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Infantile epileptic spasms syndrome (IESS) is a devastating developmental epileptic encephalopathy (DEE) consisting of epileptic spasms, as well as one or both of developmental regression or stagnation and hypsarrhythmia on EEG. A myriad of aetiologies are associated with the development of IESS; broadly, 60% of cases are thought to be structural, metabolic or infectious in nature, with the remainder genetic or of unknown cause. Epilepsy genetics is a growing field, and over 28 copy number variants and 70 single gene pathogenic variants related to IESS have been discovered to date. While not exhaustive, some of the most commonly reported genetic aetiologies include trisomy 21 and pathogenic variants in genes such as TSC1 , TSC2 , CDKL5 , ARX , KCNQ2 , STXBP1 and SCN2A . Understanding the genetic mechanisms of IESS may provide the opportunity to better discern IESS pathophysiology and improve treatments for this condition. This narrative review presents an overview of our current understanding of IESS genetics, with an emphasis on animal models of IESS pathogenesis, the spectrum of genetic aetiologies of IESS (i.e., chromosomal disorders, single-gene disorders, trinucleotide repeat disorders and mitochondrial disorders), as well as available genetic testing methods and their respective diagnostic yields. Future opportunities as they relate to precision medicine and epilepsy genetics in the treatment of IESS are also explored.

Background: KBG syndrome is a genetic disorder characterized by short stature, dysmorphic features, macrodontia, cognitive impairment, and limb anomalies. Epilepsy is an important comorbidity associated with KBG syndrome, although the entire phenotypic spectrum may not be fully appreciated., Methods: We identified five new patients with KBG syndrome-related epilepsy and compared their phenotype to previously reported cases in the literature., Results: Five patients with KBG syndrome-related epilepsy were identified. Three patients (60%) were male. Median age of seizure onset was 18 months (interquartile range 5, 32). The epilepsy type was generalized in three patients (60%); in two, the epilepsy type was combined (40%), with focal and generalized seizures. In one patient (20%), the epilepsy syndrome was classifiable and the child was diagnosed with myoclonic-atonic epilepsy. All five patients had pathogenic variants in the ANKRD11 gene. Epilepsy was refractory in two patients (40%). No specific antiseizure medication (ASM) was found to be superior. Literature review yielded 134 cases, median age of seizure onset was 4 years, and seizures were generalized (n = 60, 44%), focal (n = 26, 19%), or combined (n = 13, 10%). An epilepsy syndrome was diagnosed in 12 patients (8.8%). In those with documented response to ASM (n = 49), 22.4% were refractory (n = 11)., Conclusions: Our study confirms that few patients with epilepsy and KBG syndrome have an identifiable epilepsy syndrome and generalized seizures are most common. We highlight that epilepsy associated with KBG syndrome may occur before age one year and should be an important diagnostic consideration in this age group., Competing Interests: Declaration of competing interest None of the authors has any conflict of interest to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: Due to variability in reports, the aim of this meta-analysis was to evaluate the incidence and risk factors of post-stroke early seizures (ES) and post-stroke epilepsy (PSE)., Methods: The MEDLINE, EMBASE and Web of Science databases were searched for post-stroke ES/PSE articles published on any date up to November 2020. Post-stroke ES included seizures occurring within 7 days of stroke, and PSE included at least one unprovoked seizure. Using random effects models, the incidence and risk factors of post-stroke ES and PSE were evaluated. The study was retrospectively registered with INPLASY (INPLASY2023100008)., Results: Of 128 included studies in total, the incidence of post-stroke ES was 0.07 (95% confidence interval [CI] 0.05, 0.10) and PSE was 0.10 (95% CI 0.08, 0.13). The rates were higher in children than adults. Risk factors for post-stroke ES included hemorrhagic stroke (odds ratio [OR] 2.14, 95% CI 1.44, 3.18), severe strokes (OR 2.68, 95% CI 1.73, 4.14), cortical involvement (OR 3.09, 95% CI 2.11, 4.51) and hemorrhagic transformation (OR 2.70, 95% CI 1.58, 4.60). Risk factors for PSE included severe strokes (OR 4.92, 95% CI 3.43, 7.06), cortical involvement (OR 3.20, 95% CI 2.13, 4.81), anterior circulation infarcts (OR 3.28, 95% CI 1.34, 8.03), hemorrhagic transformation (OR 2.81, 95% CI 1.25, 6.30) and post-stroke ES (OR 7.24, 95% CI 3.73, 14.06)., Conclusion: Understanding the risk factors of post-stroke ES/PSE may identify high-risk individuals who might benefit from prophylactic treatment., Competing Interests: Declaration of conflicting interestsThe authors declare that there are no conflicts of interest.

Competing Interests: None declared.

