Models of KPTN-related disorder implicate mTOR signalling in cognitive and overgrowth phenotypes.

KPTN-related disorder is an autosomal recessive disorder associated with germline variants in KPTN (previously known as kaptin), a component of the mTOR regulatory complex KICSTOR. To gain further insights into the pathogenesis of KPTN-related disorder, we analysed mouse knockout and human stem cell KPTN loss-of-function models. Kptn -/- mice display many of the key KPTN-related disorder phenotypes, including brain overgrowth, behavioural abnormalities, and cognitive deficits. By assessment of affected individuals, we have identified widespread cognitive deficits (n = 6) and postnatal onset of brain overgrowth (n = 19). By analysing head size data from their parents (n = 24), we have identified a previously unrecognized KPTN dosage-sensitivity, resulting in increased head circumference in heterozygous carriers of pathogenic KPTN variants. Molecular and structural analysis of Kptn-/- mice revealed pathological changes, including differences in brain size, shape and cell numbers primarily due to abnormal postnatal brain development. Both the mouse and differentiated induced pluripotent stem cell models of the disorder display transcriptional and biochemical evidence for altered mTOR pathway signalling, supporting the role of KPTN in regulating mTORC1. By treatment in our KPTN mouse model, we found that the increased mTOR signalling downstream of KPTN is rapamycin sensitive, highlighting possible therapeutic avenues with currently available mTOR inhibitors. These findings place KPTN-related disorder in the broader group of mTORC1-related disorders affecting brain structure, cognitive function and network integrity.

Brain volumes and functional outcomes in children without cerebral palsy after therapeutic hypothermia for neonatal hypoxic-ischaemic encephalopathy.

AIM: To investigate whether brain volumes were reduced in children aged 6 to 8 years without cerebral palsy, who underwent therapeutic hypothermia for neonatal hypoxic-ischaemic encephalopathy (patients), and matched controls, and to examine the relation between subcortical volumes and functional outcome. METHOD: We measured regional brain volumes in 31 patients and 32 controls (median age 7 years and 7 years 2 months respectively) from T1-weighted magnetic resonance imaging (MRI). We assessed cognition using the Wechsler Intelligence Scales for Children, Fourth Edition and motor ability using the Movement Assessment Battery for Children, Second Edition (MABC-2). RESULTS: Patients had lower volume of whole-brain grey matter, white matter, pallidi, hippocampi, and thalami than controls (false discovery rate-corrected p < 0.05). Differences in subcortical grey-matter volumes were not independent of total brain volume (TBV). In patients, hippocampal and thalamic volumes correlated with full-scale IQ (hippocampi, r = 0.477, p = 0.010; thalami, r = 0.452, p = 0.016) and MABC-2 total score (hippocampi, r = 0.526, p = 0.004; thalami, r = 0.505, p = 0.006) independent of age, sex, and TBV. No significant correlations were found in controls. In patients, cortical injury on neonatal MRI was associated with reduced volumes of hippocampi (p = 0.001), thalami (p = 0.002), grey matter (p = 0.015), and white matter (p = 0.013). INTERPRETATION: Children who underwent therapeutic hypothermia have reduced whole-brain grey and white-matter volumes, with associations between hippocampal and thalamic volumes and functional outcomes.

Mammillary body abnormalities and cognitive outcomes in children cooled for neonatal encephalopathy.

