Granulomatous Herpetic Encephalitis A Possible Role for Inflammasomes

Abstract

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.

The immunobiology of herpes simplex virus encephalitis and post-viral autoimmunity

“…For instance, a smouldering inflammatory response has been observed in the CNS following acute HSE. 14 , 15 , 122 , 123 Typically, this process occurs in the absence of CSF viral DNA and neuroglial surface autoantibodies (NSAbs), but neuropathological evaluation can often identify the presence of HSV DNA from brain tissue. Chronic HSE has only been phenotyped to a limited extent and likely occurs on a spectrum shared with relapses secondary to AE.…”

“…Current available evidence suggests that chronic HSE can manifest clinically from months to over a decade in some cases. 15 …”

“…Phenotypic presentations observed include seizures, raised intracranial pressure and psychomotor symptoms. 15 CSF has shown to be sterile or reveal a mild lymphocytic pleocytosis, typically with the presence of unpaired oligoclonal bands and negative HSV PCR but with evidence of intrathecal HSV-specific IgG synthesis. 13-15 , 122-124 Distinct from classical HSE and relapsing secondary autoantibody encephalitis, an MRI brain characteristically reveals confluent gyriform cortical and adjacent white matter enhancement with vasogenic oedema.…”

“… 13-15 , 122-124 Distinct from classical HSE and relapsing secondary autoantibody encephalitis, an MRI brain characteristically reveals confluent gyriform cortical and adjacent white matter enhancement with vasogenic oedema. 15 , 124 Optimal management is unclear but some reports describe patients receiving repeat intravenous aciclovir, with steroid treatment, albeit with variable outcomes. 15 , 124 …”

“… 15 , 124 Optimal management is unclear but some reports describe patients receiving repeat intravenous aciclovir, with steroid treatment, albeit with variable outcomes. 15 , 124 …”