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  • Updated 01.06.2023
  • Released 06.27.1995
  • Expires For CME 01.06.2026

Genital herpes: neurologic complications



The author reviews the neurologic complications of genital herpes and herpes simplex virus type 2 (HSV-2) infections in adults and neonates, updates the changing epidemiology of genital herpes with the growing proportion of HSV-1 cases, and reviews herpes simplex virus disease in patients with heritable or treatment-acquired immunodeficiencies. The recommendations for acute and suppressive treatments from the International Herpes Management Forum (IHMF) are summarized. Illustrative cases of HSV-2 lumbosacral radiculomyelitis in an immunocompromised patient and HSV-2 meningoencephalitis in a child are presented.

This update expands the list of target antigens for herpes simplex encephalitis-triggered autoimmune encephalitis, presents HSV-1 and HSV-2 complications of immunomodulatory drugs, and examines evidence linking herpes simplex virus infection and Alzheimer disease.

Key points

• HSV-1 and HSV-2 are prevalent viruses with the capacity to establish lifelong infections and episodic reactivation. As all herpesviruses, HSV-2 performs two distinct genetic programs, lytic replication and latency, to produce primary and recurrent infections.

• The clinical presentation of HSV-2 infection of the CNS in adults is mainly meningitis, but encephalitis, myelitis, and lumbosacral radiculitis also occur.

• In immunocompetent adults, HSV-2 is responsible for 10% of herpes simplex virus encephalitis cases, with the rest due to HSV-1.

• Recurring lymphocytic meningitis is most often a reactivation of HSV-2.

• HSV-2 infection is common. Currently HSV-2 seroprevalence (persons 14-49 years) is an estimated 13% in the United States (40). Annual crude incidence rate of HSV-2 CNS disease is 0.26 per 100,000 in Denmark (169) and of HSV-2 meningitis is 0.37 per 100,000 in Finland (122). When a pathogen is detected, HSV-2 is one of the leading causes of aseptic meningitis in adults.

• Within the past few years, HSV-1 has become the most common cause of genital herpes, shifting the cause of neonatal herpes to HSV-1 in many parts of the world. Estimates of 60% to 78% of new genital herpes cases in the United States are attributed to HSV-1 (12). Ever-increasing HSV-1 genital disease contributes to the enduring HSV-1 disease burden in the United States.

• In 2018, the most recent year for which data were available, Centers for Disease Control and Prevention estimated there were 572,000 new genital herpes infections and 18.6 million existing cases in the United States (120). Globally, there are approximately 500 million individuals living with genital herpes (234).

Historical note and terminology

“Throughout nature, infection without disease is the rule rather than the exception” (62) is a statement appropriate to certain primary, latent, and recurrent herpetic syndromes. The term "herpes" was first used in ancient Greece for migratory (creeping or crawling) skin lesions. The ancient Greek historian Herodotus labeled mouth and lip ulcers during fever "herpes febrilis" (145; 233). Shakespeare referred to recurrent herpes simplex virus labial lesions in Romeo and Juliet (235). In the 1700s, the French royal court physician introduced genital herpes infections in the medical literature (09).

Transmissibility was established by passage of material from human lip and genital lesions to cornea or abraded skin of rabbits. CNS transmission was demonstrated when Goodpasture showed that material from herpes labialis lesions inoculated onto scarified rabbit cornea produced encephalitis (84). Herpes simplex virus was isolated from a case of encephalitis in 1941 (201), and two antigenic types of herpes simplex virus (HSV) were recognized in 1968 (158). It is estimated that HSV-1 and HSV-2 diverged 6 to 8 million years ago (229). Viral typing distinguished herpes simplex virus type 1 (HSV-1), which mainly was responsible for infections “above the belt,” from herpes simplex virus type 2 (HSV-2), which was primarily responsible for infections “below the belt.” Later studies, however, have shown either virus can infect the mouth, genital tract, or brain.

At present, eight herpesviruses are known causes of human disease. They are herpes simplex virus types 1 and 2, varicella-zoster virus, cytomegalovirus, human herpesvirus-6 and -7, Epstein-Barr virus, and Kaposi sarcoma virus (human herpesvirus-8). HSV-2 causes a lifelong genital viral infection characterized by high rates of clinical and subclinical reactivation in genital mucosa and risk of sexual transmission. Although HSV-2-associated syndromes such as meningitis may have been under-recognized in the past, now widespread use of polymerase chain reaction amplification of herpes simplex virus DNA has expanded recognized spectrum of HSV-2-related infections of the CNS. Advances in laboratory detection, together with epidemiologic and pathogenesis studies, have enhanced understanding of acquisition of infection, natural history of disease, and strategies for prevention.

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