Neuroanatomical correlates of gross manual dexterity in children with unilateral spastic cerebral palsy.

Unilateral spastic Cerebral Palsy (UCP) results from congenital brain injury, and Magnetic Resonance Imaging (MRI) has a role in understanding the etiology and severity of brain insult. In UCP, functional impairment predominantly occurs in the upper limb (UL) of the more affected side, where manual ability and dexterity are typically reduced. Also, mirror movements (MMs), are often present in UCP, with a further possible negative functional impact. This study aims to investigate the relationships among neuroanatomical characteristics of brain injury at MRI, manual functional impairment and MMs, in children with UCP. Thirty-five children with UCP participated in the study (20, M = 15, F, mean age 9.2 ± 3.5 years). Brain lesions at MRI were categorized according to the Magnetic Resonance Classification System (MRICS) and by using a semi-quantitative MRI (sqMRI) scale. Gross manual performance was assessed through Manual Ability Classification System (MACS) and the Box and Block Test (BBT), and MMs by Woods and Teuber scale, for both hands. Non-parametric correlation analyses were run to determine the relationship between neuroanatomical and functional features. Regression models were run to explore the contribution of neuroanatomical features and MMs to UL function. Correlation analyses revealed moderate to strong associations between sqMRI scores contralateral to the more affected side and UL functional impairment on MACS and BBT, with more severe brain injuries significantly correlating with poorer function in the more affected hand. No association emerged between brain lesion severity scores and MMs. MRICS showed no association with MACS or BBT, while a significant correlation emerged between MRICS category and MMs in the more affected hand, with brain lesion category that are suggestive of presumed earlier injury being associated with more severe MMs. Finally, exploratory regression analyses showed that neuroanatomical characteristics of brain injury and MMs contributed to the variability of UL functional impairment. This study contributes to the understanding of the neuroanatomical and neurological correlates of some aspects of manual functional impairment in UCP by using a simple clinical brain MRI assessment.

Longitudinal assessment of brain lesions in children with cerebral palsy and association with motor functioning.

BACKGROUND: The semi-quantitative scale of structural brain Magnetic Resonance Imaging (sqMRI) is a valid and reliable measure of brain lesion extent in children with cerebral palsy (CP) >3-years. This system scores lesion burden for each major brain region. The sum of the scores gives a global score ranging from 0 to 48. PURPOSE: To investigate how sqMRI scores changed from infancy to school-age, and whether these were associated with lesion load, age at first assessment, and gross motor function and its changes. MATERIALS AND METHODS: Twenty-eight children with CP underwent MRI and motor (Gross Motor Function Measure-66; GMFM-66) assessments when <40-months and again when 8-12-years. We investigated whether (i) toddler/preschool-age sqMRI scores (Time 1) reflected school-age sqMRI scores (Time 2); (ii) temporal changes in sqMRI scores (Time 1-Time 2 difference) were related to the child's age at Time 1 and lesion extent; (iii) early or later sqMRI scores were associated with motor functioning; (iv) sqMRI scores' longitudinal changes were associated with motor changes. RESULTS: Except for the corticosubcortical (grey-matter only) layers, sqMRI scores were significantly higher ('higher lesion load') at Time 1 than at Time 2. Age at Time 1 was not associated with temporal changes in global sqMRI scores. Higher lesion load at Time 2, but not at Time 1, was associated with smaller temporal changes in the global sqMRI score. The sqMRI scores were associated with concurrent, but not future or past motor GMFM-66 scores. Longitudinal changes in sqMRI scores were not associated with longitudinal changes in motor GMFM-66 scores. CONCLUSION: sqMRI scores of brain lesion extent at school-age are lower and a better indication of later-life motor functioning than very early life sqMRI scores. It may be best to interpret MRI white matter lesions with caution in very early life due to possible changes in lesion appearance and the unpredictable role of functional plasticity.

