Childs Nerv Syst

https://doi.org/10.1007/s00381-017-3636-2

FOCUS SESSION

Hydrocephalus associated to congenital Zika syndrome: does

shunting improve clinical features?
Eduardo Jucá 1,2,3 & André Pessoa 2,4 & Erlane Ribeiro 2,3 & Rafaela Menezes 3 &
Saile Kerbage 2 & Thayse Lopes 3 & Luciano Pamplona Cavalcanti 5

Received: 9 October 2017 / Accepted: 16 October 2017

# Springer-Verlag GmbH Germany 2017

Abstract Conclusion This series points out the possibility of hyperten-

Purpose Congenital Zika syndrome (CZS) is a new entity
with little information about its course and natural history. It
is known that prenatal infection by Zika virus is associated to
disrupted nervous system development, leading to typical
neurological disabilities and deformities. Some children pres-
ent progressive ventriculomegaly and hydrocephalus associ-
ated to aggravation of seizures and neurological impairment.
The aim of this study is to evaluate the development of hy-
drocephalus and the impact of ventriculoperitoneal shunt in-
sertion in the clinical condition of these children.
Methods Data was obtained from chart review, direct inter-
views with patients’ parents, direct neurological examination,
and analysis of pre- and postoperative neuroimages.
Results A group of 115 patients had CZS diagnosis from
November 2015 to July 2017. Among them, 21 (18.3%) pa-
tients had ventricular enlargement noted on follow-up CT
scans. Six children (28.6%) underwent a ventriculoperitoneal
shunt and all had some improvement after surgery concerning
either waking time during the day and better interaction.
Overall improvement was also noted in seizures. Spasticity
decrease and more cervical control were also achieved. In
two out of six cases, a slight increase in parenchymal length
could be noted on the CT scans.
* Eduardo Jucá
eduardojuca@gmail.com
1
Universidade de Fortaleza (UNIFOR), Fortaleza, Ceará, Brazil
2
Hospital Infantil Albert Sabin, Fortaleza, Ceará, Brazil
3
Centro Universitário Christus, Fortaleza, Ceará, Brazil
4
Universidade Estadual do Ceará-UECE, Fortaleza, Brazil
5
Universidade Federal do Ceará, Fortaleza, Ceará, Brazil
sive hydrocephalus development in CZS patients. Affected
children may benefit from VP shunt insertion. These findings
suggest a dual pathology association: fetal brain disruption
and primary cortical malformation by the virus itself and hy-
pertensive hydrocephalus. This is already seen in some cases
of congenital rubella, toxoplasmosis, or cytomegalovirus-
associated hydrocephalus.
Keywords Zika virus . Microcephaly . Hydrocephalus .
Ventriculoperitoneal shunt
Introduction
Congenital Zika syndrome (CZS) is a newly identified entity
provoked by infection by the Zika virus that affects children
during fetal development by vertical transmission from infect-
ed mothers. This virus, whose first descriptions point to an
origin in central African jungles, had already circulated in
the pacific islands leading to some isolated cases and limited
outbreaks [1, 2]. It has arrived in Brazil probably in 2014,
leading to a large amount of cases, mainly in the northeast
region of the country [3, 4].
Zika virus is transmitted via the bite of an infected Aedes
mosquito. In adults, it commonly leads to a self-limited febrile
disease associated to malaise, disseminated pain, and cutane-
ous rash, although many cases are asymptomatic. However,
when the infection affects pregnant women, mainly in the first
trimester, the virus may pass through the placental barrier and
cause CZS, leading to dysregulation of genes involved in neu-
ronal development and apoptosis, resulting in severe damage
to the embryonic brain, fetal brain disruption, primary cortical
malformation, and microcephaly [5].

