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Treatment of epileptic encephalopathies can be very challenging as most anticonvulsant drugs fail to achieve good seizure control. Steroids are disease modifying as well as anticonvulsant in these conditions. Though steroids are accepted as the first-line treatment for infantile spasms, there are many unanswered questions with regard to the preparation, dose and duration of treatment. In this review a re-exploration of the literature is attempted. Putative mechanism of action of steroids in infantile spasms is also discussed. As steroids are being increasingly used in other epileptic encephalopathies and Rasmussen′s encephalitis, a brief discussion on the role of steroids in these conditions is attempted. The review ends with the discussion on newer neuroactive steroids in the management of epilepsy.

Background: The ketogenic diet is a dietary therapy with anti-seizure effects. The efficacy of the diet is variable, with initial animal studies suggesting the intestinal microbiome may have a modulating effect. Initial research on the role of the human microbiome in pediatric epilepsy management has been inconclusive., Methods: In this single-center prospective cohort study, stool samples were collected from 4 patients with drug resistant epilepsy on the ketogenic diet and 9 with drug resistant epilepsy as controls. The samples were analyzed by 16S RNA sequencing., Results: A trend towards increased alpha diversity was noted among patients on the ketogenic diet compared to the control group. Patients on the ketogenic diet also trended towards a higher relative abundance of Bacteroidaceae, Ruminococcaceae , and Prevotellaceae species. A subset of the control group had a high relative abundance of Bifidobacterium , which may make them a candidate for a trial of the ketogenic diet as a therapeutic option., Conclusion: These findings add to the growing field of research of how the ketogenic diet modulates the intestinal microbiome in pediatric epilepsy patients. Future emphasis on multi-centre trials, consistent stool collection practices and the establishment of standardized stool biobanking protocols are needed further to validate these novel findings in a pediatric population., Competing Interests: 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., (© 2025 The Authors. Published by Elsevier Ltd.)

Sudden deaths in infants and children represent a profound and tragic event that continues to challenge researchers despite extensive investigation over several decades. The predominant phenotype, sudden infant death syndrome (SIDS), has evolved into the broader category of sudden unexpected infant death (SUID). In older children, a less understood phenomenon known as sudden unexplained death in childhood (SUDC) has garnered attention. Additionally, sudden unexpected death in epilepsy (SUDEP) constitutes a rare but recognized complication of epilepsy. Recent investigations indicate overlapping clinical, neuropathological, and genetic characteristics among SUID, SUDC, and SUDEP. Common features include death occurring during sleep, discovery in the prone position, hippocampal abnormalities, and genetic variations associated with epilepsy or cardiac arrhythmias. Notably, video recordings in certain examples of SUDC have captured 'convulsive' episodes preceding death in children without prior seizure history, suggesting that seizures may contribute more significantly to sudden paediatric deaths than previously presumed. This review explores these shared elements, underscoring their importance in formulating possible preventative measures against these devastating conditions., (© 2024 The Author(s). Developmental Medicine & Child Neurology published by John Wiley & Sons Ltd on behalf of Mac Keith Press.)

Introduction: This study investigated low-density scalp electrical source imaging of the ictal onset zone and interictal spike ripple high-frequency oscillation networks using source coherence maps in the pediatric epilepsy surgical workup. Intracranial monitoring, the gold standard for determining epileptogenic zones, has limited spatial sampling. Source coherence analysis presents a promising new non-invasive technique., Methods: This was a retrospective review of 12 patients who underwent focal resections. Source coherence maps were generated using standardized low-resolution electromagnetic tomography and concordance to resection margins was assessed, noting outcomes at 3 years post-surgery., Results: Ictal source coherence maps were performed in 7/12 patients. Six of seven included the surgical resection. Five of seven cases were seizure free post-resection. Interictal spike ripple electrical source imaging and interictal spike ripple high-frequency oscillation networks using source coherence maps were performed for three cases, with two of three included in the resection and all three were seizure free., Discussion: These findings may provide proof of principle supporting low-density scalp electrical source imaging of the ictal onset zone and spike ripple network using source coherence maps. This promising method is complementary to ictal and interictal electrical source imaging in the pediatric epilepsy surgical workup, guiding electrode placement for intracranial monitoring to identify the epileptogenic zone., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Sadeghzadeh, Freibauer, RamachandranNair, Whitney, Al Nassar, Jain, Donner, Ochi and Jones.)

Objective: We systematically reviewed the existing literature on the efficacy of corpus callosotomy (CC) in children and adults with refractory epileptic spasms (ES) and analyzed clinical determinants of seizure outcomes., Methods: The Preferred Report Items for Systematic Reviews and Meta-Analysis Guidelines (PRISMA) were followed. We systematically searched MEDLINE, EMBASE and Cochrane databases up to December 2023 for original research articles on using CC to treat refractory ES. The primary outcome measure was the proportion of study participants who achieved seizure freedom following initial CC at the last follow-up. Meta-regression using mixed-effects models was performed to obtain clinical determinants of seizure outcomes., Results: A total of 12 studies were included (253 individuals). Initial complete total CC was most common (n = 218/253, 86%), followed by anterior CC (n = 29/253, 12%) and other forms of CC (i.e., anterior to posterior, posterior, staged total) (n = 6/253, 2%). The pooled proportion of patients achieving spasm freedom following CC was 0.31 (95% CI: 0.22, 0.42) (mean follow-up 47 months). Meta-regression showed that structural etiology and mean age at the time of CC were significant moderators of the pooled effect. For every 1% increase in the proportion of structural etiology, the proportion of spasm-free outcome was found to reduce by 0.45 (95% CI: -0.86, -0.03, p < 0.0001). In addition, increasing the mean age by 1 month led to a reduction in the proportion of spasms-free patients by 0.003 (95% CI: -0.005, -0.0006, p = 0.01). Sixty-two individuals (24%) from seven studies underwent further surgery for residual ES; 34 became spasm free (55%)., Conclusions: Corpus callosotomy may be an effective treatment option in selected individuals with refractory epileptic spasms. Structural aetiologies and increased age at the time of corpus callosotomy are important clinical determinants. In some cases, CC may lead to further epilepsy surgery., Competing Interests: Declaration of competing interest None of the authors has any conflict of interest to declare., (Copyright © 2024 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

With the advent of high-throughput sequencing and computational methods, genetic testing has become an integral part of contemporary clinical practice, particularly in epilepsy. The toolbox for genetic testing has evolved from conventional chromosomal microarray and epilepsy gene panels to state-of-the-art sequencing techniques in the modern genomic era. Beyond its potential for therapeutic benefits through precision medicine, optimizing the choice of antiseizure medications, or exploring nonpharmacological therapeutic modalities, genetic testing carries substantial diagnostic, prognostic, and personal implications. Developmental and epileptic encephalopathies, the coexistence of neurodevelopmental comorbidities, early age of epilepsy onset, unexplained drug-refractory epilepsy, and positive family history have demonstrated the highest likelihood of yielding positive genetic test results. Given the diagnostic efficacy across different testing modalities, reducing costs of next-generation sequencing tests, and genetic diversity of epilepsies, exome sequencing or genome sequencing, where feasible and available, have been recommended as the first-tier test. Comprehensive clinical phenotyping at the outset, corroborative evidence from radiology and electrophysiology-based investigations, reverse phenotyping, and periodic reanalysis are some of the valuable strategies when faced with inconclusive test results. In this narrative review, the authors aim to simplify the approach to genetic testing in epilepsy by guiding on the selection of appropriate testing tools in the indicated clinical scenarios, addressing crucial aspects during pre- and post-test counseling sessions, adeptly navigating the traps posed by uncertain or negative genetic variants, and paving the way forward to the emerging testing modalities beyond DNA sequencing., 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 © 2024 Elsevier Inc. All rights reserved.)

