Early Gross Motor Development Among Brazilian Children with Microcephaly Born Right After Zika Virus Infection Outbreak.

OBJECTIVE: To assess the gross motor development of children with presumed congenital Zika virus (ZIKV) infection over the first 2 years of their lives. METHODS: Seventy-seven children were assessed at the median ages of 11, 18, and 24 months, using the evaluative instrument Gross Motor Function Measure (GMFM-66). At the third assessment, the children with diagnoses of cerebral palsy (CP) were classified by severity through the Gross Motor Function Classification System (GMFCS) and stratified by topography indicating the predominantly affected limbs. With these instruments in combination and using the motor development curves as reference, the rate of development and functional ability were estimated. RESULTS: At 2 years of age, all children had the diagnosis of CP. Seventy-four (96.1%) presented gross motor skills similar to those of children aged 4 months or younger, according to the World Health Organization's standard. The GMFM-66 median score among the 73 (94.8%) children with quadriplegia and GMFCS level V showed significant change between 11 and 18 months (p < 0.001) and between 11 and 24 months (p < 0.001). No significant difference (p = 0.076) was found between 18 and 24 months. CONCLUSION: Despite showing some gross motor progress during the initial 18 months of life, these children with presumed congenital ZIKV infection and CP experienced severe motor impairment by 2 years of age. According to the motor development curves, these children with quadriplegia have probably already reached about 90% of their motor development potential.

Cerebral Palsy in Children With Congenital Zika Syndrome: A 2-Year Neurodevelopmental Follow-up.

OBJECTIVE: To describe the 2-year neurodevelopmental outcome in children with cerebral palsy associated with congenital Zika (CZ) and explore variables associated with a more severe presentation. METHODS: Data on 69 children with cerebral palsy associated with CZ, followed in a neurorehabilitation hospital, who consecutively attended the neurodevelopmental assessment at 2 years of age, were collected. Bayley III Scales of Infant and Toddler Development, Hammersmith Infant Neurological Examination, and Gross Motor Function Classification System were used for the outcome evaluation. Descriptive and inferential statistical analysis were performed. RESULTS: The median age at follow-up was of 24.0 (23-32) months. Only 3 (4.3%) children were not microcephalic. The majority presented with bilateral (94.2%), spastic (100.0%), Gross Motor Function Classification System grade IV or V (92.8%) cerebral palsy, epilepsy (73.1%), extremely low performances on cognitive (94.2%), language (95.7%), and motor (95.7%) Bayley-III Scales of Infant and Toddler Development Test scores. The median Hammersmith Infant Neurological Examination score was of 21.0 (range 9-75). There was a correlation between birth head circumference with the cognitive (r = 0.3, P < .01), language (r = 0.3, P < .01), and motor (r = 0.3, P < .01) Bayley-III Scales of Infant and Toddler Development Test scores, as well as with the Hammersmith Infant Neurological Examination score (r = 0.2, P < .03). An association was observed between an inferior median Hammersmith Infant Neurological Examination score with congenital microcephaly (P = .04), arthrogryposis (P = .02), and epilepsy in the first year (P < .01). CONCLUSION: Cerebral palsy related to CZ presents with a severe global impairment at a 2-year follow-up. Birth head circumference, arthrogryposis, and early epilepsy are associated with a worse outcome and may be considered as prognostic markers. These findings are important for the neurorehabilitation planning, parents' guiding, and future prognostic studies.

Clinical and neurodevelopmental features in children with cerebral palsy and probable congenital Zika.

OBJECTIVE: To describe the neurological and neurodevelopmental features at 1 year of age in children with cerebral palsy (CP) related to probable congenital Zika (CZ), followed in a referral neurorehabilitation hospital. METHODS: Data on 82 children with CP associated with probable CZ, who consecutively attended the neurodevelopmental and neurological assessment around one year of age, were collected. For neurodevelopmental evaluation, Bayley-III Scales of Infant and Toddler Development was used. Descriptive statistical analysis was performed. RESULTS: The children were admitted into the rehabilitation program at a young age (mean age: 4.8 months, SD 3.1), followed beyond the first year of life (mean age of follow up: 13.2 months, SD 2.1), born to young mothers (mean age: 28.1 years, SD 5.9), in their first pregnancy (62.2%). The majority had severe congenital microcephaly (62.0%), spastic CP (96.3%), epilepsy (63.4%), absent expected postural reactions (93.2%), abnormal persistence of primitive reflexes (94.7%), and severe neuroimaging abnormalities, predominantly calcifications (97.6%). Extremely low performances on cognitive (95.1%), language (97.6%) and motor (97.6%) developmental composite scores were observed. There was a correlation between the cognitive score with the birth head circumference (HC) (r = 0.3, p = 0.01) and with the follow up HC (r = 0.4, p < 0.01), as well as between the follow up HC with the motor score (r = 0.2, p = 0.03). CONCLUSION: Congenital Zika may be associated with a severe form of CP, mainly bilateral spastic, with a severe global neurodevelopmental impairment and early signs of a poor prognosis for independent walking. Head circumference may be a prognostic marker among those children. These results may help establish goals for the rehabilitation program and identify priority health services.

Clinical, Neuroimaging, and Neurophysiological Findings in Children with Microcephaly Related to Congenital Zika Virus Infection.

Zika virus (ZIKV) infection appeared in Brazil in 2015, causing an epidemic outbreak with increased rates of microcephaly and other serious birth disorders. We reviewed 102 cases of children who were diagnosed with microcephaly at birth and who had gestational exposure to ZIKV during the outbreak. We describe the clinical, neuroimaging, and neurophysiological findings. Most mothers (81%) reported symptoms of ZIKV infection, especially cutaneous rash, during the first trimester of pregnancy. The microcephaly was severe in 54.9% of the cases. All infants presented with brain malformations. The most frequent neuroimaging findings were cerebral atrophy (92.1%), ventriculomegaly (92.1%), malformation of cortical development (85.1%), and cortical⁻subcortical calcifications (80.2%). Abnormalities in neurological exams were found in 97.0% of the cases, epileptogenic activity in 56.3%, and arthrogryposis in 10.8% of the infants. The sensorineural screening suggested hearing loss in 17.3% and visual impairment in 14.1% of the infants. This group of infants who presented with microcephaly and whose mothers were exposed to ZIKV early during pregnancy showed clinical and radiological criteria for congenital ZIKV infection. A high frequency of brain abnormalities and signs of early neurological disorders were found, and epileptogenic activity and signs of sensorineural alterations were common. This suggests that microcephaly can be associated with a worst spectrum of neurological manifestations.

Congenital Zika Virus Infection with Normal Neurodevelopmental Outcome, Brazil.

We describe a case of a 20-month-old girl with probable congenital Zika virus infection and normal neurodevelopment, despite microcephaly and abnormal neuroimaging. This case raises questions about early prognostic markers and draws attention to the need for investigation in suspected Zika cases, even if the child's early neurodevelopment is normal.