AIM: To evaluate mammillary body abnormalities in school-age children without cerebral palsy treated with therapeutic hypothermia for neonatal hypoxic-ischaemic encephalopathy (cases) and matched controls, and associations with cognitive outcome, hippocampal volume, and diffusivity in the mammillothalamic tract (MTT) and fornix. METHOD: Mammillary body abnormalities were scored from T1-weighted magnetic resonance imaging (MRI) in 32 cases and 35 controls (median age [interquartile range] 7 years [6 years 7 months-7 years 7 months] and 7 years 4 months [6 years 7 months-7 years 7 months] respectively). Cognition was assessed using the Wechsler Intelligence Scale for Children, Fourth Edition. Hippocampal volume (normalized by total brain volume) was measured from T1-weighted MRI. Radial diffusivity and fractional anisotropy were measured in the MTT and fornix, from diffusion-weighted MRI using deterministic tractography. RESULTS: More cases than controls had mammillary body abnormalities (34% vs 0%; p < 0.001). Cases with abnormal mammillary bodies had lower processing speed (p = 0.016) and full-scale IQ (p = 0.028) than cases without abnormal mammillary bodies, and lower scores than controls in all cognitive domains (p < 0.05). Cases with abnormal mammillary bodies had smaller hippocampi (left p = 0.016; right p = 0.004) and increased radial diffusivity in the right MTT (p = 0.004) compared with cases without mammillary body abnormalities. INTERPRETATION: Cooled children with mammillary body abnormalities at school-age have reduced cognitive scores, smaller hippocampi, and altered MTT microstructure compared with those without mammillary body abnormalities, and matched controls. WHAT THIS PAPER ADDS: Cooled children are at higher risk of mammillary body abnormalities than controls. Abnormal mammillary bodies are associated with reduced cognitive scores and smaller hippocampi. Abnormal mammillary bodies are associated with altered mammillothalamic tract diffusivity.

Effectiveness of anodal transcranial direct current stimulation to improve muscle strength and motor functionality after incomplete spinal cord injury: a systematic review and meta-analysis.

STUDY DESIGN: Systematic review and meta-analysis. OBJECTIVES: We aimed to investigate the effects of anodal transcranial direct current stimulation (tDCS) against sham on muscle strength and motor functionality after incomplete spinal cord injury (iSCI). SETTING: University of São Paulo, Brazil. METHODS: A preplanned protocol was registered (PROSPERO, CRD42016050444). Pubmed, Embase, Web of Science, Cochrane Central Library and BVS databases were searched independently by two authors up to March 2018. Cochrane Collaboration's Tool was used for the risk of bias assessments. Generic inverse variance and random-effects model were used to calculate pooled effect sizes (ES), 95% confidence intervals (CIs) and p-values in meta-analyses. RESULTS: Six randomized clinical trials met inclusion criteria (n = 78 iSCI individuals) and were included in the meta-analysis. Results showed a marginal significant pooled effect of active tDCS in improving motor functionality with a small ES (SMD = 0.26, 95% CI = -0.00 to 0.53, p = 0.05, I2 = 0%). On the other hand, the pooled effect of active tDCS on muscle strength did not reach statistical significance, in parallel with a small ES (SMD = 0.35, 95% CI = -0.21 to 0.92, p = 0.22, I2 = 0%) when compared with sham tDCS. No significant adverse events were reported. CONCLUSIONS: Overall, there was a significant effect of tDCS in improving motor functionality following iSCI. However, a small ES and the marginal p-value suggest that these results should be interpreted with caution. Further high-quality clinical trials are needed to support or refute the use of tDCS in daily clinical practice.

Attention and visuo-spatial function in children without cerebral palsy who were cooled for neonatal encephalopathy: a case-control study.

Objectives: Dorsal-stream functions are vulnerable to early brain injury associated with neonatal encephalopathy (NE) following perinatal asphyxia, even in children not developing cerebral palsy (CP). Since therapeutic hypothermia (TH) became the standard treatment for NE, the incidence of CP is reduced but the impact on dorsal-stream functions is unknown. We aimed to compare dorsal-stream functions in TH-treated survivors of NE, without CP, with those of matched controls. Methods: We administered tests of dorsal-stream function to 29 case children aged 6-to-8 years treated with TH for NE and without CP, and 20 age, sex and social class matched controls. We used the Conner's Continuous Performance Test (CPT) 2nd Edition to assess attentiveness, based upon Hit Reaction Time (HRT) percentile score and HRT standard error percentile, the CPT HRT block change measure to assess sustained attention and the NEPSY-II block construction and arrows tests to assess visuo-spatial performance and mental rotation. Results: Case children performed significantly worse than controls on measures of attention and visuo-spatial function. Conclusions: Children given TH treatment for NE can have subtle attention difficulties with slower reaction times and reduced visuo-spatial processing. These findings illustrate the continued vulnerability of dorsal-stream functions following NE despite the use of TH.

