JOURNAL OF NEUROSCIENCE AND NEUROSURGERY (ISSN:2517-7400)

Background: An increase in the prevalence of microcephaly (MCP) was observed in Rio Grande do Norte State (RN) beginning in September 2015. This Brazilian Northeast state was highly impacted by a Zika vírus (ZIKV) outbreak over the subsequent two years. The highest rate of MCP was measured in November 2015, at 20.1 cases per 1,000 live births, compared with only 1.8 cases/year in the previous years. This study aimed to evaluate the neurological disorders in children with MCP whose mothers had exanthematous dermatitis (ED) during the pregnancy, a hallmark (and surrogate clinical marker) of ZIKV infection.

Methods: We evaluated children up to 17 months old followed at a pediatric rehabilitation center in RN. Cohort enrollment occurred with children born between January 2015 and May 2016. We interviewed their mothers about the occurrence of ED during pregnancy, as a surrogate for possible ZIKV infection.

Results: Of the 37 cases of MCP (25 male, 12 girls), 10 mothers did not know how to describe the presence of ED during pregnancy. Of the 24 cases of MCP with maternal ED, 9 patients were classified as having severe spasticity (Ashworth score 3 and 4), 4 patients were classified as mild (Ashworth score 1 and 2) and 11 had no spasticity. Eleven patients had seizure disorders and 5 reported irritability.

Conclusions: According to these data, there is a high prevalence of neurological complications in MCP cases related to ED. These patients need close follow-up care and intensive medical interventions. Longer follow-up will provide data regarding these chronic complications.

Zika virus; Congenital zika syndrome 

Zika virus (ZIKV) may cause an acute febrile illness commonly associated with exanthematous dermatitis (ED) [5,6]. This flavivirus is transmitted to humans by a mosquito bite. Due to the neurotropism of ZIKV, many studies have demonstrated a causal link between ZIKV infection, microcephaly (MCP) and other neurological disorders [1]. According to the Center for Disease Control and Prevention there is sufficient evidence from epidemiological, laboratory and imaging studies to prove a direct, causal association between ZIKV congenital infection and MCP in newborns [2], which has been substantiated by several studies [3,4].

Congenital ZIKV infection is associated with severe congenital neurological abnormalities. An increased number of newborns with MCP was noted in late 2015 in the Northeast of Brazil during the ongoing ZIKV outbreak [1]. We evaluated the neurological complications in babies born in Rio Grande do Norte State (RN) during this outbreak whose mothers reported an ED during pregnancy. RN is a Brazilian Northeast state highly impacted by this outbreak which has a population of 3,400,000 inhabitants, approximately. These data might help better describe the congenital Zika syndrome, its clinical outcomes and natural history.

We evaluated 37 children up to 17 months old followed at a pediatric rehabilitation center in RN State. Cohort enrollment occurred with children born between January 2015 and May 2016. We interviewed their mothers about the occurrence of ED during their pregnancy.

I. Ashworth scale measures resistance during passive soft-tissue stretching and is used as a simple measure of spasticity. Its classification range from “0” (no increase in muscle tone) to “4” (affected part(s) rigid in flexion or extension)

II. Exanthematous rash was described as maculopapular, pruritic, symmetrical and was usually accompanied by fever. 

Of the 37 cases of MCP, 25 were male and 12 were female. Ten mothers did not recall an exanthematous rash during pregnancy. Of the 24 cases of MCP with maternal ED, 9 patients were classified as having severe spasticity (Ashworth score 3 and 4), 4 patients were classified as mild (Ashworth score 1 and 2) and 11 had no spasticity. Eleven patients had seizure disorders and 5 reported irritability.

According to these data, there is a high prevalence of neurological complications in children with MCP born to mothers who experienced an exanthematous rash during pregnancy while living in a region of Brazil suffering a major ZIKV outbreak at the time. These data from a relatively large study, describe the neurological consequences in children with a possible intrauterine exposure to ZIKV. These findings provide supportive evidence linkingneurological disorders to ZIKV infection, reflecting its neurotropism. Limitations of our study include that at the time of this follow-up the children and their mothers had not yet been tested by serological and/or RT-PCR, due to lack of resources for diagnostic tests and poor clinical research infrastructure development. However, given the high frequency of ED with ZIKV infection [5,6] and given that these babies with MCP were born to mothers who were pregnant during a major ZIKV outbreak, it is reasonable to determine the extent to which ED and MCP are linked in this setting. It is likely that the cases of MCP reported here were a result of ZIKV infection. An increased prevalence of MCP and other congenital abnormalities was observed, especially after September 2015, with the highest rate in November 2015 (22.3 cases per 1000 live births). Before this ZIKV outbreak, the rate in RGN between 2010 and 2014 was approximately 1.8 cases/year [1]. Due to the high prevalence of neurological complications, these patients need close follow-up care and intensive medical interventions. Longer follow-up will provide data regarding these chronic neurological complications and how best to intervene.

We thank Dr. Martin Hirsch from Harvard Medical School for his support and assistance with this investigation.

Previous data of this research was first presented as an oral presentation at the annual meeting of Infectious Diseases Society of America (IDWEEK 2017) and at the 70th annual meeting of American Academy of Neurology (2018).

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