Background: Most neonatal and infantile-onset epilepsies have presumed genetic aetiologies, and early genetic diagnoses have the potential to inform clinical management and improve outcomes. We therefore aimed to determine the feasibility, diagnostic yield, and clinical utility of rapid genome sequencing in this population., Methods: We conducted an international, multicentre, cohort study (Gene-STEPS), which is a pilot study of the International Precision Child Health Partnership (IPCHiP). IPCHiP is a consortium of four paediatric centres with tertiary-level subspecialty services in Australia, Canada, the UK, and the USA. We recruited infants with new-onset epilepsy or complex febrile seizures from IPCHiP centres, who were younger than 12 months at seizure onset. We excluded infants with simple febrile seizures, acute provoked seizures, known acquired cause, or known genetic cause. Blood samples were collected from probands and available biological parents. Clinical data were collected from medical records, treating clinicians, and parents. Trio genome sequencing was done when both parents were available, and duo or singleton genome sequencing was done when one or neither parent was available. Site-specific protocols were used for DNA extraction and library preparation. Rapid genome sequencing and analysis was done at clinically accredited laboratories, and results were returned to families. We analysed summary statistics for cohort demographic and clinical characteristics and the timing, diagnostic yield, and clinical impact of rapid genome sequencing., Findings: Between Sept 1, 2021, and Aug 31, 2022, we enrolled 100 infants with new-onset epilepsy, of whom 41 (41%) were girls and 59 (59%) were boys. Median age of seizure onset was 128 days (IQR 46-192). For 43 (43% [binomial distribution 95% CI 33-53]) of 100 infants, we identified genetic diagnoses, with a median time from seizure onset to rapid genome sequencing result of 37 days (IQR 25-59). Genetic diagnosis was associated with neonatal seizure onset versus infantile seizure onset (14 [74%] of 19 vs 29 [36%] of 81; p=0·0027), referral setting (12 [71%] of 17 for intensive care, 19 [44%] of 43 non-intensive care inpatient, and 12 [28%] of 40 outpatient; p=0·0178), and epilepsy syndrome (13 [87%] of 15 for self-limited epilepsies, 18 [35%] of 51 for developmental and epileptic encephalopathies, 12 [35%] of 34 for other syndromes; p=0·001). Rapid genome sequencing revealed genetic heterogeneity, with 34 unique genes or genomic regions implicated. Genetic diagnoses had immediate clinical utility, informing treatment (24 [56%] of 43), additional evaluation (28 [65%]), prognosis (37 [86%]), and recurrence risk counselling (all cases)., Interpretation: Our findings support the feasibility of implementation of rapid genome sequencing in the clinical care of infants with new-onset epilepsy. Longitudinal follow-up is needed to further assess the role of rapid genetic diagnosis in improving clinical, quality-of-life, and economic outcomes., Funding: American Academy of Pediatrics, Boston Children's Hospital Children's Rare Disease Cohorts Initiative, Canadian Institutes of Health Research, Epilepsy Canada, Feiga Bresver Academic Foundation, Great Ormond Street Hospital Charity, Medical Research Council, Murdoch Children's Research Institute, National Institute of Child Health and Human Development, National Institute for Health and Care Research Great Ormond Street Hospital Biomedical Research Centre, One8 Foundation, Ontario Brain Institute, Robinson Family Initiative for Transformational Research, The Royal Children's Hospital Foundation, University of Toronto McLaughlin Centre., Competing Interests: Declaration of interests APa is a current member of the National Institute of Health and Clinical excellence (NICE) technology appraisal committee B and has a financial interest in Genedrive PLC. KW has consulted for Stoke Therapeutics. JHC has received renumeration for lectures by GW pharma/Jazz, UCB/Zogenix, Biocodex, and Biogen; is a member of the Data Monitoring and Safety Committee for Admiral Trial (Stroke Therapeutics); and is Chair of the Medical Advisory Board for Matthews Friends, Dravet UK, and Hope for Hypothalamic Hamartoma. IES has served on scientific advisory boards for BioMarin, Chiesi, Eisai, Encoded Therapeutics, GlaxoSmithKline, Knopp Biosciences, Nutricia, Rogcon, Takeda Pharmaceuticals, UCB, and Xenon Pharmaceuticals; has received speaker honoraria from GlaxoSmithKline, UCB, BioMarin, Biocodex, Chiesi, Liva Nova, Nutricia, Zuellig Pharma, and Eisai; has received funding for travel from UCB, Biocodex, GlaxoSmithKline, Biomarin, Encoded Therapeutics, and Eisai; has served as an investigator for Anavex Life Sciences, Cerecin, Cerevel Therapeutics, Eisai, Encoded Therapeutics, EpiMinder, Epygenyx, ES-Therapeutics, GW Pharma, Marinus, Neurocrine BioSciences, Ovid Therapeutics, Takeda Pharmaceuticals, UCB, Ultragenyx, Xenon Pharmaceuticals, Zogenix, and Zynerba; and has consulted for Care Beyond Diagnosis, Epilepsy Consortium, Atheneum Partners, Ovid Therapeutics, UCB, Zynerba Pharmaceuticals, BioMarin, Encoded Therapeutics, and Biohaven Pharmaceuticals; and is a Non-Executive Director of Bellberry and a Director of the Australian Academy of Health and Medical Sciences and the Australian Council of Learned Academies. IES might accrue future revenue on pending patent WO61/010176 (filed in 2008; therapeutic compound); has a patent for SCN1A testing held by Bionomics and licensed to various diagnostic companies; has a patent molecular diagnostic or theranostic target for benign familial infantile epilepsy (PRRT2; 2011904493, 2012900190, and PCT/AU2012/001321 [TECH ID:2012-009]). GC has received honorarium from CADTH and serves as the Co-Lead of the Can-GARD Initiative and on the SickKids Precision Child Health steering committee. APo serves on the scientific advisory boards for TevardBio and Syngap Research Fund, and on the American Epilepsy Society Board of Directors. KBH has received support from RogCon Biosciences and Praxis Precision Medicines. AM has received consulting fees from Rocket Pharmaceuticals; honorarium from Jazz Pharmaceuticals; support for attending conferences from Jazz Pharmaceuticals and European Paediatric Neurology Society; fees for participating on boards for Biogen and Biocodex; and serves unpaid roles on the ILAE Genetic Literacy Task Force, EPICARE, and Great Ormond Street Hospital National Institute for Health and Care Research Biomedical Research Centre Chair of Junior Faculty. All other authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Objective: ST3GAL3-related developmental and epileptic encephalopathy (DEE-15) is an autosomal recessive condition characterized by intellectual disability, language and motor impairments, behavioral difficulties, stereotypies, and epilepsy. Only a few cases have been reported, and the epilepsy phenotype is not fully elucidated., Methods: A retrospective chart review of two siblings with ST3GAL3-related DEE was completed. In addition, we reviewed all published cases of ST3GAL3-related congenital disorder of glycosylation., Results: Two brothers presented with global developmental delay, motor and language impairment, hypotonia, and childhood-onset seizures. Seizures started between 2.5 and 5 years and had tonic components. Both siblings had prolonged periods of seizure freedom on carbamazepine. Tremor was present in the younger sibling. Whole exome sequencing revealed two novel pathogenic variants in ST3GAL3, (a) c.302del, p.Phe102Serfs*34 and (b) c.781C>T, p.Arg261*, which were inherited in trans. Magnetic resonance imaging showed T2 hyperintensities and restricted diffusion in the brainstem and middle cerebellar peduncle in the older sibling, also described in two reported cases. A review of the literature revealed 24 cases of ST3GAL3-related CDG. Twelve cases had information about seizures, and epilepsy was diagnosed in 8 (67%). The median age of seizure onset was 5.5 months. Epileptic spasms were most common (67%). Four children were diagnosed with Infantile Epileptic Spasms syndrome and Lennox Gastaut syndrome (57%). Most children (n = 6, 75%) had seizures despite anti-seizure medication treatment., Significance: Seizures related to ST3GAL3-related DEE often occur in infancy and may present as epileptic spasms. However, seizure onset may also occur outside of infancy with mixed seizure types and show good response to treatment with prolonged seizure freedom. Tremor may also be uniquely observed in this condition., (© 2023 The Authors. Epilepsia Open published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Children with epilepsy commonly have comorbid neurocognitive impairments that severely affect their psychosocial well-being, education, and future career prospects. Although the provenance of these deficits is multifactorial, the effects of interictal epileptiform discharges (IEDs) and anti-seizure medications (ASMs) are thought to be particularly severe. Although certain ASMs can be leveraged to inhibit IED occurrence, it remains unclear whether epileptiform discharges or the medications themselves are most deleterious to cognition. To examine this question, 25 children undergoing invasive monitoring for refractory focal epilepsy performed one or more sessions of a cognitive flexibility task. Electrophysiological data were recorded to detect IEDs. Between repeated sessions, prescribed ASMs were either continued or titrated to <50% of the baseline dose. Hierarchical mixed-effects modeling assessed the relationship between task reaction time (RT), IED occurrence, ASM type, and dose while controlling for seizure frequency. Both presence (β ± SE = 49.91 ± 16.55 ms, p = .003) and number of IEDs (β ± SE = 49.84 ± 12.51 ms, p < .001) were associated with slowed task RT. Higher dose oxcarbazepine significantly reduced IED frequency (p = .009) and improved task performance (β ± SE = -107.43 ± 39.54 ms, p = .007). These results emphasize the neurocognitive consequences of IEDs independent of seizure effects. Furthermore, we demonstrate that inhibition of IEDs following treatment with select ASMs is associated with improved neurocognitive function., (© 2023 International League Against Epilepsy.)