Measurement Issues: Neuropsychological assessment with children and adolescents; unlocking the mysticism, methods and measures with the help of Tom Swift.

BACKGROUND AND SCOPE: In this article, we provide a brief overview of the principles that guide paediatric neuropsychological assessment, the methods used and some examples of the measures available. FINDINGS: We explore intellectual, adaptive and social functioning from a neuropsychological perspective and describe suitable measures for use in paediatric neuropsychological assessment in each domain. CONCLUSIONS: We provide an example of assessment and interpretation using a fictional character (Tom Swift) to demonstrate that neuropsychological assessment is important in understanding the everyday questions that arise in children's services around risk, needs, level of understanding and capacity to engage with services.

Ambivalence, equivocation and the politics of experimental knowledge: a transdisciplinary neuroscience encounter.

This article is about a transdisciplinary project between the social, human and life sciences, and the felt experiences of the researchers involved. 'Transdisciplinary' and 'interdisciplinary' research-modes have been the subject of much attention lately--especially as they cross boundaries between the social/humanistic and natural sciences. However, there has been less attention, from within science and technology studies, to what it is actually like to participate in such a research-space. This article contributes to that literature through an empirical reflection on the progress of one collaborative and transdisciplinary project: a novel experiment in neuroscientific lie detection, entangling science and technology studies, literary studies, sociology, anthropology, clinical psychology and cognitive neuroscience. Its central argument is twofold: (1) that, in addition to ideal-type tropes of transdisciplinary conciliation or integration, such projects may also be organized around some more subterranean logics of ambivalence, reserve and critique; (2) that an account of the mundane ressentiment of collaboration allows for a more careful attention to the awkward forms of 'experimental politics' that may flow through, and indeed propel, collaborative work more broadly. Building on these claims, the article concludes with a suggestion that such subterranean logics may be indissociable from some forms of collaboration, and it proposes an ethic of 'equivocal speech' as a way to live with and through these kinds of transdisciplinary experiences.

Communication skills in children aged 6-8 years, without cerebral palsy cooled for neonatal hypoxic-ischemic encephalopathy.

We assessed communication skills of 48 children without cerebral palsy (CP) treated with therapeutic hypothermia (TH) for neonatal hypoxic-ischemic encephalopathy (HIE) (cases) compared to 42 controls at early school-age and examined their association with white matter diffusion properties in both groups and 18-month Bayley-III developmental assessments in cases. Parents completed a Children's Communication Checklist (CCC-2) yielding a General Communication Composite (GCC), structural and pragmatic language scores and autistic-type behavior score. GCC ≤ 54 and thresholds of structural and pragmatic language score differences defined language impairment. Using tract-based spatial statistics (TBSS), fractional anisotropy (FA) was compared between 31 cases and 35 controls. Compared to controls, cases had lower GCC (p = 0.02), structural (p = 0.03) and pragmatic language score (p = 0.04) and higher language impairments (p = 0.03). GCC correlated with FA in the mid-body of the corpus callosum, the cingulum and the superior longitudinal fasciculus (p < 0.05) in cases. Bayley-III Language Composite correlated with GCC (r = 0.34, p = 0.017), structural (r = 0.34, p = 0.02) and pragmatic (r = 0.32, p = 0.03) language scores and autistic-type behaviors (r = 0.36, p = 0.01).

