Advancing thalamic neuromodulation in epilepsy: Bridging adult data to pediatric care.

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

The role of focused ultrasound for pediatric brain tumors: current insights and future implications on treatment strategies.

INTRODUCTION: Focused ultrasound (FUS) is an innovative and emerging technology for the treatment of adult and pediatric brain tumors and illustrates the intersection of various specialized fields, including neurosurgery, neuro-oncology, radiation oncology, and biomedical engineering. OBJECTIVE: The authors provide a comprehensive overview of the application and implications of FUS in treating pediatric brain tumors, with a special focus on pediatric low-grade gliomas (pLGGs) and the evolving landscape of this technology and its clinical utility. METHODS: The fundamental principles of FUS include its ability to induce thermal ablation or enhance drug delivery through transient blood-brain barrier (BBB) disruption, emphasizing the adaptability of high-intensity focused ultrasound (HIFU) and low-intensity focused ultrasound (LIFU) applications. RESULTS: Several ongoing clinical trials explore the potential of FUS in offering alternative therapeutic strategies for pathologies where conventional treatments fall short, specifically centrally-located benign CNS tumors and diffuse intrinsic pontine glioma (DIPG). A case illustration involving the use of HIFU for pilocytic astrocytoma is presented. CONCLUSION: Discussions regarding future applications of FUS for the treatment of gliomas include improved drug delivery, immunomodulation, radiosensitization, and other technological advancements.

Outcomes of stereoelectroencephalography following failed epilepsy surgery in children.

INTRODUCTION: Stereoelectroencephalography (SEEG) is valuable for delineating the seizure onset zone (SOZ) in pharmacoresistant epilepsy when non-invasive presurgical techniques are inconclusive. Secondary epilepsy surgery after initial failure is challenging and there is limited research on SEEG following failed epilepsy surgery in children. OBJECTIVE: The objective of this manuscript is to present the outcomes of children who underwent SEEG after failed epilepsy surgery. METHODS: In this single-institution retrospective study, demographics, previous surgery data, SEEG characteristics, management, and follow-up were analyzed for pediatric patients who underwent SEEG after unsuccessful epilepsy surgery between August 2016 and February 2023. RESULTS: Fifty three patients underwent SEEG investigation during this period. Of this, 13 patients were identified who had unsuccessful initial epilepsy surgery (24%). Of these 13 patients, six patients (46%) experienced unsuccessful resective epilepsy surgery that targeted the temporal lobe, six patients (46%) underwent surgery involving the frontal lobe, and one patient (8%) had laser interstitial thermal therapy (LITT) of the right insula. SEEG in two thirds of patients (4/6) with initial failed temporal resections revealed expanded SOZ to include the insula. All 13 patients (100%) had a subsequent surgery after SEEG which was either LITT (54%) or surgical resection (46%). After the subsequent surgery, a favorable outcome (Engel class I/II) was achieved by eight patients (62%), while five patients experienced an unfavorable outcome (Engel class III/IV, 38%). Of the six patients with secondary surgical resection, four patients (67%) had favorable outcomes, while of the seven patients with LITT, two patients (29%) had favorable outcomes (Engel I/II). Average follow-up after the subsequent surgery was 37 months ±23 months. CONCLUSION: SEEG following initial failed resective epilepsy surgery may help guide next steps at identifying residual epileptogenic cortex and is associated with favorable seizure control outcomes.

Socioeconomic Disparities Affecting the Presentation and Outcomes in Pediatric Subdural Empyema Patients.