Aim: To report seizure outcomes in children with GATOR1 gene complex disorders who underwent epilepsy surgery and perform a systematic literature search to study the available evidence., Methods: The records of children with pathogenic/likely pathogenic variants in GATOR1 gene complex who underwent epilepsy surgery were reviewed. Clinical, radiological, neurophysiological, and histological data were extracted/summarized. The systematic review included all case series/reports and observational studies reporting on children or adults with genetic (germline or somatic) variants in the GATOR1 complex genes (DEPDC5, NPRL2, NPRL3) with focal epilepsy with/without focal cortical dysplasia who underwent epilepsy surgery; seizure outcomes were analyzed., Results: Eight children with pathogenic/likely pathogenic variants in GATOR1 complex genes were included. All had drug-resistant epilepsy. Six children had significant neurodevelopmental delay. Epilepsy surgery was performed in all; clinical seizure freedom was noted in 4 children (50%). Systematic literature search identified 17 eligible articles; additional 30 cases with patient-level data were studied. Lesional MRI brain was seen in 80% cases. The pooled rate of seizure freedom following surgery was 60%; FCD IIa was the most encountered pathology., Interpretation: Epilepsy surgery may be effective in some children with GATOR1 complex gene variants. Seizure outcomes may be compromised by extensive epileptogenic zones., Competing Interests: Declaration of Competing Interest None of the authors have any conflict of interest to declare. We affirm that: •The manuscript is being submitted only to your journal, that it will not be submitted elsewhere, while under consideration, that it has not been published elsewhere, and, should it be published in your journal, that it will not be published elsewhere. •All authors are responsible for reported research. •All authors have participated in the concept and design, analysis and interpretation of data, and drafting or revising of the manuscript, and that they have approved the manuscript as submitted. •The manuscript has not been posted on any preprint server., (Copyright © 2023 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Background: Infantile epileptic spasms syndrome is an epileptic encephalopathy, characterized by spasms, hypsarrhythmia, and developmental regression. Appropriately selected patients with infantile epileptic spasms syndrome may be candidates for epilepsy surgery. Methods: This is a single-center retrospective case series of children 0-18 years with a current or previous diagnosis of infantile epileptic spasms syndrome with a lesion on magnetic resonance imaging (MRI) and/or positron emission tomography scan who underwent epilepsy surgery at The Hospital for Sick Children (HSC) in Toronto, Canada. The records of 223 patients seen in the infantile epileptic spasms syndrome clinic were reviewed. Results: Nineteen patients met inclusion criteria. The etiology of infantile epileptic spasms syndrome was encephalomalacia in 6 patients (32%), malformations of cortical development in 12 patients (63%), and atypical hypoglycemic injury in 1 patient (5%). Nine patients (47%) underwent hemispherectomy, and 10 patients (53%) underwent lobectomy/lesionectomy. Three patients (16%) underwent a second epilepsy surgery. Fifteen patients (79%) were considered ILAE seizure outcome class 1 (completely seizure free; no auras) at their most recent follow-up visit. The percentage of patients who were ILAE class 1 at most recent follow-up decreased with increasing duration of epilepsy prior to surgery. Developmental outcome after surgery was improved in 14 of 19 (74%) and stable in 5 of 19 (26%) patients. Conclusions: Our study found excellent seizure freedom rates and improved developmental outcomes following epilepsy surgery in patients with a history of infantile epileptic spasms syndrome with a structural lesion detected on MRI brain. Patients who undergo surgery earlier have improved seizure freedom rates and improved developmental outcomes.

Objective: Working memory deficits are prevalent in childhood epilepsy. Working memory processing is thought to be supported by the phase of hippocampal neural oscillations. Disruptions in working memory have previously been linked to the occurrence of transient epileptic activity. This study aimed to resolve the associations between oscillatory neural activity, transient epileptiform events, and working memory in children with epilepsy., Methods: Intracranial recordings were acquired from stereotactically implanted electrodes in the hippocampi, epileptogenic zones, and working memory-related networks of children with drug-resistant epilepsy during a 1-back working memory task. Interictal epileptic activity was captured using automated detectors. Hippocampal phase and interregional connectivity within working memory networks were indexed by Rayleigh Z and the phase difference derivative, respectively. Trials with and without transient epileptiform events were compared., Results: Twelve children (mean age = 14.3 ± 2.8 years) with drug-resistant epilepsy were included in the study. In the absence of transient epileptic activity, significant delta and theta hippocampal phase resetting occurred in response to working memory stimulus presentation (Rayleigh z-score = 9, Rayleigh z-score = 8). Retrieval trials that were in phase with the preferred phase angle were associated with faster reaction times (p = .01, p = .03). Concurrently, delta and theta coordinated interactions between the hippocampi and working memory-related networks were enhanced (phase difference derivative [PDD] z-scores = 6-11). During retrieval trials with pre-encoding or pre-retrieval transient epileptic activity, phase resetting was attenuated (Rayleigh z-score = 5, Rayleigh z-score = 1), interregional connectivity was altered (PDD z-scores = 1-3), and reaction times were prolonged (p = .01, p = .03)., Significance: This work highlights the role of hippocampal phase in working memory. We observe poststimulus hippocampal phase resetting coincident with enhanced interregional connectivity. The precision of hippocampal phase predicts optimal working memory processing, and transient epileptic activity prolongs working memory processing. These findings can help guide future treatments aimed at restoring memory function in this patient population., (© 2022 International League Against Epilepsy.)

Objective: The theory of transient cognitive impairment in epilepsy posits that lapses in attention result from ephemeral disruption of attentional circuitry by interictal events. Eye movements are intimately associated with human attention and can be monitored in real time using eye-tracking technologies. Here, we sought to characterize the associations between interictal epileptiform discharges (IEDs), gaze, and attentional behavior in children with epilepsy., Methods: Eleven consecutive children undergoing invasive monitoring with stereotactic electrodes for localization-related epilepsy performed an attentional set-shifting task while tandem intracranial electroencephalographic signals and eye-tracking data were recorded. Using an established algorithm, IEDs were detected across all intracranial electrodes on a trial-by-trial basis. Hierarchical mixed-effects modeling was performed to delineate associations between trial reaction time (RT), eye movements, and IEDs., Results: Hierarchical mixed-effects modeling revealed that both the presence of an IED (β ± SE = 72.74 ± 24.21 ms, p = .003) and the frequency of epileptiform events (β ± SE = 67.54 ± 17.30 ms, p < .001) were associated with prolonged RT on the attentional set-shifting task. IED occurrence at the time of stimulus presentation was associated with delays in gaze initiation toward the visual targets (p = .017)., Significance: The occurrence of epileptiform activity in close temporal association with stimulus presentation is associated with delays in target-directed gaze and prolonged response time, hallmarks of momentary lapses in attention. These findings provide novel insights into the mechanisms of transient impairments in children and support the use of visual tracking as a correlate of higher order attentional behavior., (© 2022 International League Against Epilepsy.)

