Neonatal herpes encephalitis

Catherine Amlie-Lefond MD (Dr. Amlie-Lefond of the University of Washington has no relevant financial relationships to disclose.)
Richard T Johnson MD, editor. (Dr. Johnson of the Johns Hopkins University School of Medicine and Bloomberg School of Public Health has no relevant financial relationships to disclose.)
Originally released February 25, 1994; last updated October 21, 2014; expires October 21, 2017
Notice: This article has expired and is therefore not available for CME credit.

This article includes discussion of neonatal herpes encephalitis, disseminated herpes infection with encephalitis, localized CNS neonatal herpes infections, and congenital herpes encephalitis. The foregoing terms may include synonyms, similar disorders, variations in usage, and abbreviations.


Herpes simplex virus encephalitis is a catastrophic disease of newborns. Without specific therapy, 40% to 50% of neonates die, and survivors have a high rate of neurologic sequelae. Herpes simplex virus cultures and polymerase chain reaction can demonstrate herpes simplex virus infection in many neonates with herpes simplex encephalitis disease, but antiviral treatment should be started immediately in all cases of suspected neonatal herpes simplex virus encephalitis and continued for at least 21 days, or until herpes simplex virus disease has been excluded. Oral acyclovir suppression following acute disease has been shown to improve neurodevelopmental outcome.

Key points


• Neonatal herpes encephalitis is a rare, but devastating, infection with significant mortality and neurodevelopmental sequelae.


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


• As CNS disease continues to have significant morbidity, strategies of prevention of vertical transmission are key.


• Oral acyclovir suppression following acute treatment of neonatal herpes encephalitis improves neurodevelopmental outcome at 1 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 virus, varicella-zoster virus, cytomegalovirus, and Epstein-Barr virus. Although any of these viruses can cause intrauterine and neonatal CNS infections, herpes simplex virus is the most common cause of acute, life-threatening neonatal encephalitis.

Although the clinical manifestations of herpes simplex virus infections in older children and adults have been known for centuries, it was not until the 1930s that clinical reports began to appear that distinguished neonatal herpes infection as a distinct clinical entity (Hass 1935; Whitley 1990).

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 (Nahmias and Dowdle 1968). Using these laboratory techniques, investigators have been able to define more clearly the epidemiology and pathogenesis of infections with these 2 types of herpes simplex virus (Nahmias and Roizman 1973). Herpes simplex virus-1 infects primarily the mouth, lips, eyes, and skin of the upper body and is the major cause of herpes encephalitis seen after the neonatal period. Herpes simplex virus-2 infects primarily the genital tract and skin of the lower body and causes 75% of cases of neonatal herpes simplex virus encephalitis. With further advances in virology and immunology during the 1970s and 1980s, knowledge about herpes simplex virus transmission, replication, latency, and reactivation expanded markedly. 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.

The content you are trying to view is available only to logged in, current MedLink Neurology subscribers.

If you are a subscriber, please log in.

If you are a former subscriber or have registered before, please log in first and then click select a Service Plan or contact Subscriber Services. Site license users, click the Site License Acces link on the Homepage at an authorized computer.

If you have never registered before, click Learn More about MedLink Neurology  or view available Service Plans.