Head circumference is usually under 32 cm at birth (− 2
SD, 31.5 cm for girls and 31.9 cm for boys on term), and the
shape of the head is typically altered, with fall of the top of the
skull and excess of skin in the front. Head computer tomog-
raphy (CT) scans show a characteristic pattern of brain atro-
phy, polymicrogyria, and spread calcifications (Fig. 1) [6–9].
Neurological impairment is remarkable in these children,
and consequently their development is severely delayed.
Many of the babies present epilepsy, with difficult seizures
control [10, 11].
There is abundant literature concerning hydrocephalus in
other congenital infections as toxoplasmosis [12–14] and cy-
tomegalovirus [15, 16], but no sufficient data has been pub-
lished about hydrocephalus in the context of CZS. The aim of
this study is to report a series of patients with CZS submitted
to ventriculoperitoneal (VP) shunt to treat hydrocephalus,
discussing its consequences and the global physiopathological
process involved in the disease.
Methods
The present study is a descriptive cohort of patients presenting
CZS followed by a multidisciplinary team at the Hospital
Infantil Albert Sabin (Fortaleza, Brazil), which is the reference
unit for the management of the disease in the state of Ceará,
northeast of Brazil, the most affected region in the world
concerning CZS.
Data was collected from the specific CZS outpatient ser-
vice and from the pediatric neurosurgery unit from September
2016 to July 2017. Information was obtained from patients’
charts, direct interviews with parents, neurological assess-
ment, and neuroimage evaluation. A specific clinical form
was used to obtain variables as age, gender, head circumfer-
ence (HC), gestational age, CT scan results, and neurological
examination.
HC was monitored using an inelastic measuring tape pass-
ing at the glabella and at the external occipital prominence.
Intergrowth table for preterm newborns and the World Health
Fig. 1 Clinical aspect of an infant with characteristic pattern of anomalies in congenital Zika syndrome. a Excessive scalp with folds. b Severe decrease
in cranial vault, irregularity of the skull, and collapse of the cranial bones with prominent occiput. c Craniofacial disproportion
Childs Nerv Syst
Organization table for newborns delivered at term were used
to analyze head circumference measures.
CT scans were assessed focusing on ventricles’ size, pres-
ence of sulci and giri, existence of subdural spaces, and indi-
rect signs of intracranial hypertension. Evans’ index was not
used to analyze ventricles’ dimensions because the dispropor-
tional size and the distortion of ventricles morphology made
the images not suitable to analysis by this index.
Parents were contacted to be informed and to sign the con-
sent form. The study was evaluated and approved by the re-
search ethics committee of the Hospital Infantil Albert Sabin
under process n° 56309716.6.0000.5049.
Results
A group of 115 patients is followed by the CZS task force.
Twenty-one (18.3%) children presented a progressive enlarge-
ment of the ventricles noted on systematic follow up CT scans.
Among these, six patients (28.6%), four boys and two girls,
presented, in addition to ventriculomegaly, an increase in fre-
quency and morbidity of seizures, drowsiness, or worsening
of neurological performance noted during rehabilitation ses-
sions. These patients were submitted to surgical implantation
of a VP shunt.
The chosen surgical technique was a classical VP shunt
with standard pediatric medium opening pressure valve.
As a whole, all operated patients showed clinical improve-
ment after surgery. There was increase in daily waking hours
and better eye contact. A general decrease in amount and
morbidity of seizures was observed. Regarding neurologic
examination, patients presented less spasticity and better cer-
vical control. In two cases, a slight thickening of brain paren-
chyma was observed on CT scans.
Clinical data are shown in Table 1. Patient 3 was submitted
to emergency surgery, with no head circumference measure at
diagnosis. At birth, patient 4 had normal head circumference
according to gestational age.
A concise description of each case is presented below:
Childs Nerv Syst

Table 1 Clinical data from 6 infants with congenital Zika infection and hydrocephalus

Patient/ Gender Gestational age Birth head HC—z Age of diagnosis of Corrected HC at the diagnosis HC—z score at
case in weeks at birth circumference scorea hydrocephalus age of hydrocephalus diagnosis of
(HC) in cm (month) hydrocephalusb

