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.

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.

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.

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.

Deep brain stimulation and intrathecal/intraventricular baclofen for glutaric aciduria type 1: A scoping review, individual patient data analysis, and clinical trials review.

Glutaric aciduria type 1 (GA1) is an autosomal recessive disease frequently leading to dystonia. Deep brain stimulation (DBS), intrathecal baclofen (ITB), and intraventricular baclofen (IVB) are the current interventional treatment options for refractory dystonia. We performed a scoping review, individual patient data (IPD) analysis, and clinical trials review to summarize the existing literature on these interventions in this population, characterize outcomes, and suggest directions for future investigation. PubMed, Embase, and Scopus were searched following PRISMA guidelines. IPD were extracted from studies providing IPD for GA1 patients. ClinicalTrials.gov was reviewed. Of 139 articles, 7 studies with 10 patients were included. In study-level data, 2/4 (50.0%) DBS studies found no improvement in dystonia and 3/3 (100%) on baclofen found decreased dystonia and enteral medication regimen. In the IPD analysis, four studies with 5 patients (2 IVB, 2 DBS, 1 ITB) were included. The average percent reduction in dystonia was 29.9% ± 32.5% (median:18%, IQR:18%-29.2%). Function improved in 4 (80.0%) patients. All patients with reported changes in enteral dystonia-related medication regimen (3/3, 100%) reported reduction in medication usage. No patients (0%) had perioperative complications. Mean follow-up length was 14.8 ± 12.2 months. No interventional clinical trials were found. ITB, IVB, and DBS represent present neuromodulatory approaches for the treatment of GA1. ITB and IVB reduce dystonia, while DBS has a heterogeneous effect. ITB and IVB improved function and reduced enteral medication regimens. These findings must be viewed with caution considering limited data and a serious risk of bias. Further large-scale studies are necessary to determine indications for ITB, IVB, and DBS and elucidate treatment algorithms.

Virtual reality-based 3-dimensional localization of stereotactic EEG (SEEG) depth electrodes and related brain anatomy in pediatric epilepsy surgery.

INTRODUCTION: The increasing use of stereoelectroencephalography (SEEG) in the USA and the need for three-dimensional (3D) appreciation of complex spatial relationships between implanted stereotactic EEG depth electrodes and surrounding brain and cerebral vasculature are a challenge to clinicians who are used to two-dimensional (2D) appreciation of cortical anatomy having been traditionally trained on 2D radiologic imaging. Virtual reality and its 3D renderings have grown increasingly common in the multifaceted practice of neurosurgery. However, there exists a paucity in the literature regarding this emerging technology in its utilization of epilepsy surgery. METHODS: An IRB-approved, single-center retrospective study identifying all SEEG pediatric patients in which virtual reality was applied was observed. RESULTS: Of the 46 patients identified who underwent an SEEG procedure, 43.5% (20/46) had a 3D rendering (3DR) of their SEEG depth electrodes. All 3DRs were used during patient-family education and discussion among the Epilepsy multidisciplinary team meetings, while 35% (7/20) were used during neuronavigation in surgery. Three successful representative cases of its application were presented. DISCUSSION: Our institution's experience regarding virtual reality in the 3D representation of SEEG depth electrodes and the application to pre-surgical planning, patient-family education, multidisciplinary communication, and intraoperative neuronavigation demonstrate its applicability in comprehensive epilepsy patient care.

Technical case report: intractable focal seizures related to bifrontal transmantle heterotopia subserving peculiar homotopic motor distribution treated by responsive neurostimulation therapy.

NeuroPace responsive neurostimulation (RNS®) therapy was used in a case of intractable focal epilepsy with bifrontal transmantle heterotopia subserving peculiar homotopic motor distribution in a 16-year-old, right-handed male with intractable seizures. Brain MRI demonstrated bifrontal transmantle heterotopia extending from the central sulcus to subjacent lateral ventricles along with polymicrogyria along the overlying cortex suspected to be the motor cortex. Functional MRI demonstrated homotopic distribution of finger and foot motor function (deeper) within the polymicrogyria. Invasive intracranial monitoring with depth electrodes and extraoperative brain mapping revealed eloquent cortical tissue which corresponded to the right leg and right shoulder motor function.

