Herpes simplex encephalitis constitutes an uncommon infectious disease, leading to inflammation of the brain parenchyma, as a result of a herpes simplex virus type I (HSV-I) infection. Rarely, in neonates, the encephalitis is caused by herpes simplex virus type II (HSV-II).
Herpes simplex encephalitis (HSE) is an infectious inflammation of the brain, caused, in adults and adolescents, by the herpes simplex virus type I. It leads to a multitude of neurological symptoms, that can either be generalized or focal.
The symptoms most typically related to HSE include fever, which is present in up to 90% of the patients and cephalalgia . The full course of the clinical symptomatology tends to develop over a period of some days. Convulsions and psychiatric sequelae, such as psychotic incidences and behavioral pattern modifications are also common . Patients may progress to a lethargy, confusion, and delirium. Profound neurological symptomatology also encompasses memory loss, speech impairment or aphasia, anosmia, limb weakness or even hemiparesis. Retinitis may also occur as a result of HSE and meningismus may be observed. The clinical picture in herpes simplex encephalitis infection is extremely broad and there is no pathognomonic clinical finding that can aid towards a precise diagnosis of the disorder . Immunocompromised individuals tend to present with a less typical or less profound set of symptoms as compared to the immunocompetent population .
Neonatal herpes simplex encephalitis is usually a result of a herpes simplex type II infection and initial symptoms develop during the first two weeks after birth. The clinical picture includes seizures, loss of appetite, weakness, and lethargy, along with irritability and tremors. Lesions on the skin may also be observed.
The diagnosis of herpes simplex encephalitis requires a plethora of tests for confirmation. These include a medical history that is expected to be compatible with the main symptoms of the infection, a lumbar puncture to drain cerebrospinal fluid (CSF) for analysis, a CSF polymerase-chain-reaction test (PCR), a brain magnetic resonance imaging scan (MRI) and, possibly, a computed tomography scan (CT) of the brain or brain biopsy  .
Cerebrospinal fluid analysis in a case of HSE is expected to display red blood cells and xanthochromia. Pleocytosis, with white blood cell levels of mononuclear type approximately at 10-500 per mL and augmented protein levels at 60-700 mg/dL are also exhibited in a typical analysis. Glucose may be slightly diminished. During the initial phase of the infection, CSF analysis may be normal in a considerable number of patients (app 10-15%) . A viral HSV-II culture is solely possible in neonates.
Neuroimaging is widely used to detect brain inflammation in patients with a suspected HSE and, additionally, to differentiate between this disorder and other conditions that could result in the same symptomatology, such as a tumor. MRI scans are substantially preferred to CT scans with reference to the HSE diagnosis since the sensitivity of an MRI scan is superior .
A PCR test, carried out on the CSF sample, can directly detect viral load and greatly accelerate the diagnosis of HSE, both in adults and neonates. With the advent of PCR, the use of brain biopsy has diminished, since PCR constitutes a non-invasive, accurate tool for the detection of herpes simplex encephalitis, whose specificity and sensitivity amount to 98-100% and 94-98% respectively  .