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  • Updated 03.04.2024
  • Released 02.25.1994
  • Expires For CME 03.04.2027

Neonatal herpes encephalitis



Herpes simplex virus encephalitis is a catastrophic disease of newborns. Without specific therapy, 40% to 50% of neonates with this infection will die, and survivors have a high rate of neurologic sequelae. Herpes simplex virus polymerase chain reaction (PCR) on CSF can reliably demonstrate herpes simplex virus infection in many neonates with herpes simplex encephalitis. However, antiviral treatment should be started immediately, without waiting for laboratory confirmation, in all cases of suspected neonatal herpes simplex virus encephalitis because delay of treatment can substantially worsen outcomes. In addition, the authors discuss how maternally-derived antibodies, from earlier maternal infection, may protect the fetus against herpes-induced morbidity and mortality.

Key points

• In most cases of neonatal herpes encephalitis, the infection is acquired during vaginal delivery.

• The application of polymerase chain reaction to CSF samples has revolutionized the diagnosis of central nervous system viral infection in neonates, as this method allows rapid and reliable detection of the pathogen.

• Prompt institution of antiviral therapy is critical to minimize mortality and morbidity.

• As CNS disease has significant morbidity, strategies to prevent vertical transmission are of fundamental importance.

• Oral acyclovir suppression following acute treatment of neonatal herpes encephalitis improves neurodevelopmental outcome at one year.

Historical note and terminology

"Herpes," from the Greek meaning "creeping or crawling," has been used historically as a descriptor for a variety of febrile illnesses associated with vesicular exanthems or enanthems. Many of these infectious illnesses, such as herpangina, are recognized today, however, as being caused by infective agents other than the herpes viruses. More than 50 viruses are classified in the family of herpesviruses, but the most important with regard to human illness are herpes simplex viruses 1 and 2 (HSV-1 and HSV-2), varicella-zoster virus, cytomegalovirus, Epstein-Barr virus, and human herpes viruses 6, 7, and 8 (HHV-6, HHV-7, and HHV-8). Although all of these viruses can cause intrauterine and neonatal CNS infections, herpes simplex virus type 2 is the most common cause of acute, life-threatening neonatal encephalitis.

The clinical manifestations of herpes simplex virus infections in older children and adults have been known for centuries. However, it was not until the 1930s that clinical reports began to appear that distinguished neonatal herpes infection as a distinct clinical entity (20; 58).

In the early and mid-1960s, viral culture and immunologic techniques were developed that made it possible to distinguish herpes simplex virus 1 from herpes simplex virus 2 (41). Using these laboratory techniques, investigators have defined more clearly the epidemiology and pathogenesis of infections with these two types of herpes simplex virus (42; 43; 44). Herpes simplex virus 1 infects primarily the mouth, lips, eyes, and skin of the upper body. In recent decades, herpes simplex virus 1 has emerged as the most common cause of new cases of genital herpes in the United States and several other developed countries (17). In addition, herpes simplex virus 1 is the major cause of herpes encephalitis seen after the neonatal period, but it is rarely the cause of neonatal disease. Herpes simplex virus 2 infects primarily the genital tract and skin of the lower body and causes most cases of neonatal herpes simplex virus encephalitis. With further advances in virology and immunology during the 1970s and 1980s, knowledge regarding herpes simplex virus transmission, replication, latency, and reactivation expanded markedly (10; 50). Based on the better understanding of the epidemiology, pathogenesis, and biology of herpes simplex virus infections that has been achieved during the past 15 to 20 years, major advances have occurred in prevention of neonatal herpes simplex virus infection and in the development of effective, safe, and specific anti-herpes simplex virus drugs.

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