1 Male 39 27 − 4.81 9 8.8 40 − 3.91

2 Male 39 29 − 3.76 8 7.8 38.5 − 5.17
3 Female 40 27 − 4.82 13 13 NA NA
4 Female 26 21.5 − 1.51 15 11.8 41 − 2.82
5 Male 41 28 − 4.85 9 9.2 37 − 6.42
6 Male 40 30 − 3.19 13 13 40.5 − 4.91

NA not available
a
Standard deviations calculated using INTERGROWTH-21st Newborn Size Application Tool (https://intergrowth21.tghn.org/global-perinatal-package/
intergrowth-21st-comparison-application/)
b
Standard deviations calculated using PediTools for World Health Organization growth standard for age 0–24 months (http://peditools.org/growthwho/
index.php)

Case 1 the first trimester of pregnancy and serological tests per-

An 11-month-old boy was first evaluated at the outpa-
tient service of the CZS task force at age 3 months. From
the beginning, he presented hypertonia, hyperexcitability,
global hyperreflexia, and incomplete cervical control.
Primitive reflexes persisted along the months. CT scan
performed at age 6 days showed spread calcifications,
subcortical atrophy, and ventriculomegaly. At age
6 months, he started to present seizures manifested by
infantile spasms, which became more frequent at
8 months and followed by somnolence and irritability.
A new CT scan showed important increase of the ventric-
ular size. Decision was taken to perform a VP shunt,
which had no complications. The child was discharged
from hospital 3 days after surgery. At the first follow-up
consultation, there was an important decrease in seizure
frequency, improvement of interaction with the environ-
ment and more awareness. On clinical examination, the
patient was alert and had less global hypertonia.
Case 2
An 8-month-old boy was initially evaluated at the 6th
day of life. Initial neurological assessment showed hyper-
tonia, hyperreflexia, limb tremors, convergent strabis-
mus, and the typical CZS dimorphisms. CT scan at the
2nd week of life showed calcifications, global atrophy,
increase of the subarachnoid spaces, and cerebellar atro-
phy. At age 8 months, he started to present spasms and
irritability. A new CT scan showed important ventricular
increase. A VP shunt was inserted with no complications
and the patient was discharged at the 2nd postoperative
day. At 1-month follow-up, there was complete remission
of seizures and tremors, less irritability, more alertness,
and better cervical control.
Case 3
A 14-month-old girl was previously known as having
CZS. The mother had symptoms of mild Zika infection at
formed during pregnancy and just after birth were posi-
tive. The baby was under anticonvulsive treatment since
the second semester of life and was referred from the
countryside due to vomits and irritability starting 3 days
before admission. CT scan showed very large ventricles
and signs of intracranial hypertension. A VP shunt was
inserted as emergency procedure. The patient had a good
recovery, being discharged at the 3rd day post-op. At the
follow-up, there were less seizures and irritability, and no
vomits.
Case 4
A 15-month-old girl was followed since age 1 month
with phenotypical and radiological aspects consistent
with CZS. She was admitted after exacerbation of sei-
zures just after receiving pentavalent vaccine. During
hospital stay, a CT scan showed important ventricular
dilatation. Taking into account clinical aggravation and
ventricular increase, a VP shunt was inserted without
complications. The patient was discharged at 2nd postop-
erative day. Two days later, she was readmitted due to a
febrile state. Although a cerebrospinal fluid (CSF) exam-
ination was normal, antibiotics were maintained for
14 days. After 2 weeks at home in good condition, she
was admitted for the 3rd time with marked respiratory
distress and died after 19 days due to sepsis of pulmonary
origin.
Case 5
An 11-month-old boy presented with microcephaly,
arthrogryposis, craniofacial disproportion, hypertonia,
and hyperreflexia. Initial CT scan showed the typical fea-
tures of CZS, including spread calcifications and
polymicrogyria. At age 9 months, he started to present
spasms and persistent irritability, with periods of drows-
iness and stupor. Follow-up CT scan showed important
ventricular enlargement and a thinner brain parenchyma.