Neonatal hypoxic-ischemic encephalopathy after acute carbon monoxide intoxication during pregnancy. A case report and brief review of the literature.

Carbon monoxide (CO) poisoning during pregnancy is a rare occurrence, associated with high maternal and fetal mortality rates. As CO can cross the placenta, leading to intrauterine hypoxia, CO intoxication can result in neurological sequelae and neurologic complications in fetuses who survive. We report a case of a preterm newborn acutely exposed to CO in-utero and delivered by emergent cesarean section at the 31st week of gestation due to the severe burns suffered by the mother following an indoor boiler explosion. As CO has serious adverse effects both on the mother and fetus, it is important to recognize and treat poisoning in a timely manner. Despite maternal blood CO levels, CO intoxication at critical stage of central nervous system development can lead to hypoxic-ischemic lesions, thus interdisciplinary care and follow up for these patients are mandatory.

Lung ultrasound supports clinical evaluation of feeding competence development in preterm neonates.

Introduction: The achievement of alimentary competencies is a milestone in the development of preterm neonates. Ten percent of neonates <37 weeks of gestational age and 25% of those VLBW experience swallowing disorders, with an increased risk of problems in the early phase of life (failure to thrive, growth retardation, inhalation, and consequent risk of pulmonary infection) and later in life due to delayed development of oromotor skills.The main diagnostic tools for swallowing disorders are endoscopic (fiber-optic endoscopic examination of swallowing, FEES) or radiographic (videofluoroscopic swallowing study, VFSS) exams. Given the invasiveness of these methods and the bias due to rheologic differences between bolus and contrast medium, FEES and VFSS are poorly reproducible. Moreover, neither of the technique is capable of detecting post-meal inhalations, especially microinhalations or those consequent to a whole meal rather than to a single swallowing.Lung ultrasound (LUS) is a widespread, repeatable, safe, fast point-of-care tool and we reported previous encouraging results in detecting silent and overt inhalation related to the meal in children with dysphagia/gastroesophageal reflux disease (GERD) risk factors. Methods: We report a pilot study, that investigated LUS approach (performing imaging before and after meals) to assess feeding competence development in a cohort of n. 19 newborns <32 weeks of age. Results: Meal monitoring by LUS did not show any significant difference in scoring before/after eating. The achievement of full enteral feeding correlates with GA at birth (p < 0.001) but not with LUS scoring. The introduction of the first meal by bottle correlates both with gestational age (p < 0.001) and ultrasound scores (p = 0.004). LUS score at 7 days of life resulted predictive for length of invasive/non-invasive respiratory support (p = 0.002) and length of oxygen supply (p = 0.001), while LUS score at 48 h of life did not (p n.s.). Discussion: Our study suggests that the development of oral feeding skills is not strictly dependent on gestational age. Moreover, our research suggests the predominant role of LUS in predicting the time of readiness to oral feeding, as the LUS score can be a marker of respiratory and lung wellness, and consequently a predictor of neonate stability during deglutitory apnea.

Glycaemic Imbalances in Seizures and Epilepsy of Paediatric Age: A Literature Review.

Cerebral excitability and systemic metabolic balance are closely interconnected. Energy supply to neurons depends critically on glucose, whose fluctuations can promote immediate hyperexcitability resulting in acute symptomatic seizures. On the other hand, chronic disorders of sugar metabolism (e.g., diabetes mellitus) are often associated with long-term epilepsy. In this paper, we aim to review the existing knowledge on the association between acute and chronic glycaemic imbalances (hyper- and hypoglycaemia) with seizures and epilepsy, especially in the developing brain, focusing on clinical and instrumental features in order to optimize the care of children and adolescents and prevent the development of chronic neurological conditions in young patients.

White matter microstructure and receptive vocabulary in children with cerebral palsy: The role of interhemispheric connectivity.

