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Spontaneous cortical waves have been widely observed, although previous evidence from humans has been indirect, using functional magnetic resonance imaging. This study reports that there are slow modulations in neuronal firing rates and gamma local field potentials in human auditory cortex in the absence of sensory stimuli or task. Animal studies have shown robust electrophysiological activity in the sensory cortex in the absence of stimuli or tasks. Similarly, recent human functional magnetic resonance imaging (fMRI) revealed widespread, spontaneously emerging cortical fluctuations. However, it is unknown what neuronal dynamics underlie this spontaneous activity in the human brain. Here we studied this issue by combining bilateral single-unit, local field potentials (LFPs) and intracranial electrocorticography (ECoG) recordings in individuals undergoing clinical monitoring. We found slow (<0.1 Hz, following 1/ f -like profiles) spontaneous fluctuations of neuronal activity with significant interhemispheric correlations. These fluctuations were evident mainly in neuronal firing rates and in gamma (40–100 Hz) LFP power modulations. Notably, the interhemispheric correlations were enhanced during rapid eye movement and stage 2 sleep. Multiple intracranial ECoG recordings revealed clear selectivity for functional networks in the spontaneous gamma LFP power modulations. Our results point to slow spontaneous modulations in firing rate and gamma LFP as the likely correlates of spontaneous fMRI fluctuations in the human sensory cortex.

SNAP25 is a core component of the soluble N-ethylmaleimide-sensitive factor attachment receptor complex, which plays a critical role in synaptic vesicle exocytosis. To date, six de novo SNAP25 mutations have been reported in patients with neurological features including seizures, intellectual disability, severe speech delay, and cerebellar ataxia. Here, we analyzed an Israeli family with two affected siblings showing seizures and cerebellar dysfunction by whole-exome sequencing, and identified a novel missense SNAP25 mutation (c.176G > C, p.Arg59Pro) inherited from their unaffected father. Two SNAP25 isoforms are known, SNAP25a and SNAP25b, which each contain a different exon 5. The c.176G > C mutation found in this study was specific to SNAP25b, while five previously reported mutations were identified in exons common to both isoforms. Another was previously reported to be specific to SNAP25b. Comparing clinical features of reported patients with SNAP25 mutations, the current patients demonstrated apparently milder clinical features with normal intelligence, and no magnetic resonance imaging abnormality or facial dysmorphism. Our results expand the clinical spectrum of SNAP25 mutations.

Background West syndrome is a convulsive disorder of infancy with unique seizures and a characteristic background electroencephalograph pattern. Adrenocorticotropic hormone (ACTH) is effective in spasm cessation, yet metabolic consequences of this therapeutic agent in childhood have not been published. Methods In this observational study we explored the cardiometabolic outcomes of 117 children with West syndrome (78 ACTH-treated and 39 non-ACTH-treated) monitored at a single medical center from 1995 to 2019 (median follow-up 7.2 years). Outcomes included the prevalence of cardiometabolic derangements (obesity, hypertension, and dyslipidemia) during infancy (< 2 years), early childhood (2–6 years), and childhood/adolescence (6–18 years). Results The rates of metabolic derangements during infancy in the West syndrome cohort were high compared to childhood/adolescence (obesity 27.3 % vs. 3.3 %, [ p  = 0.010], diastolic hypertension 48.8 % vs. 5.1 % [ p  < 0.001], hypertriglyceridemia 71 % vs. 40 % [ p  = 0.008], low high-density lipoprotein cholesterol [HDL-c] 54.2 % vs. 12.9 % [ p  = 0.001], and elevated triglycerides/HDL-c ratios 62.5 % vs. 12.9 % [ p  < 0.001]). The proportion of systolic and/or diastolic blood pressure levels categorized as hypertensive was 58.5 % during infancy, 48.1 % during early childhood, and 26.3 % during childhood/adolescence. ACTH-treated patients had higher weight and weight-to-length z-scores and higher triglyceride levels during infancy compared to non-ACTH-treated patients ( p  = 0.008, p  = 0.001, and p  = 0.037, respectively), and higher triglyceride levels during early childhood ( p  = 0.050), with no significant group differences during childhood/adolescence. Conclusions Children with West syndrome apparently have an increased prevalence of cardiometabolic derangements more pronounced in infants and in ACTH-treated patients. These findings highlight the need to monitor these children for cardiometabolic derangements, even though these cardiometabolic abnormalities are transitory and tend to decrease with time. The health implications of cardiometabolic derangements during critical windows of growth and development warrant further investigation.

Background Many genes are candidates for involvement in epileptic encephalopathy (EE) because one or a few possibly pathogenic variants have been found in patients, but insufficient genetic or functional evidence exists for a definite annotation. Methods To increase the number of validated EE genes, we sequenced 26 known and 351 candidate genes for EE in 360 patients. Variants in 25 genes known to be involved in EE or related phenotypes were followed up in 41 patients. We prioritized the candidate genes, and followed up 31 variants in this prioritized subset of candidate genes. Results Twenty‐nine genotypes in known genes for EE (19) or related diseases (10), dominant as well as recessive or X‐linked, were classified as likely pathogenic variants. Among those, likely pathogenic de novo variants were found in EE genes that act dominantly, including the recently identified genes EEF1A2, KCNB1 and the X‐linked gene IQSEC2. A de novo frameshift variant in candidate gene HNRNPU was the only de novo variant found among the followed‐up candidate genes, and the patient's phenotype was similar to a few recent publications. Conclusion Mutations in genes described in OMIM as, for example, intellectual disability gene can lead to phenotypes that get classified as EE in the clinic. We confirmed existing literature reports that de novo loss‐of‐function HNRNPUmutations lead to severe developmental delay and febrile seizures in the first year of life. Genes that were previously reported to have been found mutated in patients with epileptic encephalopathy were tested in a new patient cohort. Probably pathogenic variants were found in known genes for epileptic encephalopathy and in genes for intellectual disability syndromes. A de novo variant in HNRNPU contributes to growing evidence for this gene.

