Interventions for children with cerebral visual impairment: A scoping review.

AIM: To examine the nature and scope of the literature on interventions implemented for children with cerebral visual impairment (CVI). METHOD: Using a scoping review methodology, a systematic search of the literature was conducted using four databases including PubMed, Web of Science, Scopus, and Embase. Titles and abstracts were screened and data were extracted and synthesized from full-text, eligible studies. Twenty-three articles were identified and evaluated using quality criteria. RESULTS: Twenty-three of the 895 studies were included with children aged between 1 month and 17 years 6 months. Interventions were grouped into six categories including visual stimulation, task/environmental adaptations, vision training, acupuncture, stem cell transplantation, and transcranial electric stimulation. Outcome measures examined changes in visual function, functional vision, and visual processing. INTERPRETATION: Intervention research for children with CVI is in its infancy. Interventions for children with CVI may be beneficial; however, comparing results is difficult due to inconsistency in outcome measures. Most of the intervention studies had lower-level evidence and included small sample sizes. High-quality studies with larger samples and comparison groups are needed to fully understand which evidence-based interventions are most effective for children with CVI. With the incidence of CVI increasing, further development and validation of intervention methods is imperative. WHAT THIS PAPER ADDS: Intervention studies for children with cerebral visual impairment (CVI) are sparse. Most intervention studies for children with CVI have low-level evidence with low critical appraisal scores. High-quality, controlled intervention studies are needed to guide families and clinicians toward evidence-based practice.

Magnetic resonance spectroscopy brain metabolites at term and 3-year neurodevelopmental outcomes in very preterm infants.

BACKGROUND: Noninvasive advanced neuroimaging and neurochemical assessment can identify subtle abnormalities and predict neurodevelopmental impairments. Our objective was to quantify white matter metabolite levels and evaluate their relationship with neurodevelopmental outcomes at age 3 years. METHODS: Our study evaluated a longitudinal prospective cohort of very premature infants (<32 weeks gestational age) with single-voxel proton magnetic resonance spectroscopy from the centrum semiovale performed at term-equivalent age and standardized cognitive, verbal, and motor assessments at 3 years corrected age. We separately examined metabolite ratios in the left and right centrum semiovale. We also conducted an exploratory interaction analysis for high/low socioeconomic status (SES) to evaluate the relationship between metabolites and neurodevelopmental outcomes, after adjusting for confounders. RESULTS: We found significant relationships between choline/creatine levels in the left and right centrum semiovale and motor development scores. Exploratory interaction analyses revealed that, for infants with low SES, there was a negative association between choline/creatine in the left centrum semiovale and motor assessment scores at age 3 years. CONCLUSIONS: Brain metabolites from the centrum semiovale at term-equivalent age were associated with motor outcomes for very preterm infants at 3 years corrected age. This effect may be most pronounced for infants with low SES. IMPACT: Motor development at 3 years corrected age for very preterm infants is inversely associated with choline neurochemistry within the centrum semiovale on magnetic resonance spectroscopy at term-equivalent age, especially in infants with low socioeconomic status. No prior studies have studied metabolites in the centrum semiovale to predict neurodevelopmental outcomes at 3 years corrected age based on high/low socioeconomic status. For very preterm infants with lower socioeconomic status, higher choline-to-creatine ratio in central white matter is associated with worse neurodevelopmental outcomes.

An iPad-based intervention to improve visual-motor, visual-attention, and visual-perceptual skills in children with surgically treated hydrocephalus: A pilot study.

PURPOSE: Develop and pilot an iPad-based intervention for improving visual-motor coordination, visual-spatial processing/reasoning, and visual attention in children with surgically treated hydrocephalus (HCP). METHODS: We developed an intervention protocol targeting visual-motor coordination, visual-spatial processing/reasoning, and visual attention. Fourteen participants with HCP completed 30 h of training over 6 weeks. The primary outcome measure was the Perceptual Reasoning Index from the Wechsler Abbreviated Scale of Intelligence, Second Edition. Secondary measures included subtests from the Wechsler Intelligence Scale for Children, Fourth Edition, Developmental NEuroPSYchological Assessment, Second Edition (NEPSY-II), and Purdue Pegboard. RESULTS: Children with HCP demonstrated gains with statistical significance on the Perceptual Reasoning Index. We also observed significant improvement on a timed test of visuo-motor coordination (Wechsler Intelligence Scale for Children, Fourth Edition, Coding). CONCLUSION: Our iPad-application-based intervention may promote visual-motor coordination, visual-spatial processing/reasoning, and visual attention skills in children with HCP, offering an engaging and economical supplement to more conventional therapies.