BACKGROUND: Communication and cognitive impairments are common impediments to participation and social functioning in children with cerebral palsy (CP). Bilateral language networks underlie the function of some high-level language-related cognitive functions. PURPOSE: To explore the association between receptive vocabulary and white-matter microstructure in the temporal lobes and the central part of the temporo-temporal bundles in children with CP. MATERIALS AND METHODS: 37 children with spastic motor type CP (mean age 9.6 years, 25 male) underwent a receptive vocabulary test (Peabody Picture Vocabulary Test, PPVT-IV) and 3T MRI. Mean fractional anisotropy (FA) and mean diffusivity (MD) were calculated for the temporal lobes and the interhemispheric bundles traversing the splenium of the corpus callosum and the anterior commissure. Associations between microstructure and receptive vocabulary function were explored using univariable linear regression. RESULTS: PPVT-IV scores were significantly associated with mean white matter MD in the left temporal lobe, but not the right temporal lobe. There was no association between PPVT-IV and mean white matter FA in the temporal lobes. PPVT-IV scores were not significantly associated with the laterality of these diffusion tensor metrics. Within the corpus callosum, FA, but not MD of the temporo-temporal bundles was significantly associated with the PPVT-IV scores. Within the anterior commissure no equivalent relationship between diffusion metrics and PPVT-IV was found. CONCLUSION: Our findings add further understanding to the pathophysiological basis underlying receptive vocabulary skills in children with CP that could extend to other patients with early brain damage. This study highlights the importance of interhemispheric connections for receptive vocabulary.

School Attendance, Chronotype, and Day-of-the-Week Effect in Adolescent Male Basketball Players.

Adolescents' conflict between circadian rhythm and early school start time is more pronounced in evening chronotypes, who tend to reduce sleep duration during school days compensating during the free days by oversleeping (i.e., social jetlag). Cumulative weekly sleep debt may impair sport performance, which relies on physical and cognitive skills modulated by sleep. We hypothesized that chronotype predicts sport performance, and that it may interact with the day of the week. Moreover, given the role sleep plays in motor memory consolidation, we tested the hypothesis that school attendance, and the related chronic sleep deprivation, might be detrimental for participants in a training phase. Ninety-three adolescent male basketball players performed multiple free throw sessions (n = 7880) during both the school and holiday periods. Chronotype and its interaction with the day of the week significantly predicted shooting accuracy when attending school, but not on holidays. Evening types' performance gradually decreased from Monday to Friday. Participants with a more unstable performance (i.e., who did not complete the acquisition of the free throw motor scheme) worsened their accuracy when attending school. Our results suggest that the impact of chronotype and day of the week on sport performance is related to the presence of an externally imposed sleep/wake schedule and is consistent with evening types' increased likelihood of experiencing social jetlag. Possibly due to early school start time, attending school worsened the performance of participants in a training phase. Further investigations are required to assess whether reducing the mismatch between biological and social clocks might improve sport performance, along with other aspects of adolescents' life.

Predicting motor and cognitive outcomes from MRIs of brain structure in children with acquired brain injury: A pilot study.

BACKGROUND: Acquired Brain Injury (ABI) describes a range of brain injuries occurring after birth, including tumor, traumatic brain injury or stroke. Although MRIs are routinely used for diagnosis, prediction of outcome following brain injury is challenging. Quantitative structural information from brain images may provide an opportunity to predict patient outcomes; however, due to the high prevalence of severe pathology in children with ABI, quantitative approaches must be robust to injury severity. METHODS: In this pilot cross-sectional study, automated quantitative measures were extracted from the MRIs of a cohort of children with ABI (n = 30, 8-16 years, follow up MRI taken 1.8-13.4 years after time of injury) as well as 36 typically developing controls with no brain injury (7-17 years) using a pathology-robust technique. Measures of brain volume, lesion volume and cortical morphology were associated with concurrent motor, behavioral, visual and communicative function using Least Absolute Shrinkage and Selection Operator (LASSO) regression. RESULTS: These regression models were validated on a separate test set (n = 8 of the ABI cohort), which revealed significant correlations between measures of brain structure with motor, cognitive, visual and communicative function (r = 0.65-0.85, all p < 0.01). Furthermore, comparisons of the structural measures to the typically developing cohort revealed overall reductions in global grey matter volume among the ABI cohort, as well as cortical thinning in several cortical areas. CONCLUSIONS: These preliminary associations reveal that motor and behavioral function can be estimated from MRI alone, highlighting the potential utility of the proposed pathology-robust MRI quantification tools to provide estimates of long-term clinical prognosis of children with ABI following injury.