BACKGROUND AND OBJECTIVES: Pediatric subdural empyemas (SDE) carry significant morbidity and mortality, and prompt diagnosis and treatment are essential to ensure optimal outcomes. Nonclinical factors affect presentation, time to diagnosis, and outcomes in several neurosurgical conditions and are potential causes of delay in presentation and treatment for patients with SDE. To evaluate whether socioeconomic status, race, and insurance status affect presentation, time to diagnosis, and outcomes for children with subdural empyema. METHODS: We conducted a retrospective cohort study with patients diagnosed with SDE between 2005 and 2020 at our institution. Information regarding demographics (age, sex, zip code, insurance status, race/ethnicity) and presentation (symptoms, number of prior visits, duration of symptoms) was collected. Outcome measures included mortality, postoperative complications, length of stay, and discharge disposition. RESULTS: 42 patients were diagnosed with SDE with a mean age of 9.5 years. Most (85.7%) (n = 36) were male ( P = .0004), and a majority, 28/42 (66.7%), were African American ( P < .0001). There was no significant difference in socioeconomic status based on zip codes, although a significantly higher number of patients were on public insurance ( P = .015). African American patients had a significantly longer duration of symptoms than their Caucasian counterparts (8.4 days vs 1.8 days P = .0316). In total, 41/42 underwent surgery for the SDE, most within 24 hours of initial neurosurgical evaluation. There were no significant differences in the average length of stay. The average length of antibiotic duration was 57.2 days and was similar for all patients. There were no significant differences in discharge disposition based on any of the factors identified with most of the patients (52.4%) being discharged to home. There was 1 mortality (2.4%). CONCLUSION: Although there were no differences in outcomes based on nonclinical factors, African American men on public insurance bear a disproportionately high burden of SDE. Further investigation into the causes of this is warranted.

Seizure Control Outcomes following Resection of Cortical Dysplasia in Patients with DEPDC5 Variants: A Systematic Review and Individual Patient Data Analysis.

There is insufficient evidence regarding the efficacy of epilepsy surgery in patients with pharmacoresistant focal epilepsy and coexistent DEPDC5 (dishevelled EGL-10 and pleckstrin domain-containing protein 5) pathogenic (P), likely pathogenic (LP), or variance of unknown significance (VUS) variants. To conduct a systematic review on the literature regarding the use and efficacy of epilepsy surgery as an intervention for patients with DEPDC5 variants who have pharmacoresistant epilepsy. A systematic review of the current literature published regarding the outcomes of epilepsy surgery for patients with DEPDC5 variants was conducted. Demographics and individual patient data were recorded and analyzed. Subsequent statistical analysis was performed to assess significance of the findings. A total of eight articles comprising 44 DEPDC5 patients with genetic variants undergoing surgery were included in this study. The articles primarily originated in high-income countries (5/8, 62.5%). The average age of the subjects was 10.06 ± 9.41 years old at the time of study. The most common form of epilepsy surgery was focal resection (38/44, 86.4%). Thirty-seven of the 40 patients (37/40, 92.5%) with reported seizure frequency results had improvement. Twenty-nine out of 38 patients (29/38, 78.4%) undergoing focal resection achieved Engel Score I postoperatively, and two out of four patients achieved International League Against Epilepsy I (50%). Epilepsy surgery is effective in patients with pharmacoresistant focal epilepsy and coexistent DEPDC5 P, LP, or VUS variants.

Added value of corpus callosotomy following vagus nerve stimulation in children with Lennox-Gastaut syndrome: A multicenter, multinational study.

OBJECTIVE: Lennox-Gastaut syndrome (LGS) is a severe form of epileptic encephalopathy, presenting during the first years of life, and is very resistant to treatment. Once medical therapy has failed, palliative surgeries such as vagus nerve stimulation (VNS) or corpus callosotomy (CC) are considered. Although CC is more effective than VNS as the primary neurosurgical treatment for LGS-associated drop attacks, there are limited data regarding the added value of CC following VNS. This study aimed to assess the effectiveness of CC preceded by VNS. METHODS: This multinational, multicenter retrospective study focuses on LGS children who underwent CC before the age of 18 years, following prior VNS, which failed to achieve satisfactory seizure control. Collected data included epilepsy characteristics, surgical details, epilepsy outcomes, and complications. The primary outcome of this study was a 50% reduction in drop attacks. RESULTS: A total of 127 cases were reviewed (80 males). The median age at epilepsy onset was 6 months (interquartile range [IQR] = 3.12-22.75). The median age at VNS surgery was 7 years (IQR = 4-10), and CC was performed at a median age of 11 years (IQR = 8.76-15). The dominant seizure type was drop attacks (tonic or atonic) in 102 patients. Eighty-six patients underwent a single-stage complete CC, and 41 an anterior callosotomy. Ten patients who did not initially have a complete CC underwent a second surgery for completion of CC due to seizure persistence. Overall, there was at least a 50% reduction in drop attacks and other seizures in 83% and 60%, respectively. Permanent morbidity occurred in 1.5%, with no mortality. SIGNIFICANCE: CC is vital in seizure control in children with LGS in whom VNS has failed. Surgical risks are low. A complete CC has a tendency toward better effectiveness than anterior CC for some seizure types.

