Expanding the scope of pediatric epilepsy surgery: Access, indications, and outcomes in a modern cohort.

Background: Paediatric epilepsy surgery reduces seizure burden in drug-refractory epilepsy reducing long-term neurocognitive damage. Methods: Single-centre retrospective audit of pre-surgical evaluations and outcomes of the paediatric epilepsy and epilepsy surgery programme over eleven years at KK Women’s and Children’s Hospital, Singapore. Data were collected based on National Institute of Neurological Disorders and Stroke Common Data Elements guidelines. Outcome was categorized using Engel classification scale, and favourable outcome defined as greater than 50% decrease in seizure frequency or drop attacks. Results: Thirty-three children underwent epilepsy surgery, with mean follow-up 3.8±3.1 years. Median age at surgery was 10.9 years. Twenty-four children with focal epilepsy underwent resection of the epileptogenic focus, including lesionectomy (n=8), anterior temporal lobectomy (n=7), extratemporal lobectomy (n=7) and hemispherectomy (n=2). Nine children underwent corpus callosotomy for Lennox Gastaut Syndrome (n=8) and West Syndrome (n=1). Median hospital stay duration was ten days. All twenty-three focal epilepsy patients with minimum three-month follow-up achieved greater than 50% seizure reduction. Fifteen (65%) focal epilepsy patients achieved seizure-freedom (Engel Class IA) after first surgeries. Four patients required second surgeries, with two achieving seizure-freedom. Intraoperative MRI (iMRI) is beneficial. All nine corpus callosotomy patients (100%) achieved greater than 50% decrease in drop attacks. Number of antiepileptic drugs was weaned for 21/32 (66%) patients. Post-operative complications were low and some patients had anticipated neurological deficits. Outcomes were comparable to current literature. Conclusions: In well-selected candidates with tailored evaluation, paediatric epilepsy surgery is a safe therapeutic option with favourable outcomes and can be performed across the entire paediatric age range.

Advances in electrophysiological assessment with improved structural and functional neuroimaging have been very helpful in the use of surgery as a tool for drug-resistant epilepsy. Increasing interest in epilepsy surgery has had a major impact on adult patients; a refined evaluation process and new criteria for drug resistance combined with refined surgical techniques resulted in large surgical series in many centers. Pediatric surgery has lagged behind this evolution, possibly because of the diverse semiology and electrophysiology of pediatric epilepsy obscuring the focal nature of the seizures and frustrating the treatment of catastrophic epileptic syndromes specific to children. Unfortunately, refractory -epilepsy is more -devastating in children than in adults as it interferes with all aspects of neural development. Nevertheless, during the last few decades, the efforts of a small number of centers with encouraging results in pediatric epilepsy surgery have motivated pediatric neurologists to gain interest. Although well behind in the number of patients compared with that of adults, pediatric series are increasing exponentially. While temporal lobe epilepsy is the focus of interest in adults, with almost 70 % of resections in the temporal lobe, the pediatric epilepsy spectrum is different. Resective or functional surgery techniques devoted to resistant extratemporal epilepsy are the major improvements in pediatric epilepsy surgery. Temporal lobe epilepsy in adults has been studied extensively but only recently has begun to receive attention in children. Several aspects of temporal lobe epilepsy in childhood remain unclear or controversial in terms of seizure semiology and its pathology. This is reflected in the surgical treatment. Information on the major contributors to a favorable outcome, such as type or extent of resection, in terms of seizure control and morbidity is not available as in adult temporal lobe epilepsy. This chapter discusses the major discrepancies between adult and pediatric temporal lobe epilepsy and outlines the current concepts in surgical treatment. The resection strategy based on the different substrates at different locations in the temporal lobe causing seizures is emphasized with respect to available literature.

