Zika virus: neurologic complications

Katherine Hutchins MD (

Dr. Hutchins of Indiana University School of Medicine has no relevant financial relationships to disclose.

Karen L Roos MD FAAN (Dr. Roos of Indiana University School of Medicine has no relevant financial relationships to disclose.)
Originally released September 11, 2016; last updated January 15, 2020; expires January 15, 2023


First discovered in 1947, Zika virus is a single-stranded RNA, mosquito-borne flavivirus that closely resembles dengue, West Nile, and yellow fever viruses. Initially, few documented cases of human Zika infection occurred, and the virus was contained within Africa and Asia. Infection was thought to be largely asymptomatic or cause no more than a mild febrile illness. Common clinical manifestations of Zika infection include maculopapular rash, conjunctivitis, arthralgia, frontal headache, malaise, and fever. Within the past decade, Zika has expanded globally to the Western Pacific and the Americas, with the first documented case in Brazil in 2015 and the first case in the United States in 2016. Since then, researchers have noticed a rise in the incidence of neurologic complications ranging from Guillain-Barre syndrome, encephalomyelitis, sensory neuropathy, seizures, and stroke to congenital Zika syndrome in infants born to mothers infected during pregnancy. The association between Zika virus infection and these severe neurologic sequelae contradicts what was once believed to be a relatively benign virus and is the focus of this article.

Key points


• Zika virus is a mosquito-borne flavivirus that is asymptomatic in 80% of those infected and, when symptomatic, generally results in a mild febrile illness.


• Studies have shown that the virus is highly neurotropic in both mice and in vitro cell studies with human embryonic cortical neural progenitor cells.


• Major neurologic complications of Zika virus infection include Guillain-Barre syndrome and congenital Zika syndrome.


• Additional neurologic complications have been suggested as occurring secondary to Zika virus infection, including meningoencephalitis, transverse myelitis, seizure, and stroke.

Historical note and terminology

In 1947, researchers studying yellow fever in Uganda isolated a new virus from the blood of a caged rhesus macaque. They named this virus Zika, after the forest in which it was discovered (Dick et al 1952). Before the first major outbreak in 2007 in Yap State, Micronesia, only 14 cases of human infection had been documented in the literature (Lanciotti et al 2008; Duffy et al 2009; Hayes 2009). The virus then spread to French Polynesia in 2013 to 2014 (Zanluca and Dos Santos 2016). One study demonstrated a 1:1 ratio of symptomatic to asymptomatic infection in the general population and a 2:1 ratio amongst school age children (Aubry et al 2017). The virus arrived in Brazil in March 2015 and has since spread to over 30 additional countries (Zanluca et al 2015; Petersen et al 2016). Local transmission in the United States was first reported in Miami Beach in 2016, and in that year, there were 5168 cases of symptomatic Zika virus infection documented in the United States, mostly in travelers (Centers for Disease Control and Prevention 2018b). So far in 2018, only 34 cases of symptomatic infection have been reported in the U.S. (Centers for Disease Control and Prevention 2018c). Association of Zika virus infection with Guillain-Barre syndrome first occurred during the 2013 to 2014 outbreak in French Polynesia, whereas the first association of the virus with microcephaly occurred during the 2015 outbreak in Brazil (Broutet et al 2016).

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