Limbic network co-localization predicts pharmacoresistance in dysplasia-related epilepsy.

To evaluate the role of focal cortical dysplasia co-localization to cortical functional networks in the development of pharmacoresistance. One hundred thirty-six focal cortical dysplasia patients with 3.0 T or 1.5 T MRI were identified from clinical databases at Children's National Hospital. Clinico-radio-pathologic factors and network co-localization were determined. Using binomial logistic regression, limbic network co-localization (odds ratio 4.164 95% confidence interval 1.02-17.08, p = 0.048), and focal to bilateral tonic-clonic seizures (4.82, 1.30-18.03, p = 0.019) predicted pharmacoresistance. These findings provide clinicians with markers to identify patients with focal cortical dysplasia-related epilepsy at high risk of developing pharmacoresistance and should facilitate earlier epilepsy surgical evaluation.

Focal to bilateral tonic-clonic seizures predict pharmacoresistance in focal cortical dysplasia-related epilepsy.

OBJECTIVE: Focal cortical dysplasia (FCD) is the most common etiology of surgically-remediable epilepsy in children. Eighty-seven percent of patients with FCD develop epilepsy (75% is pharmacoresistant epilepsy [PRE]). Focal to bilateral tonic-clonic (FTBTC) seizures are associated with worse surgical outcomes. We hypothesized that children with FCD-related epilepsy with FTBTC seizures are more likely to develop PRE due to lesion interaction with restricted cortical neural networks. METHODS: Patients were selected retrospectively from radiology and surgical databases from Children's National Hospital. INCLUSION CRITERIA: 3T magnetic resonance imaging (MRI)-confirmed FCD from January 2011 to January 2020; ages 0 days to 22 years at MRI; and 18 months of documented follow-up. FCD dominant network (Yeo 7-network parcellation) was determined. Association of FTBTC seizures with epilepsy severity, surgical outcome, and dominant network was tested. Binomial regression was used to evaluate predictors (FTBTC seizures, age at seizure onset, pathology, hemisphere, lobe) of pharmacoresistance and Engel outcome. Regression was used to evaluate predictors (age at seizure onset, pathology, lobe, percentage default mode network [DMN] overlap) of FTBTC seizures. RESULTS: One hundred seventeen patients had a median age at seizure onset of 3.00 years (interquartile range [IQR] .42-5.59 years). Eighty-three patients had PRE (71%); 34 had pharmacosensitive epilepsy (PSE) (29%). Twenty patients (17%) had FTBTC seizures. Seventy-three patients underwent epilepsy surgery. Multivariate regression showed that FTBTC seizures are associated with an increased risk of PRE (odds ratio [OR] 6.41, 95% confidence interval [CI] 1.21-33.98, p = .02). FCD hemisphere/lobe was not associated with PRE. Percentage DMN overlap predicts FTBTC seizures. Seventy-two percent (n = 52) overall and 53% (n = 9) of patients with FTBTC seizures achieved Engel class I outcome. SIGNIFICANCE: In a heterogeneous population of surgical and non-operated patients with FCD-related epilepsy, the presence of FTBTC seizures is associated with a tremendous risk of PRE. This finding is a recognizable marker to help neurologists identify those children with FCD-related epilepsy at high risk of PRE and can flag patients for earlier consideration of potentially curative surgery. The FCD-dominant network also contributes to FTBTC seizure clinical expression.

