KCNQ2 encephalopathy

Objective: To advance the understanding of KCNQ2 encephalopathy genotype–phenotype relationships and to begin to assess the potential of selective KCNQ channel openers as targeted treatments. Methods: We retrospectively studied 23 patients with KCNQ2 encephalopathy, including 11 treated with ezogabine (EZO). We analyzed the genotype–phenotype relationships in these and 70 previously described patients. Results: The mean seizure onset age was 1.8 ± 1.6 (SD) days. Of the 20 EEGs obtained within a week of birth, 11 showed burst suppression. When new seizure types appeared in infancy (15 patients), the most common were epileptic spasms (n = 8). At last follow-up, seizures persisted in 9 patients. Development was delayed in all, severely in 14. The KCNQ2 variants identified introduced amino acid missense changes or, in one instance, a single residue deletion. They were clustered in 4 protein subdomains predicted to poison tetrameric channel functions. EZO use (assessed by the treating physicians and parents) was associated with improvement in seizures and/or development in 3 of the 4 treated before 6 months of age, and 2 of the 7 treated later; no serious side effects were observed. Conclusions: KCNQ2 variants cause neonatal-onset epileptic encephalopathy of widely varying severity. Pathogenic variants in epileptic encephalopathy are clustered in “hot spots” known to be critical for channel activity. For variants causing KCNQ2 channel loss of function, EZO appeared well tolerated and potentially beneficial against refractory seizures when started early. Larger, prospective studies are needed to enable better definition of prognostic categories and more robust testing of novel interventions. Classification of evidence: This study provides Class IV evidence that EZO is effective for refractory seizures in patients with epilepsy due to KCNQ2 encephalopathy

Subdural porous and notched mini-grid electrodes for wireless intracranial electroencephalographic recordings

BACKGROUND: Intracranial electroencephalography (EEG) studies are widely used in the presurgical evaluation of drug-refractory patients with partial epilepsy. Because chronic implantation of intracranial electrodes carries a risk of infection, hemorrhage, and edema, it is best to limit the number of electrodes used without compromising the ability to localize the epileptogenic zone (EZ). There is always a risk that an intracranial study may fail to identify the EZ because of suboptimal coverage. We present a new subdural electrode design that will allow better sampling of suspected areas of epileptogenicity with lower risk to patients. METHOD: Impedance of the proposed electrodes was characterized in vitro using electrochemical impedance spectroscopy. The appearance of the novel electrodes on magnetic resonance imaging (MRI) was tested by placing the electrodes into a gel solution (0.9% NaCl with 14 g gelatin). In vivo neural recordings were performed in male Sprague Dawley rats. Performance comparisons were made using microelectrode recordings from rat cortex and subdural/depth recordings from epileptic patients. Histological examinations of rat brain after 3-week icEEG intracerebral electroencephalography (icEEG) recordings were performed. RESULTS: The in vitro results showed minimum impedances for optimum choice of pure gold materials for electrode contacts and wire. Different attributes of the new electrodes were identified on MRI. The results of in vivo recordings demonstrated signal stability, 50% noise reduction, and up to 6 dB signal-to-noise ratio (SNR) improvement as compared to commercial electrodes. The wireless icEEG recording system demonstrated on average a 2% normalized root-mean-square (RMS) deviation. Following the long-term icEEG recording, brain histological results showed no abnormal tissue reaction in the underlying cortex. CONCLUSION: The proposed subdural electrode system features attributes that could potentially translate into better icEEG recordings and allow sampling of large of areas of epileptogenicity at lower risk to patients. Further validation for use in humans is required

Mice Doubly-Deficient in Lysosomal Hexosaminidase A and Neuraminidase 4 Show Epileptic Crises and Rapid Neuronal Loss

