PENDAH program for parents with children with attention deficit hyperactivity disorder. French adaptation of a behavioral parent training group: pilot study.

Behavioral parent training (BPT) is recognized as an effective part of the care offered to children with attention deficit hyperactivity disorder (ADHD). The aim of this pilot study was to objectively examine the effect that this intervention may have on motor activity, in addition to the measures classically found in this type of study. Parents of 24 school-aged children (6-12 year) with ADHD who met eligibility criteria were enrolled in the study. Before, after and five months after the intervention, we used three-dimensional accelerometers over one-week periods to measure the children's motor activity, and questionnaires for parental stress, quality of life, ADHD symptoms, anxiety and sensory disorders. To measure motor activity, a control group of normotypic children matched for age, sex and socio-professional category was set up. The experimental group showed slight decreases in motor activity compared with the control group, particularly in the classroom. The intervention showed improvements for parents in average stress and quality of life, and for children in average intensity global ADHD symptom, inattention, opposition and aggression, in line with previous studies on the effectiveness of BPT. The trial is the first clinical study to assess the effects of BPT on motor activity in children with ADHD.

A Systematic Review on Visual-Processing Deficits in Neurofibromatosis Type 1: What Possible Impact on Learning to Read?

This systematic review aimed to examine the possible implication of visual-perceptual, visuo-attentional and oculomotor processing in the reading deficits frequently experienced by children with Neurofibromatosis type 1 (NF1), as previously shown in dyslexia. Using PRISMA methodological guidelines, we examined 49 studies; most of these reported visual-processing deficits in this population, raising the importance of directly studying the visuo-perceptual and visuo-attentional processes and eye-movement control involved in the learning-to-read process in NF1. The discussion provides a reflection for a better understanding of how visual-processing skills interact with reading deficits in NF1, as well as new avenues for their screening and care.

Long-term outcomes of paediatric Guillain-Barré syndrome.

AIM: To study long-term sequelae in children with Guillain-Barré syndrome (GBS). METHOD: This was a prospective observational study with children from two French tertiary centres. Data were from clinical and several standardized scales or questionnaires. RESULTS: Fifty-one patients were included with a median follow-up of 6 years 4 months (range 3-20 years) after the acute phase. The sequelae rate was 67% (95% confidence interval [CI] 53-78) and did not vary with time. Most children had minor sequelae (Guillain-Barré Syndrome Disability Score [GBSDS] = 1); only one was unable to run (GBSDS = 2). The most frequent complaints were paraesthesia (43%), pain (35%), and fatigue (31%). The neurological examination was abnormal in 18% of children, autonomy was compromised in 14%, and symptoms of depression occurred in 34%. The factors associated with late-onset sequelae were correlated with severity during the initial phase (i.e. initial GBSDS >4, odds ratio 6.6, 95% CI 1.8-33; p = 0.009). The predictive factors of more severe late-onset conditions were initial severity (p = 0.002) and sex (female patients; p = 0.01). INTERPRETATION: Two-thirds of children with GBS had late-onset sequelae following an episode, often minor, but sometimes with continuing effects on their everyday lives. Particularly affected were those who had severe GBS during the acute phase and who lost the ability to walk. WHAT THIS PAPER ADDS: Two-thirds of children with Guillain-Barré syndrome (GBS) had persistent sequelae. Sequelae were often minor, but daily repercussions of them were sometimes serious. Sequelae were significantly associated with severe GBS during the acute phase.

Behavioral Parent Training for School-Aged Children With ADHD: A Systematic Review of Randomized Control Trials.