Objective: Electroencephalography (EEG) is an essential tool for the diagnosis and management of epilepsy. There is a gap in EEG education for residents in Canadian neurology programs as EEG is only listed in the training requirements as a procedural skill. There is currently no standardized EEG curriculum among Canadian epilepsy fellowship programs., Methods: We conducted two iterations of a structured virtual EEG course from June to October 2021, and from March to June 2022. Trainees were recruited via Canadian neurology residency and epilepsy fellowship programs and were required to join the Canadian League Against Epilepsy (CLAE) as junior members. We obtained trainee demographic information before and after each course as well as analytical data on the video recordings posted on the CLAE website., Results: A total of 77 trainees registered for the two courses; majority of trainees were adult neurology residents (34%) and adult epilepsy fellows (32%). Prior theoretical EEG teaching was reported as limited by more than half (53%) of participants. The average number of unique viewers per recorded video in 2021 was 29.7 interquartile range (16-35.5), while in 2022, the average was 22.5, interquartile range (16-28). Post-course questionnaire data revealed that 82% of participants strongly agreed that the course enhanced their knowledge. All participants were either likely (27%) or very likely (73%) to recommend the course to their peers., Significance: National virtual EEG education is both feasible and accessible; therefore, this is a promising modality of teaching to meet the significant demand for high-quality EEG education among neurology trainees., (© 2024 The Authors. Epileptic Disorders published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

There are numerous challenges pertaining to epilepsy care across Ontario, including Epilepsy Monitoring Unit (EMU) bed pressures, surgical access and community supports. We sampled the current clinical, community and operational state of Ontario epilepsy centres and community epilepsy agencies post COVID-19 pandemic. A 44-item survey was distributed to all 11 district and regional adult and paediatric Ontario epilepsy centres. Qualitative responses were collected from community epilepsy agencies. Results revealed ongoing gaps in epilepsy care across Ontario, with EMU bed pressures and labour shortages being limiting factors. A clinical network advising the Ontario Ministry of Health will improve access to epilepsy care.

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.

The 2017 classification of the epilepsies of International League Against Epilepsy (ILAE) defined three diagnostic levels, including seizure type, epilepsy type and epilepsy syndrome. Epilepsy syndromes have been recognized as distinct electroclinical entities well before the first ILAE classification of Epilepsies and Epilepsy Syndromes in 1985. A formally accepted classification of epilepsy syndromes was not available, and hence, the 2017-2021 Nosology and Definitions Task Force of ILAE was formulated. The ILAE position papers were published in 2022, which classified epilepsy syndromes into (1) syndromes with onset in neonates and infants (up to 2 years of age), (2) syndromes with onset in childhood, (3) syndromes that may begin at a variable age and (4) idiopathic generalized epilepsies. This classification recognized the concept of etiology-specific syndrome. These papers have addressed the specific clinical and laboratory features of epilepsy syndromes and specify the rationale for any significant changes in terminology or definition. This paper will review some pertinent changes and essential points relevant to pediatricians.

Background: The ketogenic diet may be difficult for some patients and their families to implement and can impact physical, emotional, and social well-being., Methods: Through principles of fundamental qualitative description, we completed an exploratory study on parents' experiences and expectations on the use and efficacy of the ketogenic diet for children with medically refractory epilepsy., Results: Seventeen parents (10 mothers and 7 fathers) of 12 children with epilepsy participated. At the time of the interview, parents had experienced an average of 25 months of ketogenic diet treatment for their child (range 2 months to 98 months). Half of the caregivers learned about the ketogenic diet from their neurologist, whereas the remainder had heard about it from another source (ie, the internet). Most caregivers' (n = 13) diet expectations were related to seizure control. However, child development (n = 5) and quality of life (n = 5) were also crucial to some. Physical impacts of the diet were most commonly gastrointestinal for children (n = 9). Social and emotional effects were noted in some older children with typical development. Most caregivers described negative impacts on finances (n = 15), relationships (n = 14), and emotional well-being (ie, stress) (n = 12). Caregivers benefited from the ketogenic diet team's regular communication, close follow-up, and family-centered care., Conclusions: Despite the impacts that the ketogenic diet may have on caregivers' emotional and social well-being, the positive impacts of the diet were felt to outweigh any perceived risks. Effects (both positive and negative) on quality of life and child development (eg, social, emotional, cognitive) are essential for caregivers and require additional investigation., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Rajesh RamachandranNair received a research grant from the Ontario Brain Institute and served as a paid consultant to UCB Canada Inc and Sunovion Pharmaceuticals Canada Inc. Eric Kossoff has served as a paid consultant for Simply Good Foods Inc, Nutricia, Inc, Bloom Science, Cerecin, and LivaNova, and has received royalties from Springer Medical Publishing, UpToDate, and the Oxford University Press. The remaining authors have no conflicts of interest.

Objective: This longitudinal cohort study aimed to identify trajectories of parent well-being over the first 2 years after their child's evaluation for candidacy for epilepsy surgery, and to identify the baseline clinical and demographic characteristics associated with these trajectories. Parent well-being was based on parent depressive and anxiety symptoms and family resources (i.e., family mastery and social support)., Methods: Parents of 259 children with drug-resistant epilepsy (105 of whom eventually had surgery) were recruited from eight epilepsy centers across Canada at the time of their evaluation for epilepsy surgery candidacy. Participants were assessed at baseline and 6-month, 1-year, and 2-year follow-up. The trajectories of parents' depressive symptoms, anxiety symptoms, and family resources were jointly estimated using multigroup latent class growth models., Results: The analyses identified three trajectories: an optimal-stable group with no/minimal depressive or anxiety symptoms, and high family resources that remained stable over time; a mild-decreasing-plateau group with mild depressive and anxiety symptoms that decreased over time then plateaued, and intermediate family resources that remained stable; and a moderate-decreasing group with moderate depressive and anxiety symptoms that decreased slightly, and low family resources that remained stable over time. Parents of children with higher health-related quality of life, fathers, and parents who had higher household income were more likely to have better trajectories of well-being. Treatment type was not associated with the trajectory groups, but parents whose children were seizure-free at the time of the last follow-up were more likely to have better trajectories (optimal-stable or mild-decreasing-plateau trajectories)., Significance: This study documented distinct trajectories of parent well-being, from the time of the child's evaluation for epilepsy surgery. Parents who present with anxiety and depressive symptoms and low family resources do not do well over time. They should be identified and offered supportive services early in their child's epilepsy treatment history., (© 2023 International League Against Epilepsy.)

