- Clinical science
Herpes simplex encephalitis (HSE) is an inflammation of the brain parenchyma, typically in the medial temporal lobe, that is caused by either herpes simplex virus type-1 (HSV-1) or type-2 (HSV-2). It is the most common cause of fatal sporadic encephalitis in the US. HSE has a bimodal distribution, commonly affecting patients younger than 20 years of age and older than 50 years of age. Patients with HSE typically present with a prodrome of headaches and fever, followed by sudden focal neurological deficits and altered mental status. Characteristic clinical findings and brain imaging showing temporal lesions should raise suspicion of HSE. Lumbar puncture often reveals lymphocytic pleocytosis. The diagnosis is best confirmed with polymerase chain reaction (PCR) testing of cerebrospinal fluid. Because HSE has a rapidly progressive and potentially fatal course, treatment with acyclovir should begin as soon as the disease is suspected. Relapse of HSE is possible. The mortality rate is as high as 70% in the absence of appropriate treatment.
- Bimodal distribution: < 20 years and > 50 years of age
- Most common cause of fatal sporadic encephalitis in the US
Epidemiological data refers to the US, unless otherwise specified.
Acute or subacute encephalopathy
- Focal neurological deficits (primarily affects the medial temporal lobe) 
- Seizures (focal or generalized)
- Altered mental status (e.g., confusion, disorientation, lowered level of consciousness)
- Behavioral changes (e.g., hypersexuality, hypomania, agitation)
- Meningeal signs (e.g., nuchal rigidity, photophobia) may occur.
- Magnetic resonance imaging
- Often normal during the early stages
- A unilateral hypodense zone can be observed in the insular cortex, which may become bitemporal with disease progression.
When imaging points to potential meningoencephalitis and temporal lobe involvement, HSE should always be considered.
- PCR (gold standard): : direct, early detection of the pathogen 
- Other parameters
- Unilateral or bilateral lobe discharge
Treatment should be initiated while awaiting definitive diagnosis of the condition, as the progression of HSE is very rapid! 
- First-line: immediate IV acyclovir
- Second-line : foscarnet 
- To prevent relapses following the relief of symptoms: valacyclovir
- Treatment of mannitol, glycerol) in the event of raised intracranial pressure with proper positioning (head up) and/or hyperosmolar substances (
- If necessary, anticonvulsant treatment (e.g., ) 
- Fatal in up to 70% of cases if left untreated 
- In patients receiving treatment, the mortality rate is still as a high as 20–30%. 
- Relapse may occur
- Residual deficits may remain in some cases (e.g., paresis, cognitive deficits, psychopathological symptoms)