Motor and cognitive response to intensive multidisciplinary therapy: the first reported case of congenital Zika virus syndrome.

PURPOSE: To provide a detailed description of the development of the first case of congenital Zika syndrome (CZS) to be reported in the literature worldwide. CASE DESCRIPTION: This report describes the case of a child with CZS monitored from pregnancy until four years of age, with periodic evaluations of head circumference, weight, height, motor function according to the Gross Motor Function Measure (GMFM-88), and the occurrence of comorbidities. OUTCOMES: The child's birth weight and length were normal (z-score = 1.1 and -1.95, respectively), while head circumference was below the expected value (z-score = -3.15). At 48 months, head circumference reached 43 cm (z-score = -4.48). During daily home physiotherapy sessions, the child achieved developmental milestones, standing unsupported at 17 months, with a GMFM-88x score of 137. With specialist therapy, the child walked independently at 36 months and a total GMFM-66 score of 214 was achieved by 42 months. In the four years of follow-up, the child was hospitalized four times for different reasons. No convulsive seizures occurred. CONCLUSIONS: Despite severe neurological impairment, the child's weight and height are adequate for age, with motor and cognitive function improving over the first four years of life.

Effect of Intensive Physiotherapy Training for Children With Congenital Zika Syndrome: A Retrospective Cohort Study.

OBJECTIVE: To investigate the effect of intensive physiotherapy training on the motor function of children with congenital Zika syndrome (CZS). DESIGN: A retrospective cohort study. SETTING: A support center for children with microcephaly. PARTICIPANTS: Children (N=7) aged 14 to 18 months old who were diagnosed with CZS and previously monitored more than 1 year. INTERVENTIONS: A 2-stage protocol repeated uninterruptedly for 1 year. In the first stage, the children were submitted to 1 hour of conventional physiotherapy and 1 hour of suit therapy 5 times a week for 4 weeks. The second stage consisted of 1 hour of suit therapy 3 times a week for 2 weeks. MAIN OUTCOME MEASURES: Gross motor function measure (GMFM) and body weight. RESULTS: Six evaluations were conducted approximately 3 months apart. An increase in the overall GMFM score was observed between the first and second (P=.046), first and third (P=.018), first and fourth (P=.018), first and fifth (P=.043), and first and sixth evaluations (P=.018). Differences in the scores of the individual GMFM dimensions were found only for dimension A (lying and rolling) between the first and fourth evaluations (P=.027) and for dimension B (sitting) between the first and third (P=.018), first and fourth (P=.046), and first and sixth evaluations (P=.027). No difference was found in body weight between the first and sixth evaluations (P=.009). During follow-up, only 1 child required hospitalization, and another had increased irritability. CONCLUSIONS: Children with CZS were able to perform 2 hours of motor physiotherapy daily with no serious complications, resulting in an increase or stabilization in GMFM scores.

Obstetric and perinatal outcomes in cases of congenital Zika syndrome.

OBJECTIVE: To describe obstetric and perinatal outcomes in cases of congenital Zika syndrome (CZS). METHODS: A dual prospective and retrospective cohort study involving 102 pairs of mothers and fetuses/children with CZS whose infection was confirmed by testing for the Zika virus in amniotic fluid, umbilical cord blood, and fragments from the placenta of the newborn infant (confirmed CZS), or by intrauterine imaging tests (neurosonography), and/or postnatal computed tomography (presumed CZS). RESULTS: Suspicion of CZS was investigated by ultrasonography during pregnancy in 52.9% of cases. The principal prenatal imaging findings were ventriculomegaly (43.1%) and microcephaly (42.2%). Median gestational age at delivery was 39 weeks, with 15.7% being premature. Mean head circumference at birth was 30.0 ± 2.3 cm, with 66% of cases being classified as having microcephaly. Arthrogryposis was found in 10 cases (9.8%). There were no fetal deaths; however, nine neonatal deaths were recorded, and three autopsies were performed. CONCLUSION: Neonatal mortality was high, almost 10%. Regarding the abnormalities of CZS, microcephaly, although common, was not present in all cases and intracranial findings need to be taken into consideration for diagnosis. Therefore, ultrasound screening during pregnancy should be systematized and expanded in endemic zones.

Neurological outcomes of congenital Zika syndrome in toddlers and preschoolers: a case series.

BACKGROUND: Congenital Zika syndrome causes a spectrum of neurological symptoms with varying effects on function that require different therapeutic strategies. To date, this spectrum of effects and its clinical implications have not been completely described. We describe the neurological examination findings in toddlers and preschoolers, including predominant symptom complexes and comorbidities. METHODS: This study is a case-series neurological evaluation of 75 children with congenital Zika syndrome in Campina Grande, Brazil. The study is part of a cohort of children with congenital Zika syndrome that started in 2015 and is still ongoing. Children with Zika virus infection detected during pregnancy (mothers exhibited rash and were followed and diagnosed by fetal ultrasound abnormalities or RT-PCR) or through microcephaly screening after birth, using Intergrowth 21 guidelines, were selected by laboratory and radiological criteria. Children were examined during a 10-day period in September, 2018, and underwent neurological interview, examination, and assessment of functional outcomes and comorbidities. Children were divided in groups of predominant corticospinal or neuromuscular clinical signs and the associations between these groups and clinical comorbidities were assessed. FINDINGS: All of the children recruited to the study from Nov 29, 2015 to Nov 30, 2017 had imaging correlates of congenital Zika syndrome. Children were assigned to groups depending on the signs exhibited, either corticospinal or neuromuscular, with or without dyskinetic signs. 75 children completed the evaluation, 38 (51%) girls and 37 (49%) boys. Median age was 33 months (range 26-40 months; IQR 29-34). Microcephaly was present at birth in 56 (75%) children, and 19 (25%) children were born with normal head circumference, 15 of whom later developed microcephaly. Neurological examination grouped four children as having isolated dyskinetic signs, 48 children were assigned to the corticospinal group and 23 into the neuromuscular group. Dyskinetic findings were present in 30 (40%) children, either alone (four [5%]) or combined with corticospinal (19 [40%] of 48) or neuromuscular (seven [30%] of 23) findings. Comorbidities were highly prevalent, and the neuromuscular group had worse functional outcomes, evaluated by gross motor function (p=0·026), manual abilities (p=0·0013), and communication function (p<0·0005) classification scales, than the corticospinal group, whereas pneumonia (p<0·0005) and urinary tract infections (p<0·0005) were more frequent in the corticospinal group. Cortical hyperexcitability was supported by several clinical correlates, such as early onset epilepsy, persistence of primitive reflexes, and dystonia. INTERPRETATION: We describe distinct neurological profiles in the congenital Zika syndrome spectrum, with functional outcomes tending to correlate with these groups. The clinical division of children based on the disease signs proposed here is supported by the literature on central and peripheral nervous system pathology in congenital Zika syndrome. The high prevalence of dyskinetic symptoms merits special attention. FUNDING: Brazilian National Council for Scientific and Technological Development and by the Coordination for the Improvement of Higher Education Personnel.