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Table of Contents    
CORRESPONDENCE
Year : 2016  |  Volume : 64  |  Issue : 5  |  Page : 1102-1104

Zika virus: New interest in neurology


1 Department of Internal Medicine, IPGMER, Kolkata, West Bengal, India
2 Department of Accident and Emergency, Lady Hardinge Medical College, New Delhi, India
3 Member of Association of Physician of India, Cardiological Society of India. Attached to NMB Diagnostic Centre, Serampore, West Bengal, India

Date of Web Publication12-Sep-2016

Correspondence Address:
Adrija Hajra
Department of Internal Medicine, IPGMER, Kolkata, West Bengal
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0028-3886.190249

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How to cite this article:
Hajra A, Bandyopadhyay D, Hajra SK. Zika virus: New interest in neurology. Neurol India 2016;64:1102-4

How to cite this URL:
Hajra A, Bandyopadhyay D, Hajra SK. Zika virus: New interest in neurology. Neurol India [serial online] 2016 [cited 2019 Aug 23];64:1102-4. Available from: http://www.neurologyindia.com/text.asp?2016/64/5/1102/190249




Zika virus (ZIKV) infection has already drawn a lot of attention in the recent times. This mosquito-borne disease causes a subtle infection in most of the cases. But the threat is still present.

Fetal brain development has been reported to be affected by ZIKV infection. Particularly, infections occurring during the 7-13 weeks of gestation have been found to be strongly associated with microcephaly.[1]

Viral ribose nucleic acid (RNA) has been detected in placenta, amniotic fluid and brain tissues of stillborn babies with microcephaly. ZIKV has been postulated to infect and replicate robustly in neural progenitor cells. Interestingly, ZIKV was found to be less infectious for the developed nerve cells in comparison with the progenitor cells. Due to this fact, fetal brains are more susceptible to ZIKV than adult brains.[2]

A retrospective observational study from the French Polynesia Hospital Center was done during the ZIKV epidemic from October 2013 to April 2014. Here, fetuses with brain anomaly were followed up by ultrasonography and magnetic resonance imaging (MRI). The cerebral biparietal diameter and fronto-occipital diameters below the 3rd percentile were defined as micocephaly. 7 cases were found to be affected with microcephaly. MRI was done in 5 cases. Zika virus was positive in 3 cases. In rest of the 2 cases of microcephaly, where MRI was not done, 1 case was found to be ZIKV positive. In the 3 MRI-detected cases, the MRI finding were:

  • Marked microcephaly with very low cerebral biometric parameters and enlarged peri-cerebral space
  • Transverse cerebellar diameter below the lower limit
  • Absent bulge of the pons with enlarged vermian primary fissure, and
  • Abnormality of the corpus callosum.


The precise effect of ZIKV on the developing brain is not known as yet. ZIKV may affect neural precursor cells resulting in a developmental anomaly of the brain. Diffuse polymicrogyria, gyral abnormalities, parenchymal calcifications, laminar necrosis, and corpus callosal abnormalities have already been found to be associated with several other intra-uterine infections. Their exact association with ZIKV infection is yet to be proven. The brainstem and cerebellum may be the specific targets for ZIKV infection.[3]

Another explanation for the neural involvement in ZIKV infection is the presence of an inflammatory process in the placenta. It disrupts the production of neuropeptides as well as growth factors necessary for the normal brain development.[4]

By October 2015, an increase in the number of birth defects like microcephaly was observed in the north-east region of Brazil, although at that time, the association of ZIKV infection with these birth defects had not been clearly established. Later cases showed the relationship between ZIKV infection and microcephaly.[5] In November 2015, the Evandro Chagas Institute of Brazil declared the presence of ZIKV genome in the blood and tissues of a neonate with microcephaly.[6] In Brazil, a cohort of 35 infants with microcephaly was studied. The mothers were found to have lived in or to have visited the ZIKV affected areas during pregnancy.[7]

Zika-specific IgM was detected in 30 of 31 cerebrospinal fluid samples and 28 of 31 serum samples in neonates with microcephaly in Brazil. As IgM does not cross the placenta, it is clear that the neonates had acquired the infection. It was also suggested that the ZIKV infection has an effect on their brain development.[8] Another interesting fact is that offspring of mothers with hyperglycemia in the first trimester are at an increased risk of developing congenital malformations.[9] The relationship between ZIKV infection during pregnancy and microcephaly in neonates has been established by the Brazilian Ministry of Health.[6],[10]

Recently, organoids (3-dimensional stem cell culture) using bioreactors have been developed to form a model for the human developing brain. In these models, ZIKV (both Asian and African lineage) infection has been shown to increase cell death and reduce cellular proliferation. This results in a decreased neuronal cell-layer volume and the development of microcephaly. This technique will help to detect the effects of ZIKV infection in various stages of brain development. It will also be useful to test the efficacy of antiviral drugs for the prevention of brain malformation.[11]

Recently, two cases of encephalopathy have been reported in patients with ZIKV infection. The cases were reported in Martinique in February 2016, during the ZIKV outbreak.[12] It is possible that encephalopathy and other neurologic problems will be found to be caused by ZIKV infection in further studies that will be conducted related to this infection.