Effect of Longitudinal Practice in Real and Virtual Environments on Motor Performance, Physical Activity and Enjoyment in People with Autism Spectrum Disorder: A Prospective Randomized Crossover Controlled Trial.

(1) Background: People with ASD commonly present difficulty performing motor skills and a decline in physical activity (PA) level and low enjoyment of PA. We aimed to evaluate whether longitudinal practice of an activity in virtual and real environments improves motor performance and whether this improvement is transferred to a subsequent practice when changing the environment, promoting PA and providing enjoyment; (2) Methods: People with ASD, aged between 10 and 16 years, were included and distributed randomly into two opposite sequences. The participants performed a 10 session protocol, with five sessions practicing in each environment (virtual or real). Heart rate measurement was carried out and an enjoyment scale was applied; (3) Results: 22 participants concluded the protocol. Sequence A (virtual first) presented an improvement in accuracy and precision and transferred this when changing environment; they also had a greater change in heart rate reserve. The majority of participants reported "fun" and "great fun" levels for enjoyment; (4) Conclusions: The virtual reality activity presented a higher level of difficulty, with greater gains in terms of transference to the real environment. Considering PA, our task provided very light to light activity and the majority of participants enjoyed the task.

Resilience and the mediating effects of executive dysfunction after childhood brain injury: a comparison between children aged 9-15 years with brain injury and non-injured controls.

PRIMARY OBJECTIVE: Acquired brain injury (ABI) during childhood can be associated with enduring difficulties related to impairments to executive functioning (EF). EF impairments may detrimentally affect outcome by restricting an individual's ability to access 'resiliency' resources after ABI. RESEARCH DESIGN: The purpose of this study was to explore whether there is deterioration in children's resilience compared with peers after ABI and whether EF is influential in mediating relationships between resilience and behaviour. METHODS AND PROCEDURES: Measures of resilience, depression and anxiety were administered with 21 children with ABI and 70 matched healthy children aged 9-15 years. Parents completed measures of behaviour and EF. MAIN OUTCOMES AND RESULTS: Children with ABI were identified as less resilient and more depressed and anxious than controls. Resiliency measures were correlated with depression and anxiety in both groups. Relationships between resiliency and socio-emotional behaviour were mediated by EF. CONCLUSIONS: Assessment of resilience after ABI may be useful in supporting or defining the delivery of more individualized rehabilitation programmes according to the resources and vulnerabilities a young person has. However, an accurate understanding of the role of EF in the relationship between resilience and behavioural outcome after ABI is essential.

'Trails B or not Trails B?' Is attention-switching a useful outcome measure?

PRIMARY OBJECTIVE: Difficulties with attention contribute to behavioural and cognitive problems during childhood and may reflect subtle deficits in executive functioning (EF). Attention problems in early childhood have also been found to predict higher levels of anxiety and depression symptoms at 10 years old. It has also been reported that attention problems during childhood may be differentially related to later-emerging distinct EF difficulties. Many of these findings, however, rely on teacher-ratings of attention difficulties. METHODS AND PROCEDURES: This study administered neuropsychological tests of attention-switching and EF to 67 healthy children aged 9-15 years of age. It additionally measured socio-emotional behavioural functioning. MAIN OUTCOMES AND RESULTS: A critical phase of improvement was found at 10 years of age. Correlations were found between attention-switching skills and EF. Attention-switching skills were also correlated with socio-emotional functioning. CONCLUSIONS: Attention-switching skills have some interdependence with EF, but in paediatric assessment such skills are easier to routinely assess than many of the currently available tests of EF. It is suggested that attention-switching ability may prove to be a useful predictor of EF performance in understanding long-term outcome after a neurological event such as traumatic brain injury.

Training emotional recognition in a child with acquired brain injury: A single case study.

