrospinal fluid (CSF) polymerase chain reaction (PCR) results. This report describes a rare case of chronic granulomatous HSV encephalitis in a child with an underlying immunodeficiency disorder- DiGeorge syndrome (DGS).

Case presentation: A developmentally normal 10-month-old girl initially presented with fever and seizures, was diagnosed with acute encephalitis, and received intravenous acyclovir. Following the illness, she exhibited neurodevelopmental delay and gliotic changes in brain imaging. At 12 years of age, she was admitted with refractory seizures and a respiratory infection. MRI revealed new cortical lesions and CSF analysis showed mild pleocytosis with elevated proteins. Despite symptomatic management, her condition worsened, with progressive neurological decline and radiological evidence of tumefactive or granulomatous lesions. A brain biopsy was performed, revealing HSV-1 positivity on PCR and immunohistochemistry, confirming chronic HSE. Given the atypical course, genetic testing was conducted, showing a 22q11.2 microdeletion consistent with DGS. The patient was treated with intravenous acyclovir and corticosteroids, followed by long-term oral acyclovir prophylaxis. Over two years of follow-up, she showed significant clinical and radiological improvement, with seizure resolution and partial recovery of developmental milestones.

Conclusion: This case highlights the potential for HSV to cause chronic granulomatous encephalitis, particularly among children with underlying immunodeficiency. It underscores the diagnostic challenge posed by prolonged latency and false-negative CSF PCR results and the importance of brain biopsy for definitive diagnosis. Additionally, this report suggests a potential link between DGS-related immunodeficiency and chronic HSV infection, emphasizing the need for genetic evaluation in atypical encephalitis cases. Long-term acyclovir therapy may be beneficial in such patients, although the optimal duration remains uncertain.