Association between brain structural network efficiency at term-equivalent age and early development of cerebral palsy in very preterm infants.

Very preterm infants (born at less than 32 weeks gestational age) are at high risk for serious motor impairments, including cerebral palsy (CP). The brain network changes that antecede the early development of CP in infants are not well characterized, and a better understanding may suggest new strategies for risk-stratification at term, which could lead to earlier access to therapies. Graph theoretical methods applied to diffusion MRI-derived brain connectomes may help quantify the organization and information transfer capacity of the preterm brain with greater nuance than overt structural or regional microstructural changes. Our aim was to shed light on the pathophysiology of early CP development, before the occurrence of early intervention therapies and other environmental confounders, to help identify the best early biomarkers of CP risk in VPT infants. In a cohort of 395 very preterm infants, we extracted cortical morphometrics and brain volumes from structural MRI and also applied graph theoretical methods to diffusion MRI connectomes, both acquired at term-equivalent age. Metrics from graph network analysis, especially global efficiency, strength values of the major sensorimotor tracts, and local efficiency of the motor nodes and novel non-motor regions were strongly inversely related to early CP diagnosis. These measures remained significantly associated with CP after correction for common risk factors of motor development, suggesting that metrics of brain network efficiency at term may be sensitive biomarkers for early CP detection. We demonstrate for the first time that in VPT infants, early CP diagnosis is anteceded by decreased brain network segregation in numerous nodes, including motor regions commonly-associated with CP and also novel regions that may partially explain the high rate of cognitive impairments concomitant with CP diagnosis. These advanced MRI biomarkers may help identify the highest risk infants by term-equivalent age, facilitating earlier interventions that are informed by early pathophysiological changes.

Early micro- and macrostructure of sensorimotor tracts and development of cerebral palsy in high risk infants.

Infants born very preterm (VPT) are at high risk of motor impairments such as cerebral palsy (CP), and diagnosis can take 2 years. Identifying in vivo determinants of CP could facilitate presymptomatic detection and targeted intervention. Our objectives were to derive micro- and macrostructural measures of sensorimotor white matter tract integrity from diffusion MRI at term-equivalent age, and determine their association with early diagnosis of CP. We enrolled 263 VPT infants (≤32 weeks gestational age) as part of a large prospective cohort study. Diffusion and structural MRI were acquired at term. Following consensus guidelines, we defined early diagnosis of CP based on abnormal structural MRI at term and abnormal neuromotor exam at 3-4 months corrected age. Using Constrained Spherical Deconvolution, we derived a white matter fiber orientation distribution (fOD) for subjects, performed probabilistic whole-brain tractography, and segmented nine sensorimotor tracts of interest. We used the recently developed fixel-based (FB) analysis to compute fiber density (FD), fiber-bundle cross-section (FC), and combined fiber density and cross-section (FDC) for each tract. Of 223 VPT infants with high-quality diffusion MRI data, 14 (6.3%) received an early diagnosis of CP. The cohort's mean (SD) gestational age was 29.4 (2.4) weeks and postmenstrual age at MRI scan was 42.8 (1.3) weeks. FD, FC, and FDC for each sensorimotor tract were significantly associated with early CP diagnosis, with and without adjustment for confounders. Measures of sensorimotor tract integrity enhance our understanding of white matter changes that antecede and potentially contribute to the development of CP in VPT infants.

Associations Between Early Structural Magnetic Resonance Imaging, Hammersmith Infant Neurological Examination, and General Movements Assessment in Infants Born Very Preterm.