Background: This study aimed to determine the parent-child agreement of the Hague Restrictions in Childhood Epilepsy Scale (HARCES) and identify the clinical factors associated with parent-child disagreement and the restrictions., Methods: Data come from a clinical sample of 90 children ages 9-17 (mean age = 12.9, SD = 6.9, 54% male) attending a pediatric neurology clinic. Parents completed the HARCES, and children completed a modified child-friendly scale (HARCES-M). The parent-child agreement was assessed using intraclass correlation coefficients (ICC) and paired t-tests to compare parent and child responses. Logistic regression examined clinical factors associated with disagreement > 0.5 standard deviation. Associations between clinical factors and restriction scores were examined using linear regression., Results: Parent-child agreement on the HARCES was poor (ICC = 0.36, 95% CI: 0.03, 0.58), and parents reported fewer restrictions in daily activities (t(89) = 2.45, p = .016) and to attend parties (t(89) = 2.12, p = .038); however, the overall restrictions scores were not different (t(89) = 1.55, p = .125). The presence of convulsive seizures (OR = 0.20, 95% CI: 0.05, 0.75) and longer duration of epilepsy (OR = 1.19, 95% CI: 1.01, 1.41) were associated with parent-child disagreement. No clinical factors were significantly related to either the HARCES or HARCES-M scores., Conclusions: The disagreement in perceptions of restrictions highlights the need to use child-reported measures along with parental reports to comprehensively understand restrictions on children with epilepsy fully. More research is needed to understand what factors explain parent- and child-rated restrictions due to epilepsy., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Rajesh RamachandranNair received research grants from the Ontario Brain Institute, Hamilton Health Sciences Foundation, Department of Pediatrics at McMaster University, and the SUDEP Aware, and served as a paid consultant to UCB Canada Inc. and Sunovion Pharmaceuticals Canada Inc. Dr. Bedard is funded by a CIHR Fellowship, and Dr. Ferro is supported by the Canada Research Chairs Program. The remaining authors have no conflicts of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose: Seizure freedom is an important predictor of health-related quality of life (HRQOL) after pediatric epilepsy surgery. This study aimed to identify the pre-operative predictors of HRQOL 2 years after epilepsy surgery in children with drug-resistant epilepsy., Methods: This multicenter prospective cohort study assessed pre-operative predictors including child (demographics and clinical variables), caregiver (including caregiver depressive and anxiety symptoms) and family characteristics. HRQOL was assessed using the Quality of Life in Childhood Epilepsy Questionnaire (QOLCE)-55 pre-operatively and 2-years after surgery. Univariable linear regression analyses were done to identify significant preoperative predictors of HRQOL 2-years after surgery, followed by multivariable regression., Results: Ninety-five children underwent surgery, mean age was 11.4 (SD=4.2) years, and 59 (62%) were male. Mean QOLCE scores were 57.4 (95%CI: 53.8, 61.0) pre-operatively and 65.6 (95%CI: 62.0, 69.1) after surgery. Univariable regression showed fewer anti-seizure medications (ß=-6.1 [95%CI: -11.2, -1.0], p = 0.019), older age at seizure onset (ß=1.6 [95%CI: 0.8, 2.4], p<0.001), higher pre-operative HRQOL (ß=0.7 [95%CI: 0.5, 0.8], p<0.001), higher family resources (ß=0.6 [95%CI: 0.3, 0.9], p<0.001), better family relationships (ß=1.7 [95%CI: 0.3, 3.1], p = 0.017) and lower family demands (ß=-0.9 [95%CI: -1.5, -0.4], p<0.001) were associated with higher HRQOL after surgery. Caregiver characteristics did not predict HRQOL after surgery (p>0.05). Multivariable regression showed older age at seizure onset (ß=4.6 [95%CI: 1.6, 7.6], p = 0.003) and higher pre-operative HRQOL (ß=10.2 [95%CI: 6.8, 13.6], p<0.001) were associated with higher HRQOL after surgery., Conclusion: This study underscores the importance of optimizing pre-operative HRQOL to maximize HRQOL outcome after pediatric epilepsy surgery., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Sudden unexpected death in epilepsy (SUDEP) is the leading cause of epilepsy-related mortality in children and adults living with epilepsy. The incidence of SUDEP is comparable in both children and adults; it is approximately 1.2 per 1000 person years. The pathophysiology of SUDEP is not well understood but may involve mechanisms such as cerebral shutdown, autonomic dysfunction, altered brainstem function, and cardiorespiratory demise. Risk factors for SUDEP include the presence of generalized tonic-clonic seizures, nocturnal seizures, possible genetic predisposition, and non-adherence to antiseizure medications. Pediatric-specific risk factors are not fully elucidated. Despite recommendations from consensus guidelines, many clinicians still do not follow the practice of counseling their patients about SUDEP. SUDEP prevention has been an area of important research focus and includes several strategies, such as obtaining seizure control, optimizing treatment regimens, nocturnal supervision, and seizure detection devices. This review discusses what is currently known about SUDEP risk factors and reviews current and future preventive strategies for SUDEP., (© 2023 The Authors. Developmental Medicine & Child Neurology published by John Wiley & Sons Ltd on behalf of Mac Keith Press.)

Objective: To understand how knowledge of sudden unexpected death in epilepsy (SUDEP) impacted the lives of adult persons with epilepsy (PWE) and primary caregivers of both adults and children with epilepsy., Methods: The principles of fundamental qualitative description guided this descriptive and exploratory qualitative study to document patients' and caregivers' perceptions and experiences. A purposeful sample of individuals (18 years or older) diagnosed with epilepsy or primary caregivers of PWE completed a single in-depth, semi-structured, one-to-one telephone interview. Categories of findings were developed using directed content analysis., Results: A total of twenty-seven participants completed the study. This consisted of eight adult females and six adult males with epilepsy, ten female caregivers, and three male caregivers of PWE. All participants had become aware of SUDEP at least 12 months before their interview. Most were not informed about SUDEP by their treating neurologist and instead learned about SUDEP via alternative sources (e.g., the internet). All participants believed that knowledge of SUDEP outweighed the risks of being informed about it. Anxiety/fear related to SUDEP disclosure was generally not long-lasting. Caregivers of PWE were more directly impacted by SUDEP disclosure than adult PWE. Caregivers were more likely to make lifestyle/management changes due to learning about SUDEP (e.g., increased supervision and co-sleeping). Participants agreed that follow-up clinical support should be provided after SUDEP disclosure., Conclusions: Disclosure of SUDEP risk may have more significant impacts on caregivers of PWE than adult PWE in the form of lifestyle changes and epilepsy management. After SUDEP disclosure, follow-up support should be offered to PWE and their caregivers, which should be incorporated into future guidelines., Competing Interests: Conflicts of interests Rajesh RamachandranNair received research grant from the Ontario Brain Institute and the Ontario Ministry of Health and Long-Term Care through the Hamilton Academic Health Sciences Organization. The remaining authors have no conflicts of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Sudden unexpected death in epilepsy (SUDEP) is the leading cause of epilepsy-related deaths in children and adults with epilepsy. The incidence of SUDEP in children and adults is equal, approximately 1.2 per 1000-person years. Although inroads have been made in our understanding of SUDEP, its pathophysiology remains unknown. The most important risk factor for SUDEP is the presence of tonic-clonic seizures. Recently there has been growing interest in the contribution of genetic risk factors to SUDEP deaths. Pathogenic variants in epilepsy-related and cardiac genes have been found in some cases of SUDEP post-mortem. Pleiotropy may occur in which a single gene when altered may cause multiple phenotypes (i.e., epilepsy and cardiac arrhythmia). Recently it has been shown that some developmental and epileptic encephalopathies (DEEs) may also be at heightened risk of SUDEP. In addition, polygenic risk has been postulated to effect SUDEP risk with current models evaluating the additive effect of variants in multiple genes. However, the mechanisms underpinning polygenic risk in SUDEP are likely more complex than this. Some preliminary studies also highlight the feasibility of detecting genetic variants in brain tissue post-mortem. Despite the advances in the field of SUDEP genetics, the use of molecular autopsy remains underutilized in SUDEP cases. Several challenges exist concerning genetic testing post-mortem in SUDEP cases, such as interpretation, cost of testing, and availability. In this focused review, we highlight the current landscape of genetic testing in SUDEP cases, its challenges, and future directions., Competing Interests: Declaration of Competing Interest R. RamachandranNair received a research grant from the Ontario Brain Institute and served as a paid consultant to UCB Canada Inc. and Sunovion Pharmaceuticals Canada Inc. The remaining authors have no conflicts of interest., (Crown Copyright © 2023. Published by Elsevier Ltd. All rights reserved.)