Lung ultrasound in young children with neurological impairment: A proposed integrative clinical tool for deaeration-detection related to feeding.

Infants and children with neurological impairment, such as cerebral palsy (CP), often experience abnormal ingestion functions, including oropharyngeal dysphagia and gastroesophageal reflux disease, which led to aspiration-related respiratory complications, morbidity, hospitalization, or death. There is a lack of evidence-based, repeatable, infant-friendly instrumental procedures to assess aspiration-risk in infants with CP or other neurological disorders, with also a lack of clinical assessment measures to support the use of more invasive diagnostic techniques. To this purpose, in the current study we explore the feasibility of lung ultrasound (LUS), to assess lung deaeration possibly related to aspiration during meal, in a cohort of 35 subjects affected by CP or other encephalopathies, and 10 controls in the same age-range. We coupled LUS procedure with meal caregiver administration for each child. Our results support the feasibility of this innovative approach in the clinical setting. Exploratory findings revealed a number of lung abnormalities likely related to abnormal ingestion function in subjects. Subgroup analyses revealed possible differences in LUS abnormalities between CP and other encephalopathies, possibly related to different mechanism of disease or dysfunction. Also, some evidences arose about the possible relationship between such LUS abnormalities and feeding and swallowing abilities in CP or other encephalopathies. LUS showed preliminarily feasibility and effectiveness in detecting meal-related LUS abnormalities in a dynamic manner in the clinical setting. This approach demonstrated usefulness as a potential tool for improving assessment and management in complex care of infants and young children with severe neurological disorders.

Cognitive, academic, executive and psychological functioning in children with spastic motor type cerebral palsy: Influence of extent, location, and laterality of brain lesions.

PURPOSE: To investigate, in spastic motor-type cerebral palsy, the association between 1) the location and extent of brain lesions and numerous psychological outcomes; 2) the laterality of brain lesions and performance of verbal-related cognitive functions. METHODS: The semi-quantitative scale for MRI (sqMRI) was scored for 101 children with cerebral palsy. Non-verbal and verbal proxy intelligence quotients (IQ), word reading, spelling, numerical operations skills, executive functioning, and psychological adjustment were assessed. Relationships between global and regional sqMRI scores and clinical scores were examined. The best multivariable linear regression model for each outcome was identified using the Bayesian Information Criteria. Regional sqMRI scores, gross motor functioning, manual ability, and epilepsy status were considered for inclusion as covariables. Where sqMRI scores made statistically significant contributions to models of verbal-related functioning, data were reanalysed including these sqMRI scores' laterality index. Verbal-related outcomes were compared between participants with left-sided versus bilateral brain lesions. RESULTS: Medial dorsal thalamus and parietal lobe lesions significantly accounted for poorer verbal proxy-IQ. Left-hemisphere lateralization of temporal lobe lesions was associated with poorer verbal proxy-IQ. Participants with bilateral lesions performed significantly better than those with unilateral left-sided lesions in verbal cognitive functions. Controlling for epilepsy diagnosis, participants with ventral posterior lateral thalamus lesions presented with better Behaviour Rating Inventory of Executive Function scores, although within the normal range. sqMRI scores were not significantly associated with some psychological outcomes or these only bordered on significance after accounting for relevant control variables. CONCLUSION: The laterality of early-life lesions influences the development of verbal-related cognitive functions.

