Summary
Objective
Corpus callosotomy is a palliative neurosurgical treatment for patients with either generalized or multifocal refractory epilepsy and injurious drop attacks. This report aims to ...systematically review the pediatric literature.
Methods
Medline, Embase, Web of Knowledge, and Scopus were searched systematically for published articles on treatment outcomes of corpus callosotomy for refractory epilepsy. Studies were included if the patient population was younger than 18 at the time of surgery and median follow‐up was >1 year. Studies were excluded if resective surgery was also performed.
Results
A total of 12 articles met inclusion criteria. All articles were retrospective case series, with the exception of one being a prospectively designed retrospective case series. There was very little agreement among authors on the definition of a good seizure outcome. Articles that used the Engel classification found that 88.2% of total corpus callosotomy patients had a worthwhile reduction in seizures compared with 58.6% of patients who underwent anterior corpus callosotomy (p < 0.05). Drop attacks improved from corpus callosotomy more than other generalized seizure types. Reported complications were minor in all but one patient, and one death was reported. Transient disconnection syndrome was significantly more likely in total corpus callosotomy than in anterior corpus callosotomy (12.5% vs. 0%; p < 0.05). Improvements in quality of life, behavior, and intelligence/development quotient, as well as parental satisfaction, were generally correlated with seizure outcome. There was no postcallosotomy change in the number of antiepileptic drugs.
Significance
Total corpus callosotomy was significantly more likely to result in a reduction in seizures. Anterior corpus callosotomy was unlikely to result in disconnection syndrome. Although all of the papers drew a similar conclusion, the quality of evidence was low. At best, the evidence raises the hypothesis that corpus callosotomy is a safe and effective treatment for refractory generalized epilepsy. It is clear that a case–control or randomized trial is warranted.
Epilepsy is well-recognized as a disorder of brain networks. There is a growing body of research to identify critical nodes within dynamic epileptic networks with the aim to target therapies that ...halt the onset and propagation of seizures. In parallel, intracranial neuromodulation, including deep brain stimulation and responsive neurostimulation, are well-established and expanding as therapies to reduce seizures in adults with focal-onset epilepsy; and there is emerging evidence for their efficacy in children and generalized-onset seizure disorders. The convergence of these advancing fields is driving an era of 'network-guided neuromodulation' for epilepsy. In this review, we distil the current literature on network mechanisms underlying neurostimulation for epilepsy. We discuss the modulation of key 'propagation points' in the epileptogenic network, focusing primarily on thalamic nuclei targeted in current clinical practice. These include (i) the anterior nucleus of thalamus, now a clinically approved and targeted site for open loop stimulation, and increasingly targeted for responsive neurostimulation; and (ii) the centromedian nucleus of the thalamus, a target for both deep brain stimulation and responsive neurostimulation in generalized-onset epilepsies. We discuss briefly the networks associated with other emerging neuromodulation targets, such as the pulvinar of the thalamus, piriform cortex, septal area, subthalamic nucleus, cerebellum and others. We report synergistic findings garnered from multiple modalities of investigation that have revealed structural and functional networks associated with these propagation points - including scalp and invasive EEG, and diffusion and functional MRI. We also report on intracranial recordings from implanted devices which provide us data on the dynamic networks we are aiming to modulate. Finally, we review the continuing evolution of network-guided neuromodulation for epilepsy to accelerate progress towards two translational goals: (i) to use pre-surgical network analyses to determine patient candidacy for neurostimulation for epilepsy by providing network biomarkers that predict efficacy; and (ii) to deliver precise, personalized and effective antiepileptic stimulation to prevent and arrest seizure propagation through mapping and modulation of each patients' individual epileptogenic networks.
Objective
The accurate prediction of seizure freedom after epilepsy surgery remains challenging. We investigated if (1) training more complex models, (2) recruiting larger sample sizes, or (3) using ...data‐driven selection of clinical predictors would improve our ability to predict postoperative seizure outcome using clinical features. We also conducted the first substantial external validation of a machine learning model trained to predict postoperative seizure outcome.