OBJECTIVE: To evaluate the prevalence and associations between structural magnetic resonance imaging (sMRI) injury/abnormality at term-equivalent age and absent fidgety General Movements Assessment (GMA) and abnormal Hammersmith Infant Neurological Examination (HINE) scores among infants born very preterm at 3-4 months of corrected age. STUDY DESIGN: This prospective cohort study enrolled 392 infants born ≤2 weeks of gestation from 5 neonatal intensive care units in the greater Cincinnati area between September 2016 and October 2019. Infants completed sMRI at term-equivalent age and GMA and HINE at 3-4 months of corrected age. All assessors were blinded. RESULTS: Of 392 infants, 375 (96%) had complete data. Of these, 44 (12%) exhibited moderate or severe brain abnormalities, 17 (4.5%) had abnormal GMA, and 77 (20.3%) had abnormal HINE. Global and regional abnormality scores on sMRI were significantly correlated with GMA (R2 range 0.05-0.17) and HINE at 3-4 months of corrected age (R2 range 0.01-0.17). These associations remained significant in multivariable analyses after adjusting for gestational age and sex. There was a significant but low correlation (R2 0.14) between GMA and HINE. CONCLUSIONS: We observed a low prevalence of moderate or severe brain abnormalities in survivors born very preterm in this geographically defined cohort. The much greater prevalence of abnormal motor examination on the HINE compared with GMA and their low correlation suggests that these tests evaluate different constructs and, thus, should be used in combination with sMRI rather than interchangeably.

Effects of intraventricular hemorrhage on white matter microstructural changes at term and early developmental outcomes in infants born very preterm.

PURPOSE: Very preterm (VPT) infants are at high risk for motor and behavioral deficits. We investigated microstructural differences using diffusion tensor imaging (DTI) among VPT infants with different grades of intraventricular hemorrhage (IVH), their association with early motor function and temperament ratings, and the potential moderating effect of IVH severity on the above structure-function relations. METHODS: Fifty-seven VPT (≤32 weeks gestational age) infants with IVH (Low Grade (Papile grading I/II): 42; High Grade (III/IV): 15) were studied. DTI was acquired between 39 and 44 weeks postmenstrual age and was analyzed using the tract-based spatial statistics approach. Early motor function and temperament were assessed at 3-month corrected age based on the Hammersmith Infant Neurological Examination (HINE) and Infant Behavioral Questionnaire - Revised, Short Version (IBQ-R-S), respectively. RESULTS: Significantly lower fractional anisotropy and higher mean, axial, and/or radial diffusivity were found in VPT infants with High Grade IVH compared to Low Grade IVH (p < 0.05). Significant associations were found between DTI metrics and motor function in both IVH groups and between DTI and Fear temperament ratings in the High Grade IVH Group (all p < 0.05). IVH severity had a significant moderating effect on the relation between DTI and motor and Fear ratings (p < 0.05). CONCLUSION: DTI is a sensitive neuroimaging biomarker providing a refined understanding of the impact and location of differing severities of IVH on the developing white matter of VPT infants. Early motor and behavioral outcomes are associated with microstructural changes that are influenced by severity of IVH.

Discovering the sense of touch: protocol for a randomised controlled trial examining the efficacy of a somatosensory discrimination intervention for children with hemiplegic cerebral palsy.