Background and Objectives: Neurocognitive outcomes after surgery for temporal lobe epilepsy in childhood are variable. Postoperative changes are not directly predicted by seizure freedom, and associations between epilepsy, neuropsychological function, and developing neural networks are poorly understood. Here, we leveraged whole-brain connectomic profiling in magnetoencephalography (MEG) to retrospectively study associations between brain connectivity and neuropsychological function in children with temporal lobe epilepsy undergoing resective surgery., Methods: Clinical and MEG data were retrospectively analyzed for children who underwent temporal lobe epilepsy surgery at the Hospital for Sick Children from 2000 to 2021. Resting-state connectomes were constructed from neuromagnetic oscillations via the weighted-phase lag index. Using a partial least-squares (PLS) approach, we assessed multidimensional associations between patient connectomes, neuropsychological scores, and clinical covariates. Bootstrap resampling statistics were performed to assess statistical significance., Results: A total of 133 medical records were reviewed, and 5 PLS analyses were performed. Each PLS analysis probed a particular neuropsychological domain and the associations between its baseline and postoperative scores and the connectomic data. In each PLS analysis, a significant latent variable was identified, representing a specific percentage of the variance in the data and relating neural networks to clinical covariates, which included changes in rote verbal memory (n = 41, p = 0.01, σ 2 = 0.38), narrative/verbal memory (n = 57, p = 0.00, σ 2 = 0.52), visual memory (n = 51, p = 0.00, σ 2 = 0.43), working memory (n = 44, p = 0.00, σ 2 = 0.52), and overall intellectual function (n = 59, p = 0.00, σ 2 = 0.55). Children with more diffuse, bilateral intrinsic connectivity across several frequency bands showed lower scores on all neuropsychological assessments but demonstrated a greater propensity for gains after resective surgery., Discussion: Here, we report that connectomes characterized by diffuse connectivity, reminiscent of developmentally immature networks, are associated with lower preoperative cognition and postoperative cognitive improvement. These findings provide a potential means to understand neurocognitive function in children with temporal lobe epilepsy and expected changes postoperatively., (© 2022 American Academy of Neurology.)

Tuberous sclerosis complex (TSC) is a rare autosomal dominant condition that affects multiple body systems. Disruption of the mammalian target of rapamycin (mTOR) pathway results in abnormal cell growth, proliferation, protein synthesis, and cell differentiation and migration in TSC. In the central nervous system, mTOR disruption is also believed to influence neuronal excitability and promote epileptogenesis. Epilepsy is the most common neurological manifestation of TSC and affects 80% to 90% of individuals with high rates of treatment resistance (up to 75%). The onset of epilepsy in the majority of individuals with TSC occurs before the age of two years, which is a critical time in neurodevelopment. Both medically refractory epilepsy and early-onset epilepsy are associated with intellectual disability in TSC, while seizure control and remission are associated with lower rates of cognitive impairment. Our current knowledge of the treatment of epilepsy in TSC has expanded immensely over the last decade. Several new therapies such as preemptive vigabatrin therapy in infants, cannabidiol, and mTOR inhibitors have emerged in recent years for the treatment of epilepsy in TSC. This review will provide clinicians with a comprehensive overview of the pharmacological and nonpharmacological therapies available for the treatment of epilepsy related to TSC., (Crown Copyright © 2021. Published by Elsevier Inc. All rights reserved.)

Purpose: To investigate the utility of Low Density (LD) Electrical Source Imaging (ESI) to model the ictal onset zone (IOZ) for the surgical work up of children with medically refractory epilepsy., Methods: This was a retrospective review of 12 patients from a district and regional pediatric epilepsy center, who underwent focal resections between 2014 and 2019. ESI was generated using the Curry 8 software, incorporating T1 Magnetic Resonance Imaging (MRI) scans and scalp electroencephalogram (EEG) recordings. Concordance of the ictal LD-ESI localizations to the epileptogenic zone was assessed by comparing the location of the ictal LD-ESI to the focal resection margins on neuroimaging and noting the post-operative outcomes at one year. Localizations determined by ictal LD-ESI were also compared to interictal LD-ESI, positron emission tomography (FDG-PET) and interictal magnetoencephalography (MEG)., Results: Ictal ESI correctly localized the ictal onset zone in 4/6 patients, with all four being seizure free at one year. Similarly, interictal ESI localized the irritative zone in 7/9 patients with focal resections, with 6/7 being seizure free at one year. Additionally, we observed ictal ESI to be concordant to interictal ESI in 5/6 patients. Ictal ESI and interictal ESI were concordant to interictal MEG in 3/6 patients. Ictal ESI was concordant with FDG-PET in 6/7 cases., Conclusion: IOZ source localization through LD-ESI is a promising complementary method of assessing the epileptogenic focus in children. These findings may support the inclusion of ictal LD-ESI within the pre-surgical evaluation of children to supplement current diagnostic tools., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The neural mechanisms that underlie selective attention in children are poorly understood. By administering a set-shifting task to children with intracranial electrodes stereotactically implanted within anterior cingulate cortex (ACC) for epilepsy monitoring, we demonstrate that selective attention in a set-shifting task is dependent upon theta-band phase resetting immediately following stimulus onset and that the preferred theta phase angle is predictive of reaction time during attentional shift. We also observe selective enhancement of oscillatory coupling between the ACC and the dorsal attention network and decoupling with the default mode network during task performance. When transient focal epileptic activity occurs around the time of stimulus onset, phase resetting is impaired, connectivity changes with attentional and default mode networks are abolished, and reaction times are prolonged. The results of the present work highlight the fundamental mechanistic role of oscillatory phase in ACC in supporting attentional circuitry and present novel opportunities to remediate attention deficits in children with epilepsy., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Routine electroencephalogram (EEG) has many limitations, especially the inability to capture reported habitual events in question. A prolonged EEG with synchronized video (video-EEG) overcomes some of these limitations by improving the sensitivity, specificity and the diagnostic yield by attempting to record the habitual events when they are frequent and when indicated. Video-EEG is employed commonly for the diagnosis and classification of epilepsy/epilepsy syndromes, to distinguish between seizures and seizures mimickers, for pre-surgical evaluation and in the management of critically ill children. The duration of recording would vary depending on the indication and frequency of events. Ambulatory EEG is another cost effective and convenient alternative in certain circumstances. However, availability of the machines and expertise, accessibility, affordability and labor intensive nature of the procedure limit widespread use in India. This review explores the role of video-EEG in the management of children with epileptic and non-epileptic paroxysmal events with respect to routine clinical practice in India., (© 2021. Dr. K C Chaudhuri Foundation.)