Fig. 2 Tomographical findings in a child with congenital Zika syndrome and progressive ventriculomegaly. a CT at diagnosis of congenital Zika
syndrome. b CT showing hypertensive hydrocephalus. c Post-op CT scan
Clinical and image association lead to insertion of a VP
shunt, which had no complications. He was discharged from
hospital 3 days after surgery. At the 1-month follow-up
consultation, seizures were controlled with anticonvulsants.
The child was alert and calm, interacting with the
examiners.
Case 6
A 14-month-old boy had phenotypical and radiologi-
cal features consistent with CZS. At age 11 months, he
started with infantile spasms and worsening of dysphagia.
Follow-up CT scan showed global enlargement of the
ventricles. After VP shunt insertion, the child had
laryngospasm followed by a cardiac arrest. He was suc-
cessfully reanimated and currently is in good general con-
dition, with fewer seizures, less spasticity, and better so-
cial interaction.
Discussion
As a recently described entity, CZS is imposing several difficul-
ties to the teams who care for these patients, given the lack of
established standards for treatment and the scarce literature [17].
This study is one of the first efforts to report the development of
hydrocephalus associated to CZS and its treatment with VP
shunt. To our knowledge, there are no other series reported in
the literature.
The cohort of children with CZS in our service shares the
same phenotypical and clinical features of other affected
Childs Nerv Syst
populations in Brazil. These characteristics have been already
described in literature and include microcephaly due to severe
brain damage and impaired neurological development [6–9].
Some of the individuals presented epilepsy with different
levels of severity [10, 11] and ophthalmologic abnormalities
as macular circumscribed chorioretinal atrophy, focal mottled
retinal pigment epithelium, optic nerve pallor, early-onset stra-
bismus, nystagmus, and low visual acuity [18, 19].
Likewise, neuroimaging findings show a consistent homoge-
neous pattern in the affected populations: cortico-subcortical at-
rophy, cortical malformation mainly polymicrogyria, subcortical
and basal ganglia calcification, ventriculomegaly, cerebellar al-
terations, and subdural space enlargement (Fig. 2) [6–9, 17, 20].
Given the recent onset of the outbreak, some complications
are being detected and becoming part of the natural history of the
disease as the patients grow older. This has been observed in
cases of epilepsy and ventricular enlargement that are not detect-
ed immediately after birth but only around the end of the first
semester and the end of the 1st year of life, respectively.
During follow-up, some children presented remarkable ven-
tricular enlargement on CT scans. This was associated in most
cases with clinical aggravation manifested by drowsiness, apathy,
neurological deterioration, and epilepsy worsening. Although
ventricular increase has been usually ascribed to continuous brain
damage, a few patients with these characteristics were submitted
to VP shunt due to combined clinical and radiological worsening.
As shown in Table 1, increase in HC is not a remarkable marker
for hydrocephalus decompensation in these cases.
The choice for VP shunt as treatment for hydrocephalus
was based on the supposition of CSF flow disturbance, with
Childs Nerv Syst
no clear obstruction of its pathways, which leads us to classify
the hydrocephalus as Bcommunicating^ [21–23]. Moreover,
hydrocephalus in the context of CZS seems to appear a little
before or around the first year of life. In this age range, endo-
scopic treatment for hydrocephalus is known to have worse
results than VP shunts [21–23].
Although one could argue that the increase of ventricular
volume might be due to continuous direct brain damage by the
virus leading to wider CSF spaces and ex-vacuum non-hyper-
tensive ventriculomegaly, the rapid enlargement of the ventri-
cles associated to clinical deterioration suggests hypertensive
hydrocephalus as part of the course of the disease in some
cases.
The response of the children in this series to ventricular
shunt reinforces this hypothesis. As a whole, children had less
somnolence and apathy and less seizure episodes following
surgery. There has been one death in the late post-operatory
period from causes not related to shunting. Even this patient
had a general neurological improvement in the weeks after
surgery.
In fact, such complex physiopathological picture has al-
ready been established for other congenital infectious diseases