BACKGROUND: All guidelines for the treatment of ADHD in children include behavioral parent training in combination with other strategies. In the past, several systematic reviews have been carried out that were either outdated or not sufficiently specific to ADHD. We wanted to conduct a new review focusing on a specific ADHD population of school age (4-12 years) and on behavioral and cognitive programs. We aimed to test our hypothesis that behavioral parent training would improve parents' difficulties, children's symptomatology, and the quality of life of families with ADHD. METHODS: PUBMED, PsychInfo, Web of Science, ERIC, and Cochrane databases were searched for original articles on randomized control trials on behavioral parent training group for children with ADHD aged from 4 to 12 years until July 2023. RESULTS: A total of 20 studies were included in the systematic review. The results were divided into four categories: parent data, child data collected by parents, teachers, or researchers. A qualitative analysis revealed for parents, effects on parental stress, feelings of parental efficacy, and negative parental educational behavior. As regard children, only effects are noted for parental assessment, on ADHD symptomatology, externalized disorders, and social skills. CONCLUSION: Despite the heterogeneity or small number of studies in some categories, BPTs have positive effects on both parents and children. There are no convincing results to support the generalization of progress. This would seem to indicate that it remains essential to consider actions specific to each problematic environment for the child.

The long-term impact of irradiation on functional connectivity in brain circuits involved in memory processes after pediatric posterior fossa tumor.

PURPOSE: Memory is one of the main specific cognitive domains impaired with attention and processing speed after a pediatric brain tumor. This work explored the long-term impact of radiotherapy in children with posterior fossa tumor (PFT) on brain connectivity in neural circuits involved in memory using resting-state functional magnetic resonance imaging (rs-fMRI). METHODS: A total of 20 irradiated and 15 non-irradiated PFT survivors, and 21 healthy controls, prospectively included in the IMPALA study (NCT04324450), performed memory tests assessing episodic, procedural, and working memories and were subjected to an rs-fMRI. We manually contoured main structures involved in memory to explore connectivity at rest in a seed-to-voxel analysis. The groups were compared and differences in connectivity were correlated with behavioral scores and irradiation doses. RESULTS: The performance of all mnesic tasks was lower in PFT survivors with a greater alteration in working and episodic memory in irradiated patients. Irradiated survivors had atypical connectivities in all memory circuits compared to controls and in cortico-caudate and cortico-cerebellar circuits compared to non-irradiated survivors. Non-irradiated survivors had only atypical connectivities in the cortico-cerebellar circuits compared to controls. In irradiated survivors, atypical connectivities in cortico-hippocampal circuits were linked with episodic memory scores and dose of irradiation to the left hippocampus and in cortico-striatal circuits with procedural memory scores and dose of irradiation to the striatum. CONCLUSION: The results of this study highlight that irradiation has a long-term impact on brain connectivity in brain circuits involved in memory after pediatric PFT with a specific radiation-dose effect in supratentorial structures.

Speech disfluencies in children with developmental dyslexia: How do they differ from typical development?

BACKGROUND: Disfluency is a multifactorial concept that can be linked to several of the language production levels, in both typical and atypical populations. In children, the language system is still developing and few studies have explored disfluency patterns. In typical development (TD), in particular, studies have shown discrepancies according to the language being considered. In neurodevelopmental disorders, such as developmental dyslexia (DD), it is still unclear whether the pattern of disfluency is similar to TD. AIMS: To analyse the type of disfluency and their evolution in French children aged 8-12 years. Also to compare the pattern of disfluency in DD and TD, and to test whether disfluencies were correlated with reading difficulties. METHODS & PROCEDURES: A total of 25 children with DD and 21 children with TD aged 8-12.6 years produced an autobiographical narrative. Seven types of disfluencies were coded: part-word repetitions; repetitions of monosyllabic words; other types of repetitions (words and phrases); filled pauses; revisions-substitutions; revisions-additions; and abandoned utterances. We compared the proportion of each disfluency in DD and TD. Spearman correlations were then performed between disfluencies, reading performance and age. OUTCOMES & RESULTS: The results showed that both DD and TD children mainly produced filled pauses, repetitions of monosyllabic words and substitutions. Both groups displayed a high rate of disfluency (> 10%). No correlations with age were found. Correlations with reading performance were significant in the TD group only. CONCLUSIONS & IMPLICATIONS: The study showed that DD is not characterized by a specific pattern of disfluency. Additionally, disfluency rates were similar in children aged 8-12 years. In contrast to other languages, the current study suggests that French-speaking children have a high rate of disfluency. The study also suggests that disfluency should be interpreted with caution in DD, given that TD children also have a high rate of disfluency. Therefore, it seems important to adapt the pathological threshold of disfluency to the language being spoken in order to avoid an overestimation of the prevalence of these deficits in French-speaking children. WHAT THIS PAPER ADDS: What is already known on this subject TD children produce a high rate of disfluency, which is also influenced by the language being spoken. No study looked at the effect of DD on disfluency production. Nonetheless, problems in reading comprehension and reduced reading experience may impact lexical development and speech fluency. What this paper adds to the existing knowledge In our study, both groups (French-speaking children) produced a substantial amount of disfluency as compared with other languages (> 10%). Additionally, the pattern of disfluency was similar in TD and DD (namely, filled pauses, prolongations repetitions of monosyllabic words and substitutions). In the DD group, disfluency production was not correlated with reading performance. What are the potential or actual clinical implications of this work? These results indicate that it is crucial to consider the language being spoken when examining disfluency in order to avoid an overestimation of language difficulties in some languages, such as in French. Moreover, the production of disfluencies in DD should not be considered as language dysfunction since the pattern of disfluency what quite similar in TD and DD, and did not correlate with their reading difficulties.