Epilepsy surgery in infants up to 3 months of age: Safety, feasibility, and outcomes: A multicenter, multinational study.

OBJECTIVE: Drug-resistant epilepsy (DRE) during the first few months of life is challenging and necessitates aggressive treatment, including surgery. Because the most common causes of DRE in infancy are related to extensive developmental anomalies, surgery often entails extensive tissue resections or disconnection. The literature on "ultra-early" epilepsy surgery is sparse, with limited data concerning efficacy controlling the seizures, and safety. The current study's goal is to review the safety and efficacy of ultra-early epilepsy surgery performed before the age of 3 months. METHODS: To achieve a large sample size and external validity, a multinational, multicenter retrospective study was performed, focusing on epilepsy surgery for infants younger than 3 months of age. Collected data included epilepsy characteristics, surgical details, epilepsy outcome, and complications. RESULTS: Sixty-four patients underwent 69 surgeries before the age of 3 months. The most common pathologies were cortical dysplasia (28), hemimegalencephaly (17), and tubers (5). The most common procedures were hemispheric surgeries (48 procedures). Two cases were intentionally staged, and one was unexpectedly aborted. Nearly all patients received blood products. There were no perioperative deaths and no major unexpected permanent morbidities. Twenty-five percent of patients undergoing hemispheric surgeries developed hydrocephalus. Excellent epilepsy outcome (International League Against Epilepsy [ILAE] grade I) was achieved in 66% of cases over a median follow-up of 41 months (19-104 interquartile range [IQR]). The number of antiseizure medications was significantly reduced (median 2 drugs, 1-3 IQR, p < .0001). Outcome was not significantly associated with the type of surgery (hemispheric or more limited resections). SIGNIFICANCE: Epilepsy surgery during the first few months of life is associated with excellent seizure control, and when performed by highly experienced teams, is not associated with more permanent morbidity than surgery in older infants. Thus surgical treatment should not be postponed to treat DRE in very young infants based on their age.

Long-term outcomes of posterior fossa decompression for Chiari malformation type 1: which patients are most prone to failure?

PURPOSE: The role of an osseous-only posterior fossa decompression (PFD) for Chiari malformation type 1 (CM1) remains controversial. We reviewed long-term outcomes for patients with CM1 undergoing a PFD to evaluate if there was any difference for failure when compared to patients undergoing a PFD with duraplasty (PFDD). METHODS: Consecutive patients surgically treated at a single tertiary pediatric neurosurgery clinic over a 25-year period with at least 5 years of follow-up were evaluated. PFD patients were compared to those that initially received a PFDD. Demographics, surgical indications, surgical approach, outcomes, and complications were reviewed. RESULTS: A total of 60 patients were included in this study of which 25 (41.67%) underwent PFD and 35 (58.33%) underwent PFDD. Mean age at surgery was 7.41 years (range 0.4 to 18 years) with a mean follow-up of 8.23 years (range 5 to 21 years). Those that received a PFD had a lower rate of radiographic syrinx improvement (p = 0.03), especially in the setting of holocord syringes. Failure rate was significantly higher in the PFD group (20% vs 2.90%, p = 0.03). However, complications were significantly higher in the PFDD group (17.14% vs 4.0%, p = 0.04). CONCLUSIONS: PFD provides a safe treatment option with similar clinical improvements and lower post-operative complication rate compared to PFDD, albeit at the cost of greater chance of reoperation, especially in the setting of a holocord syrinx. Patients with a holocord syrinx should be considered for a PFDD as their initial procedure.

Cerebellar mutism syndrome: current approaches to minimize risk for CMS.

