Neurological Presentation of Zika Virus Infection Beyond the Perinatal Period

  • Thomas De Broucker
  • Alexandra Mailles
  • Jean-Paul Stahl
Central Nervous System Infections (K Bloch, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Central Nervous System Infections


Purpose of Review

Our purpose was to summarize the current knowledge about the neurological presentation of Zika virus infection after the perinatal period. Other Flaviviruses infections, such as West Nile virus (WNV) or Japanese encephalitis virus (JEV), can result in neuro-invasive disease such as myelitis, encephalitis, or meningitis. We aimed at describing the specificities of ZV neurological infection.

Recent Findings

The recent outbreaks demonstrated clearly the neurotropism of ZV. However, by contrast with other Flaviviruses, the most frequent neurological presentation of ZV infection beyond the perinatal period was Guillain-Barré syndrome, especially the demyelination form of GBS. Encephalitis and myelitis seem to occur less frequently after ZV infection than after WNV or JEV infection.


The pathophysiology of neurological ZV infections is still poorly understood and no specific treatment is available. Moreover, no data is available about long-term persisting symptoms and possible impairment of patients after the acute clinical episode.


Zika Arbovirus Guillain-Barré syndrome Encephalitis Myelitis Acute disseminated encephalomyelitis (ADEM) 


Compliance with Ethical Standards

Conflict of Interest

Drs De Broucker, Mailles, and Stahl declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.


Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    DICK GW. Epidemiological notes on some viruses isolated in Uganda; Yellow fever, Rift Valley fever, Bwamba fever, West Nile, Mengo, Semliki forest, Bunyamwera, Ntaya, Uganda S and Zika viruses. Trans R Soc Trop Med Hyg. 1953;47:13–48.CrossRefPubMedGoogle Scholar
  2. 2.
    • Duffy MR, Chen TH, Hancock WT, Powers AM, Kool JL, Lanciotti RS, et al. Zika virus outbreak on Yap Island, Federated States of Micronesia. N Engl J Med. 2009;360:2536–43. doi: 10.1056/NEJMoa0805715. Discusses viral outbreak on Yap Island and the transmission of the virus outside of Africa and Asia CrossRefPubMedGoogle Scholar
  3. 3.
    Campos GS, Bandeira AC, Sardi SI. Zika Virus Outbreak, Bahia, Brazil. Emerg Infect Dis. 2015;21:1885–6. doi: 10.1128/JCM.00877-16.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Machado-Alba JE, Machado-Duque ME, Gaviria-Mendoza A, Orozco-Giraldo V. Diagnosis of neurological disorders and the Zika virus epidemic in Colombia 2014-2016. Int J Infect Dis. 2016;51:133–4. doi: 10.1016/j.ijid.2016.09.010.CrossRefPubMedGoogle Scholar
  5. 5.
    Paho. Regional Zika epidemiological Update (Americas). 25 May 2017. Available from: Accessed 6 June 2017.
  6. 6.
    WHO. WHO statement on the first meeting of the International Health Regulations (2005) Emergency Committee on Zika virus and observed increase in neurological disorders and neonatal malformations. 1 February 2016. Available from: Accessed 6 June 2017.
  7. 7.
    Parra B, Lizarazo J, Jiménez-Arango JA, Zea-Vera AF, González-Manrique G, Vargas J, et al. Guillain-Barré syndrome associated with Zika virus infection in Colombia. N Engl J Med. 2016;375:1513–23. doi: 10.1056/NEJMoa1605564.CrossRefPubMedGoogle Scholar
  8. 8.
    Oehler E, Watrin L, Larre P, Leparc-Goffart I, Lastere S, Valour F, et al. Zika virus infection complicated by Guillain-Barre syndrome—case report, French Polynesia, December 2013. Euro Surveill. 2014;19 pii: 20720Google Scholar
  9. 9.
    •• Cauchemez S, Besnard M, Bompard P, Dub T, Guillemette-Artur P, Eyrolle-Guignot D, et al. Association between Zika virus and microcephaly in French Polynesia, 2013–15: a retrospective study. Lancet. 2016;387:2125–32. doi: 10.1016/S0140-6736(16)00651-6. Paper discusses quantitative estimate of the risk of microcephaly in zika infected mothers CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Schuler-Faccini L, Ribeiro EM, Feitosa IM, Horovitz DD, Cavalcanti DP, Pessoa A, et al. Possible association between Zika virus infection and microcephaly-Brazil, 2015. MMWR Morb Mortal Wkly Rep. 2016;65(3):59–62. doi: 10.15585/mmwr.mm6503e2.CrossRefPubMedGoogle Scholar
  11. 11.
    Foy BD, Kobylinski KC, Chilson Foy JL, Blitvich BJ, Travassos da Rosa A, Haddow AD, et al. Probable non-vector-borne transmission of Zika virus, Colorado, USA. Emerg Infect Dis. 2011;17(5):880–2. doi: 10.3201/eid1705.101939.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Musso D, Roche C, Robin E, Nhan T, Teissier A, Cao-Lormeau VM. Potential sexual transmission of Zika virus. Emerg Infect Dis. 2015;21(2):359–61. doi: 10.3201/eid2102.141363. Erratum in: Emerg Infect Dis. 2015 Mar;21(3):552CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    •• Hills SL, Russell K, Hennessey M, Williams C, Oster AM, Fischer M, et al. Transmission of Zika virus through sexual contact with travelers to areas of ongoing transmission—Continental United States, 2016. MMWR Morb Mortal Wkly Rep. 2016;65(8):215–6. doi: 10.15585/mmwr.mm6508e2. Overview of Zika Virus ability to transfer between victims via sexual contact CrossRefPubMedGoogle Scholar
  14. 14.
    •• Musso D, Nhan T, Robin E, Roche C, Bierlaire D, Zisou K, et al. Potential for Zika virus transmission through blood transfusion demonstrated during an outbreak in French Polynesia, November 2013 to February 2014. Euro Surveill.2014;19(14). Erratum in: Euro Surveill.2014;19(15). Discusses possibility of transmission of Zika via blood transfusions Google Scholar
