Lionel Carmant

De Novo SYNGAP1 Mutations in Nonsyndromic Intellectual Disability and Autism

BACKGROUNDnLittle is known about the genetics of nonsyndromic intellectual disability (NSID). Recently, we reported de novo truncating mutations in the SYNGAP1 gene of 3 of 94 NSID cases, suggesting that its disruption represents a common cause of autosomal dominant NSID.nnnMETHODSnTo further explore the involvement of SYNGAP1 in NSID, we sequenced its exons and intronic boundaries in 60 additional sporadic cases of NSID, including 30 patients with autism spectrum disorders (ASD) and 9 with epilepsy, and in 380 control individuals.nnnRESULTSnWe identified de novo out-of-frame deletions in two patients with NSID and mild generalized epilepsy (c.2677delC/p.Q893RfsX184 and c.321_324delGAAG/p. K108VfsX25) and a de novo splicing mutation (c.2294 + 1G>A), which results in the creation of a premature stop codon, in a patient with NSID and autism. No splicing or truncating mutations were found in control subjects.nnnCONCLUSIONSnWe provide evidence that truncating mutations in SYNGAP1 are common in NSID and can be also associated with autism.

Neonatal Seizures: Do They Damage the Brain?

Seizures are an early sign of brain injury in newborns. These seizures are in most cases repetitive or associated with asymptomatic electrographic seizures. Despite the relative resistance of the immature brain to seizure-induced brain damage, there is more and more evidence that neonatal seizures impair normal brain development. This review addresses the changes associated with neonatal seizures and discusses current and future potential neuroprotective strategies.

The clinical spectrum of nodular heterotopias in children: Report of 31 patients

Purpose:u2002 The phenotypic and etiologic spectrum in adults with nodular heterotopias (NHs) has been well characterized. However, there are no large pediatric case series. We, therefore, wanted to review the clinical features of NHs in our population.

A noninvasive, presurgical expressive and receptive language investigation in a 9-year-old epileptic boy using near-infrared spectroscopy

The intracarotid amobarbital test (IAT) is used for presurgical evaluation of language lateralization. However, this procedure has many limitations, especially in children. As an alternative to IAT, in the case described here, near-infrared spectroscopy (NIRS) was used to investigate expressive and receptive language lateralization as part of the presurgical evaluation of a 9-year-old Yiddish-speaking boy with a probable left temporal epileptic focus. This child could not tolerate IAT or functional MRI. He underwent two NIRS recording sessions while performing expressive and receptive language tasks. Results indicated predominantly left-sided expressive language in Brocas area with ipsilateral cortical recruitment of more posterior regions. Receptive language showed a bilateral cerebral pattern, perhaps as an expression of cerebral plasticity or compensation in this young patient. This case report illustrates that NIRS may contribute to presurgical investigation and could become a noninvasive alternative to IAT and functional MRI in determining speech lateralization in children.

Synchronized gamma oscillations (30–50 Hz) in the amygdalo-hippocampal network in relation with seizure propagation and severity

In this study, we demonstrate that gamma oscillations (30-50 Hz) recorded in the local field potentials (LFP) of the hippocampus are a marker of temporal lobe seizure propagation and that the level of LFP synchrony in the amygdalo-hippocampal network, during these oscillations, is related to the severity of seizures. Sprague-Dawley rats were given a single systemic dose of kainic acid (KA; 6 mg/kg, i.p.) and local field potential activity (1-475 Hz) of the dorsal hippocampus, the amygdala and the neocortex was recorded. Of 135 ictal discharges, 55 (40.7%) involved both limbic structures. We demonstrated that 78.2% of seizures involving both the hippocampus and amygdala showed hippocampal gamma oscillations. Seizure duration was also significantly correlated with the frequency of hippocampal gamma oscillations (r2=0.31, p<0.01) and LFP synchrony in the amygdalo-hippocampal network (r2=0.21, p<0.05). These results suggest that gamma oscillations in the amygdalo-hippocampal network could facilitate long-range synchrony and participate in the propagation of seizures.