Differences and Commonalities in Children with Childhood Apraxia of Speech and Comorbid Neurodevelopmental Disorders: A Multidimensional Perspective.

Childhood apraxia of speech (CAS) is a motor speech disorder often co-occurring with language impairment and complex neurodevelopmental disorders. A cohort of 106 children with CAS associated to other neurodevelopmental disorders underwent a multidimensional investigation of speech and language profiles, chromosome microarray analysis and structural brain magnetic resonance (MR). Our aim was to compare the clinical profiles of children with CAS co-occurring with only language impairment with those who, in addition to language impairment, had other neurodevelopmental disorders. Expressive grammar was impaired in the majority of the sample in the context of similar alterations of speech, typical of the core symptoms of CAS. Moreover, children with complex comorbidities also showed more severe and persistent receptive language deficits. About 25% of the participants harbored copy number variations (CNVs) already described in association to neurodevelopmental disorders. CNVs occurred more frequently in children with complex comorbidities. MR structural/signal alterations were found in a small number of children and were of uncertain pathogenic significance. These results confirm that CAS needs multidimensional diagnostic and clinical management. The high frequency of language impairment has important implications for early care and demands a personalized treatment approach in which speech and language goals are consistently integrated.

The Diagnostic Approach to Mitochondrial Disorders in Children in the Era of Next-Generation Sequencing: A 4-Year Cohort Study.

Mitochondrial diseases (MDs) are a large group of genetically determined multisystem disorders, characterized by extreme phenotypic heterogeneity, attributable in part to the dual genomic control (nuclear and mitochondrial DNA) of the mitochondrial proteome. Advances in next-generation sequencing technologies over the past two decades have presented clinicians with a challenge: to select the candidate disease-causing variants among the huge number of data provided. Unfortunately, the clinical tools available to support genetic interpretations still lack specificity and sensitivity. For this reason, the diagnosis of MDs continues to be difficult, with the new "genotype first" approach still failing to diagnose a large group of patients. With the aim of investigating possible relationships between clinical and/or biochemical phenotypes and definitive molecular diagnoses, we performed a retrospective multicenter study of 111 pediatric patients with clinical suspicion of MD. In this cohort, the strongest predictor of a molecular (in particular an mtDNA-related) diagnosis of MD was neuroimaging evidence of basal ganglia (BG) involvement. Regression analysis confirmed that normal BG imaging predicted negative genetic studies for MD. Psychomotor regression was confirmed as an independent predictor of a definitive diagnosis of MD. The findings of this study corroborate previous data supporting a role for neuroimaging in the diagnostic approach to MDs and reinforce the idea that mtDNA sequencing should be considered for first-line testing, at least in specific groups of children.

Neural Changes Induced by a Speech Motor Treatment in Childhood Apraxia of Speech: A Case Series.

We report a case series of children with childhood apraxia of speech, by describing behavioral and white matter microstructural changes following 2 different treatment approaches.Five children with childhood apraxia of speech were assigned to a motor speech treatment (PROMPT) and 5 to a language, nonspeech oral motor treatment. Speech assessment and brain MRI were performed pre- and post-treatment. The ventral (tongue/larynx) and dorsal (lips) corticobulbar tracts were reconstructed in each subject. Mean fractional anisotropy and mean diffusivity were extracted. The hand corticospinal tract was assessed as a control pathway. In both groups speech improvements paralleled changes in the left ventral corticobulbar tract fractional anisotropy. The PROMPT treated group also showed fractional anisotropy increase and mean diffusivity decrease in the left dorsal corticobulbar tract. No changes were detected in the hand tract. Our results may provide preliminary support to the possible neurobiologic effect of a multimodal speech motor treatment in childhood apraxia of speech.

Neural substrates of neuropsychological profiles in dystrophynopathies: A pilot study of diffusion tractography imaging.