Segmental spinal dysgenesis: insights from three consecutive cases and a review of the literature.

OBJECTIVE: Segmental spinal dysgenesis (SSD) is a rare congenital spinal abnormality affecting the thoracic and lumbar region of the spine, as well as the spinal cord of neonates and infants. The purpose of the study was to analyze our institution's surgical case series to provide insights into our best practices to contribute to SSD management principles, while conducting a comprehensive literature review. METHODS: Following institutional review board approval, a retrospective review of SSD surgical cases was examined to observe clinical findings, radiographic findings, management, surgical intervention, and outcomes. Keywords in the comprehensive literature review included SSD, congenital spinal dysgenesis, congenital spinal stenosis, spinal aplasia, and surgery. RESULTS: Three cases underwent successful surgical management with either improvement or maintenance of neurological baseline. Patients were diagnosed at an average age of 2.7 months, while surgical intervention averaged at 40.3 months with fecal incontinence, neurogenic bladders, spinal cord compression, clubfoot, and concerns for worsening spinal deformity as surgical indicators. The average time for follow-up was 33.7 months and no complications were reported. CONCLUSIONS: Operative management for SSD is a clinically complex decision that requires multidisciplinary input and care. Patients should be observed at neurological baseline and receive intervention at the appropriate time to allow sufficient growth for functioning without permitting drastic disease progression. Consideration of patient size and spinal instrumentation are significant towards surgical success.

Development and validation of a Bayesian network predicting neurosurgical intervention after injury in children and adolescents.

BACKGROUND: Timely surgical decompression improves functional outcomes and survival among children with traumatic brain injury and increased intracranial pressure. Previous scoring systems for identifying the need for surgical decompression after traumatic brain injury in children and adults have had several barriers to use. These barriers include the inability to generate a score with missing data, a requirement for radiographic imaging that may not be immediately available, and limited accuracy. To address these limitations, we developed a Bayesian network to predict the probability of neurosurgical intervention among injured children and adolescents (aged 1-18 years) using physical examination findings and injury characteristics observable at hospital arrival. METHODS: We obtained patient, injury, transportation, resuscitation, and procedure characteristics from the 2017 to 2019 Trauma Quality Improvement Project database. We trained and validated a Bayesian network to predict the probability of a neurosurgical intervention, defined as undergoing a craniotomy, craniectomy, or intracranial pressure monitor placement. We evaluated model performance using the area under the receiver operating characteristic and calibration curves. We evaluated the percentage of contribution of each input for predicting neurosurgical intervention using relative mutual information (RMI). RESULTS: The final model included four predictor variables, including the Glasgow Coma Scale score (RMI, 31.9%), pupillary response (RMI, 11.6%), mechanism of injury (RMI, 5.8%), and presence of prehospital cardiopulmonary resuscitation (RMI, 0.8%). The model achieved an area under the receiver operating characteristic curve of 0.90 (95% confidence interval [CI], 0.89-0.91) and had a calibration slope of 0.77 (95% CI, 0.29-1.26) with a y intercept of 0.05 (95% CI, -0.14 to 0.25). CONCLUSION: We developed a Bayesian network that predicts neurosurgical intervention for all injured children using four factors immediately available on arrival. Compared with a binary threshold model, this probabilistic model may allow clinicians to stratify management strategies based on risk. LEVEL OF EVIDENCE: Prognostic and Epidemiological; Level III.

Magnetic resonance imaging-guided stereotactic laser ablation therapy for the treatment of pediatric epilepsy: a retrospective multiinstitutional study.