Objective: Epileptic Encephalopathy / Developmental Epileptic Encephalopathy with spike-and-wave activation in sleep (EE/DEE-SWAS) is defined as an epilepsy syndrome characterized by neurodevelopmental regression temporally related to the emergence of significant activation of spike-wave discharges in EEG during sleep. The availability of genetic testing has made it evident that monogenic and chromosomal abnormalities play an aetiological role in the development of EE/DEE-SWAS. We sought to review the literature to better understand the genetic landscape of EE/DEE-SWAS., Methods: In this systematic review, we reviewed cases of EE/DEE-SWAS associated with a genetic aetiology, collecting information related to the underlying aetiology, onset, management, and EEG patterns., Results: One hundred and seventy-two cases of EE/DEE-SWAS were identified. Genetic causes of note included pathogenic variants in GRIN2A, ZEB2, CNKSR2 and chromosome 17q21.31 deletions, each of which demonstrated unique clinical characteristics, EEG patterns, and age of onset. Factors identified to raise suspicion of a potential genetic aetiology included the presentation of DEE-SWAS and onset of SWAS under the age of five years. Treatment of EE/DEE-SWAS due to genetic causes was diverse, including a combination of anti-seizure medications, steroids, and other clinical strategies, with no clear consensus on a preferred or superior treatment. Data collected was significantly heterogeneous, with a lack of consistent use of neuropsychology testing, EEG patterns, or use of established clinical definitions., Conclusions: Uniformity concerning the new definition of EE/DEE-SWAS, guidelines for management and more frequent genetic screening will be needed to guide best practices for the treatment of patients with EE/DEE-SWAS., Competing Interests: Declaration of Competing Interest Rajesh RamachandranNair received a research grant from the Ontario Brain Institute and served as a paid consultant to UCB Canada Inc. and Sunovion Pharmaceuticals Canada Inc. The remaining authors have no conflicts of interest., (Crown Copyright © 2023. Published by Elsevier Ltd. All rights reserved.)

Objectives: The purpose of this longitudinal cohort study was to examine the variables that influence health-related quality of life (HRQOL) after epilepsy surgery in children. We examined whether treatment type (surgical vs medical therapy) and seizure control are related to other variables that have been shown to influence HRQOL, namely depressive symptoms in children with epilepsy or their parents, and the availability of family resources., Methods: In total, 265 children with drug-resistant epilepsy were recruited from eight epilepsy centers across Canada at the time of their evaluation for candidacy for epilepsy surgery and were assessed at baseline, 6-month, 1-year, and 2-year follow-up. Parents completed the Quality of Life in Childhood Epilepsy Questionnaire (QOLCE-55) and measures of family resources and depression; children completed depression inventories. Causal mediation analyses using natural effect models were used to evaluate the extent to which the relationship between treatment and HRQOL was explained by seizure control, child and parent depressive symptoms, and family resources., Results: Overall, 111 children underwent surgery and 154 were treated with medical therapy only. The HRQOL scores of surgical patients were 3.4 points higher (95% confidence interval [CI]: -0.2, 7.0) relative to medical patients at the 2-year follow-up after adjusting for baseline covariates, with 66% of the effect of surgery attributed to seizure control. Child or parent depressive symptoms and family resources had negligible mediation effects between treatment and HRQOL. The effect of seizure control on HRQOL was not mediated by child or parent depressive symptoms, or by family resources., Significance: The findings demonstrate that seizure control is on the causal pathway between epilepsy surgery and improved HRQOL in children with drug-resistant epilepsy. However, child and parent depressive symptoms and family resources were not significant mediators. The results highlight the importance of achieving seizure control to improve HRQOL., (© 2023 International League Against Epilepsy.)

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.)