Background: Pediatric patients undergoing epilepsy surgeries are under high risks of bleeding, hemodynamic instability and complications related to transfusions. This study aimed to investigate whether combined application of tranexamic acid (TXA) and thrombelastography (TEG) in pediatric epilepsy surgery can decrease blood loss, transfusion requirements and post-operation complications.Methods: Thirty-two pediatric patients undergoing elective epilepsy surgery were randomized into two groups. Group T (Group T=Group Treatment, n=16) was given a loading dose of 10 mg/kg TXA in 15 minutes and then maintained at the speed of 5 mg/kg/h, while Group C (Group C=Group Control, n=16) was given the same dosage of normal saline. TEG tests were performed at the beginning of surgery (T1), opening the dura mater (T2), closing the dura mater (T3) and the end of surgery (T4) in both groups. In Group T, transfusion decision was made according to TEG results; while in Group C, it was made by anesthetist's experience without knowing the TEG results. The volume of blood loss, blood transfusion, post-operative drainage and complications were recorded.Results: In Group T, intraoperative bleeding volume was significantly lower than Group C ([8.23±4.10] ml/kg vs [12.86±5.30] ml/kg, P=0.010]), and subsequently the ratio of transfusion of red blood cells (RBC) (18.75% vs 56.25%, P=0.026), fresh frozen plasma (FFP) (32.15% vs 43.75%, P=0.465) were significantly reduced. Maximal amplitude (MA) value of TEG at T3 (Group T=[61.11±4.58] mm vs Group C=[56.09±8.03] mm, P=0.038) and T4 (Group T=[60.31±6.23] mm vs Group C=[54.08±7.28] mm, P=0.014) in Group T were significantly higher than those in Group C. A significant difference existed between two groups in postoperative drainage volume in the first 24 hours (Group T=[4.19±1.55] ml/kg vs Group C=[5.83±2.07] ml/kg, P=0.017). Postoperative hospital stay was significantly shortened in Group T, compared to Group C ([7.9±2.1] days vs [10.8±3.8] days, P=0.014). No transfusion related complications occurred in both groups.Conclusions: Combined application of TXA and TEG in pediatric epilepsy surgery may decrease blood loss, reduce transfusion requirements. The risk of thromboembolism may not be increased. Citation: Qing-Fang Duan, Wen-Ya Fu, Wei Xiao, Jia-Jian Qi, Guo-Guang Zhao, Yong-Zhi Shan, et al. Combined application of tranexamic acid and thrombelastography in pediatric epilepsy surgery. J Anesth Perioper Med 2017; 4: 213-9. doi: 10.24015/JAPM.2017.0007This is an open-access article, published by Evidence Based Communications (EBC). This work is licensed under the Creative Commons Attribution 4.0 International License, which permits unrestricted use, distribution, and reproduction in any medium or format for any lawful purpose. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

Referral patterns for pediatric epilepsy surgery in publicly funded healthcare systems remain unclear. This study quantified referral intervals and identified predictors of prolonged referrals at Finland's primary pediatric epilepsy surgery center. Additionally, the authors examined time intervals from drug-resistant epilepsy (DRE) diagnosis to surgical referral. A retrospective analysis of the charts of 251 pediatric epilepsy surgery patients treated between 2002 and 2024 was conducted (median age at surgery: 9.63 years). Geographical regions were categorized based on university hospitals' catchment areas to southern, western, central, and northern regions. The authors collected data on clinical, diagnostic, and surgical characteristics; referral centers; and time intervals across different stages of the referral process. Predictors of prolonged referral duration (above median) were identified using an adjusted logistic regression model. The median (IQR) onset-to-referral interval was 3.24 (5.34) years, with no significant regional differences (p = 0.73). Among 155 patients with detailed data on prescription of a third antiseizure medication, the median (IQR) interval from DRE to surgical referral was 2.02 (3.37) years. Referral hospitals with systematic epileptologist consultants had a shorter onset-to-surgery interval (3.89 vs 5.31 years, p = 0.043) than those without. Adjusted predictors of prolonged onset-to-referral interval included seizure remission (OR 8.70, p < 0.001) and MRI negativity (OR 3.73, p = 0.037). Furthermore, active infantile spasms at referral (OR 0.076, p = 0.046), daily seizures (OR 0.27, p < 0.001), and low-grade tumors (OR 0.25, p = 0.011) were associated with shorter onset-to-referral interval. Prolonged durations of epilepsy before surgical referral are linked to epilepsy severity and pre-referral MRI findings. In Finland, referral intervals are consistent across regions despite long travel distances. Overall, epilepsy treatment is efficient nationwide, with relatively short and equal referral intervals. Epileptologist outreach consultations should be considered to facilitate earlier identification of surgical candidates and reduce referral delays.

Neuropsychological assessment in pediatric epilepsy surgery: A French procedure consensus

