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.

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.

Genome-wide association study reveals new insights into the heritability and genetic correlates of developmental dyslexia.

Developmental dyslexia (DD) is a learning disorder affecting the ability to read, with a heritability of 40-60%. A notable part of this heritability remains unexplained, and large genetic studies are warranted to identify new susceptibility genes and clarify the genetic bases of dyslexia. We carried out a genome-wide association study (GWAS) on 2274 dyslexia cases and 6272 controls, testing associations at the single variant, gene, and pathway level, and estimating heritability using single-nucleotide polymorphism (SNP) data. We also calculated polygenic scores (PGSs) based on large-scale GWAS data for different neuropsychiatric disorders and cortical brain measures, educational attainment, and fluid intelligence, testing them for association with dyslexia status in our sample. We observed statistically significant (p < 2.8 × 10-6) enrichment of associations at the gene level, for LOC388780 (20p13; uncharacterized gene), and for VEPH1 (3q25), a gene implicated in brain development. We estimated an SNP-based heritability of 20-25% for DD, and observed significant associations of dyslexia risk with PGSs for attention deficit hyperactivity disorder (at pT = 0.05 in the training GWAS: OR = 1.23[1.16; 1.30] per standard deviation increase; p = 8 × 10-13), bipolar disorder (1.53[1.44; 1.63]; p = 1 × 10-43), schizophrenia (1.36[1.28; 1.45]; p = 4 × 10-22), psychiatric cross-disorder susceptibility (1.23[1.16; 1.30]; p = 3 × 10-12), cortical thickness of the transverse temporal gyrus (0.90[0.86; 0.96]; p = 5 × 10-4), educational attainment (0.86[0.82; 0.91]; p = 2 × 10-7), and intelligence (0.72[0.68; 0.76]; p = 9 × 10-29). This study suggests an important contribution of common genetic variants to dyslexia risk, and novel genomic overlaps with psychiatric conditions like bipolar disorder, schizophrenia, and cross-disorder susceptibility. Moreover, it revealed the presence of shared genetic foundations with a neural correlate previously implicated in dyslexia by neuroimaging evidence.

Procedural learning and retention of audio-verbal temporal sequence is altered in children with developmental coordination disorder but cortical thickness matters.

Rhythmic abilities are impaired in developmental coordination disorder (DCD) but learning deficit of procedural skills implying temporal sequence is still unclear. Current contradictory results suggest that procedural learning deficits in DCD highly depend on learning conditions. The present study proposes to test the role of sensory modality of stimulations (visual or auditory) on synchronization, learning, and retention of temporal verbal sequences in children with and without DCD. We postulated a deficit in learning particularly with auditory stimulations, in association with atypical cortical thickness of three regions of interesting: sensorimotor, frontal and parietal regions. Thirty children with and without DCD (a) performed a synchronization task to a regular temporal sequence and (b) practiced and recalled a novel non-regular temporal sequences with auditory and visual modalities. They also had a magnetic resonance imaging to measure their cortical thickness. Results suggested that children with DCD presented a general deficit in synchronization of a regular temporal verbal sequence irrespective of the sensory modality, but a specific deficit in learning and retention of auditory non-regular verbal temporal sequence. Stability of audio-verbal synchronization during practice correlated with cortical thickness of the sensorimotor cortex. For the first time, our results suggest that synchronization deficits in DCD are not limited to manual tasks. This deficit persists despite repeated exposition and practice of an auditory temporal sequence, which suggests a possible alteration in audio-verbal coupling in DCD. On the contrary, control of temporal parameters with visual stimuli seems to be less affected, which opens perspectives for clinical practice.

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 value of screening tests in children with neurofibromatosis type 1 (NF1).

Neurofibromatosis type 1 (NF1) is one of the most prevalent rare diseases. Whilst penetrance is complete by adulthood, its expressivity is extremely variable with potential multi-systemic complications. Although NF1 is diagnosed clinically, molecular analysis has a part to play in the screening of atypical forms and in genetic counselling. The screening of complications is primarily based on a full annual clinical examination and an ophthalmological examination. Targeted paraclinical examinations will be carried out when clinical signs appear (neurological, ophthalmological, cutaneous, endocrinological, orthopaedic and cardiovascular, etc.). The implementation of routine paraclinical examinations, which are stressful for families, expensive and sometimes invasive (MRI under general anaesthetic), is only of minor interest and does not lead to any change in treatment if the child is asymptomatic. Part of the consultation should focus on evaluation of psychomotor development and learning difficulties, which are common features of this condition (50%), and impact the child's quality of life.