Purpose: This study evaluated the seizure outcomes in children with drug-resistant epilepsy (DRE), having a pre-existing VNS device, after generator replacement with cardiac-based VNS device., Methods: This retrospective study enrolled 30 children with DRE from 2 centers with an existing VNS device nearing end-of-service who underwent generator replacement with cardiac-based VNS device and had at least 1 year follow up. Seizure outcomes and adverse effects were studied., Results: The mean age at insertion of cardiac-based VNS device was 15.03 years. 26.7 % patients showed at least one class improvement at last follow up (mean 2.08 years) and half of the patients maintained their McHugh seizure-outcome class. Thirty-six percent of patients had > 50 % seizure reduction at last follow up. Ten patients reported improvement in ictal severity. Most of the patients tolerated the replacement well., Conclusions: Nearly one-third of patients with DRE showed additional improvement after replacement with cardiac based VNS device. Half of the patients maintained their seizure control., (Copyright © 2020. Published by Elsevier B.V.)

Objective: This systematic review and meta-analyses assessed seizure outcome following pediatric epilepsy surgery., Methods: MEDLINE, EMBASE, and Cochrane were searched for pediatric epilepsy surgery original research from 1990 to 2017. The outcome was seizure freedom at 12 months or longer follow-up. Using random-effects models, the effect sizes for controlled studies, uncontrolled studies on surgery locations (temporal lobe [TL], extratemporal lobe [ETL], or hemispheric surgery), pathologies, nonlesional epilepsy, and incomplete resection were estimated. Meta-regression assessed the relationship between age at surgery, age at seizure onset, and seizure outcome. Random-effects network meta-analysis was conducted for surgery locations., Results: Two hundred fifty-eight studies were included. Surgery achieved higher seizure freedom than medical therapy (odds ratio [OR] = 6.49 [95% confidence interval [CI]: 2.87-14.70], p < 0.001). Seizure freedom declined over time after surgery, from 64.8% (95% CI: 51.2%-76.4%; p = 0.034) at 1 year, to 60.3% (95% CI: 52.9%-67.4%; p = 0.007) at 5 years, and to 39.7% (95% CI: 28.4%-52.2%, p = 0.106) at 10 years. Seizure freedom was (1) highest for hemispheric surgery, followed by TL and ETL surgery, and (2) highest for tumor and lower for malformations of cortical development. Seizure freedom was lower for nonlesional than lesional epilepsy (OR = 0.54 [95% CI: 0.34, 0.88], p = 0.013) and incomplete than complete resection (OR = 0.13 [95% CI: 0.08, 0.21], p < 0.001). Age at surgery and age at seizure onset were associated with seizure freedom for mixed pathologies and surgery locations and TL surgery., Conclusion: Epilepsy surgery was more effective than medical therapy to control seizures. Understanding seizure outcomes of different surgery locations, pathologies, nonlesional epilepsy, and incomplete resection will assist with presurgical counseling., (© 2020 American Academy of Neurology.)

Purpose: To review our experience with the Etomidate speech test (EST) for lateralizing language in children undergoing epilepsy surgery evaluation METHODS: This retrospective study included children (<18 years) with drug refractory focal epilepsy undergoing EST for bilateral or poorly reliable language representation on functional MRI. Data for consecutive children who underwent EST between January 2013 to June 2017 were reviewed., Results: Twenty-one children (mean age at EST, 13.1 ± 4.4 years) were studied, with 19-right hemispheric and 20 left hemispheric injections. Six patients had neurological co-morbidities. Duration of ipsilateral EEG slowing was sufficient for speech testing in all children with a single bolus of Etomidate per carotid artery. Language was lateralized to one hemisphere in 17 (80.9%) and bilateral in two cases. EST was unsuccessful in two patients because of diffuse EEG slowing. Contralateral transient frontal EEG slowing was seen in 14 (73.7%) cases. EST was well tolerated in all the patients., Conclusions: The EST was found to be successful and safe in lateralizing language in most of our drug refractory pediatric epilepsy cohort., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Competing Interests: None.

Multiple genes/variants have been implicated in various epileptic conditions. However, there is little general guidance available on the circumstances in which genetic testing is indicated and test selection in order to guide optimal test appropriateness and benefit. This is an account of the development of guidelines for genetic testing in epilepsy, which have been developed in Ontario, Canada. The Genetic Testing Advisory Committee was established in Ontario to review the clinical utility and validity of genetic tests and the provision of genetic testing in Ontario. As part of their mandate, the committee also developed recommendations and guidelines for genetic testing in epilepsy. The recommendations include mandatory prerequisites for an epileptology/geneticist/clinical biochemical geneticist consultation, prerequisite diagnostic procedures, circumstances in which genetic testing is indicated and not indicated and guidance for selection of genetic tests, including their general limitations and considerations. These guidelines represent a step toward the development of evidence-based gene panels for epilepsy in Ontario, the repatriation of genetic testing for epilepsy into Ontario molecular genetic laboratories and public funding of genetic tests for epilepsy in Ontario.

Objectives: The objective of this study was to review our experience with intra-operative "train of five" stimulation using subdural grid for motor mapping in children undergoing epilepsy surgery evaluation., Methods: Twenty consecutive children below 18-years of age with drug-refractory epilepsy who underwent invasive-EEG monitoring using subdural-grid placement and intra-operative motor mapping using direct cortical stimulation by sub-dural grid electrodes (IODCS-SDG) at our institution between January-2016 and June-2017 were reviewed. Stimulation was delivered through the subdural-grid electrodes using a train-of-five pulses and muscle responses were recorded by motor-evoked-potentials (MEPs). Intra-operative direct cortical stimulation delivered through a ball-tipped probe (IODCS-probe) and extra-operative motor-mapping (EODCS-SDG) were also performed., Results: IODCS-SDG was completed in 20 patients and subsequent EODCS-SDG was done in 17/20 patients. MEP responses were more commonly obtained in the deltoid (19/20), extensor-digitorum-communis (20/20) and first-dorsal-interosseus (19/20). The median thresholds varied between 40 V and 60 V for the six muscle groups. The respective IODCS-probe thresholds tended to be similar. No stimulation-provoked seizures or anaesthesia-related complications were noted during IODCS-SDG. EODCS-SDG could not be completed in 4/17 children and mapping data obtained was frequently inadequate. Nine patients demonstrated 100% concordance between IODCS-SDG and EODCS-SDG for the common mapped body regions. Stimulation-provoked seizures during EODCS-SDG were seen in 6/17 (35.3%) and after-discharges in 7/17 (41.2%) children., Conclusions: IODCS-SDG could be performed safely in children with drug refractory epilepsy undergoing invasive EEG monitoring., Significance: IODCS-SDG may be a useful adjunct to EODCS-SDG in motor mapping for children., (Copyright © 2018 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Objective: To study the magnitude and pattern of injuries in children with epilepsy., Methods: This prospective cohort study enrolled children with epilepsy (CWE) aged 2-16 years on treatment with anti-epileptics for a minimum duration of one-month and compared them with their own siblings (controls). A semi-structured questionnaire was used to enquire about epilepsy and type and frequency of injuries sustained at monthly follow-up visits. Participants were followed up for 12-months for occurrence of injuries., Results: 208 cases and 212 controls were analyzed. 21 cases (10.1%) and 10 controls (4.7%) had sustained injuries (P=0.03) (RR 2.1; 95% CI, 1.0 - 4.4). Seizure-related injuries were present in 4.3% of cases., Conclusion: Children with epilepsy are at an increased risk of injuries and hence need supervision.