Surgical volumes at large epilepsy centers are decreasing. Pediatric cohorts, however, show a trend toward more resections and superior outcome. Differences in pediatric and adult epilepsy surgery were investigated in our cohort. The Bethel database between 1990 and 2014 was retrospectively analyzed. A total of 1916 adults and 1300 children underwent presurgical workup. The most common etiologies were medial temporal sclerosis (35.4%) in adults, and focal cortical dysplasias (21.1%) and diffuse hemispheric pathologies (14.7%) in children. Only 1.4% of the total cohort had normal histopathology. A total of 1357 adults (70.8%) and 751 children (57.8%) underwent resections. Surgery types for children were more diverse and showed a higher proportion of extratemporal resections (32.8%) and functional hemispherectomies (20.8%). Presurgical evaluations increased in both groups; surgical numbers remained stable for children, but decreased in the adult group from 2007 on. The patients' decision against surgery in the adult nonoperated cohort increased over time (total = 44.9%, 27.4% in 1995-1998 up to 53.2% in 2011-2014; for comparison, in children, total = 22.1%, stable over time). Postsurgical follow-up data were available for 1305 adults (96.2%) and 690 children (91.9%) 24 months after surgery. The seizure freedom rate was significantly higher in children than in adults (57.8% vs 47.5%, P < 0.001) and significantly improved over time (P = 0.016). Pediatric epilepsy surgery has stable surgical volumes and renders more patients seizure-free than epilepsy surgery in adults. A relative decrease in hippocampal sclerosis, the traditional substrate of epilepsy surgery, changes the focus of epilepsy surgery toward other pathologies.

Surgery has been and is now a well-established treatment indicated for adults and children with drug-resistant epilepsy (DRE). The surgical landscape for children with DRE appears to be expanding, and surgical cases of pediatric epilepsy have increased significantly in the past decade, contrary to adult epilepsy. Several fundamental changes have led to the widespread surgical treatment for DRE in children, based on a risk-benefit analysis of pediatric epilepsy surgery, and a change in our overall approach to evaluation. There are unique and age-related differences associated with pediatric epilepsy surgery, characterized by different types of etiologies, concerns for developmental progress, and safety issues. Indications for “pediatric epilepsy surgery” have been broadened to include a wide spectrum of etiologies without excluding children with “generalized” seizures, “generalized or multifocal eletroencephlography”, or patients with contra-lateral epileptiform activity or magnetic resonance imaging abnormalities. Furthermore, epilepsy surgery is increasingly considered in infancy and early childhood, which has similar surgical outcomes as the case of late childhood, in an effort to improve the eventual development outcome. Seizure freedom, or at least seizure reduction, is an excellent result with resolution of the associated epileptic encephalopathy, normalization of the EEG, and decrease in the total epileptic burden in the pediatric field.

A surgical "treatment gap" in pediatric epilepsy persists despite the demonstrated safety and effectiveness of surgery. For this reason, the national surgical landscape should be investigated such that an updated assessment may more appropriately guide health care efforts. In our retrospective cross-sectional observational study, the National Inpatient Sample (NIS) database was queried for individuals 0 to <18 years of age who had an International Classification of Diseases (ICD) code for drug-resistant epilepsy (DRE). This cohort was then split into a medical group and a surgical group. The former was defined by ICD codes for -DRE without an accompanying surgical code, and the latter was defined by DRE and one of the following epilepsy surgeries: any open surgery; laser interstitial thermal therapy (LITT); vagus nerve stimulation; or responsive neurostimulation (RNS) from 1998 to 2020. Demographic variables of age, gender, race, insurance type, hospital charge, and hospital characteristics were analyzed between surgical options. Continuous variables were analyzed with weight-adjusted quantile regression analysis, and categorical variables were analyzed by weight-adjusted counts with percentages and compared with weight-adjusted chi-square test results. These data indicate an increase in epilepsy surgeries over a 22-year period, primarily due to a statistically significant increase in open surgery and a non-significant increase in minimally invasive techniques, such as LITT and RNS. There are significant differences in age, race, gender, insurance type, median household income, Elixhauser index, hospital setting, and size between the medical and surgical groups, as well as the procedure performed. An increase in open surgery and minimally invasive surgeries (LITT and RNS) account for the overall rise in pediatric epilepsy surgery over the last 22 years. A positive inflection point in open surgery is seen in 2005. Socioeconomic disparities exist between medical and surgical groups. Patient and hospital sociodemographics show significant differences between the procedure performed. Further efforts are required to close the surgical "treatment gap."

Background and ObjectiveDrug-resistant epilepsy (DRE), also known as medically refractory epilepsy, is a disorder of high prevalence and negatively impacts a patients quality of life, neurodevelopment, and life expectancy. Pediatric epilepsy surgery has been conducted since the late 1800s, and randomized controlled trials have demonstrated the marked effectiveness of surgery on seizure reduction and the potential for cure. Despite the strong evidence for pediatric epilepsy surgery, there is also strong evidence describing its underutilization. The objective of this narrative review is to describe the history, strength, and limitations in the evidence of surgery for pediatric drug resistant epilepsy.MethodsThis narrative review was conducted utilizing standard search engines to include the relevant articles on the topic of surgery for drug resistant epilepsy in children, with main keywords including surgery in pediatric epilepsy and drug-refractory epilepsy.Key Content and FindingsThe first components describe the historical perspective of pediatric epilepsy surgery and the evidence that highlight the strengths and limitations of epilepsy surgery. We then highlight the importance of presurgical referral and evaluation, followed by a section detailing the surgical options for children with DRE. Lastly, we provide a perspective on the future of pediatric epilepsy surgery.ConclusionsEvidence supports the role for surgery in pediatric medically refractory epilepsy in seizure frequency reduction, improved curative rates, and improvements in neurodevelopment and quality of life.

