Neurologic Characterization of Craniosynostosis: Can Direct Brain Recordings Predict Language Development?

PURPOSE: Nonsyndromic craniosynostosis (NSC) is associated with language deficits. Conventional tests, such as the Bayley Scales of Infant Development (BSID), may not reflect accurate long-term cognition. Alternatively, mismatch negativity (MMN) waves recorded via electroencephalogram (EEG) measure neural responses to speech and may objectively predict language development. This study aimed to (1) correlate infant MMN to future language achievement and (2) compare MMN among subtypes of NSC. METHODS: Pre and postoperatively (mean operative age 9.5 months), NSC participants received the BSID and EEG phoneme-discrimination paradigm(80 dB,250 Hz). The MMN was the largest negative amplitude in the difference wave 80 to 300 ms after stimuli. To measure cognitive outcome, patients completed a neurodevelopmental battery (Wechsler-Abbreviated Scale of Intelligence and Wechsler-Fundamentals) at >6 years of age. RESULTS: Eleven NSC patients with EEG testing in infancy were neurocognitively tested (average age 8.0 years; 27% female; 55% sagittal, 27% metopic, 9% unicoronal, 9% sagittal/metopic). The left frontal cluster MMN strongly correlated with word-reading (r = 0.713, P = 0.031), reading-comprehension (r = 0.745, P = 0.021), and language-composites (r = 0.0771, P = 0.015). Conversely, BSID scores did not yield significant predictive value (r < 0.5, P > 0.05). Follow-up event related potentials (ERP) comparison included 39 normal control, 18 sagittal, 17 metopic, 6 unilateral-coronal infants. Preoperatively, sagittal (P = 0.003) and metopic (P = 0.003) patients had attenuated left frontal MMN compared to controls. Postoperatively, the sagittal cohort was normalized to controls while metopic patients retained attenuations (P = 0.041). CONCLUSION: ERP assessment in NSC had significantly better predictive value for future neurocognition than the BSID. Preoperatively, sagittal and metopic patients had attenuated neural response to language; postoperatively, sagittal patients had improved responses in comparison to metopic patients. Use of ERP assessment may help tailor treatment for language deficits earlier in development.

Bringing the Laboratory Home: PANDABox Telehealth-Based Assessment of Neurodevelopmental Risk in Children.

BACKGROUND: Advances in clinical trials have revealed a pressing need for outcome measures appropriate for children with neurogenetic syndromes (NGS). However, the field lacks a standardized, flexible protocol for collecting laboratory-grade experimental data remotely. To address this challenge, we developed PANDABox (Parent-Administered Neurodevelopmental Assessment), a caregiver-facilitated, remotely administered assessment protocol for collecting integrated and high quality clinical, behavioral, and spectral data relevant to a wide array of research questions. Here, we describe PANDABox development and report preliminary data regarding: (1) logistics and cost, (2) caregiver fidelity and satisfaction, and (3) data quality. METHODS: We administered PANDABox to a cohort of 16 geographically diverse caregivers and their infants with Down syndrome. Tasks assessed attention, language, motor, and atypical behaviors. Behavioral and physiological data were synchronized and coded offline by trained research assistants. RESULTS: PANDABox required low resources to administer and was well received by families, with high caregiver fidelity (94%) and infant engagement (91%), as well as high caregiver-reported satisfaction (97% positive). Missing data rates were low for video frames (3%) and vocalization recordings (6%) but were higher for heart rate (25% fully missing and 13% partially missing) and discrete behavioral presses (8% technical issues and 19% not enough codable behavior), reflecting the increased technical demands for these activities. CONCLUSION: With further development, low-cost laboratory-grade research protocols may be remotely administered by caregivers in the family home, opening a new frontier for cost-efficient, scalable assessment studies for children with NGS other neurodevelopmental disorders.

Brief Report: Assessment Experiences of Children with Neurogenetic Syndromes: Caregivers' Perceptions and Suggestions for Improvement.

It is well-recognized that measurement options for diagnosing and monitoring children with neurogenetic syndromes (NGS) associated with moderate to severe intellectual impairment are limited (Berry-Kravis, Dev Med Child Neurol https://doi.org/10.1111/dmcn.13018, 2016), and caregivers experience significant concerns regarding the assessment process. However to date, these concerns have not been summarized into actionable steps for clinicians and test-makers. As such, we used a mixed methods approach to assess caregiver-derived perceptions and suggestions for improving assessments in NGS. Results indicated many shared challenges and suggestions for improvement, particularly in the domains of testing procedures and examiner communication. Integrating these suggestions into future protocols is an important next step toward improving the quality of assessment procedures for children with NGS and their families across both clinical and research contexts.