Tay-Sachs disease is a severe lysosomal disorder caused by mutations in the HexA gene coding for the α-subunit of lysosomal β-hexosaminidase A, which converts GM2 to GM3 ganglioside. Hexa−/− mice, depleted of β-hexosaminidase A, remain asymptomatic to 1 year of age, because they catabolise GM2 ganglioside via a lysosomal sialidase into glycolipid GA2, which is further processed by β-hexosaminidase B to lactosyl-ceramide, thereby bypassing the β-hexosaminidase A defect. Since this bypass is not effective in humans, infantile Tay-Sachs disease is fatal in the first years of life. Previously, we identified a novel ganglioside metabolizing sialidase, Neu4, abundantly expressed in mouse brain neurons. Now we demonstrate that mice with targeted disruption of both Neu4 and Hexa genes (Neu4−/−;Hexa−/−) show epileptic seizures with 40% penetrance correlating with polyspike discharges on the cortical electrodes of the electroencephalogram. Single knockout Hexa−/− or Neu4−/− siblings do not show such symptoms. Further, double-knockout but not single-knockout mice have multiple degenerating neurons in the cortex and hippocampus and multiple layers of cortical neurons accumulating GM2 ganglioside. Together, our data suggest that the Neu4 block exacerbates the disease in Hexa−/− mice, indicating that Neu4 is a modifier gene in the mouse model of Tay-Sachs disease, reducing the disease severity through the metabolic bypass. However, while disease severity in the double mutant is increased, it is not profound suggesting that Neu4 is not the only sialidase contributing to the metabolic bypass in Hexa−/− mice

Nouveau modèle animal d’épilepsie temporale

L’épilepsie touche de 1 à 2 % de notre population. Pour 30 % des patients atteints, il s’agit d’un syndrome réfractaire au traitement médical avec pour conséquences des complications médicales et psychosociales importantes. Dans cet article, nous démontrons comment, en nous basant sur notre expérience clinique, nous avons établi un nouveau modèle d’épilepsie qui reproduit la situation clinique de façon surprenante. Nous espérons que ce modèle pourra nous amener à des traitements pour la prévention de l’épileptogenèse

Conflit entre la démocratisation et la planification dans l'enseignement supérieur aux U.S.A., en U.R.S.S. et en France /

Mémoire présenté à la Faculté des études supérieures en vue de l'obtention du grade de maîtrise es arts (éducation comparée

CARDIOPATHIES CONGÉNITALES : PHYSIOPATHOLOGIE, FACTEURS DE RISQUE ET PROFILS NEUROPSYCHOLOGIQUES

Les cardiopathies congénitales (CC) sont les malformations les plus fréquentes chez le nouveau-né. La littérature des dernières décennies a mis en évidence des retards développementaux fréquents dans cette population, notamment sur le plan de la motricité, du fonctionnement intellectuel global, du langage, de la mémoire, de l’attention et des fonctions exécutives. Le présent article propose une revue de littérature concernant la physiopathologie de ces retards et les facteurs susceptibles d’en augmenter les risques. Les profils neuropsychologiques associés à la présence d’une CC, ainsi que leur impact sur les acquisitions scolaires, l’adaptation comportementale et la qualité de vie seront présentés.Congenital heart diseases (CHD) are the most common congenital anomalies in newborns. The literature of the last decades demonstrates that developmental delays are frequent in this population, especially in the areas of gross and fine motor skills, global intellectual functioning, language, memory, attention and executive abilities. This article offers a literature review covering the pathophysiology of these delays and their risk factors. Neuropsychological profiles associated with CHD and their impact on school achievement, behavioral adaptation and quality of life will be presented

Développement cognitif des enfants épileptiques : contribution du stress

L’épilepsie est un désordre neurologique souvent infantile associé à des comorbidités qui impliquent des troubles cognitifs. Depuis quelques années, les études des chercheurs suggèrent que la qualité de vie des personnes atteintes d’épilepsie est plus sévèrement impactée par les comorbidités associées à la maladie que par les crises. Il importe donc de diminuer la sévérité des troubles cognitifs chez les personnes épileptiques. Dans cet article, nous relevons les hypothèses de la littérature actuelle qui stipulent que le stress pourrait être un facteur affectant négativement le développement cognitif des enfants épileptiques. Ainsi, nous décrivons les atteintes neuropsychologiques inhérentes aux syndromes convulsifs, la relation biologique du stress et la relation entre le stress et les syndromes convulsifs. Deux modes d’action, évoqués par les chercheurs, par lesquels le stress serait un facteur aggravant les comorbidités des personnes qui présentent un syndrome convulsif seront aussi décrits.Epilepsy is a neurodevelopmental disorder with an onset mainly during childhood, and is linked to life-long cognitive deficits. In this article, we suggest that stress could negatively influence the cognitive development in children suffering from epilepsy. The object of this article is to present two explanations that are complementary and cumulative regarding the link between stress and cognitive development in epileptic children and to review the current knowledge regarding them. First, stress influences seizures’ frequency and severity, which influences cognitive development. Secondly, stress causes cognitive deficits which might be added to the cognitive deficits caused by seizures