Neonatal herpes encephalitis

Nancy E Bonthius PharmD (Dr. Bonthius of the University of Iowa has no relevant financial relationships to disclose.)
Daniel J Bonthius MD PhD (

Dr. Bonthius of Atrium Health/Levine Children’s Hospital has no relevant financial relationships to disclose.

Karen L Roos MD FAAN, editor. (Dr. Roos of Indiana University School of Medicine has no relevant financial relationships to disclose.)
Originally released February 25, 1994; last updated March 4, 2018; expires March 4, 2021

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 with this infection will die, and survivors have a high rate of neurologic sequelae. Herpes simplex virus cultures and polymerase chain reaction can reliably demonstrate herpes simplex virus infection in many neonates with herpes simplex encephalitis. However, antiviral treatment should be started immediately in all cases of suspected neonatal herpes simplex virus encephalitis because delay of treatment can substantially worsen outcome. In this update, the authors present a vignette of herpes simplex encephalitis with typical symptoms, laboratory findings, and outcome. In addition, the authors discuss the most effective means of preventing this devastating infection.

Key points


• In most cases of neonatal herpes encephalitis, the infection is acquired during the birthing process.


• Prompt diagnostic evaluation and 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 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 all of these viruses can cause intrauterine and neonatal CNS infections, herpes simplex virus 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 (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 defined more clearly the epidemiology and pathogenesis of infections with these two types of herpes simplex virus (Nahmias and Roizman 1973a; Nahmias and Roizman 1973b; Nahmias and Roizman 1973c). 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 most of 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. 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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