  15. 15.
    PAHO. Zika cumulative number of cases. 1st June 2017. Available from: . Accessed 6 June 2017.
  16. 16.
    WHO. Zika virus infection—India. Disease outbreak news, 26 May 2017. Available from . Accessed 6 June 2017.
  17. 17.
    DICK GW. Zika virus. II. Pathogenicity and physical properties. Trans R Soc Trop Med Hyg. 1952;46:521–34.CrossRefPubMedGoogle Scholar
  18. 18.
    Wolfe ND, Kilbourn AM, Karesh WB, Rahman HA, Bosi EJ, Cropp BC, et al. Sylvatic transmission of arboviruses among Bornean orangutans. Am J Trop Med Hyg. 2001;64(5-6):310–6.CrossRefPubMedGoogle Scholar
  19. 19.
    Abushouk AI, Negida A, Ahmed H. An updated review of Zika virus. J Clin Virol. 2016;84:53–8. doi: 10.1016/j.jcv.2016.09.012.CrossRefPubMedGoogle Scholar
  20. 20.
    Chouin-Carneiro T, Vega-Rua A, Vazeille M, Yebakima A, Girod R, Goindin D, et al. Differential susceptibilities of Aedes aegypti and Aedes albopictus from the Americas to Zika virus. PLoS Negl Trop Dis. 2016;10:e0004543. doi: 10.1371/journal.pntd.0004543.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Shuaib W, Stanazai H, Abazid AG, Mattar AA. Re-emergence of Zika virus: a review on pathogenesis, clinical manifestations, diagnosis, treatment, and prevention. Am J Med. 2016;129:879.e7-879.e12. doi: 10.1016/j.amjmed.2016.02.027.CrossRefPubMedGoogle Scholar
  22. 22.
    Doughty CT, Yawetz S, Lyons J. Emerging causes of Arbovirus encephalitis in North America: Powassan, Chikungunya, and Zika viruses. Curr Neurol Neurosci Rep. 2017;17:12. doi: 10.1007/s11910-017-0724-3.CrossRefPubMedGoogle Scholar
  23. 23.
    Grossi-Soyster EN, LaBeaud AD. Clinical aspects of Zika virus. Curr Opin Pediatr. 2017;29:102–6. doi: 10.1097/MOP.0000000000000449.CrossRefPubMedGoogle Scholar
  24. 24.
    Pastula DM, Durrant JC, Smith DE, Beckham JD, Tyler KL. Zika virus disease for the Neurointensivist. Neurocrit Care. 2017;26:457–63. doi: 10.1007/s12028-016-0333-z.CrossRefPubMedGoogle Scholar
  25. 25.
    •• Paz-Bailey G, Rosenberg ES, Doyle K, Munoz-Jordan J, Santiago GA, Klein L, et al. Persistence of Zika virus in body fluids-preliminary report. N Engl J Med. 2017; doi: 10.1056/NEJMoa1613108. Epud ahead of print. Review how long Zika RNA is detected in human body fluid over 6 month period
  26. 26.
    •• Lanciotti RS, Kosoy OL, Laven JJ, Velez JO, Lambert AJ, Johnson AJ, et al. Genetic and serologic properties of Zika virus associated with an epidemic, Yap State, Micronesia, 2007. Emerg Infect Dis. 2008;14:1232–9. doi: 10.3201/eid1408.080287. Breakdown of Zika virus’ genetic and serologic properties within Micronesia CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Gourinat AC, O'Connor O, Calvez E, Goarant C, Dupont-Rouzeyrol M. Detection of Zika virus in urine. Emerg Infect Dis. 2015;21:84–6. doi: 10.3201/eid2101.140894.CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Zhang FC, Li XF, Deng YQ, Tong YG, Qin CF. Excretion of infectious Zika virus in urine. Lancet Infect Dis. 2016;16:641–2. doi: 10.1016/S1473-3099(16)30070-6.CrossRefPubMedGoogle Scholar
  29. 29.
    •• Lustig Y, Mendelson E, Paran N, Melamed S, Schwartz E. Detection of Zika virus RNA in whole blood of imported Zika virus disease cases up to 2 months after symptom onset, Israel, December 2015 to April 2016. Euro Surveill. 2016;21 doi: 10.2807/1560-7917.ES.2016.21.26.30269. Explores utility of whole blood in Zika virus diagnosis
  30. 30.
