CSF HSV PCR is currently the standard biological test for HSVE diagnosis.
PCR can raise false negative results in HSVE patients when carried out on a CSF sample taken during the first 4 days of the diseases.
A recent review (14) summarizes current knowledge about modern imaging in HSVE. Brain MRI has a high sensitivity for the diagnosis of HSVE, showing brain abnormalities in 80 to 100% of cases.
The frequent seizures associated with HSVE may also lead to reversible hyper-intense FLAIR signal in the thalamus of patients.
Before the use of acyclovir, the CFR of HSVE was up to 70%.
Sequelae following HSVE affect mainly the cognitive functions, the mood and behavior.
The most frequent sequelae after HSVE are memory impairment, language disorders (aphasia, agnosia, etc.).
501 patients with proven HSVE (positive molecular diagnosis) were included in a multicentric multinational study (35 referral centers in 10 countries).
An association between HSVE and auto-immune encephalitis was reported in a first case-series, performed with few patients (25).
A prospective follow up (2 - 3 weeks after discharge and 3 months after), looking for autoantibody secretion, was performed by Swedish authors (28), in 49 patients with proven HSVE, treated by acyclovir.
Genetic screenings in children with HSVE demonstrated that mutations in the Toll-like receptor 3 (TLR3) gene or in other genes participating to the TLR3 pathway (TLR3, TICAM1, TRAF3, UNC93B1, TBK1, and IRF3) are risk factors for HSVE.