INTRODUCTION: Cognitive difficulties and neuropsychological alterations in Duchenne and Becker muscular dystrophy (DMD, BMD) boys are not yet sufficiently explored, although this topic could have a relevant impact, finding novel biomarkers of disease both at genetics and neuroimaging point of view. The current study aims to: 1) analyze the neuropsychological profile of a group of DMD and BMD boys without cognitive impairment with an assessment of their executive functions; 2) explore the structural connectivity in DMD, BMD, and age-matched controls focusing on cortico-subcortical tracts that connect frontal cortex, basal ganglia, and cerebellum via the thalamus; 3) explore possible correlations between altered structural connectivity and clinical neuropsychological measures. MATERIALS AND METHODS: This pilot study included 15 boys (5 DMD subjects, 5 BMD subjects, and 5 age-matched typically developing, TD). They were assessed using a neuropsychological assessment protocol including cognitive and executive functioning assessment and performed a 1.5T MRI brain exam including advance Diffusion Weighted Imaging (DWI) method for tractography. Structural connectivity measurements were extracted along three specific tracts: Cortico-Ponto-Cerebellar Tract (CPCT), Cerebellar-Thalamic Tract (CTT), and Superior Longitudinal Fasciculus (SLF). Cortical-Spinal Tract (CST) was selected for reference, as control tract. RESULTS: Regarding intellectual functioning, a major impairment in executive functions compared to the general intellectual functioning was observed both for DMD (mean score = 86.20; SD = 11.54) and for BMD children (mean score = 88; SD = 3.67). Mean FA resulted tendentially always lower in DMD compared to both BMD and TD groups for all the examined tracts. The differences in FA were statistically significant for the right CTT (DMD vs BMD, p = 0.002, and DMD vs TD, p = 0.0015) and the right CPCT (DMD vs TD, p = 0.008). Concerning DMD, significant correlations emerged between FA-R-CTT and intellectual quotients (FIQ, p = 0.044; ρs = 0.821), and executive functions (Denomination Total, p = 0.044, ρs = 0.821; Inhibition Total, p = 0.019, ρs = 0.900). BMD showed a significant correlation between FA-R-CPCT and working memory index (p = 0.007; ρs = 0.949). DISCUSSION AND CONCLUSION: In this pilot study, despite the limitation of sample size, the findings support the hypothesis of the involvement of a cerebellar-thalamo-cortical loop for the neuropsychological profile of DMD, as the CTT and the CPCT are involved in the network and the related brain structures are known to be implied in executive functions. Our results suggest that altered WM connectivity and reduced fibre organization in cerebellar tracts, probably due to the lack of dystrophin in the brain, may render less efficient some neuropsychological functions in children affected by dystrophinopathies. The wider multicentric study could help to better establish the role of cerebellar connectivity in neuropsychological profile for dystrophinopathies, identifying possible novel diagnostic and prognostic biomarkers.

Early clinical and MRI biomarkers of cognitive and motor outcomes in very preterm born infants.

