Referral patterns for pediatric resective epilepsy surgery in a publicly funded healthcare system.

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/.

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.

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.

Pediatric drug-resistant epilepsy remains a significant neurological challenge, with up to one-third of affected children failing to achieve seizure control with pharmacologic therapy. Surgical intervention offers the greatest likelihood of seizure reduction or freedom; however, precise localization and treatment of epileptogenic networks in pediatric patients are often complicated by multilobar onset patterns, evolving neurodevelopmental anatomy, and limitations of conventional invasive monitoring. Over the past two decades, stereoelectroencephalography (SEEG) has emerged as a preferred invasive diagnostic modality due to its minimally invasive approach, three-dimensional sampling capability, and favorable safety profile. Parallel advances in robotic stereotaxy have further enhanced the precision, efficiency, and reproducibility of electrode implantation and stereotactic interventions. Robotic assistance has expanded beyond diagnostic SEEG implantation to include stereotactic ablative therapies, such as radiofrequency thermocoagulation and magnetic resonance-guided laser interstitial thermal therapy, as well as neuromodulation procedures including deep brain stimulation and responsive neurostimulation. These technologies enable precise targeting of deep and distributed epileptogenic networks while minimizing surgical morbidity. Pediatric clinical studies demonstrate that robotic-assisted SEEG achieves high diagnostic yield, excellent safety profiles, and accuracy comparable to or exceeding conventional stereotactic techniques. Similarly, robot-assisted ablative and neuromodulation procedures show promising efficacy in carefully selected pediatric populations, although complete seizure freedom remains less common in neuromodulatory approaches. Despite increasing adoption, the pediatric robotic epilepsy surgery literature remains predominantly retrospective and heterogeneous, with limited prospective comparative data. This review synthesizes current evidence regarding robotic applications in pediatric epilepsy surgery, including SEEG implantation, stereotactic ablation, and neuromodulation. We highlight technical considerations, clinical outcomes, and safety profiles, while identifying critical gaps in evidence related to long-term outcomes, and the direct clinical impact of robotic accuracy. Continued prospective and multicenter investigations are essential to define the optimal role of robotic assistance in improving outcomes for pediatric patients with drug-resistant epilepsy.

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.

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.

Several instruments and outcomes measures have been reported in pediatric patients undergoing epilepsy surgery. The objective of this systematic review is to summarize, evaluate, and quantify outcome metrics for the surgical treatment of pediatric epilepsy that address seizure frequency, neuropsychological, and health-related quality of life (HRQL). We performed a systematic review according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to identify publications between 2010 and June 2021 from PubMed, Embase, and the Cochrane Database of Systematic Reviews that report clinical outcomes in pediatric epilepsy surgery. Eighty-one articles were included for review. Overall, rates of postoperative seizure frequency were the most common metric reported (n=78 studies, 96%). Among the seizure frequency metrics, the Engel Epilepsy Surgery Outcome Scale (n=48 studies, 59%) was most commonly reported. Neuropsychological outcomes, performed in 32 studies (40%) were assessed using 36 different named metrics. HRQL outcomes were performed in 16 studies (20%) using 13 different metrics. Forty-six studies (57%) reported postoperative changes in antiepileptic drug (AED) regimen, and time-to-event analysis was performed in 15 (19%) studies. Only 13 outcomes metrics (1/5 seizure frequency, 6/13 HRQL, 6/36 neuropsychological) have been validated for use in pediatric patients with epilepsy and only 13 have been assessed through reliability studies (4/5 seizure frequency, 6/13 HRQL, and 3/36 neuropsychological). Of the 81 included studies, 17 (21%) used at least one validated metric. Outcome variable metrics in pediatric epilepsy surgery are highly variable. Although nearly all studies report seizure frequency, there is considerable variation in reporting. HRQL and neuropsychological outcomes are less frequently and much more heterogeneously reported. Reliable and validated outcomes metrics should be used to increase standardization and accuracy of reporting outcomes in pediatric patients undergoing epilepsy surgery.

Academic skills, such as reading, spelling and arithmetic, are central to meaningful engagement with society throughout adolescence and into adulthood. The disruption caused by on-going seizure activity places children with drug-resistant epilepsy at a particularly high risk of poor academic attainment. Though epilepsy surgery during childhood has long-been associated with various cognitive changes, less is known of the extent to which pediatric epilepsy surgery impacts academic attainment. The aim of the present systematic review was to identify the nature of the effect of pediatric epilepsy surgery on the core academic skills of reading, writing, and arithmetic. The electronic databases Embase, Medline, PubMed, PsychInfo, OpenAire, and the ISRCTN registry were searched for studies examining academic attainment following epilepsy surgery in childhood, over the last three decades. Two thousand three-hundred and sixty-eight articles were screened for relevance. Thirteen studies met the inclusion criteria. Study quality and reliability were independently assessed by two reviewers. Results indicate that academic attainment primarily stabilizes in the first year following epilepsy surgery. Though changes to learning ability would not be expected in this early recovery phase, this review indicates that children do not, at least, lose the academic skills they have acquired before surgery. Postoperative declines in performance were most notably recorded in assessments of arithmetic, suggesting an area of potential vulnerability in this cohort. These declines were noted in cohorts with the longest periods between seizure onset and surgery. While older age at onset and seizure freedom correlated with improved academic attainment, further research is necessary to fully understand the specific effect of epilepsy surgery on academic attainment. Still, the present review provides valuable information regarding the likely academic outcomes in the early years following surgical treatment for drug-resistant epilepsy.