Impact of a pediatric posterior fossa tumor and its treatments on motor procedural learning.

INTRODUCTION: Posterior fossa tumor (PFT) survivors have difficulty learning new skills. Procedural memory is a skill learning system that allows, through training, the automatization of procedures and progressive improvement of performance. It underlies most of the motor procedures in everyday life that we perform automatically, such as riding a bike or writing. Motor procedural memory is divided into two components: motor sequence learning involving mainly cortico-striatal networks, and motor adaptation involving mainly cortico-cerebellar networks. The aim of this work was to explore the impact of a tumor and its treatment during childhood on procedural learning hypothesizing that sequence learning would be impaired in PFT survivors who have been treated with radiotherapy, whereas motor adaptation would be impaired in all PFT survivors. METHOD: 22 irradiated survivors of PFT, 17 non-irradiated survivors and 21 healthy controls from the IMPALA study (NCT04324450) performed a motor sequence learning task and a motor adaptation task. Doses received by striatal and cerebellar structures were reported from the initial dosimetry plans. RESULTS: Sequence learning was preserved in both tumor groups, but at the individual level 7/22 irradiated, and 4/17 non-irradiated participants failed to learn the motor sequence. Motor adaptation was impaired in both tumor groups, predominantly in the irradiated group. CONCLUSION: This study sheds new light on the long-term impact of PFT treatments in childhood on a rarely-studied part of memory, which is perceptual-motor procedural learning. Our results suggest that the cerebellum and striatum could be considered as organs at risk with regard to procedural learning.

French cohort of children and adolescents with neurofibromatosis type 1 and symptomatic inoperable plexiform neurofibromas: CASSIOPEA study.

Surgery is a treatment option for neurofibromatosis type 1 (NF1)-related plexiform neurofibromas (PN), but complete resection is often not feasible. Real-world studies are warranted to understand disease burden, progression, and need for medical treatment in patients with inoperable PN. CASSIOPEA was a retrospective study of French pediatric patients (aged ≥3 to <18 years) presenting at a national multidisciplinary team (MDT) review with NF1 and ≥1 symptomatic, inoperable PN. Medical records were reviewed from the time of MDT review and over a follow-up period of up to 2 years. Primary objectives were to describe patient characteristics and target PN-associated therapy patterns. A secondary objective was evolution of target PN-related morbidities. Patients with prior, ongoing, or MDT recommendation of mitogen-activated protein kinase kinase (MEK) inhibitor treatment were excluded. Overall, 78 target PN were identified in 76 patients. At MDT review, median age was 8.4 years, with approximately 30% of patients aged 3-6 years. Target PN were primarily internal (77.3%), and 43.2% were progressive. Target PN location was evenly distributed. 34 target PN had documented MDT recommendations; of these, a majority (76.5%) were for non-medication management, including surveillance. At least one follow-up visit was recorded for 74 target PN. Despite initially being considered inoperable, 12.3% of patients underwent surgery for target PN. At MDT review, most (98.7%) target PN were associated with ≥1 morbidity, primarily pain (61.5%) and deformity (24.4%); severe morbidities were identified in 10.3%. Of 74 target PN with follow-up data, 89.2% were associated with ≥1 morbidity, primarily pain (60.8%) and deformity (25.7%). Of 45 target PN associated with pain, pain improved in 26.7%, was stable in 44.4%, and deteriorated in 28.9%. Deformity improved in 15.8% and remained stable in 84.2% of 19 target PN associated with deformity. None deteriorated. In this real-world study in France, NF1-PN disease burden was considerable, and a considerable proportion of patients were very young. Most patients received only supportive care without medication for target PN management. Target PN-related morbidities were frequent, heterogeneous, and generally did not improve during follow-up. These data highlight the importance of effective treatments that target PN progression and improve disease burden.