Background: Valproate is a commonly used anticonvulsant drug. Uridine 5΄-diphospho (UDP)-glucuronosyltransferase (UGT) contributes to around 50% of valproate metabolism and its polymorphisms may be important for explaining the considerable variation in valproate levels in patients with epilepsy., Aim: This study was aimed to analyze the genetic polymorphisms of UGT1A6 in Indian children with epilepsy and their potential influence on the pharmacokinetics of valproate., Setting and Design: This cross-sectional study was carried out in the Department of Pediatrics, All India Institutes of Medical Sciences (AIIMS), New Delhi, between March 2011 and July 2012., Materials and Methods: Children aged 3-12 years diagnosed with epilepsy on valproate monotherapy for at least 1 month were enrolled. They underwent a detailed clinical examination. The UGT1A6 polymorphisms were detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Random samples were checked by genetic sequencing. The steady-state plasma concentrations of valproate were measured by High Performance Liquid Chromatography (HPLC) and associated with UGT1A6 polymorphisms., Results: A total of 80 children were studied. The prevalence of UGT1A6 T19G was as follows: TT (45%), TG (38.8%), and GG (16.3%); that of UGT1A6 A541G was: AA (48.8%), AG (38.8%), and GG (12.5%); and that of UGT1A6 A552C was: AA (43.8%), AC (40%), and CC (16.3%). The association between valproate doses or standardized serum valproate concentration and the various UGT1A6 genotypes could not be studied reliably in this small study population., Conclusions: The frequencies of UGT1A6 geneotypes and alleles were reported in the study population.

Byline: Robyn. Whitney, Cristina. Go, Ahmed. Abushama, Puneet. Jain CNKSR2 variants have been associated with X linked intellectual disability and epilepsy including developmental and epileptic encephalopathy with spike wave activation [...]

Byline: Juhi. Gupta, Suvasini. Sharma, Sharmila. Mukherjee, Puneet. Jain, Satinder. Aneja Objectives: To assess the neurodevelopmental outcome of West syndrome (WS) in Indian children, who differ in their clinical profile [...]

This scientific commentary refers to 'Randomized placebo-controlled crossover trial of memantine in children with epileptic encephalopathy' by Schiller I et al. i (https://doi.org/10.1093/brain/awac380). Nine patients (33%) in the memantine group achieved the primary outcome compared to only two patients (7%) in the placebo group ( I P i < 0.04).[4] Of the nine responders, six had >50% seizure reduction. Trend reductions in autism probability were seen, but with both memantine and placebo, while measures of functional impairment trended lower with memantine but not placebo. [Extracted from the article]

Despite decades of clinical usage, selection of patients with drug resistant epilepsy who are most likely to benefit from vagus nerve stimulation (VNS) remains a challenge. The mechanism of action of VNS is dependent upon afferent brainstem circuitry, which comprises a critical component of the Vagus Afferent Network (VagAN). To evaluate the association between brainstem afferent circuitry and seizure response, we retrospectively collected intraoperative data from sub-cortical recordings of somatosensory evoked potentials (SSEP) in 7 children with focal drug resistant epilepsy who had failed epilepsy surgery and subsequently underwent VNS. Using multivariate linear regression, we demonstrate a robust negative association between SSEP amplitude (p < 0.01), and seizure reduction. There was no association between SSEP latency and seizure outcomes. Our findings provide novel insights into the mechanism of VNS and inform our understanding of the importance of brainstem afferent circuitry within the VagAN for seizure responsiveness following VNS. [ABSTRACT FROM AUTHOR]

Children and adults with genetic generalized epilepsy may have focal clinical seizure symptoms as well as electroencephalographic (EEG) findings. This may pose a diagnostic challenge to clinicians, especially when concomitant focal neuroimaging findings exist and the epilepsy is medically refractory. We sought to highlight the challenges that clinicians may face through the description of 2 children with suspected genetic generalized epilepsy who had both focal seizure symptoms and EEG/neuroimaging findings and underwent invasive EEG monitoring. Ultimately, invasive monitoring failed to demonstrate a focal origin for the seizures in both cases, and instead confirmed the presence of genetic generalized epilepsy. We demonstrate that ≥3-Hz generalized monomorphic spike and waves are less likely to represent secondary bilateral synchrony, that focal neuroimaging findings may not always be causal and that repeated hyperventilation is an essential activation procedure for genetic generalized epilepsy. [ABSTRACT FROM AUTHOR]

Objective: Through international collaboration, we evaluated the phenotypic aspects of a multiethnic cohort of KCNT1‐related epilepsy and explored genotype‐phenotype correlations associated with frequently encountered variants. Methods: A cross‐sectional analysis of children harboring pathogenic or likely pathogenic KCNT1 variants was completed. Children with one of the two more common recurrent KCNT1 variants were compared with the rest of the cohort for the presence of particular characteristics. Results: Twenty‐seven children (15 males, mean age = 40.8 months) were included. Seizure onset ranged from 1 day to 6 months, and half (48.1%) exhibited developmental plateauing upon onset. Two‐thirds had epilepsy of infancy with migrating focal seizures (EIMFS), and focal tonic seizures were common (48.1%). The most frequent recurrent KCNT1 variants were c.2800G>A; p.Ala934Thr (n = 5) and c.862G>A; p.Gly288Ser (n = 4). De novo variants were found in 96% of tested parents (23/24). Sixty percent had abnormal magnetic resonance imaging (MRI) findings. Delayed myelination, thin corpus callosum, and brain atrophy were the most common. One child had gray‐white matter interface indistinctness, suggesting a malformation of cortical development. Several antiepileptic drugs (mean = 7.4/patient) were tried, with no consistent response to any one agent. Eleven tried quinidine; 45% had marked (>50% seizure reduction) or some improvement (25%‐50% seizure reduction). Seven used cannabidiol; 71% experienced marked or some improvement. Fourteen tried diet therapies; 57% had marked or some improvement. When comparing the recurrent variants to the rest of the cohort with respect to developmental trajectory, presence of EIMFS, >500 seizures/mo, abnormal MRI, and treatment response, there were no statistically significant differences. Four patients died (15%), none of sudden unexpected death in epilepsy. Significance: Our cohort reinforces common aspects of this highly pleiotropic entity. EIMFS manifesting with refractory tonic seizures was the most common. Cannabidiol, diet therapy, and quinidine seem to offer the best chances of seizure reduction, although evidence‐based practice is still unavailable. [ABSTRACT FROM AUTHOR]