Discriminating between neurofibromatosis-1 and typically developing children by means of multimodal MRI and multivariate analyses.

Neurofibromatosis Type 1 leads to brain anomalies involving both gray and white matter. The extent and granularity of these anomalies, together with their possible impact on brain activity, is still unknown. In this multicentric cross-sectional study we submitted a sample of 42 typically developing and 38 neurofibromatosis-1 children to a multimodal MRI assessment including T1, diffusion weighted and resting state functional sequences. We used a pipeline involving several features selection steps coupled with multivariate statistical analysis (supporting vector machine) to discriminate between the two groups while having interpretable models. We used MRI indexes measuring macro (gray matter volume) and microstructural (fractional anisotropy, mean diffusivity) characteristics of the brain, as well as indexes of brain activity (fractional amplitude of low frequency fluctuations) and connectivity (local and global correlation) at rest. We found that structural indexes could discriminate between the two groups, with the mean diffusivity leading to performance as high as the combination of all structural indexes combined (accuracy = 0.86), while functional indexes had worse performances. The MRI signature of NF1 brain pathology is a combination of gray and white matter abnormalities, as measured with gray matter volume, fractional anisotropy, and mean diffusivity.

Human TRAF3 adaptor molecule deficiency leads to impaired Toll-like receptor 3 response and susceptibility to herpes simplex encephalitis.

Tumor necrosis factor (TNF) receptor-associated factor 3 (TRAF3) functions downstream of multiple TNF receptors and receptors that induce interferon-α (IFN-α), IFN-ß, and IFN-λ production, including Toll-like receptor 3 (TLR3), which is deficient in some patients with herpes simplex virus-1 encephalitis (HSE). Mice lacking TRAF3 die in the neonatal period, preventing direct investigation of the role of TRAF3 in immune responses and host defenses in vivo. Here, we report autosomal dominant, human TRAF3 deficiency in a young adult with a history of HSE in childhood. The TRAF3 mutant allele is loss-of-expression, loss-of-function, dominant-negative and associated with impaired, but not abolished, TRAF3-dependent responses upon stimulation of both TNF receptors and receptors that induce IFN production. TRAF3 deficiency is associated with a clinical phenotype limited to HSE resulting from the impairment of TLR3-dependent induction of IFN. Thus, TLR3-mediated immunity against primary infection by HSV-1 in the central nervous system is critically dependent on TRAF3.

Prognostic factors for the sequelae and severity of Guillain-Barré syndrome in children.

INTRODUCTION: Guillain-Barré syndrome (GBS) is an inflammatory polyradiculoneuritis. Our aim in this study was to describe the clinical characteristics and the long-term sequelae of GBS in a French pediatric population. METHODS: In this multicenter, retrospective study we evaluated clinical signs, radiological examinations, laboratory tests, treatments, and outcomes. RESULTS: One hundred ten children were included in this investigation. These children presented with walking difficulties, muscle weakness, and cranial nerve impairment. Electrodiagnostic testing revealed 70% with acute inflammatory demyelinating polyradiculoneuropathy (AIDP) and 16% with acute motor axonal neuropathy (AMAN). One hundred children received immunoglobulins. At follow-up, 77% were cured, whereas 9% had sequelae, associated with an axonal form (P < .01) and a short interval between symptom onset and hospitalization (P < .01). The need for intubation was correlated with peripheral facial paralysis (P < .01) and dysautonomia (P < .01). DISCUSSION: Although AIDP and AMAN present in a similar way, the axonal form is associated with a worse outcome.

Atypical inter-hemispheric communication correlates with altered motor inhibition during learning of a new bimanual coordination pattern in developmental coordination disorder.

Impairment of motor learning skills in developmental coordination disorder (DCD) has been reported in several studies. Some hypotheses on neural mechanisms of motor learning deficits in DCD have emerged but, to date, brain-imaging investigations are scarce. The aim of the present study is to assess possible changes in communication between brain areas during practice of a new bimanual coordination task in teenagers with DCD (n = 10) compared to matched controls (n = 10). Accuracy, stability and number of mirror movements were computed as behavioural variables. Neural variables were assessed by electroencephalographic coherence analyses of intra-hemispheric and inter-hemispheric fronto-central electrodes. In both groups, accuracy of the new coordination increased concomitantly with right intra-hemispheric fronto-central coherence. Compared to typically developing teenagers, DCD teenagers presented learning difficulties expressed by less stability, no stabilization of the new coordination and a greater number of mirror movements despite practice. These measures correlated with reduced inter-hemispheric communication, even after practice of the new coordination. For the first time, these findings provide neuro-imaging evidence of a kind of inter-hemispheric 'disconnection' related to altered inhibition of mirror movements during motor learning in DCD.