BackgroundEpilepsy surgery is an underutilized resource for children with drug-resistant epilepsy. Palliative and definitive surgical options can reduce seizure burden and improve quality of life. Palliative epilepsy surgery is often seen as a “last resort” compared to definitive surgical options. We compare patient characteristics between palliative and definitive epilepsy surgical patients and present palliative surgical outcomes from the Pediatric Epilepsy Research Consortium surgical database. MethodsThe Pediatric Epilepsy Research Consortium Epilepsy Surgery database is a prospective registry of patients aged 0-18 years undergoing evaluation for epilepsy surgery at 20 pediatric epilepsy centers. We included all children with completed surgical therapy characterized as definitive or palliative. Demographics, epilepsy type, age of onset, age at referral, etiology of epilepsy, treatment history, time-to-referral/evaluation, number of failed anti-seizure medications (ASMs), imaging results, type of surgery, and postoperative outcome were acquired. ResultsSix hundred forty patients undergoing epilepsy surgery were identified. Patients undergoing palliative procedures were younger at seizure onset (median: 2.1 vs 4 years, P= 0.0008), failed more ASM trials before referral for presurgical evaluation (P=<0.0001), and had longer duration of epilepsy before referral for surgery (P=<0.0001). During presurgical evaluation, patients undergoing palliative surgery had shorter median duration of video-EEG data collected (P=0.007) but number of cases where ictal data were acquired was similar between groups. The most commonly performed palliative procedure was corpus callosotmy (31%), followed by lobectomy (21%) and neuromodulation (82% responsive neurostimulation vs 18% deep brain stimulation). Palliative patients were further categorized into traditionally palliative procedures vs traditionally definitive procedures. The majority of palliative patients had 50% reduction or better in seizure burden. Seizure free outcomes were significantly higher among those with traditional definitive surgeries, 41% (95% confidence interval: 26% to 57%) compared with traditional palliative surgeries and 9% (95% confidence interval: 2% to 17%). Rate of seizure freedom was 46% at 24 months or greater of follow-up in the traditional definitive group. ConclusionsPatients receiving palliative epilepsy surgery trialed more ASMs, were referred later after becoming drug resistant, and had longer gaps between drug resistance and epilepsy surgery compared with patients undergoing definitive epilepsy surgery. The extent of surgical evaluation is impacted if surgery is thought to be palliative. A majority of palliative surgery patients achieved >50% seizure reduction at follow-up, both in groups that received traditionally palliative and traditionally definitive surgical procedures. Palliative surgical patients can achieve greater seizure control and should be referred to an epilepsy surgery center promptly after failing two appropriate anti-seizure medications.

T06. Outcome of brain responsive neurostimulation in refractory epilepsy cases from a single tertiary epilepsy centre

INTRODUCTION Responsive neurostimulation (RNS) is a closed-loop neurostimulation modality for treating intractable epilepsy in patients who are not candidates for resection. A high number of patients have ictal onsets originating in the temporal lobe. In the past, implantation of depth electrodes have been placed using a transoccipital approach that transverses the long axis of the hippocampus. However, there have been no description of orthogonal approaches to RNS electrode placement into the medial temporal structures in the literature. We aimed to describe our initial experience with placing RNS depth electrodes using an orthogonal approach to target the short axis of the mesial temporal lobe. METHODS Presurgical work up included magnetic resonance imaging (MRI), video electroencephalography (vEEG), and neuropsychological testing. During the procedure, patients were placed with their heads in a neutral position. Electrodes were placed via stereotactic robotic assistance using a unilateral orthogonal approach targeting the amygdala or hippocampus. Patients who underwent RNS electrode implantation via orthogonal approach were identified after a retrospective review of all RNS patients at our institution. Multiple variables were collected, including age, disease onset, complications, follow-up, semiology, and seizure reduction. RESULTS There were 4 patients who underwent RNS implantation with orthogonal electrode placement. The mean age and follow-up were 44.8 and 1.2 yr, respectively. One of 8 patients was seizure free at last follow-up and 2 experienced over 50% reduction in seizures. There was one surgical complication but no mortality. CONCLUSION The initial experience using an orthogonal approach for depth electrode placement for RNS implantation was described. The potential advantages may include better safety, accuracy, and positioning in comparison to a transoccipital approach. Limitations included the retrospective nature of the study and a low sample size. Further research and experience are required to determine the best indications for an orthogonal approach.

