Last updated on: September 16th, 2021

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Herpes Simplex Encephalitis

Clinical: History


Herpes simplex virus type 1 (HSV-1) is a common infection that occurs worldwide. It is transmitted by close contact between infected and susceptible individuals. The spectrum of presentation is broad, including oral, labial and genital infections. Infection of the central nervous system is the most severe manifestation, with significant morbidity and mortality.


HSV-1 encephalitis can be caused by a primary infection, or reactivation of a latent infection.

A primary infection occurs when HSV-1 gains access to host tissues through mucous membranes or damaged skin. The virus travels through the dorsal root ganglion via fast retrograde axonal transport, reaching the CNS. Later on, anterograde transport occurs; this is often via the trigeminal or olfactory nerves of the peripheral nervous system (PNS). The virus then remains latent for the lifetime of the host with the possibility of reactivation. Spread through viremia may occur.

Predisposing factors

Predisposing factors include all causes that decrease immunological response. Immunomodulatory therapies such as natalizumab and the use of inhibitors of TNF-alpha have also been implicated. Host susceptibility is also an issue; defects in innate and adaptive immunity have been found to increase the risk of HSV-1 encephalitis.


Symptoms of HSV encephalitis are non-specific. Altered mental status (typically for >24h), fever, new seizures and focal neurologic deficits are the most common.

Altered mental status and decline in level of consciousness

Altered mental status and decline in the level of consciousness are typical, occurring up to 23% and 13% of affected individuals respectively. These are thought to be due to inflammation of the brain parenchyma.

Behavioral syndromes

Altered behaviors have been reported in association with HSV-1 encephalitis; these include hypomanic symptoms, Klüver-Bucy syndrome and amnesia. These are probably due to inflammation of the inferomedial temporal lobe or limbic system.


Seizures may occur in up to 40% of cases; and are usually focal. These are due to changes in the brain's electrical activity caused by the inflammatory response to the virus.


Seizures are the most common complication. In the most severe cases, cerebral edema with intracranial hypertension and a risk of uncal displacement also may occur. Neurological sequelae are related to neural damage at time of initiation of therapy. An autoimmune encephalitis may develop and lead to further neurological worsening. Early diagnosis and treatment is therefore imperative to prevent complications.

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