Emotional processing is affected by childhood brain injury. Ineffective emotional processing and poor understanding of social cues affect the development of social relationships leading to social isolation and a poorer quality of life in the long-term. Facial expression recognition is a non-verbal social cue that is used to interpret the thoughts and feelings of others. Children with brain injury have shown deficits identifying even basic emotions from facial expression, yet few intervention studies have explored how to develop facial expression recognition in children with brain injury. Enhancing the ability to recognize and interpret facial expressions for these children would have implications for their emotional processing and social-emotional behavior. In this paper we report on a short single case study intervention to increase facial expression recognition using the Facial Affect Recognition training (FAR) for a 10-year-old-child with brain injury. Following intervention, there was not only an increase in facial expression recognition but also changes in social-emotional behavior indicating some generalization to other contexts. The results suggest that rehabilitation of emotional processing difficulties may indeed be possible, and further intervention studies aimed at developing these skills in children with brain injury are warranted.

Disrupted brain connectivity in children treated with therapeutic hypothermia for neonatal encephalopathy.

Therapeutic hypothermia following neonatal encephalopathy due to birth asphyxia reduces death and cerebral palsy. However, school-age children without cerebral palsy treated with therapeutic hypothermia for neonatal encephalopathy still have reduced performance on cognitive and motor tests, attention difficulties, slower reaction times and reduced visuo-spatial processing abilities compared to typically developing controls. We acquired diffusion-weighted imaging data from school-age children without cerebral palsy treated with therapeutic hypothermia for neonatal encephalopathy at birth, and a matched control group. Voxelwise analysis (33 cases, 36 controls) confirmed reduced fractional anisotropy in widespread areas of white matter in cases, particularly in the fornix, corpus callosum, anterior and posterior limbs of the internal capsule bilaterally and cingulum bilaterally. In structural brain networks constructed using probabilistic tractography (22 cases, 32 controls), graph-theoretic measures of strength, local and global efficiency, clustering coefficient and characteristic path length were found to correlate with IQ in cases but not controls. Network-based statistic analysis implicated brain regions involved in visuo-spatial processing and attention, aligning with previous behavioural findings. These included the precuneus, thalamus, left superior parietal gyrus and left inferior temporal gyrus. Our findings demonstrate that, despite the manifest successes of therapeutic hypothermia, brain development is impaired in these children.

Traumatic brain injury in a prison population: prevalence and risk for re-offending.

BACKGROUND: TBI can lead to cognitive, behavioural and emotional difficulties. Previous studies suggest that TBI is relatively elevated in offender populations. In this study the aims were to establish the rate of TBI of various severities in a representative sample of adult offenders and patterns of custody associated with TBI. METHODS: A self-report survey of adult, male offenders within a prison. Of 453 offenders, 196 (43%) responded. RESULTS: Over 60% reported 'Head Injuries'. Reports consistent with TBI of various severities were given by 65%. Of the overall sample, 16% had experienced moderate-to-severe TBI and 48% mild TBI. Adults with TBI were younger at entry into custodial systems and reported higher rates of repeat offending. They also reported greater time, in the past 5 years, spent in prison. CONCLUSIONS: These findings indicate that there is a need to account for TBI in the assessment and management of offenders.

Self-reported traumatic brain injury in male young offenders: a risk factor for re-offending, poor mental health and violence?

Adolescence is a risk period for offending and for traumatic brain injury (TBI) and TBI is a risk factor for poor mental health and for offending. TBI has been largely neglected from guidance on managing the mental health needs of young offenders. We sought to determine the rate of self-reported TBI, of various severities, in a male, adolescent youth offending population. We also aimed to explore whether TBI was associated with number of convictions, violent offending, mental health problems and drug misuse. Young male offenders aged 11 to 19 years were recruited from a Young Offender Institute, a Youth Offending Team and a special needs school. A total of 197 participants were approached and 186 (94.4%) completed the study. They completed self-reports on TBI, crime history, mental health and drug use. TBI with loss of consciousness (LOC) was reported by 46% of the sample. LOC consistent with mild TBI was reported by 29.6%, and 16.6% reported LOC consistent with moderate to severe TBI. Possible TBI was reported by a further 19.1%. Repeat injury was common - with 32% reporting more than one LOC. Frequency of self-reported TBI was associated with more convictions. Three or more self-reported TBIs were associated with greater violence in offences. Those with self-reported TBI were also at risk of greater mental health problems and of misuse of cannabis. TBI may be associated with offending behaviour and worse mental health outcomes. Addressing TBI within adolescent offenders with neurorehabilitative input may be important for improving well-being and reducing re-offending.

