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Aim: KCNB1 encephalopathy encompasses a broad phenotypic spectrum associating intellectual disability, behavioral disturbances, and epilepsies of various severity. Using standardized parental questionnaires, we aimed to capture the heterogeneity of the adaptive and behavioral features in a series of patients with KCNB1 pathogenic variants., Methods: We included 25 patients with a KCNB1 encephalopathy, aged from 3.2 to 34.1 years (median = 10 years). Adaptive functioning was assessed in all patients using the French version of the Vineland Adaptive Behavior Scales, Second Edition (VABS-II) questionnaire. We screened global behavior with the Childhood Behavioral Check-List (CBCL, Achenbach) and autism spectrum disorder (ASD) with the Social Communication Questionnaire (SCQ). We used a cluster analysis to identify subgroups of adaptive profiles., Results: VABS-II questionnaire showed pathological adaptive behavior in all participants with a severity of adaptive deficiency ranging from mild in 8/20 to severe in 7/20. Eight out of 16 were at risk of Attention Problems at the CBCL and 13/18 were at risk of autism spectrum disorder (ASD). The adaptive behavior composite score significantly decreased with age (Spearman's Rho=-0.72, p<0.001) but not the equivalent ages, suggesting stagnation and slowing but no regression over time. The clustering analysis identified two subgroups of patients, one showing more severe adaptive behavior. The severity of the epilepsy phenotype predicted the severity of the behavioral profile with a sensitivity of 70% and a specificity of 90.9%., Conclusion: This study confirms the deleterious consequences of early-onset epilepsy in addition to the impact of the gene dysfunction in patients with KCNB1 encephalopathy. ASD and attention disorders are frequent. Parental questionnaires should be considered as useful tools for early screening and care adaptation., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021. Published by Elsevier Inc.)

Objective: Epilepsy with myoclonic atonic seizure (EMAS) occurs in young children with previously normal to subnormal development. The outcome ranges from seizure freedom with preserved cognitive abilities to refractory epilepsy with intellectual disability (ID). Routine brain imaging typically shows no abnormalities. We aimed to compare the brain morphometry of EMAS patients with healthy subjects several years after epilepsy onset, and to correlate it to epilepsy severity and cognitive findings., Methods: Fourteen EMAS patients (4 females, 5-14 years) and 14 matched healthy controls were included. Patients were classified into three outcome groups (good, intermediate, poor) according to seizure control and cognitive and behavioral functioning. Individual anatomical data (T1-weighted sequence) were processed using the FreeSurfer pipeline. Cortical volume (CV), cortical thickness (CT), local gyrification index (LGI), and subcortical volumes were used for group-comparison and linear regression analyses., Results: Morphometric comparison between EMAS patients and healthy controls revealed that patients have 1) reduced CV in frontal, temporal and parietal lobes (p = <.001; 0.009 and 0.024 respectively); 2) reduced CT and LGI in frontal lobes (p = 0.036 and 0.032 respectively); and 3) a neat cerebellar volume reduction (p = 0.011). Neither the number of anti-seizure medication nor the duration of epilepsy was related to cerebellar volume (both p > 0.62). Poor outcome group was associated with lower LGI. Patients in good and intermediate outcome groups had a comparable LGI to their matched healthy controls (p > 0.27 for all lobes)., Conclusions: Structural brain differences were detectable in our sample of children with EMAS, mainly located in the frontal lobes and cerebellum. These findings are similar to those found in patients with genetic/idiopathic generalized epilepsies. Outcome groups correlated best with LGI. Whether these anatomical changes reflect genetically determined abnormal neuronal networks or a consequence of sustained epilepsy remains to be solved with prospective longitudinal studies., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Intellectual disability (ID) and autism spectrum disorders are complex neurodevelopmental disorders occurring among all ethnic and socioeconomic groups. Pathogenic variants in the neurite extension and migration factor (NEXMIF) gene (formerly named KIAA2022) on the X chromosome are responsible for ID, autistic behavior, epilepsy, or dysmorphic features in males. Most affected females described had a milder phenotype or were asymptomatic obligate carriers. We report here for the first time mother-to-son transmission of a novel NEXMIF truncating variant without X-inactivation skewing in the blood. Truncating gene variant leads to symptomatic mother to severely affected son transmission. Our findings emphasize that NEXMIF sequencing should be strongly considered in patients with unexplained autism spectrum disorder, ID, and epilepsy, irrespective of gender. Such testing could increase our knowledge of the pathogenicity of NEXMIF variants and improve genetic counseling.