    Nicastri E, Castilletti C, Balestra P, Galgani S, Ippolito G. Zika virus infection in the central nervous system and female genital tract. Emerg Infect Dis. 2016;22:2228–30. doi: 10.3201/eid2212.161280.CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Charrel RN, Leparc-Goffart I, Pas S, de Lamballerie X, Koopmans M, Reusken C. Background review for diagnostic test development for Zika virus infection. Bull World Health Organ. 2016;94:574–84D. doi: 10.2471/BLT.16.171207.CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    •• Cao-Lormeau V-M, Blake A, Mons S, Lastère S, Roche C, Vanhomwegen J, et al. Guillain-Barré syndrome outbreak associated with Zika virus infection in French Polynesia: a case-control study. Lancet. 2016;387:1531–9. doi: 10.1016/S0140-6736(16)00562-6. One of the first to provide evidence regarding Zika virus and its ability to cause Guillain-Barré Syndrome CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Villamil-Gomez WE, Sánchez-Herrera ÁR, Hernandez H, Hernández-Iriarte J, Díaz-Ricardo K, Castellanos J, et al. Guillain-Barré syndrome during the Zika virus outbreak in Sucre, Colombia, 2016. Travel Med Infect Dis. 2017;16:62–3. doi: 10.1016/j.tmaid.2017.03.012.CrossRefPubMedGoogle Scholar
  34. 34.
    Kassavetis P, Joseph J-MB, Francois R, Perloff MD, Berkowitz AL. Zika virus-associated Guillain-Barré syndrome variant in Haiti. Neurology. 2016;87:336–7. doi: 10.1212/WNL.0000000000002759.CrossRefPubMedGoogle Scholar
  35. 35.
    Rozé B, Najioullah F, Fergé J-L, Apetse K, Brouste Y, Cesaire R, et al. Zika virus detection in urine from patients with Guillain-Barré syndrome on Martinique, January 2016. Euro Surveill. 2016;21(9) doi: 10.2807/1560-7917.ES.2016.21.9.30154.
  36. 36.
    Thomas DL, Sharp TM, Torres J, Armstrong PA, Munoz-Jordan J, Ryff KR, et al. Local transmission of Zika virus—Puerto Rico, November 23, 2015-January 28, 2016. MMWR Morb Mortal Wkly Rep. 2016;65:154–8. doi: 10.15585/mmwr.mm6506e2.CrossRefPubMedGoogle Scholar
  37. 37.
    Krauer F, Riesen M, Reveiz L, Oladapo OT, Martínez-Vega R, Porgo TV, et al. Zika virus infection as a cause of congenital brain abnormalities and Guillain-Barré syndrome: systematic review. PLoS Med. 2017;14:e1002203. doi: 10.1371/journal.pmed.1002203.CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Dos Santos T, Rodriguez A, Almiron M, Sanhueza A, Ramon P, de Oliveira WK, et al. Zika virus and the Guillain-Barré syndrome-case series from seven countries. N Engl J Med. 2016;375:1598–601. doi: 10.1056/NEJMc1609015.CrossRefPubMedGoogle Scholar
  39. 39.
    Santé publique France. Situation épidémiologique du virus Zika aux Antilles. Point au 22 décembre 2016. Available at: . Accessed 6 June 2017.
  40. 40.
    The Lancet. Another kind of Zika public health emergency. Lancet. 2017;89:573. doi: 10.1016/S0140-6736 (17)30325-2.CrossRefGoogle Scholar
  41. 41.
    Uncini A, Shahrizaila N, Kuwabara S. Zika virus infection and Guillain-Barré syndrome: a review focused on clinical and electrophysiological subtypes. J Neurol Neurosurg Psychiatry. 2017;88:266–71. doi: 10.1136/jnnp-2016-314310.CrossRefPubMedGoogle Scholar
  42. 42.
    Ikejezie J, Shapiro CN, Kim J, Chiu M, Almiron M, Ugarte C, et al. Zika virus transmission-region of the Americas, May 15, 2015-December 15, 2016. MMWR Morb Mortal Wkly Rep. 2017;66(12):329–34. doi: 10.15585/mmwr.mm6612a4.CrossRefPubMedGoogle Scholar
  43. 43.
    Willison HJ, Jacobs BC, van Doorn PA. Guillain-Barré syndrome. Lancet. 2016;388:717–27. doi: 10.1016/S0140-6736(16)00562-6.CrossRefPubMedGoogle Scholar
  44. 44.
    Watrin L, Ghawché F, Larre P, Neau J-P, Mathis S, Fournier E. Guillain-Barré syndrome (42 cases) occurring during a Zika virus outbreak in French Polynesia. Medicine (Baltimore). 2016;95:e3257. doi: 10.1097/MD.0000000000003257.CrossRefGoogle Scholar
  45. 45.
    Watrin I. [Zika virus and neurological manifestations]. Journées de Neurologie de Langue Française. Toulouse, 30 mars 2017.Google Scholar
  46. 46.
    Anaya JM, Rodríguez Y, Monsalve DM, Vega D, Ojeda E, González-Bravo D, et al. A comprehensive analysis and immunobiology of autoimmune neurological syndromes during the Zika virus outbreak in Cúcuta. Colombia J Autoimmun. 2017;77:123–38. doi: 10.1016/j.jaut.2016.12.007.CrossRefPubMedGoogle Scholar
  47. 47.
    Routhu NK, Byrareddy SN. Host-virus interaction of ZIKA virus in modulating disease pathogenesis. J NeuroImmune Pharmacol. 2017;12:219–32. doi: 10.1007/s11481-017-9736-7.CrossRefPubMedGoogle Scholar