A preliminary study of the different memory systems in neurofibromatosis type 1: What is impaired and what is spared?

BACKGROUND: Since 1990's, the cognitive profile of children with a neurofibromatosis type 1 (NF1) has been refined by many different studies. Children with NF1 may exhibit a variety of cognitive dysfunctions. Memory difficulties have been reported, but the results are contradictory and, compared to other cognitive functions, memory has been less evaluated. OBJECTIVE: The aim of this study was to investigate the memory profile in NF1 with a particular population, children with NF1 without attention deficit hyperactivity disorder (ADHD). METHODS: Eighteen children with NF1 without ADHD and eighteen typically developing aged from 8 to 12.6 years were compared in terms of both their verbal and visual working memory, anterograde memory, and procedural perceptual-motor memory. We also assessed semantic and autobiographical memory. RESULTS: Our results indicate the existence of memory difficulties in children with NF1 without ADHD in verbal working and anterograde memory but not in terms of the visual domain. They also experienced difficulties recalling personal memories but these were improved by cueing. However, semantic memory and procedural perceptual-motor memory was preserved. CONCLUSIONS: These results highlight a difference between memory systems in children with NF1 without ADHD and the importance to assess the different memory systems, the nature of information and the processes in long-term memory in NF1 population. However, our results raise questions about the possible links between these difficulties and the executive functions. The specifics of memory profile in children with NF1 must be taken into consideration in these children's clinical follow-up, in order to understand their learning difficulties and to make adaptations to their care.

Developmental dyslexia, developmental coordination disorder and comorbidity discrimination using multimodal structural and functional neuroimaging.

Developmental dyslexia (DD) and developmental coordination disorder (DCD) are two common neurodevelopmental disorders with a high co-occurrence rate. This led several authors to postulate that the two disorders share, at least partially, similar neural underpinning. However, even though several studies examined brain differences between typically developing (TD) children and children with either DD or DCD, no previous study directly compared DD, DCD and children with both disorders (COM) using neuroimaging. We acquired structural and resting-state functional MRI images of 136 children (TD = 42, DD = 45, DCD = 20, COM = 29). Difference between TD children and the other groups was assessed using univariate analysis of structural indexes including grey and white matter volumes and functional indexes quantifying activity (fraction of the amplitude of the low frequency fluctuations), local and global connectivity. Regional differences in structural and functional brain indexes were then used to train machine learning models to discriminate among DD, DCD and COM and to find the most discriminant regions. While no imaging index alone discriminated between the three groups, grouping grey and white matter volumes (structural model) or activity, local and global connectivity (functional model) made possible to discriminate among the DD, DCD and COM groups. The most important discrimination was obtained using the functional model, with regions in the cerebellum and the temporal lobe being the most discriminant for DCD and DD children, respectively. Results further showed that children with both DD and DCD have subtle but identifiable brain differences that can only be captured using several imaging indexes pertaining to both brain structure and function.

The determinants of saccade targeting strategy in neurodevelopmental disorders: The influence of suboptimal reading experience.