PURPOSE: Cerebellar mutism syndrome (CMS) is a serious source of morbidity following posterior fossa surgery in the pediatric population. However, methods for effectively decreasing its incidence and impact remain unclear. It is our aim to examine the impact of adjusting surgical factors, namely the use of a telovelar approach and avoidance of cavitronic ultrasonic aspirator, on the incidence of CMS in our population as well as outlining potential pre-, intra-, and postoperative factors that may contribute to its development. METHODS: Retrospective review was performed to identify patients undergoing posterior fossa surgery for resection of a medulloblastoma. Demographic, surgical, and postoperative data were collected. These data were analyzed for possible correlations to the risk of developing CMS via univariate analysis. For factors found to be significant, a multivariate analysis was performed to assess their independence. RESULTS: Seven of 65 patients (10.8%) developed CMS postoperatively. Factors found to be significantly associated with a higher risk of CMS were the degree of retraction utilized during the procedure (p = 0.0000) and incision of the vermis (p = 0.0294). Although they did not reach the threshold of statistical significance, tumor vascularity (p = 0.19), adoption of a transvermian approach (p = 0.19), and lack of intraoperative imaging (p = 0.17) exhibited strongly suggestive trends towards a correlation with CMS. DISCUSSION: In an effort to reduce the incidence and severity of CMS in our population, our institution adopted surgical practices that minimize tissue trauma and mitigate postoperative edema. This included the use of a telovelar over a transvermian approach to obviate the need for vermian incision, avoidance of the CUSA, and minimization of heavy retraction during surgery. This was successful in reducing the incidence of CMS from 39% in our medulloblastoma patients to 10.8%. The development of CMS after posterior fossa surgery appears to be a "two-hit" phenomenon requiring a combination of existing predisposition, surgical injury, and postoperative exacerbation. Therefore, it is critical to identify the factors involved at each stage and investigate treatments to target them appropriately.

Magnetic Resonance-Guided Laser Interstitial Thermal Therapy for the Treatment of Nonlesional Insular Epilepsy in Pediatric Patients: Technical Considerations.

INTRODUCTION: The insula presents anatomic challenges to surgical exploration and intervention. Open neurosurgical intervention is associated with high rates of complications despite improved seizure control. Minimally invasive techniques using novel energy delivery methods have gained popularity due to their relative safety and ability to overcome access-related barriers. The goal of this paper is to present an operative technical report and methodological considerations on the application of magnetic resonance-guided laser interstitial thermal therapy (MRgLITT) for the treatment of nonlesional, medically refractory, insular epilepsy in pediatric patients. METHODS: Visualase laser probe(s) were implanted using ROSA robotic stereotactic guidance into the insula using a parasagittal trajectory. After confirmation of placement using intraoperative MRI, thermal energy was delivered under real-time MR guidance. Laser wire pullback was performed when the initial dose of thermal energy was insufficient to ablate the target in its entirety. Thermal ablation within the intended target was confirmed using gadolinium-enhanced brain MRI. Following removal of laser wires, a final T1-weighted axial brain MRI was performed to confirm no evidence of hemorrhage. RESULTS: Three patients underwent MRgLITT of nonlesional insular epilepsy over an 11-month period. The epileptogenic focus was localized to the insula using stereoelectroencephalography. The anterior and middle portions of the insula were accessed using a parasagittal trajectory. Laser ablation was performed for up to 3 min using an output of 10.5 W. No complications were encountered, and all patients were discharged within 24 h after the surgery. At the most recent follow-up, all patients had an Engel I outcome without any new neurologic deficits. CONCLUSION: This small cohort shows that insular ablation can be achieved safely with promising seizure outcomes in the short term.

An Initial Cost-Effectiveness Analysis of Magnetic Resonance-Guided Laser Interstitial Thermal Therapy in Pediatric Epilepsy Surgery.