Macular pigment mottling, loss of foveal reflex and a well-defined macular atrophy have been reported in infants with ZIKV infection in Brazil. This ophthalmological involvement has caused a great deal of concern.[7]

At the time of 2013 ZIKV outbreak in French Polynesia, an apparent increase in the incidence of Guillain Barre syndrome (GBS) was noticed. Meningoencephalitis and acute myelitic complicating ZIKV infection also have also been reported during this outbreak.[1],[13] In 2014, in Rio de Janeiro, one case of GBS has been reported. Here, ZIKV was detected in the CSF by PCR.[13]

Since 1 January 2016, six patients had to be admitted to the intensive care units with GBS, in Martinique and Guadeloupe (French West Indies). Among them, two had a confirmed ZIKV infection. For critical care physicians, this new infection has proven to be challenging. The atypical presentation may delay the diagnosis of ZIKV infection in this setting.[14]

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
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Petersen LR, Jamieson DJ, Powers AM, Honein MA. Zika Virus. N Engl J Med 2016; 374:1552-63.  Back to cited text no. 1
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Guo J. Studies using IPS cells support a possible link between ZIKA and microcephaly. Cell Biosci (2016) 6:28.DOI 10.1186/s13578-016-0096-4  Back to cited text no. 2
    
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Artur PG, Besnard M, Guignot DE, Jouannic JM, Garel C. Prenatal brain MRI of fetuses with Zika virus infection. Pediatr Radiol: DOI 10.1007/s00247-016-3619-6.  Back to cited text no. 3
    
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Santos C N D, Goldenberg S. Zika virus and microcephaly: Challenges for a long-term agenda. Trends in Parasitology: Available from: http://dx.doi.org/10.1016/j.pt. 2016.03.008. [Last accessed on 2016 May 01].  Back to cited text no. 5
    
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De Carvalho NS, De Carvalho BF, Fugac CA, Dóris B, Biscaia ES. Zika virus infection during pregnancy and microcephaly occurrence: A review of literature and Brazilian data. Braz J Infect Dis 2016. Available from: http://dx.doi.org/10.1016/j. bjid.2016.02.006. [Last accessed on 2016 May 01].  Back to cited text no. 6
    
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Hajra A, Bandyopadhyay D, Hajra SK. Zika virus: A global threat to humanity: A comprehensive review and current developments. North Am J Med Sci 2016; 8:123-8.  Back to cited text no. 7
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Cordeiro MT, Pena J, Brito C A, Gil L H, Marques ET. Positive IgM for Zika virus in the cerebrospinal fluid of 30 neonates with microcephaly in Brazil. The Lancet: Available from: http://dx.doi.org/10.1016/S0140-6736 (16) 30253-7. [Last accessed on 2016 May 01].  Back to cited text no. 8
    
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Nielsen KK, Bygbjerg IC. Zika virus and hyperglycaemia in pregnancy. The Lancet. 2016; 387:1812.  Back to cited text no. 9
    
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Qian X, Nguyen HN, Song MM, Hadiono C, Ogden SC, Hammack C, et al. Brain-region-specific organoids using mini-bioreactors for modeling ZIKV exposure. Cell (2016). Available from: http://dx.doi.org/10.1016/j.cell. 2016.04.032. [Last accessed on 2016 May 01].  Back to cited text no. 11
    
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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 Apr 21; 21 (16). doi: 10.2807/1560-7917.ES.2016.21.16.30205.  Back to cited text no. 12
    
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Brasil P, Sequeira PC, Freitas AD, Zogbi HE, Calvet GA, Souza RV, et al. Guillain-Barré syndrome associated with Zika virus infection. Lancet 2016; 387:1482.  Back to cited text no. 13
    
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Thiery G, Valentino R, Meddhaoui H. Zika virus-associated Guillain–Barré syndrome: A warning for critical care physicians. Intensive Care Med: DOI 10.1007/s00134-016-4364-x.  Back to cited text no. 14
    



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