OBJECTIVE: The authors of this study evaluated the safety and efficacy of stereotactic laser ablation (SLA) for the treatment of drug-resistant epilepsy (DRE) in children. METHODS: Seventeen North American centers were enrolled in the study. Data for pediatric patients with DRE who had been treated with SLA between 2008 and 2018 were retrospectively reviewed. RESULTS: A total of 225 patients, mean age 12.8 ± 5.8 years, were identified. Target-of-interest (TOI) locations included extratemporal (44.4%), temporal neocortical (8.4%), mesiotemporal (23.1%), hypothalamic (14.2%), and callosal (9.8%). Visualase and NeuroBlate SLA systems were used in 199 and 26 cases, respectively. Procedure goals included ablation (149 cases), disconnection (63), or both (13). The mean follow-up was 27 ± 20.4 months. Improvement in targeted seizure type (TST) was seen in 179 (84.0%) patients. Engel classification was reported for 167 (74.2%) patients; excluding the palliative cases, 74 (49.7%), 35 (23.5%), 10 (6.7%), and 30 (20.1%) patients had Engel class I, II, III, and IV outcomes, respectively. For patients with a follow-up ≥ 12 months, 25 (51.0%), 18 (36.7%), 3 (6.1%), and 3 (6.1%) had Engel class I, II, III, and IV outcomes, respectively. Patients with a history of pre-SLA surgery related to the TOI, a pathology of malformation of cortical development, and 2+ trajectories per TOI were more likely to experience no improvement in seizure frequency and/or to have an unfavorable outcome. A greater number of smaller thermal lesions was associated with greater improvement in TST. Thirty (13.3%) patients experienced 51 short-term complications including malpositioned catheter (3 cases), intracranial hemorrhage (2), transient neurological deficit (19), permanent neurological deficit (3), symptomatic perilesional edema (6), hydrocephalus (1), CSF leakage (1), wound infection (2), unplanned ICU stay (5), and unplanned 30-day readmission (9). The relative incidence of complications was higher in the hypothalamic target location. Target volume, number of laser trajectories, number or size of thermal lesions, or use of perioperative steroids did not have a significant effect on short-term complications. CONCLUSIONS: SLA appears to be an effective and well-tolerated treatment option for children with DRE. Large-volume prospective studies are needed to better understand the indications for treatment and demonstrate the long-term efficacy of SLA in this population.

Invasive Intracranial Electroencephalogram (EEG) Monitoring for Epilepsy in the Pediatric Patient With a Shunt.

The use of invasive intracranial electroencephalogram (EEG) monitoring in the patient with a cerebrospinal fluid (CSF) diversionary shunt presents a conundrum -- the presence of a percutaneous electrode passing into the intracranial compartment presents a pathway for entry of pathogens to which a chronically implanted device like a shunt is especially susceptible to infection. In this case report, we describe the clinical and radiological features, medical and surgical management, and treatment outcomes of pediatric patients with shunted hydrocephalus who underwent invasive intracranial monitoring over an eight-year period. Three cases of children undergoing invasive intracranial monitoring were included in this study. Invasive monitoring for each patient occurred over three to six days. In each case, invasive intracranial monitoring was completed successfully, without resulting infection or shunt malfunction. While the second procedure was complicated by the formation of a pneumocephalus, there was no associated midline shift, and invasive intracranial monitoring was completed without incidence. Each patient received further surgery that successfully reduced seizure frequency. This study suggests that, while children with CSF diversionary shunts are at an inherently increased risk for infection and other complications, invasive intracranial monitoring is a relatively safe and feasible option in these patients. Future studies should explore the optimal duration for intracranial monitoring in pediatric patients with chronically implanted devices.

Surveillance imaging and early surgical intervention for improved CNS tumor outcomes in children with Li-Fraumeni syndrome: Children's National Hospital experience and literature review.