Methods
We performed a retrospective cohort study of 797 children who had undergone resective or disconnective epilepsy surgery at a tertiary center. We extracted patient information from medical records and trained three models—a logistic regression, a multilayer perceptron, and an XGBoost model—to predict 1‐year postoperative seizure outcome on our data set. We evaluated the performance of a recently published XGBoost model on the same patients. We further investigated the impact of sample size on model performance, using learning curve analysis to estimate performance at samples up to N = 2000. Finally, we examined the impact of predictor selection on model performance.
Results
Our logistic regression achieved an accuracy of 72% (95% confidence interval CI = 68%–75%, area under the curve AUC = .72), whereas our multilayer perceptron and XGBoost both achieved accuracies of 71% (95% CIMLP = 67%–74%, AUCMLP = .70; 95% CIXGBoost own = 68%–75%, AUCXGBoost own = .70). There was no significant difference in performance between our three models (all p > .4) and they all performed better than the external XGBoost, which achieved an accuracy of 63% (95% CI = 59%–67%, AUC = .62; pLR = .005, pMLP = .01, pXGBoost own = .01) on our data. All models showed improved performance with increasing sample size, but limited improvements beyond our current sample. The best model performance was achieved with data‐driven feature selection.
Significance
We show that neither the deployment of complex machine learning models nor the assembly of thousands of patients alone is likely to generate significant improvements in our ability to predict postoperative seizure freedom. We instead propose that improved feature selection alongside collaboration, data standardization, and model sharing is required to advance the field.
Aim
To evaluate a lesion detection algorithm designed to detect focal cortical dysplasia (FCD) in children undergoing stereoelectroencephalography (SEEG) as part of their presurgical evaluation for ...drug‐resistant epilepsy.
Method
This was a prospective, single‐arm, interventional study (Idea, Development, Exploration, Assessment, and Long‐Term Follow‐Up phase 1/2a). After routine SEEG planning, structural magnetic resonance imaging sequences were run through an FCD lesion detection algorithm to identify putative clusters. If the top three clusters were not already sampled, up to three additional SEEG electrodes were added. The primary outcome measure was the proportion of patients who had additional electrode contacts in the SEEG‐defined seizure‐onset zone (SOZ).
Results
Twenty patients (median age 12 years, range 4–18 years) were enrolled, one of whom did not undergo SEEG. Additional electrode contacts were part of the SOZ in 1 out of 19 patients while 3 out of 19 patients had clusters that were part of the SOZ but they were already implanted. A total of 16 additional electrodes were implanted in nine patients and there were no adverse events from the additional electrodes.
Interpretation
We demonstrate early‐stage prospective clinical validation of a machine learning lesion detection algorithm used to aid the identification of the SOZ in children undergoing SEEG. We share key lessons learnt from this evaluation and emphasize the importance of robust prospective evaluation before routine clinical adoption of such algorithms.
What this paper adds
The focal cortical dysplasia detection algorithm collocated with the seizure‐onset zone (SOZ) in 4 out of 19 patients.
The algorithm changed the resection boundaries in 1 of 19 patients undergoing stereoelectroencephalography for drug‐resistant epilepsy.
The patient with an altered resection due to the algorithm was seizure‐free 1 year after resective surgery.
Overall, the algorithm did not increase the proportion of patients in whom SOZ was identified.
What this paper adds
The focal cortical dysplasia detection algorithm collocated with the seizure‐onset zone (SOZ) in 4 out of 19 patients.
The algorithm changed the resection boundaries in 1 of 19 patients undergoing stereoelectroencephalography for drug‐resistant epilepsy.
The patient with an altered resection due to the algorithm was seizure‐free 1 year after resective surgery.
Overall, the algorithm did not increase the proportion of patients in whom SOZ was identified.
This original article is commented on by Dan and Seeuws on pages 144–145 of this issue.