Whether eye-movements deficits are causal in reading disorders (RD) or rather a consequence of linguistic processing difficulty experienced by disabled readers has been extensively debated.Since RD are frequently comorbid with the Neurofibromatosis type1 (NF1), children with NF1 were used as a comparison group for children with dyslexia in this study.Eye movements were recorded while 21 dyslexic, 20 NF1, and 20 typically developing children performed an oculomotor lateralized bisection task. In this experiment, we manipulated the type of stimulus - discrete (words and strings of hashes) versus continuous (solid lines) - and the visual field where the stimulus was displayed (left vs right). The results showed that (1) only proficient readers (TD and NF1 without RD) showed fully developed oculomotor mechanisms for efficient reading, with a clear preferred viewing location located to the left of the word's centre in both visual fields, and fine-tuned saccade targeting guided by the between-character space information and (2) NF1 poor readers mirrored the dyslexic eye movement behaviour, with less accuracy and more variability in saccadic programming, no sensitivity to the discreteness of the stimuli, particularly in the left visual field. We concluded that disruption to oculomotor behaviour reflectsthe fact that many of the processes involved in reading are not yet automatized for children with RD, independently of NF1. This suggests that the differences in saccade targeting strategy between children with and without RD would be secondary consequences of their reduced reading experience.

Is There a Deficit in Product and Process of Handwriting in Children with Attention Deficit Hyperactivity Disorder? A Systematic Review and Recommendations for Future Research.

Handwriting abnormalities in children with attention deficit hyperactivity disorder (ADHD) have sometimes been reported both (i) at the product level (i.e., quality/legibility of the written trace and speed of writing) and (ii) at the process level (i.e., dynamic and kinematic features, such as on-paper and in-air durations, pen pressure and velocity peaks, etc.). Conversely, other works have failed to reveal any differences between ADHD and typically developing children. The question of the presence and nature of handwriting deficits in ADHD remains open and merits an in-depth examination. The aim of this systematic review was, therefore, to identify studies that have investigated the product and/or process of handwriting in children with ADHD compared to typically developing individuals. This review was conducted and reported in accordance with the PRISMA statement. A literature search was carried out using three electronic databases. The methodological quality of the studies was systematically assessed using the Critical Appraisal Skills Program (CASP) criteria. Twenty-one articles were identified. Of these, 17 described handwriting quality/legibility, 12 focused on speed and 14 analyzed the handwriting process. All the studies (100%) with satisfactory methodology procedures reported an impaired product and process in children with ADHD, while 25% evidenced a difference in the speed of production. Most importantly, the studies differed widely in their methodological approaches. Substantial gaps remain, particularly with regard to ascertaining comorbidities, ADHD subtypes and the medical status of the included children. The lack of overall homogeneity in the samples calls for higher quality studies. We conclude with recommendations for further studies.

A review of long-term deficits in memory systems following radiotherapy for pediatric posterior fossa tumor.

INTRODUCTION: In recent years, progress in pediatric posterior fossa tumor (PFT) treatments has improved survival rates. However, the majority of survivors present neurocognitive sequelae that impact academic achievement. METHODS: This review examines the literature from 2000 to 2020 on long-term outcomes in different memory systems for survivors of pediatric PFT, considering the impact of radiotherapy which is a well-known prognostic factor for global neurocognitive function. RESULTS: Of the 43 articles selected, 31 explored working memory, 19 episodic memory, 9 semantic memory and 2 procedural memory. Irradiated survivors had scores of <-2 standard deviation (SD) (n = 4 studies/25) or between -2SD and -1SD (n = 7 studies/25) for working memory; <-1SD for anterograde memory (n = 11/13), with a progressive decline in these two memory systems; <-1SD (n = 4/7) in semantic memory, and a deficit in perceptual-motor procedural learning (n = 1/1). Reducing craniospinal irradiation dose, limiting tumor bed boosts, and using proton therapy seem to have had a beneficial effect with better preservation of the memory score and a reduction in the decline over time. Non-irradiated survivors had memory systems that were less affected, with preservation of anterograde memory and maintenance of long-term stability. CONCLUSION: Memory deficits are a core feature in survivors of pediatric PFT, especially when treatment requires radiotherapy. To limit these effects, dose constraints for specific brain areas involved in memory should be defined. During long-term follow-up, specific attention is essential to identify these deficits in order to limit their impact on the quality of life.