BACKGROUND: Of children with hemiplegic cerebral palsy, 75% have impaired somatosensory function, which contributes to learned non-use of the affected upper limb. Currently, motor learning approaches are used to improve upper-limb motor skills in these children, but few studies have examined the effect of any intervention to ameliorate somatosensory impairments. Recently, Sense© training was piloted with a paediatric sample, seven children with hemiplegic cerebral palsy, demonstrating statistically and clinically significant change in limb position sense, goal performance and bimanual hand-use. This paper describes a protocol for a Randomised Controlled Trial of Sense© for Kids training, hypothesising that its receipt will improve somatosensory discrimination ability more than placebo (dose-matched Goal Directed Therapy via Home Program). Secondary hypotheses include that it will alter brain activation in somatosensory processing regions, white-matter characteristics of the thalamocortical tracts and improve bimanual function, activity and participation more than Goal Directed Training via Home Program. METHODS AND DESIGN: This is a single blind, randomised matched-pair, placebo-controlled trial. Participants will be aged 6-15 years with a confirmed description of hemiplegic cerebral palsy and somatosensory discrimination impairment, as measured by the sense©_assess Kids. Participants will be randomly allocated to receive 3h a week for 6 weeks of either Sense© for Kids or Goal Directed Therapy via Home Program. Children will be matched on age and severity of somatosensory discrimination impairment. The primary outcome will be somatosensory discrimination ability, measured by sense©_assess Kids score. Secondary outcomes will include degree of brain activation in response to a somatosensory task measured by functional MRI, changes in the white matter of the thalamocortical tract measured by diffusion MRI, bimanual motor function, activity and participation. DISCUSSION: This study will assess the efficacy of an intervention to increase somatosensory discrimination ability in children with cerebral palsy. It will explore clinically important questions about the efficacy of intervening in somatosensation impairment to improve bimanual motor function, compared with focusing on motor impairment directly, and whether focusing on motor impairment alone can affect somatosensory ability. TRIAL REGISTRATION: This trial is registered with the Australian New Zealand Clinical Trials Registry, registration number: ACTRN12618000348257. World Health Organisation universal trial number: U1111-1210-1726.

Feasibility of Pediatric Game-Based Neurorehabilitation Using Telehealth Technologies: A Case Report.

This case report is the first in a series of reports designed to determine the feasibility of implementing game-based neurorehabilitation using telehealth technologies (GbN+TT) for children with cerebral palsy, evaluate the responsiveness of relevant outcome measures to changes in motor impairment and activity participation after intervention, and identify technological challenges associated with implementation of GbN+TT. The participant completed more than 56 hr of game-based neurorehabilitation over 8 wk using the Timocco platform in his home. The primary measures of motor impairment (Bruininks-Oseretsky Test of Motor Proficiency, Second Edition) and function (Pediatric Motor Activity Log) were both sensitive to change. Results indicate that it is feasible to administer GbN+TT to a child with cerebral palsy and monitor outcomes using standardized assessments.

Functional and structural connectivity of the visual system in infants with perinatal brain injury.

BACKGROUND: Infants with perinatal brain injury are at risk of later visual problems. Advanced neuroimaging techniques show promise to detect functional and structural alterations of the visual system. We hypothesized that infants with perinatal brain injury would have less brain activation during a visual functional magnetic resonance imaging (fMRI) task and reduced task-based functional connectivity and structural connectivity as compared with healthy controls. METHODS: Ten infants with perinatal brain injury and 20 control infants underwent visual fMRI and diffusion tensor imaging (DTI) during natural sleep with no sedation. Activation maps, functional connectivity maps, and structural connectivity were analyzed and compared between the two groups. RESULTS: Most infants in both groups had negative activation in the visual cortex during the fMRI task. Infants with brain injury showed reduced activation in the occipital cortex, weaker connectivity between visual areas and other areas of the brain during the visual task, and reduced fractional anisotropy in white matter tracts projecting to visual regions, as compared with control infants. CONCLUSION: Infants with brain injury sustained in the perinatal period showed evidence of decreased brain activity and functional connectivity during a visual task and altered structural connectivity as compared with healthy term neonates.

Changes of White Matter Diffusion Anisotropy in Response to a 6-Week iPad Application-Based Occupational Therapy Intervention in Children with Surgically Treated Hydrocephalus: A Pilot Study.

Objective Our aims were (1) to test whether diffusion tensor imaging (DTI) could detect underlying white matter (WM) changes after a 6-week iPad application-based occupational therapy (OT) intervention in children with surgically treated hydrocephalus (HCP); and (2) to explore the association between WM changes and performance outcomes. Methods Five children (age range: 6.05-9.10 years) with surgically treated HCP completed an intensive iPad-based OT intervention targeting common domains of long-term deficits in children with HCP. The intervention included 6 weekly sessions in an OT clinic supplementing home-based program (1 hour/day, 4 days/week). DTI and neuropsychological assessments were performed before and after the intervention. Observation After the therapy, significant increases in fractional anisotropy (FA) and/or decreases in radial diffusivity were found in extensive WM areas. All participants demonstrated an increased perceptual reasoning index (PRI, Wechsler Abbreviated Scale of Intelligence: 2nd edition, PRI gains = 14.20 ± 7.56, p = 0.014). A significant positive correlation was found between PRI increase and the increase of FA in the right posterior limb of the internal capsule and the right external capsule (both p < 0.05). Conclusion This study provides initial evidence of DTI's sensitivity to detect subtle WM changes associated with performance improvements in response to a 6-week OT intervention in children with HCP.