Peer-relationship difficulties in children with brain injuries: comparisons with children in mental health services and healthy controls.

Positive peer relationships are essential in healthy development. The prevalence of peer-relationship problems in children after acquired brain injury (ABI) has yet to be explored, although ABI does inevitably impact upon peer interactions. We aimed to explore how peer-relationships and emotional distress after ABI may differ from the levels reported by healthy children or mental health controls. Parents of 214 children (137 "healthy" children, 27 children using mental health services and 40 children with ABI) aged 9-15 years participated. A questionnaire measure of peer-relationship functioning and emotional distress was completed. Children with ABI experienced a greater degree of peer-relationship difficulties and emotional distress than healthy controls. No difference was found in reported peer relationship difficulties or emotional distress between ABI children and the children accessing mental health services. We conclude that emotional distress and co-occurring peer-relationship difficulties are as prevalent in a population of children after ABI as may be expected in a population of children under the care of mental health services, yet, unlike the latter group, appropriate intervention services are not commonly available. Interventions that aim to enhance peer relationships after childhood ABI may provide an essential resource to the benefit of outcome.

"Must try harder." Is effort and performance validity testing a necessary part of pediatric neuropsychological assessment?

Neuropsychological assessments results have significant implications for pediatric populations, based upon the assumption that the young person has adopted an effortful approach and has engaged in assessment. There is a commonly-accepted risk to assuming the validity of neuropsychological assessment results with adults, and, therefore, performance validity testing (PVT) has become a major topic of research and investigation and has become an accepted part of routine assessment. The same approach has not been adopted in assessment with children and a paucity of studies has focused on PVT in children. We review studies that demonstrate that children are equal to adults in their ability to use deception and that clinicians cannot detect false-effort without use of validity tests. We explore how frequently such tests are used and how well they work in assessment with children, and the limits, complexities, and constraints of adapting adult tests. We advocate that adequate performance validity testing is essential in order to maximize confidence in the results and we hypothesize that assessment with pediatric populations should take into account a range of influences, such as neuro-developmental factors associated with age of the child and suitability of proposed measures according to the evidence-base.

School-age outcomes of children without cerebral palsy cooled for neonatal hypoxic-ischaemic encephalopathy in 2008-2010.

OBJECTIVE: Since therapeutic hypothermia became standard care for neonatal hypoxic-ischaemic encephalopathy (HIE), even fewer infants die or have disability at 18-month assessment than in the clinical trials. However, longer term follow-up of apparently unimpaired children is lacking. We investigated the cognitive, motor and behavioural performances of survivors without cerebral palsy (CP) cooled for HIE, in comparison with matched non-HIE control children at 6-8 years. DESIGN: Case-control study. PARTICIPANTS: 29 case children without CP, cooled in 2008-2010 and 20 age-matched, sex-matched and social class-matched term-born controls. MEASURES: Wechsler Intelligence Scales for Children, Fourth UK Edition, Movement Assessment Battery for Children, Second Edition (MABC-2) and Strengths and Difficulties Questionnaire. RESULTS: Cases compared with controls had significantly lower mean (SD) full-scale IQ (91 [10.37]vs105[13.41]; mean difference (MD): -13.62, 95% CI -20.53 to -6.71) and total MABC-2 scores (7.9 [3.26]vs10.2[2.86]; MD: -2.12, 95% CI -3.93 to -0.3). Mean differences were significant between cases and controls for verbal comprehension (-8.8, 95% CI -14.25 to -3.34), perceptual reasoning (-13.9, 95% CI-20.78 to -7.09), working memory (-8.2, 95% CI-16.29 to -0.17), processing speed (-11.6, 95% CI-20.69 to -2.47), aiming and catching (-1.6, 95% CI-3.26 to -0.10) and manual dexterity (-2.8, 95% CI-4.64 to -0.85). The case group reported significantly higher median (IQR) total (12 [6.5-13.5] vs 6 [2.25-10], p=0.005) and emotional behavioural difficulties (2 [1-4.5] vs 0.5 [0-2.75], p=0.03) and more case children needed extra support in school (34%vs5%, p=0.02) than the control group. CONCLUSIONS: School-age children without CP cooled for HIE still have reduced cognitive and motor performance and more emotional difficulties than their peers, strongly supporting the need for school-age assessments.

