Yield of Outpatient Sleep EEG for Epileptiform Alterations' Detection in Children.

PURPOSE: Ambulatory EEGs in children are frequently ordered as sleep studies. However, the yield according to different clinical situations has received little attention to date. The authors aimed to quantify the added value in terms of detection of epileptiform features of an EEG containing sleep, as compared with only wakefulness, according to the referral diagnoses. METHODS: The authors retrospectively selected consecutive outpatients' EEG recordings of patients between 6 months to 16 years old, performed between January 2014 and February 2015. The authors excluded those lacking at least 10 minutes of waking and/or at least 5 minutes of behavioral sleep. Interictal epileptiform activity (IEA) in wakefulness and sleep was compared among referral suspected diagnoses. Additional yield of sleep was considered if at least one of the following was observed: appearance of interictal epileptiform activity or increase by >50%; interictal epileptiform activity change in localization or morphology, seizure occurrence. RESULTS: A total of 425 recordings (mean age 6.9 ± 4.7 years) were analyzed. Of them, 194 (45.6%) presented an additional yield during sleep, which was dependent on the occurrence of IEA during wakefulness: 77/251 (30.7%) in those without versus 117/174 (67.2%) in those with wakefulness IEA (P < 0.001, χ). The yield was markedly lower in studies performed for nonepileptic referral diagnoses (7% vs. 43% to 100%; P < 0.001, Fisher). CONCLUSIONS: When wakefulness EEG lacks epileptiform features, the yield of sleep EEG in our pediatric population appeared modest, especially in patients without a suspected epileptic syndrome. This information may be used to optimize the request of sleep EEG in children

Sudden unexpected death in an infant with L-2-hydroxyglutaric aciduria

Inherited metabolic disorders are the cause of a small but significant number of sudden unexpected deaths in infancy. We report a girl who suddenly died at 11months of age, during an intercurrent illness. Autopsy showed spongiform lesions in the subcortical white matter, in the basal ganglia, and in the dentate nuclei. Investigations in an older sister with developmental delay, ataxia, and tremor revealed l-2-hydroxyglutaric aciduria and subcortical white matter changes with hyperintensity of the basal ganglia and dentate nuclei at brain magnetic resonance imaging. Both children were homozygous for a splice site mutation in the L2HGDH gene. Sudden death has not been reported in association with l-2-hydroxyglutaric aciduria so far, but since this inborn error of metabolism is potentially treatable, early diagnosis may be importan

De novo variants in CACNA1E found in patients with intellectual disability, developmental regression and social cognition deficit but no seizures

Background De novo variants in the voltage-gated calcium channel subunit α1 E gene (CACNA1E) have been described as causative of epileptic encephalopathy with contractures, macrocephaly and dyskinesias. Methods Following the observation of an index patient with developmental delay and autism spectrum disorder (ASD) without seizures who had a de novo deleterious CACNA1E variant, we screened GeneMatcher for other individuals with CACNA1E variants and neurodevelopmental phenotypes without epilepsy. The spectrum of pathogenic CACNA1E variants was compared to the mutational landscape of variants in the gnomAD control population database. Results We identified seven unrelated individuals with intellectual disability, developmental regression and ASD-like behavioral profile, and notably without epilepsy, who had de novo heterozygous putatively pathogenic variants in CACNA1E. Age of onset of clinical manifestation, presence or absence of regression and degree of severity were variable, and no clear-cut genotype–phenotype association could be recognized. The analysis of disease-associated variants and their comparison to benign variants from the control population allowed for the identification of regions in the CACNA1E protein that seem to be intolerant to substitutions and thus more likely to harbor pathogenic variants. As in a few reported cases with CACNA1E variants and epilepsy, one patient showed a positive clinical behavioral response to topiramate, a specific calcium channel modulator. Limitations The significance of our study is limited by the absence of functional experiments of the effect of identified variants, the small sample size and the lack of systematic ASD assessment in all participants. Moreover, topiramate was given to one patient only and for a short period of time. Conclusions Our results indicate that CACNA1E variants may result in neurodevelopmental disorders without epilepsy and expand the mutational and phenotypic spectrum of this gene. CACNA1E deserves to be included in gene panels for non-specific developmental disorders, including ASD, and not limited to patients with seizures, to improve diagnostic recognition and explore the possible efficacy of topiramate

Could Gait Biomechanics Become a Marker of Atypical Neuronal Circuitry in Human Development?-The Example of Autism Spectrum Disorder.