Interaction between sex and early-life stress: Influence on epileptogenesis and epilepsy comorbidities

Epilepsy is a common brain disorder which is characterised by recurring seizures. In addition to suffering from the constant stress of living with this neurological condition, patients also frequently experience comorbid psychiatric and cognitive disorders which significantly impact their quality of life. There is growing appreciation that stress, in particular occurring in early life, can negatively impact brain development, creating an enduring vulnerability to develop epilepsy. This aligns with the solid connections between early life environments and the development of psychiatric conditions, promoting the possibility that adverse early life events could represent a common risk factor for the later development of both epilepsy and comorbid psychiatric disorders. The influence of sex has been little studied, but recent research points to potential important interactions, particularly with regard to effects mediated by HPA axis programming. Understanding these interactions, and the underlying molecular mechanisms, will provide important new insights into the causation of both epilepsy and of psychiatric disorders, and potentially open up novel avenues for treatment.

The protocol for the Cannabidiol in children with refractory epileptic encephalopathy (CARE-E) study: a phase 1 dosage escalation study

BackgroundInitial studies suggest pharmaceutical grade cannabidiol (CBD) can reduce the frequency of convulsive seizures and lead to improvements in quality of life in children affected by epileptic encephalopathies. With limited access to pharmaceutical CBD, Cannabis extracts in oil are becoming increasingly available. Physicians show reluctance to recommend Cannabis extracts given the lack of high quality safety data especially regarding the potential for harm caused by other cannabinoids, such as Δ9-tetrahydrocannabinol (Δ9-THC). The primary aims of the study presented in this protocol are (i) To determine whether CBD enriched Cannabis extract is safe and well-tolerated for pediatric patients with refractory epilepsy, (ii) To monitor the effects of CBD-enriched Cannabis extract on the frequency and duration of seizure types and on quality of life.MethodsTwenty-eight children with treatment resistant epileptic encephalopathy ranging in age from 1 to 10xa0years will be recruited in four Canadian cities into an open-label, dose-escalation phase 1 trial. The primary objectives for the study are (i) To determine if the CBD-enriched Cannabis herbal extract is safe and well-tolerated for pediatric patients with treatment resistant epileptic encephalopathy and (ii) To determine the effect of CBD-enriched Cannabis herbal extract on the frequency and duration of seizures. Secondary objectives include (i) To determine if CBD-enriched Cannabis herbal extracts alter steady-state levels of co-administered anticonvulsant medications. (ii) To assess the relation between dose escalation and quality of life measures, (iii) To determine the relation between dose escalation and steady state trough levels of bioactive cannabinoids. (iv) To determine the relation between dose escalation and incidence of adverse effects.DiscussionThis paper describes the study design of a phase 1 trial of CBD-enriched Cannabis herbal extract in children with treatment-resistant epileptic encephalopathy. This study will provide the first high quality analysis of safety of CBD-enriched Cannabis herbal extract in pediatric patients in relation to dosage and pharmacokinetics of the active cannabinoids.Trial registrationhttp://clinicaltrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2016 Dec 16. Identifier NCT03024827, Cannabidiol in Children with Refractory Epileptic Encephalopathy: CARE-E; 2017 Jan 19 [cited 2017 Oct]; Available from: http://clinicaltrials.gov/ct2/show/NCT03024827

Body temperature measurement of an animal by tracking in biomedical experiments

In this paper, we present a method to measure the body temperature of an animal using a thermographic camera in hyperthermia experiments, where the heat contrast between the animal and its background is low. This work was done in the context of the study of artificially induced atypical febrile seizures. In order to measure the temperature of a moving animal continuously, we need to detect it in each video frame and then select a subset of pixels to evaluate its body temperature. To detect the animal in each frame, we propose a tracking method based on the minimization of a cost function that uses constraints such as temperature smoothness and proximity. The temperature of the animal is then taken as the mean of a subset of pixels from the detected area. For videos up to 19,000 frames long, the method achieves temperature estimation within

Applied nutritional investigation Breath acetone predicts plasma ketone bodies in children with epilepsy on a ketogenic diet

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