Background Granulomatous herpetic encephalitis is a rare inflammatory complication of acute herpes simplex encephalitis. Methods We describe 3 cases of granulomatous herpetic encephalitis in children arising between 1 to 10 years after the initial presentation with acute herpes simplex encephalitis. We focus on the clinical course and neuroimaging phenotype with a discussion of possible mechanisms underpinning this entity. Results The clinical course was highly variable. However, the dominant neuroimaging phenotype in each of our cases was that of confluent gyriform cortical enhancement with predominantly solid foci of enhancement in the subjacent white matter +/− deep gray nuclei. Cerebrospinal fluid was negative for herpes simplex virus DNA in all cases. All 3 cases required brain biopsy to help establish the diagnosis. Conclusions Increased recognition of granulomatous herpetic encephalitis in children will facilitate earlier diagnosis and treatment. Although the exact role played by the host immune response, genetics, and environment in determining the different outcomes of herpes simplex encephalitis remains to be determined, we postulate a role for inflammasome dysregulation in this entity.
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