OBJECTIVE: Li-Fraumeni syndrome (LFS) is a cancer predisposition syndrome caused by germline mutations in the TP53 gene. CNS tumors are the fourth most common tumor type in LFS, and recent screening guidelines demonstrate that early tumor detection is associated with improved long-term survival. However, there is a paucity of data regarding surgical intervention when lesions are identified in asymptomatic patients on surveillance imaging. The authors investigated this through their cohort and literature review. METHODS: The cohort consisted of children seen in the Pediatric Cancer Genetics Program at Children's National Hospital between August 2012 and August 2021. The authors also include a PubMed (MEDLINE) literature search of articles from 2006 to 2021 related to surveillance and CNS tumors in patients with LFS. Studies in which CNS tumors were not identified or detailed patient information was not provided were excluded. Patients from the selected articles and the authors' cohort were added for further analysis. RESULTS: Between August 2012 and August 2021, 10 children with LFS and CNS tumors were assessed at Children's National Hospital: 4 who were known carriers of the TP53 mutation had CNS lesions found on surveillance imaging, whereas 6 presented with symptomatic CNS lesions and were either known or subsequently found to have germline TP53 mutations. The literature search identified 148 articles, 7 of which were included in this review. Patients from the literature and the present cohort were added for a total of 56 CNS lesions. A majority of the low-grade CNS lesions (22/24, 92%) were found on surveillance protocols in asymptomatic patients, whereas the majority of the high-grade lesions (22/26, 85%) presented in symptomatic patients who were not undergoing routine surveillance or as the initial diagnosis of LFS. The authors noted a significant survival advantage in pediatric patients with low-grade lesions, with an overall survival of 100% at 30 months. Minor limitations of the study include patient sample size and limitations in the patient cohort due to this being a retrospective rather than a prospective study. CONCLUSIONS: Data presented in this study support surveillance protocols in LFS and demonstrate the importance of dedicated CNS imaging and early surgical intervention when lesions are identified. Systematic review registration no.: CRD42022372610 (www.crd.york.ac.uk/prospero).

Predictors of outcomes after surgery for medically intractable insular epilepsy: A systematic review and individual participant data meta-analysis.

Insular epilepsy (IE) is an increasingly recognized cause of drug-resistant epilepsy amenable to surgery. However, concerns of suboptimal seizure control and permanent neurological morbidity hamper widespread adoption of surgery for IE. We performed a systematic review and individual participant data meta-analysis to determine the efficacy and safety profile of surgery for IE and identify predictors of outcomes. Of 2483 unique citations, 24 retrospective studies reporting on 312 participants were eligible for inclusion. The median follow-up duration was 2.58 years (range, 0-17 years), and 206 (66.7%) patients were seizure-free at last follow-up. Younger age at surgery (≤18 years; HR = 1.70, 95% CI = 1.09-2.66, P = .022) and invasive EEG monitoring (HR = 1.97, 95% CI = 1.04-3.74, P = .039) were significantly associated with shorter time to seizure recurrence. Performing MR-guided laser ablation or radiofrequency ablation instead of open resection (OR = 2.05, 95% CI = 1.08-3.89, P = .028) was independently associated with suboptimal or poor seizure outcome (Engel II-IV) at last follow-up. Postoperative neurological complications occurred in 42.5% of patients, most commonly motor deficits (29.9%). Permanent neurological complications occurred in 7.8% of surgeries, including 5% and 1.4% rate of permanent motor deficits and dysphasia, respectively. Resection of the frontal operculum was independently associated with greater odds of motor deficits (OR = 2.75, 95% CI = 1.46-5.15, P = .002). Dominant-hemisphere resections were independently associated with dysphasia (OR = 13.09, 95% CI = 2.22-77.14, P = .005) albeit none of the observed language deficits were permanent. Surgery for IE is associated with a good efficacy/safety profile. Most patients experience seizure freedom, and neurological deficits are predominantly transient. Pediatric patients and those requiring invasive monitoring or undergoing stereotactic ablation procedures experience lower rates of seizure freedom. Transgression of the frontal operculum should be avoided if it is not deemed part of the epileptogenic zone. Well-selected candidates undergoing dominant-hemisphere resection are more likely to exhibit transient language deficits; however, the risk of permanent deficit is very low.