Sudden unexpected death in epilepsy (SUDEP) is the leading cause of epilepsy-related death in children and adults living with epilepsy. Several recent clinical practice guidelines have recommended that all individuals living with epilepsy and their caregivers be informed about SUDEP as a part of routine epilepsy counseling. Furthermore, several studies over the last two decades have explored the state of SUDEP counseling. Patients with epilepsy and their families want to be informed about the risk of SUDEP at or near the time of diagnosis, and preferably in person. Despite guideline recommendations, many pediatric and adult neurologists do not routinely inform individuals with epilepsy and their families about SUDEP. Some neurologists discuss SUDEP with only a subset of patients with epilepsy, such as those with risk factors like frequent generalized or focal to bilateral tonic-clonic seizures, nocturnal seizures, noncompliance, or medically refractory epilepsy. Proponents of routine SUDEP counseling argue that patients with epilepsy and their families have a "right to know" and that counseling may positively impact epilepsy self-management (i.e., behavioral modification and risk reduction). Some neurologists still believe that SUDEP counseling may cause unnecessary stress and anxiety for patients and their families (although this is erroneous) and that they also have a "right not to know." This narrative review explores the current gaps in SUDEP counseling, patients' and caregivers' perspectives of SUDEP counseling, and SUDEP prevention., (© 2023 The Authors. Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Purpose: To understand the experiences of bereaved relatives of individuals who passed due to sudden unexpected death in epilepsy (SUDEP) and to explore the impacts of death in their lives., Methods: The principles of fundamental qualitative description informed all design decisions. Stratified purposeful sampling included 21 bereaved relatives (parent, sibling, or spouse/partner), aged at least 18 years, of persons who passed away because of SUDEP. In-depth one-to-one interviews were conducted. Directed content analysis was used to code, categorize, and synthesize the interview data., Results: There was some criticism of emergency response and medical professionals involved in providing insensitive or poor care immediately after SUDEP occurred. Personal hardships described by participants following SUDEP included loss of personal identity, feeling depressed, experiencing guilt, having panic attacks, requiring therapy, as well as having difficulty with anniversaries, dates, and cleaning up a child's room. Bereaved spouses and parents in particular spoke of experiencing challenges in maintaining other relationships following the death. Some participants spoke of experiencing increased financial hardships. Ways of coping included keeping oneself busy, honoring the memory of the loved one, relying on friends and families, and engaging in advocacy/community work, including raising awareness on epilepsy and SUDEP., Conclusions: Sudden unexpected death in epilepsy affected several aspects of the day-to-day lives of bereaved relatives. Though methods of coping were similar to the usual strategies adopted by all bereaved relatives, advocacy work related to raising awareness about epilepsy and SUDEP was unique to this group. Guidelines on SUDEP should ideally include recommendations for trauma-informed support and assessment for depression and anxiety to the bereaved relatives as well., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Rajesh RamachandranNair received a research grant from the Ontario Brain Institute, and served as a paid consultant to UCB Canada Inc. and Sunovion Pharmaceuticals Canada Inc. The remaining authors have no conflicts of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Importance: Health-related quality of life (HRQOL) is regarded as a key outcome for evaluating treatment efficacy. However, it is uncertain how HRQOL evolves after epilepsy surgery compared with medical therapy, such as whether it continues to improve over time, improves and then remains stable, or deteriorates after a period of time., Objective: To assess trajectory of HRQOL over 2 years in children with drug-resistant epilepsy (DRE) treated with surgery compared with medical therapy., Design, Setting, and Participants: Prospective cohort study assessing HRQOL longitudinally over 2 years. Participants were children recruited from 8 epilepsy centers in Canada from 2014 to 2019 with suspected DRE aged 4 to 18 years who were evaluated for surgery. Data were analyzed from May 2014 to December 2021., Exposures: Epilepsy surgery or medical therapy., Main Outcomes and Measures: HRQOL was measured using the Quality of Life in Childhood Epilepsy Questionnaire (QOLCE)-55. HRQOL and seizure frequency were assessed at baseline, 6-month, 1-year, and 2-year follow-ups. Clinical, parent, and family characteristics were assessed at baseline. A linear mixed model was used to evaluate HRQOL over time, adjusting for baseline clinical, parent, and family characteristics., Results: There were 111 surgical and 154 medical patients (mean [SD] age at baseline was 11.0 [4.1] years; 118 [45%] were female). At baseline, HRQOL was similar among surgical and medical patients. HRQOL of surgical patients was 3.0 (95% CI, -0.7 to 6.8) points higher at 6-month, 4.9 (95% CI, 0.7 to 9.1) points higher at 1-year, and 5.1 (95% CI, 0.7 to 9.5) points higher at 2-year follow-ups compared with medical patients. Surgical patients experienced greater improvements in social functioning relative to medical patients, but not for cognitive, emotional, and physical functioning. At 2-year follow-up, 72% of surgical patients were seizure-free, compared with 33% of medical patients. Seizure-free patients reported higher HRQOL than those who were not., Conclusions and Relevance: This study provided evidence on the association between epilepsy surgery and children's HRQOL, with improvement in HRQOL occurring within the first year and remaining stable 2 years after surgery. By demonstrating that surgery improved seizure freedom and HRQOL, which has downstream effects such as better educational attainment, reduced health care resource utilization, and health care cost, these findings suggest that the high costs of surgery are justified, and that improved access to epilepsy surgery is necessary.

The ketogenic diet (KD) is a widely used therapeutic option for individuals with medically refractory epilepsy. As the diet's name implies, ketosis is a historically important component of the diet, but it is not well understood how important ketosis is for seizure control. The ketogenic ratio is defined as the ratio of fat to carbohydrate plus protein by weight in the diet (grams). Traditionally, the classic KD contains a 4:1 ratio, and a very high proportion of fat in the diet. The classic KD, with its high proportion of fat and limited carbohydrate intake can be restrictive for patients with epilepsy. Recently, there is experience with use of lower ketogenic ratios and less-restrictive diets such as the modified Atkins diet and the low glycemic index treatment. In this narrative review, we examine the role of ketosis and ketogenic ratios in determining the efficacy of the KD in children with epilepsy., (© 2022 International League Against Epilepsy.)

Purpose: This study evaluated the sensitivity of nonconvulsive seizure detection by non-neurophysiologist physicians and nurses using a panel of quantitative EEG (QEEG) trends in the setting of a pediatric intensive care unit., Methods: Forty-five 1-hour QEEG epochs were obtained retrospectively from 10 patients admitted to the McMaster Children's Hospital pediatric intensive care unit, which included 184 electrographic seizures. Each epoch constituted 4 QEEG trends, a seizure probability marker, automated seizure detector, rhythmicity spectrograms, and amplitude-integrated EEG. Six pediatric residents and 5 pediatric intensive care unit nurses analyzed the epochs for possible seizures after a 15-minute power point presentation. This was compared with the gold standard of a board-certified epileptologist interpreting the conventional EEG data for seizures., Results: Sensitivity of seizure detection for pediatric residents and intensive care unit nurses were 0.90. The specificity was 0.87 and 0.89, respectively. The interrater agreement among the pediatric residents was moderate with a kappa (κ) value of 0.45 (confidence interval: 0.41-0.49), and among the nurses were moderate with a κ value of 0.59 (confidence interval: 0.54-0.63). A post hoc analysis involving 2 neurophysiologists demonstrated a sensitivity of 0.90 and a specificity of 0.93 (confidence interval: 0.90-0.96) for seizure detection and a substantial interrater agreement of κ = 0.76 (confidence interval: 0.61-0.91)., Conclusions: A panel of QEEG trends can be used by non-neurophysiologists in a pediatric critical care setting to detect nonconvulsive seizures with a reasonable accuracy, which may expedite subclinical seizure identification and timely intervention., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2020 by the American Clinical Neurophysiology Society.)

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.)

Purpose: To further define the epilepsy phenotype in a cohort of children with 15q13.3 microdeletion syndrome., Methods: We retrospectively reviewed the phenotypic spectrum of all children aged < 18 years with epilepsy and 15q13.3 microdeletion syndrome., Results: Thirteen children were included, 69% were female. The median age of children in the cohort was 12 years (age range: 3 years-15 years). Median age at seizure onset was 4 years. Eleven children (85%) had intellectual disability. Nine of 13 children (69%) had a history of typical absence seizures with median age of onset at 5 years (2 had absence status epilepticus). Thirty-one percent (4/13) had focal with impaired awareness non-motor onset seizures. ILAE recognized absence epilepsy syndromes were diagnosed in 6/13 (46%). The remainder were classified as having genetic generalized epilepsies with overlap clinical features, combined or focal epilepsies. Electroencephalogram in the cohort showed generalized (85%) and focal epileptiform discharges (62%) and posterior dominant rhythm slowing (33%). One child had electrical status epilepticus of sleep. Neuroimaging was performed in 5 children (38%) and revealed abnormal findings in 3. Seizures were drug resistant in a third of the cohort. Valproate resulted in seizure freedom in 5 (42%). Oxcarbazepine caused clinical worsening in one child with combined seizure types. Two children tried cannabidiol and one tried the ketogenic diet; neither was effective., Conclusions: The epilepsy phenotype in children with 15q13.3 microdeletion syndrome is defined by childhood onset absence seizures, and may have atypical features such as, early onset absences, persistence into adolescence, status epilepticus, intellectual disability and treatment resistance. Focal seizures and focal EEG findings may be observed and should be treated cautiously, given the possibility of combined seizure types. Valproate appeared effective, although other treatments must be explored further., (Crown Copyright © 2021. Published by Elsevier Ltd. All rights reserved.)