Visual-processing deficits in children with neurofibromatosis type 1: A clinical marker of reading difficulties.

Today's estimates indicate that nearly 50% of children with Neurofibromatosis type 1 (NF1) suffer from reading disabilities, with a high impact on their academic achievement. In addition to the well-documented importance of phonological skills in reading acquisition and neurodevelopmental disorders, visual-attention processes also appear as important factors in learning to read. The present study aimed at assessing the role of visual-processing dysfunction in the high prevalence of reading disabilities in NF1 children and providing a useful tool for clinician in the early detection of reading impairment in this neurogenetic disorder. Forty-two children with NF1 and 42 typically developing children (TD) participated in the study. All were right-handed and did not present intellectual disability or attention deficit hyperactivity disorder. Visual-attention processes were assessed with the Developmental Eye Movement (DEM) test, together with the NF1 children's reading level. NF1 children with and without reading disabilities were then compared. The results showed that visual-processing deficits were highly present among the NF1 children included in our study. Furthermore, poor readers with NF1 presented an increased risk of visual-processing deficits compared to peers. This finding supports the role of visual-processing deficits in the reading difficulties encountered in nearly half of children with NF1. Finally, in NF1 children without intellectual or attention disability, visual-processing deficits emerge as one of the clinical markers of reading disabilities. The study holds important clinical implications both for the identification, by providing a useful screening tool, and the management of reading disabilities in NF1 children.

Atypical connectivity in the cortico-striatal network in NF1 children and its relationship with procedural perceptual-motor learning and motor skills.

INTRODUCTION: Neurofibromatosis type 1 (NF1) is considered a model of neurodevelopmental disorder because of the high frequency of learning deficits, especially developmental coordination disorder. In neurodevelopmental disorder, Nicolson and Fawcett formulated the hypothesis of an impaired procedural learning system that has its origins in cortico-subcortical circuits. Our aim was to investigate the relationship between cortico-striatal connectivity and procedural perceptual-motor learning performance and motor skills in NF1 children. METHODS: Seventeen NF1 and 18 typically developing children aged between 8 and 12 years old participated in the study. All were right-handed and did not present intellectual or attention deficits. In all children, procedural perceptual-motor learning was assessed using a bimanual visuo-spatial serial reaction time task (SRTT) and motor skills using the Movement Assessment Battery for Children (M-ABC). All participants underwent a resting-state functional MRI session. We used a seed-based approach to explore cortico-striatal connectivity in somatomotor and frontoparietal networks. A comparison between the groups' striato-cortical connectivity and correlations between connectivity and learning (SRTT) and motor skills (M-ABC) were performed. RESULTS: At the behavioral level, SRTT scores are not significantly different in NF1 children compared to controls. However, M-ABC scores are significantly impaired within 9 patients (scores below the 15th percentile). At the cerebral level, NF1 children present a higher connectivity in the cortico-striatal regions mapping onto the right angular gyrus compared to controls. We found that the higher the connectivity values between these regions, differentiating NF1 and controls, the lower the M-ABC scores in the whole sample. No correlation was found for the SRTT scores. CONCLUSION: NF1 children present atypical hyperconnectivity in cortico-striatal connections. The relationship with motor skills could suggest a sensorimotor dysfunction already found in children with developmental coordination disorder. These abnormalities are not linked to procedural perceptual-motor learning assessed by SRTT.

A prospective behavioral and imaging study exploring the impact on long-term memory of radiotherapy delivered for a brain tumor in childhood and adolescence.

