• herpes simplex virus
• encephalitis
• central nervous system

Herpes simplex virus (HSV) is a human herpesvirus that causes HSV encephalitis (HSE), which is the commonest fatal sporadic encephalitis in humans.^1,2 About 90% of all HSE cases in adults and children are due to HSV-1, while HSV-2 is associated with HSE in neonates, in which there is a disseminated infection, and in immunocompromised patients, such as those with renal transplants or HIV infection.^3,4 While the exact incidence of HSE is not known, it has been estimated at about one case per million per year.^4,5 This figure is probably an underestimate since about 2000 cases occur annually in the United States.¹ The neuropathological picture of HSE is characteristic, consisting of an acute necrotising encephalitis that almost always localises, often asymmetrically, to the orbitofrontal and temporal lobes with involvement of the cingulate and insular cortex; neonatal HSE tends to produce a more diffuse pathology.¹ Untreated, HSE has an extremely high mortality rate at about 70% with fewer than 3% of survivors returning to normal function.^2,6 Among common central nervous system (CNS) viral infections, mortality in HSE is disproportionately high, taking into account a recent study that showed that HSV infections are responsible for only 11% of cases compared with 29% for varicella-zoster virus,⁷ another human herpesvirus that is not associated with such a high mortality.

The neuropathogenesis of HSE has intrigued clinicians and scientists for many years, with two of the key questions relating to, firstly, the very low incidence of the condition in the presence of the widespread carriage of latent HSV in ganglionic tissues in healthy people and, secondly, the propensity of the disease process to localise to the frontotemporal region. About 90% of normal people are seropositive …