BACKGROUND: This study aimed to identify which MRI and clinical assessments, alone or in combination, from (i) early (32 weeks postmenstrual age, PMA), (ii) term equivalent age (TEA) and (iii) 3 months corrected age (CA) are associated with motor or cognitive outcomes at 2 years CA in infants born <31 weeks gestation. METHODS: Prospective cohort study of 98 infants who underwent early and TEA MRI (n = 59 males; median birth gestational age 28 + 5 weeks). Hammersmith Neonatal Neurological Examination (HNNE), NICU Neonatal Neurobehavioural Scale and General Movements Assessment (GMs) were performed early and at TEA. Premie-Neuro was performed early and GMs, Test of Infant Motor Performance and visual assessment were performed at TEA and 3 months CA. Neurodevelopmental outcomes were determined using Bayley Scales of Infant and Toddler Development 3rd edition. RESULTS: The best combined motor outcome model included 3-month GMs (ß = -11.41; 95% CI = -17.34, -5.49), TEA MRI deep grey matter score (ß = -6.23; 95% CI = -9.47, -2.99) and early HNNE reflexes (ß = 3.51; 95% CI = 0.86, 6.16). Combined cognitive model included 3-month GMs (ß = -10.01; 95% CI = -15.90, -4.12) and TEA HNNE score (ß = 1.33; 95% CI = 0.57, 2.08). CONCLUSION: Early neonatal neurological assessment improves associations with motor outcomes when combined with term MRI and 3-month GMs. Term neurological assessment combined with 3-month GMs improves associations with cognitive outcomes. IMPACT: We present associations between 32- and 40-week MRI, comprehensive clinical assessments and later 2-year motor and cognitive outcomes for children born <31 weeks gestation. MRI and clinical assessment of motor, neurological and neurobehavioural function earlier than term equivalent age in very preterm infants is safe and becoming more available in clinical settings. Most of these children are discharged from hospital before term age and so completing assessments prior to discharge can assist with follow up. MRI and neurological assessment prior to term equivalent age while the child is still in hospital can provide earlier identification of children at highest risk of adverse outcomes and guide follow-up screening and intervention services.

Autism Spectrum Disorder and Childhood Apraxia of Speech: Early Language-Related Hallmarks across Structural MRI Study.

Autism Spectrum Disorder (ASD) and Childhood Apraxia of Speech (CAS) are developmental disorders with distinct diagnostic criteria and different epidemiology. However, a common genetic background as well as overlapping clinical features between ASD and CAS have been recently reported. To date, brain structural language-related abnormalities have been detected in both the conditions, but no study directly compared young children with ASD, CAS and typical development (TD). In the current work, we aim: (i) to test the hypothesis that ASD and CAS display neurostructural differences in comparison with TD through morphometric Magnetic Resonance Imaging (MRI)-based measures (ASD vs. TD and CAS vs. TD); (ii) to investigate early possible disease-specific brain structural patterns in the two clinical groups (ASD vs. CAS); (iii) to evaluate predictive power of machine-learning (ML) techniques in differentiating the three samples (ASD, CAS, TD). We retrospectively analyzed the T1-weighted brain MRI scans of 68 children (age range: 34-74 months) grouped into three cohorts: (1) 26 children with ASD (mean age ± standard deviation: 56 ± 11 months); (2) 24 children with CAS (57 ± 10 months); (3) 18 children with TD (55 ± 13 months). Furthermore, a ML analysis based on a linear-kernel Support Vector Machine (SVM) was performed. All but one brain structures displayed significant higher volumes in both ASD and CAS children than TD peers. Specifically, ASD alterations involved fronto-temporal regions together with basal ganglia and cerebellum, while CAS alterations are more focused and shifted to frontal regions, suggesting a possible speech-related anomalies distribution. Caudate, superior temporal and hippocampus volumes directly distinguished the two conditions in terms of greater values in ASD compared to CAS. The ML analysis identified significant differences in brain features between ASD and TD children, whereas only some trends in the ML classification capability were detected in CAS as compared to TD peers. Similarly, the MRI structural underpinnings of two clinical groups were not significantly different when evaluated with linear-kernel SVM. Our results may represent the first step towards understanding shared and specific neural substrate in ASD and CAS conditions, which subsequently may contribute to early differential diagnosis and tailoring specific early intervention.

Structural brain damage and visual disorders in children with cerebral palsy due to periventricular leukomalacia.