Monitoring Criteria of Intracranial Lesions in Children Post Mild or Moderate Head Trauma.

Head injury is the most common cause of child traumatology. However, there exist no treatment guidelines in children having intracranial lesions due to minor or moderate head trauma. There is little knowledge about monitoring, clinical exacerbation risk factors, or optimal duration of hospitalization. The aim of this retrospective study is to find predictive factors in the clinical course of non-severe head trauma in children, and thus to determine an optimal management strategy. Poor clinical progress was observed in only 4 out of 113 children. When there are no clinical signs and no eating disorders, an earlier discharge is entirely appropriate. Nevertheless, persistent clinical symptoms including headache, vomiting, and late onset seizure, especially in conjunction with hemodynamic disorders such as bradycardia, present a risk of emergency neurosurgery or neurological deterioration. Special attention should be paid to extradural hematoma (EDH) of more than 10 mm, which can have the most severe consequences. Clinical aggravation does not necessarily correlate with a change in follow-up imaging. Conversely, an apparent increase in the brain lesion on the scan is not consistently linked to a pejorative outcome.

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.

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.

Motor Adaptation Deficits in Children with Developmental Coordination Disorder and/or Reading Disorder.

Procedural learning has been mainly tested through motor sequence learning tasks in children with neurodevelopmental disorders, especially with isolated Developmental Coordination Disorder (DCD) and Reading Disorder (RD). Studies on motor adaptation are scarcer and more controversial. This study aimed to compare the performance of children with isolated and associated DCD and RD in a graphomotor adaptation task. In total, 23 children with RD, 16 children with DCD, 19 children with DCD-RD, and 21 typically developing (TD) children wrote trigrams both in the conventional (from left to right) and opposite (from right to left) writing directions. The results show that movement speed and accuracy were more impacted by the adaptation condition (opposite writing direction) in children with neurodevelopmental disorders than TD children. Our results also reveal that children with RD have less difficulty adapting their movement than children with DCD. Children with DCD-RD had the most difficulty, and analysis of their performance suggests a cumulative effect of the two neurodevelopmental disorders in motor adaptation.

Can neurodevelopmental disorders influence the course of neurodegenerative diseases? A scoping review.

This scoping review aims at giving an overview of the possible influence of neurodevelopmental disorders (NDDs) on cognitive-behavioral neurodegenerative diseases (CBNDs). Based on the PRISMA-ScR checklist, it details the methods of NDDs screening, the identified NDDs-CBNDs associations, as well as the criteria and types of association. The last literature search was performed in June 2023. In the final study, 32 articles were included. Analysis first showed that NDDs were mainly detected through medical records screening. Second, the association of specific learning disorders and major or mild neurocognitive disorder due to Alzheimer's disease was the most investigated. Third, associations were mostly based on prevalence comparisons. Finally, 66 % of studies reported a positive association between NDDs and CBNDs. Notably, up to 67 % of positive associations were observed with atypical forms of certain CBNDs. Authors' interpretations suggest that NDDs could constitute a risk factor for CBNDs. However, the influence of NDDs on CBNDs still lacks evidence and biological support, possibly due to the heterogeneity of methods and criteria employed. Developing validated assessment tools for all NDDs and conducting cohort studies could be beneficial for research, and clinical practice. Indeed, this review also underlines the importance of adopting a life-span approach regarding CBNDs.

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.

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.

Predictors of developmental dyslexia in European orthographies with varying complexity.

BACKGROUND: The relationship between phoneme awareness, rapid automatized naming (RAN), verbal short-term/working memory (ST/WM) and diagnostic category is investigated in control and dyslexic children, and the extent to which this depends on orthographic complexity. METHODS: General cognitive, phonological and literacy skills were tested in 1,138 control and 1,114 dyslexic children speaking six different languages spanning a large range of orthographic complexity (Finnish, Hungarian, German, Dutch, French, English). RESULTS: Phoneme deletion and RAN were strong concurrent predictors of developmental dyslexia, while verbal ST/WM and general verbal abilities played a comparatively minor role. In logistic regression models, more participants were classified correctly when orthography was more complex. The impact of phoneme deletion and RAN-digits was stronger in complex than in less complex orthographies. CONCLUSIONS: Findings are largely consistent with the literature on predictors of dyslexia and literacy skills, while uniquely demonstrating how orthographic complexity exacerbates some symptoms of dyslexia.

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.

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.