The Impact of Magnetoencephalography-Directed Stereo-Electroencephalography Depth Electrode Implantation on Seizure Control Outcome in Children.

Introduction The use of magnetoencephalography (MEG) in localizing epileptic foci and directing surgical treatment of medically refractory epilepsy is well established in clinical practice; however, it has not yet been incorporated into the routine planning of stereo-electroencephalography (EEG) (SEEG) depth electrode trajectories during invasive intracranial evaluation for epileptic foci localization. In this study, we assess the impact of MEG-directed SEEG on seizure outcomes in a pediatric cohort. Methods A retrospective analysis was performed on a single-institution cohort of pediatric patients with medically refractory epilepsy who underwent epilepsy surgery. The primary endpoint was the reduction in seizure burden as determined by dichotomized Engel scores (favorable outcome: Engel scores I and II; poor outcome: Engel scores III and IV). Results Thirty-seven patients met the inclusion criteria (24 males and 13 females). The median age at seizure onset was three years, the median age at surgery was 14.1 years, and the median follow-up length was 30.8 months. Concordance was noted in 7/10 (70%) patients who received MEG-directed SEEG. Good clinical outcomes were achieved in 70% of MEG-directed SEEG patients, compared to 59.4% in their counterparts; however, this difference was not statistically significant (p=0.72). We noted no statistically significant association between sex, disease laterality, or age at surgery and good clinical outcomes. Conclusions Patients who underwent MEG-directed SEEG had favorable clinical outcomes, which demonstrated the practicability of this technique for determining SEEG electrode placement. Although no significant difference in clinical outcomes was obtained between the two groups, this may have been due to low statistical power. Future prospective, multi-institutional investigations to assess the benefit of MEG-directed SEEG are warranted.

Definitive treatment of seizures due to hemimegalencephaly in neonates and young infants by transarterial embolization: technical considerations for 'endovascular embolic hemispherectomy'.

BACKGROUND: This case series describes the technical considerations and effectiveness of 'endovascular embolic hemispherectomy' for the treatment of medically intractable seizures in neonates and young infants with hemimegalencephaly (HME) and in whom surgical hemispherectomy is not a viable option. METHODS: This is a descriptive review of the endovascular technique used to treat consecutive pediatric patients with serial transarterial embolization for intractable seizures due to HME between 2018 and 2022. Clinical presentation, endovascular procedural details and complications, and efficacy were examined. RESULTS: Three infants (13-day-old, 13-week-old and 15-day-old) with HME and intractable seizures underwent a total of 10 transarterial embolizations. Anticipated intraprocedural events included vasospasm and focal subarachnoid hemorrhage in all three infants, effectively controlled endovascularly, and non-target embolization in one infant. No infants had symptomatic intracranial hemorrhage or femoral artery occlusion. EEG background quiescence and seizure cessation was achieved after the final stage of embolization in all patients. All infants were discharged home from the neonatal ICU (median length of stay 36 days, range 27-74 days) and remain seizure-free to date (4 years, 9 months, and 8 months). None have developed hydrocephalus, required surgical hemispherectomy or other neurosurgical interventions. CONCLUSION: Endovascular hemispherectomy can be safely used to provide definitive treatment of HME-related epilepsy in neonates and young infants when intraprocedural events are managed effectively. This less invasive novel approach should be considered a feasible early alternative to surgical hemispherectomy. Further studies are needed to enhance the safety profile and to assess long-term neurodevelopmental outcome and durability of freedom from seizures.

Validation of a novel path planner for stereotactic neurosurgical interventions-A retrospective clinical study.

BACKGROUND: The gold standard workflow for targeting structures in the brain involves manual path planning. This preoperative manual path planning is very time-intensive and laborious, especially when some outcome measures such as maximum ablation and penetration depth has to be optimised. METHODS: Our novel path planner generates an optimal path which maximises the hippocampus penetration and distance from critical structures using a precomputed cost map and a reward map. RESULTS: The average penetration ratio for 12 cases is 88.13 ± 23.23% for a resolution of 1° and a safety margin of 1 mm. Average run time for the path planner based on 1° resolution was 1.99 ± 0.68 min. CONCLUSIONS: Results show that the algorithm can generate safe and clinically relevant paths with a quantitative representation of the penetration depth and is faster than the average reported time for manual path planning.