BACKGROUND: Posterior fossa tumors represent two thirds of brain tumors in children. Although progress in treatment has improved survival rates over the past few years, long-term memory impairments in survivors are frequent and have an impact on academic achievement. The hippocampi, cerebellum and cerebellar-cortical networks play a role in several memory systems. They are affected not only by the location of the tumor itself and its surgical removal, but also by the supratentorial effects of complementary treatments, particularly radiotherapy. The IMPALA study will investigate the impact of irradiation doses on brain structures involved in memory, especially the hippocampi and cerebellum. METHODS/DESIGN: In this single-center prospective behavioral and neuro-imaging study, 90 participants will be enrolled in three groups. The first two groups will include patients who underwent surgery for a posterior fossa brain tumor in childhood, who are considered to be cured, and who completed treatment at least 5 years earlier, either with radiotherapy (aggressive brain tumor; Group 1) or without (low-grade brain tumor; Group 2). Group 3 will include control participants matched with Group 1 for age, sex, and handedness. All participants will perform an extensive battery of neuropsychological tests, including an assessment of the main memory systems, and undergo multimodal 3 T MRI. The irradiation dose to the different brain structures involved in memory will be collected from the initial radiotherapy dosimetry. DISCUSSION: This study will provide long-term neuropsychological data about four different memory systems (working memory, episodic memory, semantic memory, and procedural memory) and the cognitive functions (attention, language, executive functions) that can interfere with them, in order to better characterize memory deficits among the survivors of brain tumors. We will investigate the correlations between neuropsychological and neuroimaging data on the structural (3DT1), microstructural (DTI), functional (rs-fMRI), vascular (ASL) and metabolic (spectroscopy) impact of the tumor and irradiation dose. This study will thus inform the setting of dose constraints to spare regions linked to the development of cognitive and memory functions. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04324450, registered March 27, 2020, updated January 25th, 2021. Retrospectively registered, https://www.clinicaltrials.gov/ct2/show/NCT04324450.

Predicting future poor readers from pre-reading visual skills: A longitudinal study.

Reading is essential for learning, from literature to physics, from paper to screens on e-readers and smart phones. Even if it is well known that learning to read implies good language skills, children also need to develop good oculomotor and visual-perception skills. Thereby, any deficits in visual processing may affect learning. The possible impact of visual deficits is rarely considered, especially with regard to eye movements and visual perception. Hence, these deficits are usually discovered much later or remain undiagnosed. The present study aimed at assessing the usefulness of visual processing related measures in the early detection of reading difficulties. Visual skill differences that are apparent early in kindergarten might provide predictive insights into risk for learning difficulties at school entry. We used a prospective, longitudinal approach where visual processes (assessed with the Developmental Eye Movement (DEM) test) were measured in 51 preschoolers, and the impact of these processes on future reading development was explored one year later, in Grade 1. Results showed that (1) 31% of our sample of preschoolers showed visual processing impairments (without any clinical complaints) and (2) reading accuracy and speed in first graders were significantly correlated with visual skills assessed in kindergarten, thus confirming the significant role of oculomotor and visual-perception processes in the acquisition of reading skills. These suggests the potential for these measures to be used clinically for identifying children at risk for low academic achievement, enabling appropriate targeting of early interventions.

Refining Genotypes and Phenotypes in KCNA2-Related Neurological Disorders.

Pathogenic variants in KCNA2, encoding for the voltage-gated potassium channel Kv1.2, have been identified as the cause for an evolving spectrum of neurological disorders. Affected individuals show early-onset developmental and epileptic encephalopathy, intellectual disability, and movement disorders resulting from cerebellar dysfunction. In addition, individuals with a milder course of epilepsy, complicated hereditary spastic paraplegia, and episodic ataxia have been reported. By analyzing phenotypic, functional, and genetic data from published reports and novel cases, we refine and further delineate phenotypic as well as functional subgroups of KCNA2-associated disorders. Carriers of variants, leading to complex and mixed channel dysfunction that are associated with a gain- and loss-of-potassium conductance, more often show early developmental abnormalities and an earlier onset of epilepsy compared to individuals with variants resulting in loss- or gain-of-function. We describe seven additional individuals harboring three known and the novel KCNA2 variants p.(Pro407Ala) and p.(Tyr417Cys). The location of variants reported here highlights the importance of the proline(405)-valine(406)-proline(407) (PVP) motif in transmembrane domain S6 as a mutational hotspot. A novel case of self-limited infantile seizures suggests a continuous clinical spectrum of KCNA2-related disorders. Our study provides further insights into the clinical spectrum, genotype-phenotype correlation, variability, and predicted functional impact of KCNA2 variants.