Background and Objectives: To date, all reports of pathogenic variants affecting the GTPase domain of the DNM1 gene have a clinically severe neurodevelopmental phenotype, including severe delays or intractable epilepsy. We describe a case with moderate developmental delays and self-resolved epilepsy., Methods: The patient was followed by our neurology and genetics teams. After clinical examination and EEG to characterize the patient's presentation, we conducted etiologic workup including brain MRI, chromosomal microarray, genetic and metabolic investigations, and nerve conduction studies. Subsequently, we arranged an Intellectual Disability Plus Trio Panel., Results: Our patient presented with seizures at 2 days old, requiring phenobarbital. She also had hypotonia, mild dysmorphic features, and mild ataxia. Although initial workup returned unremarkable, the trio gene panel identified a de novo heterozygous pathogenic missense variant in the DNM1 GTPase domain. Now 4 years old, she has been seizure-free for 3 years without ongoing treatment and has nonsevere developmental delays (e.g., ambulates independently and speaks 2-word phrases)., Discussion: Our case confirms that not all individuals with DNM1 pathogenic variants, even affecting the GTPase domain, will present with intractable epilepsy or severe delays. Expanding the known clinical spectrum of dynamin-related neurodevelopmental disorder is crucial for patient prognostication and counseling., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Sudden unexpected death in epilepsy (SUDEP) remains an important cause of epilepsy-related mortality, especially in patients with refractory epilepsy. The exact cause is not known, but postictal cardiac, respiratory, and brainstem dysfunctions are implicated. SUDEP prevention remains a big challenge. Except for low-quality evidence of preventive effect of nocturnal supervision for SUDEP, no other evidence-based preventive modality is available. Other potential preventive strategies for SUDEP include reducing the occurrence of generalized tonic-clonic seizures using seizure detection devices, detecting cardiorespiratory distress through respiratory and heart rate monitoring devices, preventing airway obstruction (safety pillows), and reducing central hypoventilation using selective serotonin reuptake inhibitors and adenosine and opiate antagonists. However, none of the above-mentioned modalities has been proven to prevent SUDEP. The present review intends to provide insight into the available SUDEP prevention modalities.

Objective: To examine longitudinal changes and predictors of depression and anxiety 2 years following resective epilepsy surgery, compared to no surgery, in children with drug-resistant epilepsy (DRE)., Method: This multicenter cohort study involved 128 children and adolescents with DRE (48 surgical, 80 nonsurgical; 8-18 years) who completed self-report measures of depression and anxiety at baseline and follow-up (6-month, 1-year, 2-year). Child demographic (age, sex, IQ) and seizure (age at onset, duration, frequency, site and side) variables were collected., Results: Linear mixed-effects models controlling for age at enrolment found a time by treatment by seizure outcome interaction for depression. A negative linear trend across time (reduction in symptoms) was found for surgical patients, irrespective of seizure outcome. In contrast, the linear trend differed depending on seizure outcome in nonsurgical patients; a negative trend was found for those with continued seizures, whereas a positive trend (increase in symptoms) was found for those who achieved seizure freedom. Only a main effect of time was found for anxiety indicating a reduction in symptoms across patient groups. Multivariate regressions failed to find baseline predictors of depression or anxiety at 2-year follow-up in surgical patients. Older age, not baseline anxiety or depression, predicted greater symptoms of anxiety and depression at 2-year follow-up in nonsurgical patients., Conclusion: Children with DRE reported improvement in anxiety and depression, irrespective of whether they achieve seizure control, across the 2 years following surgery. In contrast, children with DRE who did not undergo surgery, but achieved seizure freedom, reported worsening of depressive symptoms, which may indicate difficulty adjusting to life without seizures and highlight the potential need for ongoing medical and psychosocial follow-up and support., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Encephalopathy associated with electrical status epilepticus of sleep (ESES) is an underdiagnosed epileptic encephalopathy syndrome. Though there is considerable controversy regarding the terminology of this condition, there is increasing acceptance of the term, 'encephalopathy associated with electrical status epilepticus of sleep,' as it implies a clinical component as well as EEG feature. Core EEG feature of sleep activation of epileptiform discharges temporarily associated with cognitive or behavioral regression in a child with epilepsy is sufficient to make a diagnosis of ESES. It is important to quantify the spike wave index (SWI) during awake state and sleep to assess for sleep activation. Since focal spikes are also included in the counting of SWI, some grading to assess the distribution of epileptiform discharges is suggested to obtain the complete sleep EEG picture. MRI of the brain does not show abnormality in a number of patients. But common structural lesions include perinatal vascular insults and cortical malformations. Response to treatment is usually variable, but highest success rate is reported with the steroids. Prognosis usually depends on the duration of ESES.

Aim: To determine whether epilepsy surgery improved health-related quality of life (HRQoL) and whether seizure freedom after surgery mediated the improvement in HRQoL., Method: This multicenter cohort study compared HRQoL after epilepsy surgery to pharmacological management in children with drug-resistant epilepsy (DRE). HRQoL was measured using the Quality of Life in Childhood Epilepsy (QOLCE) questionnaire at baseline and 1-year follow-up. The mediator between treatment type and HRQoL was seizure freedom., Results: Two hundred and thirty-seven patients were recruited (surgery group: n=147 [92 males, 45 females]; pharmacological group: n=90 [53 males, 37 females]). Mean age at seizure onset was 6 years (SD 4y 4mo) in the surgical group and 6 years 1 month (SD 4y) in the pharmacological group. The odds ratio of seizure freedom was higher for the surgery versus pharmacological group (β=4.24 [95% confidence interval {CI}: 2.26-7.93], p<0.001). Surgery had no direct effect on total QOLCE score at 1-year (β=0.24 [95% CI -2.04 to 2.51], p=0.839) compared to pharmacological management, but had an indirect effect on total QOLCE that was mediated by seizure freedom (β=0.92 [95% CI 0.19-1.65], p=0.013), adjusting for baseline total QOLCE score. Surgery had a direct effect on improving social function (p=0.043), and an indirect effect on improving physical function (p=0.016), cognition (p=0.042), social function (p=0.012) and behavior (p=0.032), mediated by seizure freedom., Interpretation: Greater seizure freedom achieved through epilepsy surgery mediated the improvement in HRQoL compared to pharmacological management in children with DRE., What This Paper Adds: Seizure freedom is higher after pediatric epilepsy surgery compared to pharmacologically managed epilepsy. Surgery indirectly improves health-related quality of life (HRQoL) mediated by seizure freedom compared to pharmacological management. Surgery has a direct effect on improving social function relative to pharmacological management. Baseline HRQoL was an important predictor of HRQoL after treatment., (© 2019 Mac Keith Press.)

Typically, the amount of daily carbohydrate in the Modified Atkins diet (MAD) is restricted to 10-20 g from the beginning of the therapy. It is possible to gradually reduce the daily carbohydrate amount to this target to increase acceptability of the diet. We report the use of the MAD with slow carbohydrate reduction in a patient with Glucose Transporter 1 Deficiency, including results of neuropsychological assessments. Seizures were controlled at 45 g of carbohydrates daily. This case report illustrates that a liberalized form of MAD with slow reduction of carbohydrate may be a therapeutic option in some children with epilepsy. It is possible that other children with epilepsy could achieve seizure control at higher carbohydrate level than current MAD recommendations., Competing Interests: Authors have no conflict of interest relevant to this manuscript. This is not a funded research., (© 2019 The Authors.)