Prevalence and Risk Factors for Pharmacoresistance in Children With Focal Cortical Dysplasia-Related Epilepsy.

BACKGROUND AND OBJECTIVES: Focal cortical dysplasia is the most common cause of surgically-remediable epilepsy in children. Little is known about the risk factors for the timing and development of pharmacoresistance in this population. This study sought to evaluate the prevalence and risk factors for pharmacoresistance in pediatric FCD-related epilepsy. METHODS: In this retrospective single-center cohort design, patients were identified from search of centralized radiology report database and a central epilepsy surgical database. Inclusion criteria consisted of: 3T MRI-confirmed FCD from January, 2011 to January, 2020; ages 0 days to 22 years at MRI; at least 18 months of documented follow-up after MRI, unless had single seizure or incidentally discovered FCD. Records were excluded if there was dual pathology (except for mesial temporal sclerosis), hemimegalencephaly, or tuberous sclerosis complex present in imaging or history. RESULTS: One hundred forty-three patients with confirmed FCD met inclusion criteria. One hundred twenty-four children had epilepsy (87% of FCD patients) with median age of seizure onset 2.7 years (IQR 0.75-6 years, range 0 to 17 years). Twelve children (8.5%) had a single lifetime seizure (provoked or unprovoked) or recurrent provoked seizures. Seven children (4.9%) had incidental FCD. Ninety-two patients (74%) of those with epilepsy met criteria for pharmacoresistance. Of children with epilepsy of all types, 93 children (75%) were seizure-free at the last visit; Eighty-two patients underwent epilepsy surgery, of whom 59 (72%) achieved seizure freedom. 7% (9/124) achieved seizure freedom with a second ASM, and 5.6% (7/124) with a third or more ASMs. Failure of only one antiseizure medication is associated with enormous increased incidence and earlier development of pharmacoresistance (OR 346, 95% CI 19.6-6100). Cox regression showed FCD lobar location, pathologic subtype, and age of seizure onset are not. CONCLUSIONS: Failure of one antiseizure medication is associated with substantial risk of pharmacoresistance. These data support an operational re-definition of pharmacoresistance, for surgical planning, in FCD-related epilepsy to the failure of one antiseizure medication, and support early, potentially curative surgery to improve outcomes in this patient population.

Resting-state functional MRI for motor cortex mapping in childhood-onset focal epilepsy.

BACKGROUND AND PURPOSE: Task-based functional MRI (fMRI) mapping of the motor function prior to epilepsy surgery has limitations in children with epilepsy. We present a data-driven method to automatically delineate the motor cortex using task-free, resting-state fMRI (rsfMRI) data. METHODS: We used whole-brain rsfMRI for independent component analysis (ICA). A template matching process with Discriminability Index-based Component Identification score was used for each participant to select and combine motor ICA components in their native brain space, resulting in a whole-brain ICA Motor Map (wIMM). We validated wIMM by comparing individual results with bilateral finger-tapping motor task fMRI activation, and evaluated its reproducibility in controls. RESULTS: Data from 64 patients and 12 controls were used to generate group wIMM maps. The hit rate between wIMM and motor task activation ranged from 60% to 79% across all participants. Sensitivity of wIMM for capturing the task activation peak was 87.5% among 32 patients and 100% in 12 controls with available motor task results. We also showed high similarity in repeated runs in controls. CONCLUSIONS: Our results show the sensitivity and reproducibility of an automated motor mapping method based on ICA analysis of rsfMRI in children with epilepsy. The ICA maps may provide different, but useful, information than task fMRI. Future studies will expand our method to mapping other brain functions, and may lead to a surgical planning tool for patients who cannot perform task fMRI and help predict their postsurgical function.