Sensory Features of Toddlers at Risk for Autism Spectrum Disorder.

OBJECTIVE: We observed sensory features in toddlers ages 12-24 mo with risk factors for autism spectrum disorder (ASD) and explored their relationship to general development and early signs of ASD. METHOD: Participants (N = 46) included toddlers with higher risk for ASD. All participants were administered standardized assessments of sensory features, early signs of ASD, and general development at a single study visit. RESULTS: Sensory features in toddlers were characterized as either adaptive or reactive. Toddlers with more difficulties in oral sensory processing displayed more early signs of ASD. Typical oral and auditory processing were associated with higher cognitive function, and toddlers with fewer sensory features overall had more mature language skills. CONCLUSION: Specific sensory features were associated with both early signs of ASD and less mature general development. Replication of this preliminary study is required.

Neuroimaging and Neurological Outcomes in Perinatal Arterial Ischemic Stroke: A Systematic Review and Meta-Analysis.

BACKGROUND: Prediction of outcomes in perinatal arterial ischemic stroke (PAIS) is challenging. We performed a systematic review and meta-analysis to determine whether infarct characteristics can predict outcomes in PAIS. METHODS: A systematic search was conducted using five databases in January 2023. Studies were included if the sample included children with neonatal or presumed PAIS; if infarct size, location, or laterality was indicated; and if at least one motor, cognitive, or language outcome was reported. The level of evidence and risk of bias were evaluated using the Risk of Bias in Non-Randomized Studies of Interventions tool. Meta-analyses were conducted comparing infarct size or location with neurological outcomes when at least three studies could be analyzed. RESULTS: Eighteen full-text articles were included in a systematic review with nine included in meta-analysis. Meta-analyses revealed that small strokes were associated with a lower risk of cerebral palsy/hemiplegia compared with large strokes (risk ratio [RR] = 0.263, P = 0.001) and a lower risk of epilepsy (RR = 0.182, P < 0.001). Middle cerebral artery (MCA) infarcts were not associated with a significantly different risk of cerebral palsy/hemiplegia compared with non-MCA strokes (RR = 1.220, P = 0.337). Bilateral infarcts were associated with a 48% risk of cerebral palsy/hemiplegia, a 26% risk of epilepsy, and a 58% risk of cognitive impairment. CONCLUSIONS: Larger stroke size was associated with worse outcomes across multiple domains. Widely heterogeneous reporting of infarct characteristics and outcomes limits the comparison of studies and the analysis of outcomes. More consistent reporting of infarct characteristics and outcomes will be important to advance research in this field.

White matter characteristics in children with cerebral palsy prior to selective dorsal rhizotomy: a multicenter diffusion tensor imaging study.