Objective: Focal cortical dysplasia (FCD) is a common cause of refractory, focal onset epilepsy in children. Interictal, scalp electroencephalograph (EEG) markers have been associated with these pathologies and epilepsy surgery may be an option for some patients. We aim to study how scalp EEG and magnetic resonance imaging (MRI) markers of FCD affect referral of these patients for surgical evaluation., Methods: A single-center, retrospective review of children with focal onset epilepsy. Patients were included if they were between 1 month and 18 years of age, had focal onset seizures, prolonged scalp EEG monitoring, and an MRI conducted after 2 years of age. Statistics were carried out using the chi-squared and student's t-test, as well as a logistic regression model., Results: Sixty-eight patients were included in the study. Thirty-seven of these patients were referred to a comprehensive pediatric epilepsy program (CPEP) for surgical evaluation, and of these 22% showed FCD EEG markers, 32% FCD MRI markers, and 10% had both. These markers were also present in patients not referred to a CPEP. The MRI markers were significantly associated with CPEP referral, whereas EEG markers were not. Neither marker type was associated with epilepsy surgery., Conclusion: This study found that children with focal onset epilepsy were more likely to be referred for surgical evaluation if they were medically refractory, or were diagnosed with FCD or tumor on MRI. Scalp EEG markers of FCD were not associated with CPEP referral. The online tool CASES may be a useful physician guide for identifying appropriate children for epilepsy surgery referral.

Surface electroencephalogram (EEG) recording remains the gold standard for noninvasive assessment of electrical brain activity. It is the most efficient way to diagnose and classify epilepsy syndromes as well as define the localization of the epileptogenic zone. The EEG is useful for management decisions and for establishing prognosis in some types of epilepsy. Electroencephalography is an evolving field in which new methods are being introduced. The Canadian Society of Clinical Neurophysiologists convened an expert panel to develop new national minimal guidelines. A comprehensive evidence review was conducted. This document is organized into 10 sections, including indications, recommendations for trained personnel, EEG yield, paediatric and neonatal EEGs, laboratory minimal standards, requisitions, reports, storage, safety measures, and quality assurance.

Objective: To assess the change in inpatient and emergency department utilization and health care costs in children on the ketogenic diet for treatment of epilepsy., Methods: Data on children with epilepsy initiated on the ketogenic diet (KD) Jan 1, 2000 and Dec 31, 2010 at Ontario pediatric hospitals were linked to province wide inpatient, emergency department (ED) data at the Institute for Clinical Evaluative Sciences. ED and inpatient visits and costs for this cohort were compared for a maximum of 2 years (730days) prior to diet initiation and for a maximum of 2 years (730days) following diet initiation. KD patient were compared to matched group of children with epilepsy who did not receive the ketogenic diet (no KD)., Results: Children on the KD experienced a mean decrease in ED visits of 2.5 visits per person per year [95% CI (1.5-3.4)], and a mean decrease of 0.8 inpatient visits per person per year [95% CI (0.3-1.3)], following diet initiation. They had a mean decrease in ED costs of $630 [95% CI (249-1012)] per person per year and a median decrease in inpatient costs of $1059 [IQR: 7890; p<0.001] per child per year. Compared with the no KD children, children on the diet experienced a mean reduction of 2.1 ED visits per child per year [95% CI (1.0-3.2)] and a mean decrease of 0.6 [95% CI (0.1-1.1)] inpatient visits per child per year. Patients on the KD experienced a reduction of $442 [95% CI (34.4-850)] per child per year more in ED costs than the matched group. The ketogenic diet group had greater median decrease in inpatient costs per child per year than the matched group [p<0.001]., Significance: Patients initiated on ketogenic diet, experienced decreased ED and inpatient visits as well as costs following diet initiation in Ontario, Canada., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Purpose: The purpose of this descriptive qualitative study was to understand the range of adult patients' views on whether and how to discuss the issue of SUDEP with patients with epilepsy and to clarify the optimal timing and formulation of this information., Method: The principles of fundamental qualitative description informed all design decisions. Twenty-three patients aged 18-65years participated in the study. Nineteen participants completed a single one-on-one telephone interview, whereas four participants shared their experiences in a focus group. Directed content analysis was used to code, categorize, and synthesize the interview data., Results: Of the 42 patients invited to participate, 23 participated in the study. There was consensus among all study participants that all individuals diagnosed with epilepsy should be informed about SUDEP. Many participants believed that the best time to be told about SUDEP was at diagnosis. The majority of participants suggested that the discussion about SUDEP should take place face to face, in a verbal discussion, followed by written information to take home. Several participants suggested that the information about SUDEP should not be shared separately but rather incorporated into the general information they received about epilepsy. Nearly all the participants felt that the information about SUDEP should come from the neurologist., Conclusion: Participants of this study wanted neurologists to inform patients about the risk of SUDEP, with the optimal timing and setting of SUDEP counseling determined on a case-by-case basis., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Purpose: Our objective was to understand the range of parental views on whether and how to approach the issue of SUDEP with families, to clarify the optimal timing and formulation of the information, and to learn from parents the optimal counseling strategies in order to minimize the inherent emotional burden., Methods: The principles of fundamental qualitative description were used to guide this descriptive and exploratory study of parental experiences and perceptions. Stratified purposeful sampling included parents (i) who lost children to SUDEP, (ii) of children with moderate to severe epilepsy, (iii) of children with mild epilepsy, and (iv) of children with new-onset epilepsy. Focus group and in-depth one-on-one interviews were conducted. The principles of directed content analysis were used to code and categorize the focus group and interview data. Key concepts from the interview guide were used as the first level of coding categories. Codes were subsequently collapsed into broader categories., Results: There was full agreement, across both genders and regardless of seizure severity, that routine counseling about SUDEP should be provided by pediatric neurologists, during the appointment when the diagnosis of epilepsy is shared with parents, and with opportunities for short-term follow-up and discussions with clinical nurses or social workers. Parents described feeling overwhelmed, worried, and increasingly anxious when the risk of SUDEP was explained to them. Parents generally expressed a preference for receiving routine SUDEP counseling at the time of the diagnosis of epilepsy. Across all groups of parents, it was identified that SUDEP counseling should occur in a face-to-face interaction with the neurologist. In learning about SUDEP, parents expressed a need to be informed of the risk of SUDEP. There was group endorsement for receiving written information about SUDEP to reinforce the content shared by the neurologist. There was a consensus that it should be the parents' decision as to whether or not the child should be present at the meeting or when to inform the child about the risk of SUDEP., Conclusion: Participants in this study opined that all parents of children with epilepsy should receive routine SUDEP counseling and have access to ongoing professional support. Based on these findings, it is imperative for pediatric neurologists to refine their communication skills when counseling parents about SUDEP., (© 2013.)