Purpose: In adults, the Status Epilepticus Severity Score (STESS), a clinical score, has been shown to be a good predictor of outcome and treatment response. We devised a pediatric modification of this score: the Status Epilepticus in Pediatric patients Severity Score (STEPSS) and evaluated it in children with status epilepticus.Methods: In this prospective study, children aged 1 month to 18 years presenting with seizure duration ≥ 5 min or actively convulsing to the emergency room were enrolled. STEPSS score was calculated at the time of admission. Outcomes included death, the Pediatric Overall Performance Category (POPC) at discharge and treatment response. The diagnostic utility of the STEPSS score to predict unfavourable outcome was evaluated.Results: One-hundred and forty children (mean age 5.8 years) were enrolled. Seven children died and overall 15 children had an unfavourable outcome. The predictive accuracy of STEPSS at a cut-off of >3: for unfavourable outcome (POPC score ≥ 3) - sensitivity (0.93 [95% CI: 68, 99.8]), specificity (0.81 [95% CI: 0.73, 0.87]), PPV (0.37 [95% CI: 0.22, 0.54]), NPV (0.99 [95% CI: 0.95-1.0]), positive likelihood ratio (4.86), F1 score (0.530); for death - sensitivity (0.86 [95% CI: 0.42, 0.99]), specificity (0.76 [95% CI: 0.68-0.83]), PPV (0.16 [95% CI: 0.06, 0.31]), NPV (0.99 [95% CI: 0.95, 1.0]), F1 score (0.270).Conclusions: The STEPSS, a simple bedside clinical score, was found to be useful to predict the outcome and treatment response in children with status epilepticus. [ABSTRACT FROM AUTHOR]

Background: The safety of hemispherectomy between staged cardiac procedures is unknown and not previously reported. Method: Retrospective review of a case with drug-resistant epilepsy due to stroke following bidirectional cavopulmonary connection (BDCPC). Results: This report describes the first case of a successful pediatric peri-insular functional hemispherectomy in the setting of a BDCPC. A discussion of the complex preoperative planning from both a cardiac and neurological perspective is presented. Considerations regarding hemispherectomy and its effects on the cardiac physiology, and perioperative considerations are emphasized in clinical decision making. Conclusions: A multidisciplinary approach was critical in this child which led to a successful outcome. [ABSTRACT FROM AUTHOR]

Summary: Objective: Polymicrogyria (PMG) is a common malformation of cortical development. Many patients with PMG will have medically refractory epilepsy but the role of epilepsy surgery is unclear. The objective of this study was to assess the efficacy of surgical resection/disconnection in achieving seizure control in pediatric patients with PMG. Methods: A retrospective review of children undergoing epilepsy surgery for PMG between 2002 and 2017 at The Hospital for Sick Children in Toronto, Canada, was performed. Results: A total of 12 children aged 6 months to 17.8 years (median 8.8 years) underwent resective surgery (7 children) or functional hemispherectomy (5 children). Gross total resection or complete disconnection of PMG was carried out in 7 of 12 children. Follow‐up duration was between 1 and 9 years (median 2.1 years). Nine children remained seizure‐free at last follow‐up. Complete resection or disconnection of PMG led to seizure freedom in 6 of 7 patients (86%), whereas subtotal resection produced seizure freedom in 3 of 5 patients (60%). Significance: We present one of the largest surgical series of pediatric PMG patients. Seizure outcomes were best with complete resection/disconnection of PMG. However, tailored resections based on electroclinical and neuroradiologic data can produce good outcomes and remain an appropriate strategy for patients with extensive PMG. [ABSTRACT FROM AUTHOR]

Background: West syndrome is a catastrophic epilepsy syndrome characterized by infantile spasms, hypsarrhythmia, and developmental arrest or regression.Aim: The aim of this study was to explore the role of pyridoxine in the management of infantile spasms.Setting and Design: This was a pilot, randomized, open-label trial conducted at a tertiary level hospital from November 2012 to March 2014.Materials and Methods: Children aged 3 months to 3 years presenting with infantile spasms in clusters (at least 1 cluster/day) with hypsarrhythmia or its variants on electroencephalogram (EEG) were enrolled. The study participants were randomized to receive either oral prednisolone (4 mg/kg/day) alone or 30 mg/kg/day of pyridoxine with oral prednisolone. The primary outcome measure was the proportion of children who achieved spasm freedom for 48 h on day-14 after treatment initiation, as per parental reports, in both the groups. The adverse effects were also monitored. The study was registered with clinicaltrials.gov (ClinicalTrials.gov Identifier: NCT01828437).Results: Sixty-two children were randomized into the two groups with comparable baseline characteristics. The proportion of children with spasm cessation on day-14 was similar in the two groups (39 vs. 37%, P = 0.98). The adverse effects were comparable in both the groups.Conclusions: The combination of pyridoxine with oral prednisolone was not found to be a beneficial therapy as compared to prednisolone alone in the treatment of infantile spasms in this pilot study. However, high dose pyridoxine may be safe in children with infantile spasms. [ABSTRACT FROM AUTHOR]

Background: The modified Atkins diet (MAD) has been used predominantly in older children, adolescents, and adults. There is a paucity of data on the use of the MAD in refractory epilepsy in young children. Objectives: This study was planned to evaluate the efficacy and tolerability of the MAD in refractory epilepsy in young children. Methods: This study recruited children aged 9 months to 3 years with refractory seizures. Children received MAD for 6‑month with the on‑going anticonvulsant medications being continued unchanged. Reduction in seizure frequency was the primary outcome measure. Adverse effects were also studied. Results: Thirty‑one children with daily seizures were studied with a median age of 18‑month (range 9–30 months). West syndrome was the most common epilepsy syndrome (26, 86.6%). Twenty‑one children remained on diet at 3 months and 13 at 6 months. The children who achieved >50% seizure reduction were 17 (54.8%) at 3 months and 9 (29%) at 6 months. Refusal to eat was a significant problem seen in eight children. Three children discontinued the diet due to adverse effects. Conclusion: The MAD was found to be feasible, effective, and well‑tolerated. [ABSTRACT FROM AUTHOR]

Objectives: Triclofos may be a better sedative in view of better palatability and less gastric irritation as compared to chloral hydrate. This study aimed to assess the efficacy of triclofos (a commonly used sedative in India) as a sedative for sleep electroencephalogram (EEG) study in children. Methods: This prospective observational study was carried out in a tertiary care pediatric center. Consecutive children aged 6 months to 5 years referred for sleep EEG evaluation were recruited. Their clinical details were noted in a proforma after an informed consent. After a trial for natural sleep, oral triclofos was administered. Sleep parameters and adverse effects were noted. Results: One‑hundred and sixty children were then enrolled. EEG was successfully recorded in 149 (93.1%) children. Median latency of sleep onset was 30 min and median duration of sleep was 90 min. The adverse effects in the following 24 h were mild and included dizziness, irritability, and vomiting. Conclusions: Oral triclofos was found to be an effective sedative for EEG in children with minimal adverse effects. [ABSTRACT FROM AUTHOR]