Abstract
Epilepsy surgery is an established safe and effective treatment for selected candidates with drug-resistant epilepsy. In this opinion piece, we outline the clinical and experimental evidence ...for selectively considering epilepsy surgery prior to drug resistance. Our rationale for expedited surgery is based on the observations that (i) a high proportion of patients with lesional epilepsies (e.g. focal cortical dysplasia, epilepsy-associated tumours) will progress to drug resistance; (ii) surgical treatment of these lesions, especially in non-eloquent areas of brain, is safe; and (iii) earlier surgery may be associated with better seizure outcomes. Potential benefits beyond seizure reduction or elimination include less exposure to antiseizure medications, which may lead to improved developmental trajectories in children and optimize long-term neurocognitive outcomes and quality of life. Further, there exists emerging experimental evidence that brain network dysfunction exists at the onset of epilepsy, where continuing dysfunctional activity could exacerbate network perturbations. This in turn could lead to expanded seizure foci and contribution to the comorbidities associated with epilepsy. Taken together, we rationalize that epilepsy surgery, in carefully selected cases, may be considered prior to drug resistance. Last, we outline the path forward, including the challenges associated with developing the evidence base and implementing this paradigm into clinical care.
Aim
To describe 20 years of experience with corpus callosotomy at Great Ormond Street Hospital for Children, London and the Children's Hospital at Westmead, Sydney.
Method
Records of patients who ...underwent corpus callosotomy between January 1995 and December 2015 were reviewed. Complications of surgery and changes in seizure type and frequency, injuries, and use of antiepileptic drugs were recorded. Drop attacks were analysed using Kaplan–Meier event‐free survival curves. Multivariable regression analysis was used to assess the effect of clinical characteristics on outcome at last follow‐up.
Results
Inclusion criteria were met for 55 patients younger than 18 years of age. Median follow‐up length was 36 months. At the last follow‐up, 26 out of 55 patients (47%) had rare or no drop attacks. In those without a good outcome at final follow‐up, 26 out of 29 (90%) had drop attacks return within 12 months of surgery. There were no preoperative predictors of developing drop attacks postoperatively. The median number of antiepileptic drugs significantly reduced from three to two. Transient neurological complications were experienced by 11 out of 55 patients (20%) and 6 out of 55 patients had surgical complications (11%).
Interpretation
Corpus callosotomy is a well‐tolerated procedure that is effective at reducing the severity of drop attacks in paediatric patients. Drop attacks that do return are likely to do so within 12 months and the number of antiepileptic drugs can be significantly reduced.
What this paper adds
Corpus callosotomy is an effective palliative treatment and well tolerated in children.
Good outcomes for the first 12 months after surgery were likely to continue.
The number of antiepileptic drugs can be significantly reduced after corpus callosotomy.
Patients with fewer than three types of seizure had better outcomes.
There were fewer injuries from drop attacks after surgery.
Resumen
Evolución de los episodios convulsivos post callosotomía en una serie pediátrica numerosa
Objetivo
Describir 20 años de experiencia en callosotomías en el Hospotial de Niños Great Ormond Street, Londres y Hospital de Niños de Westmead, Sydney.
Método
Se revisaron las historias clínicas de pacientes quienes se sometieron a callosotomía entre Enero de 1995 y Diciembre 2015. Las complicaciones quirúrgicas y los cambios en el tipo y frecuencia de los episodios convulsivos, lesiones, y uso de las drogas antiepilépticas fueron documentados. Las crisis de recaídas (Drop attacks) fueron analizados usando las curvas libres de eventos del análisis de supervivencia de Kaplan –Meier. El análisis de regresión multi‐variable fue usado para valorar el efecto de las características clínicas sobre los resultados en el último seguimiento.
Resultados
55 pacientes menores de 18 años cumplieron los criterios de inclusión. La mediana fue de 36 meses. En el último seguimiento, 26 de 55 pacientes (47%) tuvieron ausencia o escaso número de recaídas. En aquellos sin buenos resultados al finalizar el seguimiento, 26 de 29 (90%) presentaron recaidas dentro de los 12 meses de la cirugía. No hubo predictores preoperatorio del desarrollo de recaídas postoperatorios. Complicaciones neurológicas transitorias fueron experimentadas por 11 de 55 pacientes (20%) y en 6 de 55 complicaciones quirúrgicas (11%)
Interpretación
La callosotomía es un procedimiento bien tolerado que es efectivo en la reducción de la severidad de las crisis de recaídas de episodios convulsivos en la población pediátrica. Los episodios de recaídas que reaparecen es probable que lo hagan dentro de los 12 meses
Resumo
Evolução das crises convulsivas após calosotomia em uma grande população pediátrica
Objetivo
Descrever 20 anos de experiência com calosotomia no Hospital para crianças Great Ormond Street Hospital, em Londres, e no Hospital para crianças em Westmead, em Sydney.