as cytomegalovirus, rubella, toxoplasmosis, and herpes sim-
plex virus infection [24–26]. These diseases share several fea-
tures with the newly reported CZS, including pathological
aspects and natural history, with the common final result of
severe neurological impairment.
It is well known that some children suffering from these
diseases develop hypertensive hydrocephalus as part of the
disease course.
Until now, the CZS outbreak has been considered an ex-
clusively medical and pediatric subject, with no surgical im-
plications. The role of the pediatric neurosurgeon in the mul-
tidisciplinary task force was merely directed to help identify-
ing the disease and to make differential diagnosis with neuro-
surgical problems as craniosynostosis and congenital brain
malformations. With the recognition that hydrocephalus and
intracranial hypertension may be part of the clinical presenta-
tion in some cases, pediatric neurosurgeons must be defini-
tively integrated into the teams facing the problem.
Conclusions
Some children affected by CZS who develop hypertensive
hydrocephalus may benefit from VP shunt in terms of better
neurological status and seizure control. Shunting does not
implicate in specific complications in this population, and
further morbidity or mortality may arrive from other issues
involving children with CZS. As already noted for other con-
genital infections, intracranial hypertension can cause addi-
tional harm for the developing nervous system besides direct
viral aggression. More follow-up time and bigger series are
needed to establish more accurate prognosis. Pediatric neuro-
surgery services must be part of the management of this still
obscure and challenging disease.
Compliance with ethical standards
Conflict of interest All authors declare that there is no conflict of
interests to be disclosed.
References
1. Petersen LR, Jamieson DJ, Powers AM, Honein MA (2016) Zika
virus. N Engl J Med 374(16):1552–1563. https://doi.org/10.1056/
NEJMra1602113
2. Younger DS (2016) Epidemiology of Zika virus. Neurol Clin 34:
1049–1056. https://doi.org/10.1016/j.ncl.2016.06.008
3. Schuler-Faccini L, Ribeiro EM, Feitosa IML et al (2016) Possible
association between Zika virus infection and microcephaly-Brazil,
2015. MMMWR Morbility Mortal Wkly Rep 65:59–62. 10.15585/
mmwr.mm6503e2
4. Heukelbach J, Alencar CH, Kelvin AA, Oliveira WK, Pamplona de
Góes Cavalcanti L (2016) Zika virus outbreak in Brazil. J Infect
Dev Ctries 10(2):116–120. https://doi.org/10.3855/jidc.8217
5. Olagnier D, Muscolini M, Coyne CB et al (2016) Mechanisms of
Zika virus infection and neuropathogenesis. DNA Cell Biol 35:
367–372. https://doi.org/10.1089/dna.2016.3404
6. Moore CA, Staples JE, Dobyns WB et al (2016) Characterizing the
pattern of anomalies in congenital Zika syndrome for pediatric cli-
nicians. JAMA Pediatr:1–8. https://doi.org/10.1001/jamapediatrics.
2016.3982
7. del Campo M, Feitosa IML, Ribeiro EM et al (2017) The pheno-
typic spectrum of congenital Zika syndrome. Am J Med Genet Part
A 173:841–857. https://doi.org/10.1002/ajmg.a.38170
8. Van der Linden V, Pessoa A, Dobyns W et al (2016) Description of
13 infants born during October 2015–January 2016 with congenital
Zika virus infection without microcephaly at birth — Brazil.
MMWR Morb Mortal Wkly Rep 65:1343–1348. 10.15585/
mmwr.mm6547e2
9. Cavalcanti LP, Ribeiro EM, Pessoa AL, Carvalho FH, Neto MM,
Araújo FM et al (2017b) Microcephaly in Infants, Ceará State,
Brazil, 2015–2016. Rev Med UFC 57(1):30–35
10. Alves LV, Di D, Sousa C (2016) Crises epilépticas em crianças com
síndrome congênita do Zika vírus. Rev Bras Saúde Matern Infant
16:33–37. https://doi.org/10.1590/1806-9304201600s100003
11. Pastula DM, Yeargin-Allsopp M, Kobau R (2017) Enhanced epi-
lepsy surveillance and awareness in the age of Zika. JAMA Neurol.
https://doi.org/10.1001/jamaneurol.2017.0215
12. Kaiser G (1985) Hydrocephalus following toxoplasmosis. Z
Kinderchir 40(Suppl 1):10–11. https://doi.org/10.1055/s-2008-
1059757
13. Hutson SL, Wheeler KM, McLone D et al (2015) Patterns of hy-
drocephalus caused by congenital Toxoplasma gondii infection as-
sociate with parasite genetics. Clin Infect Dis 61:1831–1834.
https://doi.org/10.1093/cid/civ720
14. Jones J, Lopez A, Wilson M (2003) Congenital toxoplasmosis. Am
Fam Physician
15. Bale JF, Bray PF, Bell WE (1985) Neuroradiographic abnormalities
in congenital cytomegalovirus infection. Pediatr Neurol 1:42–47.
https://doi.org/10.1016/0887-8994(85)90008-6
16. Malinger G, Lev D, Zahalka N et al (2003) Fetal cytomegalovirus
infection of the brain: the spectrum of sonographic findings. Am J
Neuroradiol 24:28–32