AIM: To systematically explore the relationship between type and severity of brain lesion on Magnetic Resonance Imaging (MRI) and visual function in a large cohort of children with periventricular leukomalacia (PVL). METHODS: 94 children with bilateral cerebral palsy (CP) and history of PVL were recruited at Stella Maris Scientific Institute in Pisa (Italy). We included data of participants (72) with at least one MRI after the age of three years and an evaluation of visual function including fixation, following, saccades, nystagmus, acuity, visual field, stereopsis and color perception. Brain lesions location and extent were assessed by a semi-quantitative MRI-scale for children with CP. RESULTS: Brain lesion severity strongly correlated with visual function total score (global MRI score p = .000; hemispheric score p = .001 and subcortical score p = .000). Moreover, visual acuity, visual field, stereopsis and colour were compromised when a cortical damage was present, while ocular motricity (and in particular fixation and saccades) were compromised in presence of subcortical brain damage. INTERPRETATION: Structural MRI is valuable for understanding the relationship between brain lesion severity and visual function in children with CP.

Understanding the impact of bilateral brain injury in children with unilateral cerebral palsy.

The presence of bilateral brain injury in patients with unilateral cerebral palsy (CP) may impact neuroplasticity in the ipsilateral hemisphere; however, this pattern of injury is typically under-analyzed due to the lack of methods robust to severe injury. In this study, injury-robust methods have been applied to structural brain magnetic resonance imaging (MRI) data of a cohort of 91 children with unilateral CP (37 with unilateral and 54 with bilateral brain injury, 4-17 years) and 44 typically developing controls (5-17 years), to determine how brain structure is associated with concurrent motor function, and if these associations differ between patients with unilateral or bilateral injury. Regression models were used to associate these measures with two clinical scores of hand function, with patient age, gender, brain injury laterality, and interaction effects included. Significant associations with brain structure and motor function were observed (Pearson's r = .494-.716), implicating several regions of the motor pathway, and demonstrating an accurate prediction of hand function from MRI, regardless of the extent of brain injury. Reduced brain volumes were observed in patients with bilateral injury, including volumes of the thalamus and corpus callosum splenium, compared to those with unilateral injury, and the healthy controls. Increases in cortical thickness in several cortical regions were observed in cohorts with unilateral and bilateral injury compared to controls, potentially suggesting neuroplasticity might be occurring in the inferior frontal gyrus and the precuneus. These findings identify prospective useful target regions for transcranial magnetic stimulation intervention.

A de novo KCNQ2 Gene Mutation Associated With Non-familial Early Onset Seizures: Case Report and Revision of Literature Data.

Among neonatal epileptic syndromes, benign familial neonatal seizures (BFNS) are often due to autosomal-dominant mutations of the KCNQ2 gene. Seizures are usually characterized by asymmetric tonic posturing with apnea with onset in the first 7 days of life; they may even occur more than 10 times per day or evolve into status epilepticus. The delivery course of our patient was uneventful and family history was negative; on the second day of life the baby became pale, rigid, and apnoic during breastfeeding and appeared jittery and irritable when stimulated or examined. At age 3 days, she experienced clusters of generalized tonic seizures with pallor, desaturation, bradycardia, and partial response to intravenous phenobarbital; during her 4th and 5th days of life, three episodes of tonic seizures were noticed. At age 6 days, the patient experienced about 10 episodes of tonic seizures involving both sides of the body, which gradually responded to intravenous phenytoin. Electroencephalograms revealed abnormalities but brain MRI was normal. The patient is seizure-free since postnatal day 21; she is now 12 months old with cognitive development within normal limits at Bayley III Scale and mild motor delay. The patient is on maintenance therapy with phenobarbital since she was 7 months old. A de novo heterozygous mutation (c.853C>T/p.P285S) in the KCNQ2 gene was identified. We therefore describe a case of de novo KCNQ2-related neonatal convulsions with necessity of multiple anticonvulsants for the control of seizures, mutation occurring in the pore channel of the voltage-gated potassium channel subfamily Q member 2 associated with a likely benign course; furthermore, the same mutation of the KCNQ2 gene and a similar one (c.854C>A/p.P285H) have already been described in association with Ohtahara syndrome. Probably acquired environmental, perinatal and genetic risk factors are very important in determining the different phenotype; we hope that the rapid progress of analysis tools in molecular diagnosis can also be used in the search of an individualized therapeutic approach for these patients.