Método
Foram analisados registros de pacientes submetidos à calosotomia entre janeiro de 1995 e dezembro de 2015. As complicações da cirurgia, as mudanças na frequência e nos tipos de crises convulsivas, lesões e uso de drogas antiepilépticas foram registradas. A ocorrência de crises convulsivas foi analisada usando curvas de sobrevivência livres de eventos Kaplan‐Meier. Análise de regressão multivariada foi utilizada para avaliar o efeito das características clínicas na evolução no último atendimento de acompanhamento.
Resultados
Cinquenta e cinco pacientes menores de 18 anos cumpriram os critérios de inclusão. O período médio de seguimento foi de 36 meses. No último atendimento de acompanhamento, 26 dos 55 pacientes (47%) não mais tiveram crises convulsivas ou as apresentaram raramente. Daqueles que não obtiveram um bom resultado no seguimento final, 26 de 29 (90%) voltaram a apresentar crises convulsivas dentro de 12 meses após a cirurgia. Não houve preditores pré‐operatórios para desenvolvimento de crises convulsivas no pós‐operatório. Complicações neurológicas transitórias foram experimentadas por 11 dos 55 pacientes (20%) e 6 dos 55 pacientes (11%) apresentaram complicações cirúrgicas.
Interpretação
A calosotomia é um procedimento bem tolerado e efetivo na redução de crises convulsivas em crianças. Nos casos em que existe retorno das crises convulsivas, este retorno é esperado que ocorra dentro de 12 meses.
What this paper adds
Corpus callosotomy is an effective palliative treatment and well tolerated in children.
Good outcomes for the first 12 months after surgery were likely to continue.
The number of antiepileptic drugs can be significantly reduced after corpus callosotomy.
Patients with fewer than three types of seizure had better outcomes.
There were fewer injuries from drop attacks after surgery.
This article is commented on by Rydenhag on page 119 of this issue.
This article's has been translated into Spanish and Portuguese.
Follow the links from the to view the translations.
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.
Hypothalamic hamartomata (HH) not only are usually associated with drug-resistant epilepsy but can also cause precocious puberty and developmental delay. Gelastic seizures are the most common type of ...seizures. Magnetic resonance image (MRI)-guided laser interstitial thermal therapy (LiTT) is a technique whereby a laser fibre is stereotactically implanted into a target lesion and heat is used to ablate whilst tissue temperature is monitored using MRI thermography. MRI-guided LiTT has proven to be an effective and safe method to treat HH. To use the LiTT system, highly accurate stereotactic fibre implantation is required. This can be achieved by the use of frame-based or frameless neuronavigation techniques. However, these techniques generally involve rigid head immobilisation using cranial pin fixation. Patients need sufficient skull thickness to safely secure the pins and sufficient skull rigidity to prevent deformation. Hence, most of the clinical reports on the use of LiTT for children describe patients aged 2 years or older. We report a novel and practical technique of using a paste cast helmet to securely place a stereotactic frame in a 5-month-old infant with HH and drug-resistant epilepsy that allowed the successful application of MRI-guided LiTT.
The objective was to analyze seizure semiology in pediatric frontal lobe epilepsy patients, considering age, to localize the seizure onset zone for surgical resection in focal epilepsy.
Fifty ...patients were identified retrospectively, who achieved seizure freedom after frontal lobe resective surgery at Great Ormond Street Hospital. Video-electroencephalography recordings of preoperative ictal seizure semiology were analyzed, stratifying the data based on resection region (mesial or lateral frontal lobe) and age at surgery (≤4 vs >4).