The Differential Effects of Auditory and Visual Stimuli on Learning, Retention and Reactivation of a Perceptual-Motor Temporal Sequence in Children With Developmental Coordination Disorder.

This study investigates the procedural learning, retention, and reactivation of temporal sensorimotor sequences in children with and without developmental coordination disorder (DCD). Twenty typically-developing (TD) children and 12 children with DCD took part in this study. The children were required to tap on a keyboard, synchronizing with auditory or visual stimuli presented as an isochronous temporal sequence, and practice non-isochronous temporal sequences to memorize them. Immediate and delayed retention of the audio-motor and visuo-motor non-isochronous sequences were tested by removing auditory or visual stimuli immediately after practice and after a delay of 2 h. A reactivation test involved reintroducing the auditory and visual stimuli after the delayed recall. Data were computed via circular analyses to obtain asynchrony, the stability of synchronization and errors (i.e., the number of supplementary taps). Firstly, an overall deficit in synchronization with both auditory and visual isochronous stimuli was observed in DCD children compared to TD children. During practice, further improvements (decrease in asynchrony and increase in stability) were found for the audio-motor non-isochronous sequence compared to the visuo-motor non-isochronous sequence in both TD children and children with DCD. However, a drastic increase in errors occurred in children with DCD during immediate retention as soon as the auditory stimuli were removed. Reintroducing auditory stimuli decreased errors in the audio-motor sequence for children with DCD. Such changes were not seen for the visuo-motor non-isochronous sequence, which was equally learned, retained and reactivated in DCD and TD children. All these results suggest that TD children benefit from both auditory and visual stimuli to memorize the sequence, whereas children with DCD seem to present a deficit in integrating an audio-motor sequence in their memory. The immediate effect of reactivation suggests a specific dependency on auditory information in DCD. Contrary to the audio-motor sequence, the visuo-motor sequence was both learned and retained in children with DCD. This suggests that visual stimuli could be the best information for memorizing a temporal sequence in DCD. All these results are discussed in terms of a specific audio-motor coupling deficit in DCD.

Reading Comprehension Impairment in Children With Neurofibromatosis Type 1 (NF1): The Need of Multimodal Assessment of Attention.

Attention span, which has been shown to have an impact on reading quality in many other conditions, is one of the main cognitive disorders of neurofibromatosis type 1 (NF1). The aim of this work is to observe the impact of attention on reading comprehension, in NF1 and non-NF1 children. A multicenter, cross-sectional study was conducted on 150 children (8-12 years old) with or without NF1 (75 NF1 vs 75 non-NF1; 72 female, 78 male), matched for age, sex, handedness, and reading level, thus forming a continuum from good to poor readers in both NF1 and non-NF1 groups. Children with intellectual deficiency or neurologic or psychiatric disorder were excluded. Attentional skills were assessed by combining a parent questionnaire (Child Behavior CheckList) and a performance-based assessment (Conner's Continuous Performance Test-Second Edition). Reading comprehension was assessed through a standardized reading comprehension test (ORLEC Lobrot). The performance-based attention scores were associated with text and sentence comprehension ability (P = .0235 and P = .0164, respectively), while indirect questionnaire attention scores were only associated with sentence comprehension (P = .0263). For both groups, the correlations between questionnaire and performance-based measures were low. We have shown that reading comprehension is greatly influenced by attention in NF1 and non-NF1, even if predictors of good reading comprehension also include IQ score and reading accuracy. Indirect observer-rated questionnaires and direct performance-based measures of attention do not assess the same variables, are linked to different components of reading skills, and are not interchangeable assessments of attention difficulties. Both assessments are complementary and must be used simultaneously, leading to recommendations that support multimodal assessment of attention.