Antiseizure drug (ASD) therapy can significantly impact quality of life for pediatric patients whose epilepsy remains refractory to medications and who experience neuropsychological side effects manifested by impaired cognitive and social development. Contemporary patterns of ASD reduction after pediatric epilepsy surgery across practice settings in the United States are sparsely reported outside of small series. We assessed timing and durability of ASD reduction after pediatric epilepsy surgery and associated effects on health care utilization. We performed a retrospective analysis of 376 pediatric patients who underwent resective epilepsy surgery between 2007 and 2016 in the United States using the Truven MarketScan database. Filled ASD prescriptions during the pre- and postoperative periods were compared. Univariate and multivariate analyses identified factors associated with achieving a stable discontinuation of or reduction in number of ASDs. Health care utilization and costs were systematically compared. One hundred seventy-one patients (45.5%) achieved a >90-day ASD-free period after surgery, and 84 (22.3%) additional patients achieved a stable reduction in number of ASDs. Achieving ASD freedom was more common in patients undergoing total hemispherectomy (n=21, p=.002), and less common in patients with tuberous sclerosis (p=.003). A higher number of preoperative ASDs was associated with a greater likelihood of achieving ASD reduction postoperatively (hazard ratio [HR]: 1.85, 95% confidence interval [CI]: 1.50-2.28), but was not associated with a significant difference in the likelihood of achieving ASD freedom (0.83, 95% CI: 0.49-1.39). Achieving an ASD-free period was associated with fewer hospital readmissions within the first year after surgery. Patterns of ASD use and discontinuation after pediatric epilepsy surgery provide an unbiased surgical outcome endpoint extractable from administrative databases, where changes in seizure frequency are not captured. This quantitative measure can augment traditional surgical outcome scales, incorporating a significant clinical parameter associated with improved quality of life.

Neurosurgery is a safe and effective form of treatment for select children with drug-resistant epilepsy. Still, there is concern that it remains underutilized, and that seizure freedom rates have not improved over time. We investigated referral and surgical practices, patient characteristics, and postoperative outcomes over the past two decades. We performed a retrospective cohort study of children referred for epilepsy surgery at a tertiary center between 2000 and 2018. We extracted information from medical records and analyzed temporal trends using regression analyses. A total of 1443 children were evaluated for surgery. Of these, 859 (402 females) underwent surgical resection or disconnection at a median age of 8.5 years (interquartile range [IQR] = 4.6-13.4). Excluding palliative procedures, 67% of patients were seizure-free and 15% were on no antiseizure medication (ASM) at 1-year follow-up. There was an annual increase in the number of referrals (7%, 95% confidence interval [CI] = 5.3-8.6; p < .001) and surgeries (4% [95% CI = 2.9-5.6], p < .001) over time. Duration of epilepsy and total number of different ASMs trialed from epilepsy onset to surgery were, however, unchanged, and continued to exceed guidelines. Seizure freedom rates were also unchanged overall but showed improvement (odds ratio [OR] 1.09, 95% CI = 1.01-1.18; p = .027) after adjustment for an observed increase in complex cases. Children who underwent surgery more recently were more likely to be off ASMs postoperatively (OR 1.04, 95% CI = 1.01-1.08; p = .013). There was a 17% annual increase (95% CI = 8.4-28.4, p < .001) in children identified to have a genetic cause of epilepsy, which was associated with poor outcome. Children with drug-resistant epilepsy continue to be put forward for surgery late, despite national and international guidelines urging prompt referral. Seizure freedom rates have improved over the past decades, but only after adjustment for a concurrent increase in complex cases. Finally, genetic testing in epilepsy surgery patients has expanded considerably over time and shows promise in identifying patients in whom surgery is less likely to be successful.

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.

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.

Application, utility and safety of intraoperative 3T magnetic resonance imaging in pediatric epilepsy surgery: A 10-year retrospective single-center experience.

Advances: H. Kubova, K. Lukasiuk, A. Pitkanen: New Insight on the Mechanisms of Epileptogenesis in the Developing Brain. - P. Follett, N. Vora, J.H. Cross: Paediatric Intractable Epilepsy Syndromes: changing concepts in diagnosis and management. - K.K. Oguz: Magnetic Resonance Imaging in Epilepsy. Technical Standards: N. Akalan, B. Bilginer: Pediatric temporal lobe epilepsy surgery, resection based on etiology and anatomical location. - J.-U. Choi, D.-S. Kim: Treatment Modalities for Intractable Epilepsy in Hypothalamic Hamartoma. - F. Novegno, L. Massimi, C. Di Rocco: Epilepsy in Tuberous Sclerosis Complex. - S. Fauser, J. Zentner: Critical review of palliative surgical techniques for intractable epilepsy.