17. Ribeiro EM, Lopes TF, Kerbage SC, Pessoa ALS, Cavalcanti LPG
(2017) From the perception of a cluster of cases of children with
microcephaly to congenital Zika syndrome in Brazil: the lessons we
have learned and the challenges that lie ahead of us. J Venomous
Anim Toxins Incl Trop Dis 23:15. https://doi.org/10.1186/s40409-
017-0107-x
18. Verçosa I, Carneiro P, Verçosa R et al (2017) The visual system in
infants with microcephaly related to presumed congenital Zika syn-
drome. J Am Assoc Pediatr Ophthalmol Strabismus. https://doi.org/
10.1016/j.jaapos.2017.05.024
19. Ventura CV, Maia M, Dias N et al (2016) Zika: neurological and
ocular findings in infant without microcephaly. Lancet 387:2502.
https://doi.org/10.1016/S0140-6736(16)30776-0
20. Cavalheiro S, Lopez A, Serra S et al (2016) Microcephaly and Zika
virus: neonatal neuroradiological aspects. Childs Nerv Syst 32:
1057–1060. https://doi.org/10.1007/s00381-016-3074-6
Childs Nerv Syst
21. Nishiyama K, Yoshimura J, Fujii Y (2015) Limitations of
neuroendoscopic treatment for pediatric hydrocephalus and consid-
erations from future perspectives. Neurol Med Chir (Tokyo) 55:
611–616. https://doi.org/10.2176/nmc.ra.2014-0433
22. Rajshekhar V, Moorthy R (2011) Endoscopic third ventriculostomy
for hydrocephalus: a review of indications, outcomes, and compli-
cations. Neurol India 59:848. https://doi.org/10.4103/0028-3886.
91364
23. Venkataramana N (2011) Hydrocephalus Indian scenario—a review.
J Pediatr Neurosci 6:11. https://doi.org/10.4103/1817-1745.85704
24. Hahnel S (1992) Inflammatory diseases of the brain in childhood.
AJNR 13:551–567
25. Bale JF (2009) Fetal infections and brain development. Clin
Perinatol 36:639–653. https://doi.org/10.1016/j.clp.2009.06.005
26. Toma AK (2015) Hydrocephalus. Surg 33:384–389. https://doi.org/
10.1016/j.mpsur.2015.05.006