  48. 48.
    Pinto-Díaz CA, Rodríguez Y, Monsalve DM, Acosta-Ampudia Y, Molano-González N, Anaya J-M, et al. Autoimmunity in Guillain-Barré syndrome associated with Zika virus infection and beyond. Autoimmun Rev. 2017;16:327–34. doi: 10.1016/j.autrev.2017.02.002.CrossRefPubMedGoogle Scholar
  49. 49.
    Anaya JM, Ramirez-Santana C, Salgado-Castaneda I, Chang C, Ansari A, Gershwin ME. Zika virus and neurologic autoimmunity: the putative role of gangliosides. BMC Med. 2016;14:49. doi: 10.1186/s12916-016-0601-y.CrossRefPubMedPubMedCentralGoogle Scholar
  50. 50.
    Molko N, Simon O, Guyon D, Biron A, Dupont-Rouzeyrol M, Gourinat A-C. Zika virus infection and myasthenia gravis: report of 2 cases. Neurology. 2017;88:1097–8. doi: 10.1212/WNL.0000000000003697.CrossRefPubMedGoogle Scholar
  51. 51.
    WHO. Zika situation report. Zika and potential complications 2016. Available at Accessed 6 June 2017.
  52. 52.
    Dirlikov E, Major CG, Mayshack M, Medina N, Matos D, Ryff KR, et al. Guillain-Barré syndrome during ongoing Zika virus transmission-Puerto Rico, January 1-July 31, 2016. MMWR Morb Mortal Wkly Rep. 2016;65(34):910–4. doi: 10.15585/mmwr.mm6534e1.CrossRefPubMedGoogle Scholar
  53. 53.
    •• Carteaux G, Maquart M, Bedet A, Contou D, Brugières P, Fourati S, et al. Zika virus associated with meningoencephalitis. N Engl J Med. 2016;374:1595–6. doi: 10.1056/NEJMc1602964. On the first diagnosed case of encephalitis caused by Zika virus
  54. 54.
    Soares CN, Brasil P, Carrera RM, Sequeira P, de Filippis AB, Borges VA, et al. Fatal encephalitis associated with Zika virus infection in an adult. J Clin Virol. 2016;83:63–5. doi: 10.1016/j.jcv.2016.08.297.CrossRefPubMedGoogle Scholar
  55. 55.
    Venkatesan A, Tunkel AR, Bloch KC, Lauring AS, Sejvar J, Bitnun A, et al. Case definitions, diagnostic algorithms, and priorities in encephalitis: consensus statement of the international encephalitis consortium. Clin Infect Dis. 2013;57:1114–28. doi: 10.1093/cid/cit458.CrossRefPubMedPubMedCentralGoogle Scholar
  56. 56.
    Rozé B, Najioullah F, Signate A, Apetse K, Brouste Y, Gourgoudou S, et al. Zika virus detection in cerebrospinal fluid from two patients with encephalopathy, Martinique, February 2016. Euro Surveill. 2016;21(16) doi: 10.2807/1560-7917.ES.2016.21.16.30205.
  57. 57.
    Galliez RM, Spitz M, Rafful PP, Cagy M, Escosteguy C, Germano CS, et al. Zika virus causing encephalomyelitis associated with immunoactivation. Open Forum Infect Dis. 2016;3:ofw203. doi: 10.1093/ofid/ofw203.CrossRefPubMedPubMedCentralGoogle Scholar
  58. 58.
    •• Niemeyer B, Niemeyer R, Borges R, Marchiori E. Acute disseminated encephalomyelitis following Zika virus infection. Eur Neurol. 2016;77:45–6. doi: 10.1159/000453396. Report of the first diagnosed case of encephalomyelitis cause by zika virus
  59. 59.
    Roth W, Tyshkov C, Thakur K, Vargas W. Encephalomyelitis following definitive Zika virus infection. Neurol Neuroimmunol Neuroinflamm. 2017;4:e349. doi: 10.1212/NXI.0000000000000349.CrossRefPubMedPubMedCentralGoogle Scholar
  60. 60.
    Palacio E, Clavijo-Prado C, Ruiz A, Arias Antun A, Julian DE. Longitudinal extensive transverse myelitis and Zika virus: a diagnostic challenge in a hospital in Colombia. Neurologia. 2016; doi: 10.1016/j.nrl.2016.08.006. ahead of print. Accessed 5 June 2017
  61. 61.
    Mécharles S, Herrmann C, Poullain P, Tran TH, Deschamps N, Mathon G, et al. Acute myelitis due to Zika virus infection. Lancet. 2016;387:1481. doi: 10.1016/S0140-6736(16)00644-9.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  • Thomas De Broucker
    • 1
  • Alexandra Mailles
    • 2
  • Jean-Paul Stahl
    • 3
  1. 1.NeurologyCentre Hospitalier de Saint-DenisSaint-DenisFrance
  2. 2.Santé Publique FranceSaint-MauriceFrance
  3. 3.Infectious Diseases and Tropical MedicineUniversity hospitalGrenobleFrance

Personalised recommendations