OBJECTIVE: The aims of this study were to 1) assess and quantify white matter (WM) microstructural characteristics derived from diffusion tensor imaging (DTI) in children with cerebral palsy (CP) prior to selective dorsal rhizotomy (SDR), and 2) investigate potential associations between WM diffusion properties and gross motor function and spasticity in children with spastic CP who underwent SDR. METHODS: This study is a multisite study based on DT images acquired prior to SDR as well as postoperative outcome data. DTI data collected from two sites were harmonized using the ComBat approach to minimize intersite scanner difference. The DTI abnormalities between children with spastic CP and controls were analyzed and correlated with the severity of impaired mobility based on the Gross Motor Function Classification System (GMFCS). The improvement in gross motor function and spasticity after SDR surgery was assessed utilizing the Gross Motor Function Measure-66 (GMFM-66), the Modified Tardieu Scale (MTS), and the modified Ashworth scale (MAS). Alterations in these outcome measures were quantified in association with DTI abnormalities. RESULTS: Significant DTI alterations, including lower fractional anisotropy (FA) in the genu of the corpus callosum (gCC) and higher mean diffusivity (MD) in the gCC and posterior limb of the internal capsule (PLIC), were found in children in the SDR group when compared with the age-matched control group (all p < 0.05). Greater DTI alterations (FA in gCC and MD in gCC and PLIC) were associated with lower mobility levels as determined based on GMFCS level (p < 0.05). The pre- to post-SDR improvement in motor function based on GMFM-66 was statistically significant (p = 0.006 and 0.002 at 6-month and 12-month follow-ups, respectively). The SDR efficacy was also identified as improving spasticity in lower-extremity muscle groups assessed with the MTS and MAS. Partial correlation analysis presented a significant association between pre- to post-SDR MTS alteration and DTI abnormalities. CONCLUSIONS: The findings in the present study provided initial quantitative evidence to establish the WM microstructural characteristics in children with spastic CP prior to SDR surgery. The study generated data for the association between baseline DTI characteristics and mobility in children with CP prior to SDR surgery. The study also demonstrated SDR efficacy in improving motor function and spasticity based on the GMFM-66, MTS, and MAS, respectively, in association with DTI data.

"Even though a lot of kids have it, not a lot of people have knowledge of it": A qualitative study exploring the perspectives of parents of children with cerebral/cortical visual impairment.

BACKGROUND: Cerebral/Cortical Visual Impairment (CVI) is the leading cause of visual impairment in children and can negatively impact participation in daily activities. METHODS AND PROCEDURE: This qualitative study used virtual focus groups and an online questionnaire to understand the perspectives of families with children who have CVI. Constant comparison analysis was used to analyze focus group transcripts and extract themes. The PEDI-CAT and an online questionnaire were administered to characterize the study population. OUTCOMES AND RESULTS: Four themes were identified: (1) Awareness of CVI and its effect on the child and family, (2) Parent experiences, (3) Child factors and functional implications, and (4) Supports that enhance child development/vision. CONCLUSIONS AND IMPLICATIONS: Findings from this study highlight the substantial impact that lack of CVI awareness had on parent experiences. Lack of awareness led to late diagnosis, missed intervention opportunities, and caregiver burden. Due to insufficient resources, parents had to educate themselves and service providers about CVI and advocate for their child's needs. Healthcare and educational providers who work with pediatric neurodevelopmental populations must be knowledgeable about clinical features of CVI, task and environmental adaptations to support vision and implementation of family-centered care.

Motor characteristics of young children referred for possible autism spectrum disorder.

PURPOSE: To examine motor characteristics of children referred for evaluation for autism spectrum disorder (ASD) using the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III). METHODS: BSID-III scores were collected through retrospective chart review for 30 children (mean age = 31.57 ± 6 months) admitted to an outpatient autism evaluation clinic. RESULTS: Children referred to an ASD clinic demonstrated a mean delay of 6 months for gross motor skills and 8 months for fine motor skills. There were no differences in total score or item analysis in group comparisons of motor characteristics in young children who did or did not receive a diagnosis of ASD. CONCLUSIONS: These results suggest that a delay in fine and gross motor skills at an early age is a characteristic of infants referred to an ASD clinic. Furthermore, the BSID-III may not be sensitive enough to distinguish between referred children with and without ASD.

Restricted Eating in Preschoolers with Autism: Mother Stressors and Solutions.

Feeding interventions for children with Autism Spectrum Disorder (ASD) focus solely on the child, not the family milieu. This qualitative study aimed to understand mothers' perspectives on managing restricted eating among preschoolers with ASD. Focus groups were conducted with eleven mothers of preschoolers with ASD. Audio recordings were transcribed, and data analyzed for themes. Mothers experienced stressors balancing priorities of adequate nutrition with family mealtime demands and found solutions in support from other mothers, strategies from a wide array of sources, and resorting to trial and error to improve eating. Healthcare practitioners should explore and consider family stressors, competing demands, and coping skills when recommending mealtime interventions for optimal child and family well-being.