Febrile infection‐related epilepsy syndrome (FIRES) is a devastating epilepsy characterized by new‐onset refractory status epilepticus with a prior febrile infection. We performed exome sequencing in 50 individuals with FIRES, including 27 patient–parent trios and 23 single probands, none of whom had pathogenic variants in established genes for epilepsies or neurodevelopmental disorders. We also performed HLA sequencing in 29 individuals with FIRES and 529 controls, which failed to identify prominent HLA alleles. The genetic architecture of FIRES is substantially different from other developmental and epileptic encephalopathies, and the underlying etiology remains elusive, requiring novel approaches to identify the underlying causative factors.

The prevalence of epilepsy is highest during the first year of life. Approximately 50% of patients with seizure onset between 1 and 12 months of age suffer from West syndrome. The rest have one of 12 well-delineated epilepsy syndromes, or in most cases have what are classified as generalized or partial seizures. The outcome of infants with partial seizures is significantly worse than that of patients with generalized seizures. This is true not only for symptomatic partial seizures but also for a subgroup of infants with cryptogenic partial seizures.

Refractory gelastic seizures are often associated with hypothalamic hamartoma (HH). Presurgical evaluation in such children often points to a distinct cortical region as the source of the seizures. A case of a child with HH and refractory seizures is presented. Video-EEG monitoring revealed a well-defined epileptic focus in the left frontal region. In accordance with the current understanding of the nature of hamartoma-related seizures, the hamartoma was resected. Follow-up evaluations revealed a marked improvement in seizure frequency and global functioning.

The prevalence of epilepsy is highest during the first year of life. Approximately 50% of patients with seizure onset between 1 and 12 months of age suffer from West syndrome. The rest have one of 12 well-delineated epilepsy syndromes, or in most cases have what are classified as generalized or partial seizures. The outcome of infants with partial seizures is significantly worse than that of patients with generalized seizures. This is true not only for symptomatic partial seizures but also for a subgroup of infants with cryptogenic partial seizures. (J Child Neurol 1999;14:485-489).

Aim: The purpose of this study was to compare the frequency of various surgical techniques and surgical outcome between pediatric and adult populations that underwent epilepsy surgery by the same team.Methods: All patients who underwent epilepsy surgery at the Tel Aviv Medical Center between 1997 and 2006 and had been followed up for >2 years were eligible for this study. The majority (90%) of all epilepsy surgeries carried out in Israel were performed in this institution and by a single neurosurgeon. Only patients that underwent video-EEG monitoring as part of the presurgical evaluation were included in the study. Results: A total of 186 patients (131 adults and 55 children) underwent epilepsy surgery in our institute during the study period, and follow-up was available for 177 patients (95%). While the adults underwent significantly more temporal lobe resections (51 vs. 20%, p < 0.0001), the children had significantly more extra-temporal non-lesional resections (18 vs. 1%, p < 0.0001) and hemispherectomies (5 vs. 1%, p = 0.002). Over one half (54%) of all the patients had a postoperative reduction in seizures of >90%, and 72% had a reduction of >50%, with no group difference in surgical success. Among the lesionectomies, the outcome was better for tumors, especially those in the temporal lobe. Only 1% of the patients had a long-term neurological deficit.Conclusions: Children comprised 30% of the epilepsy surgical cases during the study period. Children underwent more non-lesional resections and hemispherectomies, while adults underwent more temporal lobe resections. There was no age-related difference in surgical outcome.

It has not been established whether electroencephalography (EEG) is a contributing factor in predicting the outcome of surgery for epilepsy. We conducted a prospective study on 26 patients (M/F 14/12, age: 33 ± 7.5 years, range 19–48) with mesial temporal lobe epilepsy (MTLE) who were followed for 2 years after surgery and who underwent routine EEG recordings 5.6 ± 3 months (range 3–12) postoperatively. Interictal epileptiform activity (IEA) on the EEG was compared in 17 seizure-free patients to 9 patients with recurrent seizures. The two groups were similar in gender, age, febrile convulsions, trauma, family history, seizure frequency prior to surgery, epilepsy duration and number of antiepileptic drugs. Following surgery, 17 study patients (65%) became seizure free; 9 (35%) had seizure recurrence. Postoperative EEG recordings showed IEA in 8/26 study patients (31%), 3 of whom were from the seizure-free group (3/17, 18%); 5 had seizure recurrence (5/9, 56%) (p=0.078). IEAs in postoperative EEGs were less frequently demonstrated in patients who were seizure free, but the presence of postoperative IEAs does not preclude successful surgical outcome.