Neuropsychology plays an essential role in pediatric epilepsy surgery. Evaluations provide information to inform presurgical decision-making by addressing localization and lateralization of deficits and by informing risk of postsurgical decline. The pediatric neuropsychologist also assists with multiple additional procedures, including the Wada or Intracarotid amobarbital procedure, functional magnetic resonance imaging, and brain mapping (on the ward and in the operating room), to measure localization and lateralization of eloquent cortex as well as adequacy of brain tissue to be resected and risk of resection of specific cortex. Neuropsychology provides postsurgical outcome information not only for individual patients, but as “quality control” for epilepsy surgery. Multiple factors complicate individual patient data interpretation, and these factors are essential to understand and consider. Developmental considerations are paramount. Although methodological differences between studies can also make surgical outcome studies challenging to interpret, neuropsychological data suggest that pediatric surgery can improve developmental outcomes and trajectories, particularly if resection is done early and without lengthy presurgical seizure duration, although longer seizure duration and polypharmacy, more widespread disease, and larger areas of resection, particularly of critical eloquent cortex, can be costly to the individual patient. Additional and more refined research is needed.

In this study, we aimed to define the scope of paediatric epilepsy surgery performed in Asia and Australasia. Representative surgeons from each county were emailed a survey about paediatric epilepsy surgery as it is practiced in their country. The survey covered topics including what investigations, operations and number of surgeries are performed and by whom (adult or paediatric neurosurgeons). Epilepsy surgery programmes are for the most part more common in larger countries and countries with a higher gross domestic product (GDP). Countries performing epilepsy surgery commonly have access to the full range of investigations except magneto-encephalography (MEG). Intraoperative electrocorticography (ECOG) and stereotaxy are typically available and most have access to extra-operative monitoring. There is limited availability of laser interstitial therapy (LIT) and responsive neuro-stimulation (RNS). China performs approximately 4000 paediatric epilepsy cases per year which is more than all of the other countries combined. Epilepsy surgery case numbers range from 0.2 to 22/ million population per year, and there is a correlation between the number of cases performed and the countries' GDP. A large number of children have no access to epilepsy surgery. There is a wide variation in access to epilepsy surgery in Asia and Australasia. Some counties have surgical numbers comparable with high volume Western countries, while hundreds of millions of children have no access to surgery at all.

There is substantial variability in reported seizure outcome following pediatric epilepsy surgery, and lack of individualized predictive tools that could evaluate the probability of seizure freedom postsurgery. The aim of this study was to develop and validate a supervised machine learning (ML) model for predicting seizure freedom after pediatric epilepsy surgery. This is a multicenter retrospective study of children who underwent epilepsy surgery at five pediatric epilepsy centers in North America. Clinical information, diagnostic investigations, and surgical characteristics were collected, and used as features to predict seizure-free outcome 1 year after surgery. The dataset was split randomly into 80% training and 20% testing data. Thirty-five combinations of five feature sets with seven ML classifiers were assessed on the training cohort using 10-fold cross-validation for model development. The performance of the optimal combination of ML classifier and feature set was evaluated in the testing cohort, and compared with logistic regression, a classical statistical approach. Of the 801 patients included, 61.3% were seizure-free 1 year postsurgery. During model development, the best combination was XGBoost ML algorithm with five features from the univariate feature set, including number of antiseizure medications, magnetic resonance imaging lesion, age at seizure onset, video-electroencephalography concordance, and surgery type, with a mean area under the curve (AUC) of .73 (95% confidence interval [CI] = .69-.77). The combination of XGBoost and univariate feature set was then evaluated on the testing cohort and achieved an AUC of .74 (95% CI = .66-.82; sensitivity=.87, 95% CI = .81-.94; specificity=.58, 95% CI = .47-.71). The XGBoost model outperformed the logistic regression model (AUC=.72, 95% CI = .63-.80; sensitivity=.72, 95% CI = .63-.82; specificity=.66, 95% CI = .53-.77) in the testing cohort (p= .005). This study identified important features and validated an ML algorithm, XGBoost, for predicting the probability of seizure freedom after pediatric epilepsy surgery. Improved prognostication of epilepsy surgery is critical for presurgical counseling and will inform treatment decisions.