Objectives: The prevalence of obesity is rapidly increasing among Indian children, who, in general, are more prone to develop metabolic complications at an early age. Valproate and phenytoin are commonly used antiepileptic drugs in children. This study aimed to assess the parameters of the metabolic syndrome in Indian children with epilepsy on valproate or phenytoin monotherapy. Methods: This cross‑sectional study recruited children from the Pediatric Epilepsy Clinic, Department of Pediatrics, Kalawati Saran Children Hospital, New Delhi from March 2012 to September 2012. All consecutive children diagnosed with epilepsy as per International League Against Epilepsy definition aged 3–18 years on valproate or phenytoin monotherapy for at least 6 months were enrolled at a tertiary care children’s hospital in Northern India. After clinical and anthropometric evaluation (including body mass index [BMI] and waist circumference), the blood samples were analyzed for fasting serum glucose, total cholesterol, high‑density lipoprotein‑cholesterol, and serum triglyceride. Results: Children with BMI >95th centile and waist circumference >90th centile were not significantly different among children on valproate and phenytoin monotherapy. Children on valproate had significantly higher mean serum triglyceride (96.9 mg/dL vs. 77.6 mg/dL; P < 0.001) and total cholesterol (148.3 mg/dL vs. 132.8 mg/dL; P = 0.002) levels as compared to children on phenytoin monotherapy. Conclusions: The lipid abnormalities may be observed in children on valproate or phenytoin therapy and may warrant periodic screening. [ABSTRACT FROM AUTHOR]

Neurocysticercosis, parasitic infestation of the central nervous system by the Taenia solium larvae, is a major public health problem, primarily in the developing countries. Seizures are the primary clinical manifestation which could be acute (secondary to active lesions) or remote symptomatic (due to calcified lesions). Cysticidal therapy is the standard of care for solitary parenchymal active neurocysticerci. However treatment related side effects and tendency to spontaneous resolution raises concern from time to time whether cysticidal therapy is actually required. This is a retrospective case record analysis of two groups of patients with solitary parenchymal neurocysticerci (group A; 171 patients between 2000 and 2004 who did not receive cysticidal therapy, group B; 512 patients between 2008 and 2013 who received cysticidal therapy). Group B had significantly more radiological resolution of lesions whereas group A reported significantly more seizure recurrences on antiepileptics. There was no significant difference in occurrence of calcification in the two groups. Overall patients with calcified lesions had significantly more breakthrough seizures. Well designed prospective studies should be planned in future to understand the mechanism underlying the epileptogenicity of calcified lesions and how they are linked to host and environment factors. [ABSTRACT FROM AUTHOR]

The ketogenic diet is a high-fat, low-carbohydrate, and restricted protein diet that is useful in patients with refractory epilepsy. The efficacy of the ketogenic diet is better than most of the new antiepileptic drugs. Other modifications of the diet are also beneficial, such as the modified Atkins diet and the low glycemic index treatment. There is a lack of awareness of the ketogenic diet as a treatment modality for epilepsy amongst pediatricians and neurologists. In this review, the use of the ketogenic diet and other dietary treatments in refractory epilepsy is discussed. The Indian experience with the use of these dietary treatments is also briefly reviewed. [ABSTRACT FROM AUTHOR]

The modified Atkins diet is a less restrictive variation of the ketogenic diet. This diet is started on an outpatient basis without a fast, allows unlimited protein and fat, and does not restrict calories or fluids. Recent studies have shown good efficacy and tolerability of this diet in refractory epilepsy. In this review, we discuss the use of the modified Atkins diet in refractory epilepsy. [ABSTRACT FROM AUTHOR]

The article presents a case study of a three an half‑year‑old girl was taken to hospital due to daily seizures problem. It mentions the presence of cognitive decline, behavioural abnormalities, or abnormal body movements in patient. It also mentions that absence of seizures may be associated with myoclonic jerks and limited area of the face or neck.

Our current knowledge of genetically determined forms of epilepsy has shortened the diagnostic pathway usually experienced by the families of infants diagnosed with early-onset developmental and epileptic encephalopathies. Genetic causes can be found in up to 80% of infants presenting with early-onset developmental and epileptic encephalopathies, often in the context of an uneventful perinatal history and with no clear underlying brain abnormalities. Although current disease-specific therapies remain limited and patient outcomes are often guarded, a genetic diagnosis may lead to early therapeutic intervention using new and/or repurposed therapies. In this review, an overview of epilepsy genetics, the indications for genetic testing in infants, the advantages and limitations of each test, and the challenges and ethical implications of genetic testing are discussed. In addition, the following causative genes associated with early-onset developmental and epileptic encephalopathies are discussed in detail: KCNT1, KCNQ2, KCNA2, SCN2A, SCN8A, STXBP1, CDKL5, PIGA, SPTAN1, and GNAO1. The epilepsy phenotypes, comorbidities, electroencephalgraphic findings, neuroimaging findings, and potential targeted therapies for each gene are reviewed. [ABSTRACT FROM AUTHOR]

Thalamic neuromodulation has emerged as a treatment option for drug-resistant epilepsy (DRE) with widespread and/or undefined epileptogenic networks. While deep brain stimulation (DBS) and responsive neurostimulation (RNS) depth electrodes offer means for electrical stimulation of the thalamus in adult patients with DRE, the application of thalamic neuromodulation in pediatric epilepsy remains limited. To address this gap, the Neuromodulation Expert Collaborative was established within the Pediatric Epilepsy Research Consortium (PERC) Epilepsy Surgery Special Interest Group. In this expert review, existing evidence and recommendations for thalamic neuromodulation modalities using DBS and RNS are summarized, with a focus on the anterior (ANT), centromedian(CMN), and pulvinar nuclei of the thalamus. To-date, only DBS of the ANT is FDA approved for treatment of DRE in adult patients based on the results of the pivotal SANTE (Stimulation of the Anterior Nucleus of Thalamus for Epilepsy) study. Evidence for other thalamic neurmodulation indications and targets is less abundant. Despite the lack of evidence, positive responses to thalamic stimulation in adults with DRE have led to its off-label use in pediatric patients. Although caution is warranted due to differences between pediatric and adult epilepsy, the efficacy and safety of pediatric neuromodulation appear comparable to that in adults. Indeed, CMN stimulation is increasingly accepted for generalized and diffuse onset epilepsies, with recent completion of one randomized trial. There is also growing interest in using pulvinar stimulation for temporal plus and posterior quadrant epilepsies with one ongoing clinical trial in Europe. The future of thalamic neuromodulation holds promise for revolutionizing the treatment landscape of childhood epilepsy. Ongoing research, technological advancements, and collaborative efforts are poised to refine and improve thalamic neuromodulation strategies, ultimately enhancing the quality of life for children with DRE. • Thalamic neuromodulation represents an innovative treatment approach for drug-resistant epilepsy (DRE) • Anterior thalamic DBS is the sole FDA-approved treatment for adult DRE. • Despite limited evidence, pediatric epileptic care trends towards off-label thalamic neuromodulation use. • Neurologists and neurosurgeons from the Pediatric Epilepsy Research Consortium summarized literature on thalamic neuromodulation. • The review outlines future priorities to refine thalamic neuromodulation strategies. [ABSTRACT FROM AUTHOR]