This perspective paper presents converging recent knowledge in neurosciences (motor neurophysiology, neuroimaging and neuro cognition) and biomechanics to outline the relationships between maturing neuronal network, behavior, and gait in human development. Autism Spectrum Disorder (ASD) represents a particularly relevant neurodevelopmental disorder (NDD) to study these convergences, as an early life condition presenting with sensorimotor and social behavioral alterations. ASD diagnosis relies solely on behavioral criteria. The absence of biological marker in ASD is a main challenge, and hampers correlations between behavioral development and standardized data such as brain structure alterations, brain connectivity, or genetic profile. Gait, as a way to study motor system development, represents a well-studied, early life ability that can be characterized through standardized biomechanical analysis. Therefore, developmental gait biomechanics might appear as a possible motor phenotype and biomarker, solid enough to be correlated to neuronal network maturation, in normal and atypical developmental trajectories-like in ASD

Acute infantile encephalopathy predominantly affecting the frontal lobe (AIEF): A European case.

Acute infantile encephalopathy predominantly affecting the frontal lobes (AIEF) has been described as a new entity, based on MRI findings (acute abnormal diffusion-weighted imaging signals in the frontal lobes followed by atrophy) and exclusion of other acute encephalopathies. Patients present with acute onset of fever, status epilepticus, and coma. Different causal mechanisms have been suggested such as localized viral infection, toxic insult due to cytokines, or postictal damage. Only children of Japanese descent have been described. We report the case of a Caucasian girl whose history and MRI findings were similar to the Japanese cases. She had a massive regression with verbal apraxia, while cognitive development was less affected; she initially presented with a cluster of complex partial seizures (and not convulsive status epilepticus), making epileptic or post anoxic-ischemic sequelae highly unlikely. The place of this proposed entity among other recently described acute encephalopathies with abnormal diffusion on MRI is discussed

Measuring upper limb function in children with hemiparesis with 3D inertial sensors

Upper limb assessments in children with hemiparesis rely on clinical measurements, which despite standardization are prone to error. Recently, 3D movement analysis using optoelectronic setups has been used to measure upper limb movement, but generalization is hindered by time and cost. Body worn inertial sensors may provide a simple, cost-effective alternative

Sex differences in sensory processing in children with autism spectrum disorder.

Despite the high prevalence of sensory processing difficulties in children with autism spectrum disorder (ASD), little research has focused on the sex differences in sensory processing. Furthermore, there is a lack of knowledge on the female-specific symptoms of ASD, contributing to later referral, diagnosis and intervention. In this study, we examined the sex differences in sensory processing symptoms in large cohorts of ASD children (N = 168; 26 females, 142 males) and typically developing (TD) children (N = 439; 209 females, 230 males). For this, we translated the sensory processing measure (SPM) and SPM - Preschool (SPM-P) Home Forms to French. The SPM/SPM-P are parent/caregiver questionnaires that assess typical behavioral responses to sensory stimuli. Overall, our results showed that the magnitude of the differences in sensory processing between males and females is larger in ASD children relative to TD children, with females showing more severe symptoms in Hearing, as well as Balance and Motion subscales. Additionally, linear discriminant analysis showed that the SPM/SPM-P are good at discriminating TD children from ASD, children with higher accuracy rates for females than for males. These findings are discussed in light of the heterogeneity of sensory processing difficulties present in ASD. Overall, our results suggest that there seem to be female-specific profiles in sensory processing difficulties in ASD. Implications of findings concerning sex differences in sensory processing and their potential for improving identification and diagnosis of ASD females are discussed. LAY SUMMARY: The present study examined sex differences in behavioral responses to sensory stimuli in children with autism spectrum disorder (ASD), and typically developing (TD) children. While there is a small trend for TD males to show more sensory processing atypicalities, female ASD children show significantly more atypical responses compared to their male counterparts. This has important implications for characterizing female autism profiles, and ultimately improving the chance for earlier detection, diagnosis and treatment