Pediatric frontal lobe epilepsy is characterized by frequent, short, complex seizures, similar to adult cohorts. Children with mesial onset had higher occurrence of head deviation (either direction: 55.6% vs 17.4%; p = 0.02) and contralateral head deviation (22.2% vs 0.0%; p = 0.03), ictal body-turning (55.6% vs 13.0%; p = 0.006; ipsilateral: 55.6% vs 4.3%; p = 0.0003), and complex motor signs (88.9% vs 56.5%; p = 0.037). Both age groups (≤4 and >4 years) showed hyperkinetic features (21.1% vs 32.1%), contrary to previous reports. The very young group showed more myoclonic (36.8% vs 3.6%; p = 0.005) and hypomotor features (31.6% vs 0.0%; p = 0.003), and fewer behavioral features (36.8% vs 71.4%; p = 0.03) and reduced responsiveness (31.6% vs 78.6%; p = 0.002).
This study presents the most extensive semiological analysis of children with confirmed frontal lobe epilepsy. It identifies semiological features that aid in differentiating between mesial and lateral onset. Despite age-dependent differences, typical frontal lobe features, including hyperkinetic seizures, are observed even in very young children. A better understanding of pediatric seizure semiology may enhance the accuracy of onset identification, and enable earlier presurgical evaluation, improving postsurgical outcomes. ANN NEUROL 2024;95:1138-1148.
Neuropsychological impairments are common in children with drug-resistant epilepsy. It has been proposed that epilepsy surgery may alleviate these impairments by providing seizure freedom; however, ...findings from prior studies have been inconsistent. We mapped long-term neuropsychological trajectories in children before and after undergoing epilepsy surgery, to measure the impact of disease course and surgery on functioning. We performed a retrospective cohort study of 882 children who had undergone epilepsy surgery at Great Ormond Street Hospital (1990-2018). We extracted patient information and neuropsychological functioning - obtained from IQ tests (domains: Full-Scale IQ, Verbal IQ, Performance IQ, Working Memory, and Processing Speed) and tests of academic attainment (Reading, Spelling and Numeracy) - and investigated changes in functioning using regression analyses. We identified 500 children (248 females) who had undergone epilepsy surgery (median age at surgery = 11.9 years, interquartile range = 7.8,15.0) and neuropsychology assessment. These children showed declines in all domains of neuropsychological functioning in the time leading up to surgery (all p-values ≤ 0.001; e.g., βFSIQ = -1.9, SEFSIQ = 0.3, pFSIQ < 0.001). Children lost on average one to four points per year, depending on the domain considered; 27-43% declined by 10 or more points from their first to their last preoperative assessment. At the time of presurgical evaluation, most children (46-60%) scored one or more standard deviations below the mean (<85) on the different neuropsychological domains; 37% of these met the threshold for intellectual disability (Full-Scale IQ < 70). On a group level, there was no change in performance from pre- to postoperative assessment on any of the domains (all p-values > 0.128). However, children who became seizure-free through surgery showed higher postoperative neuropsychological performance (e.g., rrb-FSIQ = 0.37, p < 0.001). These children continued to demonstrate improvements in neuropsychological functioning over the course of their long-term follow-up (e.g., βFSIQ = 0.9, SEFSIQ = 0.3, pFSIQ = 0.004). Children who had discontinued antiseizure medication (ASM) treatment at one-year follow-up showed an eight-to-13-point advantage in postoperative Working Memory, Processing Speed, and Numeracy, and greater improvements in Verbal IQ, Working Memory, Reading, and Spelling (all p-values < 0.034) over the postoperative period compared to children who were seizure-free and still receiving ASMs. In conclusion, by providing seizure freedom and the opportunity for ASM cessation, epilepsy surgery may not only halt but reverse the downward trajectory that children with drug-resistant epilepsy display in neuropsychological functioning. To halt this decline as soon as possible, or potentially prevent it from occurring in the first place, children with focal epilepsy should be considered for epilepsy surgery as early as possible after diagnosis.
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