Herpes simplex encephalitis (HSE) is the most common cause of fatal sporadic fulminant necrotizing viral encephalitis, accounting for 20 % of encephalitis cases.  HSE is caused by the infection of the central nervous system by Herpes simplex virus (HSV); childhood and adult herpes encephalitis is usually due to HSV-1 (90%) with the rest due to HSV-2.  HSE is characterized by frontal and temporal lobes, usually asymmetrically, resulting in personality changes, cognitive impairment, aphasia, seizures, and focal weakness.  Diagnosis is established in detection of HSV in cerebrospinal fluid (CSF) by Polymerase Chain Reaction (PCR), although the combination of the clinical scenario, CSF demonstrating pleocytosis and elevated protein, and Magnetic resonance imaging is usually highly suggestive and permits commencement of treatment.  HSE is treated with intravenous antivirals (e.g. acyclovir).  This disease could have a devastating clinical course and it is potentially fatal in 7-14 days with delay or lack of treatment.

Mutations in the TICAM1 gene, encoding an adaptor protein called Toll–IL-1 receptor (TIR) domain-containing adaptor molecule-1 (TICAM1), have been associated with Herpes simplex encephalitis 4 (HSE4) in response to HSV-1 infection.