Background: Neonatal thalamic hemorrhagic stroke is related to cerebral sinus venous thrombosis and associated with neurological sequelae. Predicting factors are however lacking., Methods: Clinical and radiological findings at onset and on follow-up of 5 neonates with thalamic hemorrhage stroke are described., Results: All neonates presented with abrupt lethargy, ophistotonos, irritability and/or seizures. The thalamic hemorrhagic stroke was most often unilateral (4/5), involving the posterior/entire thalamus in 3 cases and the anterior thalamus in 2. Cerebral venous thrombosis was identified in a single patient. At follow-up, children with unilateral anterior thalamic hemorrhagic stroke demonstrated thalamic atrophy without neurological symptoms, whereas children whose thalamus lesion was extensive exhibit a porencephalic cavity and presented with late-onset epilepsy., Discussion: Although deep cerebral venous thrombosis is probably the cause of neonatal thalamic hemorrhagic stroke, its radiological evidence is challenging. Outcome seems dependent of the size and location of thalamic hemorrhagic stroke. Epilepsy is a frequent morbidity after thalamic hemorrhagic stroke.

Objectives: To evaluate the epileptic, academic, and developmental status at age 7 years in a large population of term-born children who sustained neonatal arterial ischemic stroke (NAIS), and to assess the co-occurrence of these outcomes., Study Design: A cohort study including 100 term newborns with NAIS was designed. Two infants died during the neonatal period, 13 families were lost to follow-up, and 5 families declined to participate in this evaluation. Thus, 80 families completed the 7-year clinical assessment. Epileptic status, schooling, motor abilities, global intellectual functioning, spoken language, and parental opinions were recorded. Principal component analysis was applied., Results: Rates of impaired language, cerebral palsy, low academic skills, active epilepsy, and global intellectual deficiency were 49%, 32%, 28%, 11%, and 8%, respectively. All were highly correlated. Eventually, 59% of children were affected by at least 1 of the aforementioned conditions. In 30% of cases, the viewpoints of health practitioners and parents did not match., Conclusion: The prevalence of severe disabilities at 7 years after NAIS is low, but most children exhibit some impairment in developmental profile., Trial Registration: ClinicalTrials.gov (NCT02511249), Programme Hospitalier de Recherche Clinique Régional (0308052), Programme Hospitalier de Recherche Clinique Interrégional (1008026), and EudraCT (2010-A00329-30)., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Chronic epilepsy has rarely been reported after posterior reversible encephalopathy syndrome (PRES) and the association with hippocampal sclerosis has been suggested only once before. We report the case of a girl admitted at the age of 8 years with idiopathic nephrotic syndrome. On the second day of admission, she presented with focal complex seizures and cerebral MRI showed posterior encephalopathy and no hippocampal sclerosis. MRI after one month confirmed the diagnosis of PRES. The seizures recurred and the girl developed pharmacoresistant epilepsy and was admitted to our hospital for further investigation. Cerebral MRI three years after the diagnosis of PRES showed hippocampal sclerosis which was not present on the initial MRI. We conclude that there is a triggering role of PRES in the development of hippocampal sclerosis. Hippocampal sclerosis may have resulted from seizure-associated damage, alternatively, hypertensive encephalopathy may have led to hippocampal damage via a vascular mechanism.

LAMA2-related muscular dystrophy is an autosomal-recessive disorder and one of the most common forms in the group of congenital muscular dystrophies. There is a spectrum of severity ranging from a severe, early onset, congenital phenotype to a limb-girdle like pattern of ambulatory patients. Due to promising preclinical results of new therapeutic options, there is an increasing effort of several research groups worldwide to better define epidemiology and natural history of this disease. In Switzerland, we started to include pediatric patients in our national neuromuscular registry (Swiss-Reg-NMD) in 2018. Baseline data and 6-12 monthly follow-up data are collected by the treating physician in the local neuromuscular center. Baseline data include information about diagnostic investigations (genetics, laboratory results, MRI, clinical phenotype), motor function, epilepsy, lung function, cardiological investigations and motor function scores. We were able to include all diagnosed pediatric patients of the Swiss neuromuscular centers and one adult patient with a baseline data set. We present data of the baseline data set from 18 patients. 15/18 patients belong to the group of the severe congenital form, 3/18 patients show a limb-girdle muscular dystrophy pattern. Age ranges from 0 months to 31 years. Brain MRI data are available from 14 patients, where of 13 show white matter changes and one shows a normal MRI at age one month. Four patients have additional structural abnormalities, two of them a Blakes Pouch cyst. Motor function depends on the disease type, in the congenital form 13/16 are able to hold the head up, 8/14 are able to sit and roll over. We present additional data about epilepsy, ventilation and cardiological findings as well as cognitive abilities and school settings. On the basis of this newly developed registry, we are able to draw a more detailed picture of this patient group. With further prospective data collection we gain information about the natural history. [ABSTRACT FROM AUTHOR]