Objectives: Acute cognitive changes during epileptiform discharges have been studied using computer assisted cognitive tasks. We aimed to demonstrate acute behavioral change (using a simple motor response task MRT) during photoparoxysmal response (PPR) in children below 18 years., Methods: Children performed a simple repetitive motor task during intermittent photic stimulation (IPS). All episodes of PPR not associated with obvious clinical change (as observed by the technologist or reported by the patient) were analyzed for this study. The average time interval between two successive motor responses across a PPR (test time) was compared to the average time interval between two successive motor responses during IPS not associated with PPR (control time) using Wilcoxon signed ranks test., Results: 21 children who had PPR successfully completed the MRT. The difference between the mean durations was 0.894 s (p=0.002). More than 50% increase compared to the control time was considered a delay in MRT during PPR. 10 children showed slowing of MRT during PPR., Conclusion: By definition, acute behavioral change during generalized epileptiform discharges represent provoked seizures. Detecting subclinical seizures can have important safety implications in children (skiing, skating and driving) with PPR on EEG, but no clinical seizures. We recommend MRT during IPS.

Purpose: Studies of adults who underwent temporal lobectomy for intractable temporal lobe epilepsy (TLE) demonstrated declining seizure free rates over time. Using seizure and social parameters, we followed patients who had temporal lobe surgery (TLS) in childhood to determine long-term outcomes., Methods: We identified 42 patients who underwent TLS for medically intractable epilepsy during childhood. Follow-up data were collected from 10 to 20 years after surgery (median, 12 years). We studied histopathology, seizure outcome, employment, school enrolment, and driver's licensing. Patients or parents graded their satisfaction with TLS., Results: Number of Engel class I patients was 34 (81%) after 6 months; 32 (76%) after 1 year; 30 (71%) after 5 years; and 28 (67%) at last >or=10 years follow-up. Nineteen (79%) of 24 children with tumors or cavernous angioma achieved class I outcomes in contrast to 9 (50%) of 18 children with other pathologies (p<0.05). Ten (56%) of 18 recurrent seizure patients experienced seizures within the first year; 4 required reoperation for seizure freedom. More seizure free patients (24, 86%) than residual seizure patients (8, 57%) were employed or in school (p=0.05). Twelve (63%) of 19 eligible patients obtained driver's licenses. Twenty-three (82%) of 28 seizure free patients discontinued anticonvulsants. Surgery grading averaged "satisfied." Class I patients reported greater satisfaction than class III/IV patients (p<0.001)., Conclusion: Two-thirds of children who underwent TLS achieved seizure freedom at >or=10 year follow-up. Children with tumors or cavernous angiomas achieved better long-term outcomes than those with other histopathologies. Long-term seizure free patients were most often satisfied with surgery and employed or in school.

Objectives: To elucidate the pathophysiology of intractable epileptic spasms in older children by describing the interictal magnetoencephalography spike sources (MEGSSs), intracranial EEG ictal-onset zones (IOZs) and their ictal high-frequency oscillations (HFOs) and surgical outcomes., Methods: We studied five patients (4.5-14 years) who underwent surgery following intracranial video-EEG (VEEG) monitoring. We analyzed clinical profiles, MRIs, scalp and intracranial VEEGs, and MEGSSs. We localized ictal HFOs using a sampling rate of 1000 Hz and multiple band frequency analysis (MBFA)., Results: Seizure onset ranged from 0.4 to 8 years. Three patients presented with asymmetrical spasms. Interictal scalp VEEG recorded predominantly unilateral epileptiform discharges in four; generalized and multifocal in one. Ictal scalp VEEG showed generalized high-amplitude slow waves with superimposed fast waves in four patients; hemispheric electrodecremental episodes in one. MRI findings were normal in three, hemispheric polymicrogyria and periventricular heterotopia in one each. All patients had unilateral MEGSS clusters. Ictal HFOs, ranging from 150 to 250 Hz, localized over Rolandic and frontal regions in four, with one also having extensive temporo-occipital HFOs. After cortical resection, three patients were seizure free; one had >90% reduction in seizure frequency. One patient experienced residual seizures after resection of the hemispheric ictal HFO region., Conclusion: Unilateral clusters of MEGSSs overlapped regional IOZs in older patients with epileptic spasms. High spatio-temporal MBFA before and during spasms revealed the regional ictal HFOs. Seizure-free outcomes following resection of zone with MEGSS clusters and ictal HFOs suggested that a subset of epileptic spasms was focal-onset seizures.

Purpose: To identify the predictors of postsurgical seizure freedom in children with refractory epilepsy and normal or nonfocal MRI findings., Methods: We analyzed 22 children with normal or subtle and nonfocal MRI findings, who underwent surgery for intractable epilepsy following extraoperative intracranial EEG. We compared clinical profiles, neurophysiological data (scalp EEG, magnetoencephalography (MEG) and intracranial EEG), completeness of surgical resection and pathology to postoperative seizure outcomes., Results: Seventeen children (77%) had a good postsurgical outcome (defined as Engel class IIIA or better), which included eight (36%) seizure-free children. All children with postsurgical seizure freedom had an MEG cluster in the final resection area. Postsurgical seizure freedom was obtained in none of the children who had bilateral MEG dipole clusters (3) or only scattered dipoles (1). All five children in whom ictal onset zones were confined to < or = 5 adjacent intracranial electrodes achieved seizure freedom compared to three of 17 children with ictal onset zones that extended over >5 electrodes (p = 0.002). None of six children with more than one type of seizure became seizure-free, compared to eight of 16 children with a single seizure type (p = 0.04). Complete resection of the preoperatively localized epileptogenic zone resulted in seizure remission in 63% (5/8) and incomplete resections, in 21% (3/14) (p = 0.06). Age of onset, duration of epilepsy, number of lobes involved in resection, and pathology failed to correlate with seizure freedom., Conclusions: Surgery for intractable epilepsy in children with normal MRI findings provided good postsurgical outcomes in the majority of our patients. As well, restricted ictal onset zone predicted postoperative seizure freedom. Postoperative seizure freedom was less likely to occur in children with bilateral MEG dipole clusters or only scattered dipoles, multiple seizure types and incomplete resection of the proposed epileptogenic zone. Seizure freedom was most likely to occur when there was concordance between EEG and MEG localization and least likely to occur when these results were divergent.

Mirror movements may be congenital or acquired. There are few reports of acquired mirror movements in pediatric patients. Further, mirror movements in children with epilepsy have rarely been reported. A 9-year old male, with intractable partial epilepsy resulting from polymicrogyria of the right hemisphere, underwent cortical resection of the right frontotemporoparietal region for a malformation of cortical development. He developed left hemiplegia and mirror movements in the left hand in the postoperative period. Four months after surgery, he remained seizure-free with mild residual left-sided hemiplegia and persistent mirror movements. Mechanisms postulated for mirror movements include aberrant pyramidal tract development and transcallosal inhibitory pathways. The latter mechanism might have contributed to the mirror movements observed in this child. This study is the first report of mirror movements following focal cortical resection for intractable epilepsy due to polymicrogyria.

Mutations in the voltage-gated sodium channel gene SCN1A are a major cause of severe myoclonic epilepsy of infancy (Dravet syndrome) and generalized epilepsy with febrile seizures plus. This study reports the identification of six de novo SCN1A mutations in patients with severe myoclonic epilepsy of infancy, including a tetranucleotide deletion in exon 26. The same deletion was previously observed in two unrelated patients and appears to result from slipped-strand mispairing of a direct repeat during deoxyribonucleic acid replication. Review of the literature indicates that recurrent mutations account for 25% of SCN1A mutations in severe myoclonic epilepsy of infancy, including six sites of deamination at CpG dinucleotides.