Use of Augmented Reality with a Motion-Controlled Game Utilizing Alphabet Letters and Numbers to Improve Performance and Reaction Time Skills for People with Autism Spectrum Disorder.

Augmented reality (AR) uses the real-world setting but enables a person to interact with virtual objects. In this study, we aimed to explore the use of alphabet letter and number in an AR task and its influence in reaction time in a population with autism spectrum disorders (ASD) compared with the performance of typical developing (TD) controls. We evaluated reaction time before and after AR tasks that consisted of identifying correct numbers and alphabet letters in 48 people with ASD and 48 with TD controls. Results indicate that total points for TD group were higher (M = 86.4 and M = 79.0) when compared with the ASD group (M = 54.5 and M = 51.5) for alphabet letters and numbers, respectively. Moreover, in analysis of reaction time results, only the ASD group showed an improvement in performance after the practice of an AR task. The control group was faster before (M = 553.7) and after (M = 560.5) when compared with the ASD group (M = 2616.0 and M = 2374.6, respectively). Despite the need for further studies, our results support that there is potential for clinical use of an AR task-based intervention for people with ASD.

Clinical characteristics of children with congenital Zika syndrome: a case series.

BACKGROUND: The congenital Zika syndrome involves structural brain changes, including ventriculomegaly, thin cerebral cortices, abnormal gyral pattern, cortical malformations, hypoplasia of the corpus callosum, myelination delay, subcortical diffuse calcifications, brainstem hypoplasia, and microcephaly in newborns. OBJECTIVE: This study aimed to describe the clinical characteristics of children with congenital Zika syndrome; to compare the outcomes of infants infected in the first (1T, n=20) and second trimesters of pregnancy (2T, n=11); to investigate correlations between birth weight, birth and follow-up head circumference, birth gestational age, and gross motor scores. METHODS: Participants were evaluated with Alberta Infant Motor Scale (AIMS) and part A of the Gross Motor Function Measure (GMFM-A). ANOVA compared head circumference, birth gestational age, birth weight, and gross motor performance of 1T and 2T. RESULTS: The correlations were investigated by Pearson correlation coefficients. ANOVA showed differences in birth and follow-up head circumferences. Head circumference was smaller in 1T, compared to 2T. Motor performance was classified as below the fifth percentile in AIMS in all children and 1T showed lower scores in prone, sitting, and total AIMS score, compared to 2T. Children ranged from 8 to 78% on GMFM-A and there was a poorer motor performance of 1T. Nineteen children showed hypertonia, six showed normal tone and six showed hypotonia. Birth head circumference was correlated with AIMS prone postural control. Follow-up head circumference was correlated to prone, supine and total AIMS scores. Smaller head circumference at birth and follow-up denoted poorer postural control. DISCUSSION: Children with congenital Zika syndrome showed microcephaly at birth and follow-up. Smaller head circumferences and poorer motor outcomes were observed in 1T. Infants showed poor visual and motor outcomes. Moderate positive correlations between birth and follow-up head circumference and gross motor function were found.