INTRODUCTION: Magnetic resonance-guided laser interstitial thermal therapy (MRgLITT) is a new technology that provides a clinically efficacious and minimally invasive alternative to conventional microsurgical resection. However, little data exist on how costs compare to traditional open surgery. The goal of this paper is to investigate the cost-effectiveness of MRgLITT in the treatment of pediatric epilepsy. METHODS: We retrospectively analyzed the medical records of pediatric patients who underwent MRgLITT via the Visualase® thermal therapy system (Medtronic, Inc., Minneapolis, MN, USA) between December 2013 and September 2017. Direct costs associated with preoperative, operative, and follow-up care were extracted. Benefit was calculated in quality-adjusted life years (QALYs), and the cost-effectiveness was derived from the discounted total direct costs over QALY. Sensitivity analysis on 4 variables was utilized to assess the validity of our results. RESULTS: Twelve consecutive pediatric patients with medically refractory epilepsy underwent MRgLITT procedures. At the last postoperative follow-up, 8 patients were seizure free (Engel I, 66.7%), 2 demonstrated significant improvement (Engel II, 16.7%), and 2 patients showed worthwhile improvement (Engel III, 16.7%). The average cumulative discounted QALY was 2.11 over the lifetime of a patient. Adjusting for inflation, MRgLITT procedures had a cost-effectiveness of USD 22,211 per QALY. Our sensitivity analysis of cost variables is robust and supports the procedure to be cost--effective. CONCLUSION: Our data suggests that MRgLITT may be a cost-effective alternative to traditional surgical resection in pediatric epilepsy surgery.

"Laser and the Tuber": thermal dynamic and volumetric factors influencing seizure outcomes in pediatric subjects with tuberous sclerosis undergoing stereoencephalography-directed laser ablation of tubers.

PURPOSE: Tuberous sclerosis (TSC) is a well-known cause of medically refractory epilepsy (MRE). Stereoencephalography-directed magnetic resonance-guided laser interstitial thermal therapy (SEEG-directed MRgLITT) is an emerging minimally invasive technique that appears aptly suited for the surgical management of TSC. Our aims are to present our experiences with patients who had undergone SEEG-directed MRgLITT to identify and treat cortical tubers responsible for clinical seizures and to perform an in-depth analysis of volumetric and thermal dynamic factors that may be related to seizure outcomes. METHODS: We studied all pediatric patients with MRE due to TSC who underwent SEEG-directed MRgLITT, investigating seizure outcomes in relation to thermal dynamic and volumetric factors. RESULTS: Eight cortical tubers from three pediatric patients were analyzed. Two of three patients had Engel I outcomes at last follow-up (median 18 months). Average A/T (ablation volume/tuber volume) ratio for Engel I outcomes was 1.28 (variance, 0.16) and 0.84 (variance, < 0.01) for all other outcomes (P = 0.035). There was a moderate positive correlation when comparing ablation energy to ablation volume (R2 = 0.65) in cortical tuber tissue. When the calcified tuber is excluded, the correlation is stronger (R2 = 0.77). Thus, the calculated energy needed to ablate 1 cm3 of cortical tuber tissue is 1263.6 J (calcified tuber) or 1089.5 J (non-calcified tuber). CONCLUSIONS: SEEG-directed MRgLITT appears to be a safe and effective technique in the management of pediatric patients with MRE due to TSC. The A/T ratio may be a useful indicator in predicting seizure outcomes.

Magnetic resonance-guided laser interstitial thermal therapy for the treatment of non-lesional insular epilepsy in pediatric patients: thermal dynamic and volumetric factors influencing seizure outcomes.

PURPOSE: To investigate the safety and efficacy of stereoelectroencephalography (sEEG) directed magnetic resonance-guided laser interstitial thermal therapy (MRgLITT) in medically refractory insular epilepsy in pediatric patients, define the relationship between ablation volumes and seizure control, and analyze the relationship between thermal energy and ablation volumes. METHODS: A single-institution, retrospective review of pediatric patients with insular epilepsy who underwent sEEG directed MRgLITT over a 10-month period was performed. Perioperative, imaging, and outcome data were analyzed. Seizure outcomes were determined based on Engel score (Engel I versus Engel II-IV). Insula and ablation volumes were measured, and the proportion of insula volume ablated was calculated. Thermal energy was calculated in joules. RESULTS: Four patients underwent sEEG directed MRgLITT of insular epileptogenic foci. The ablation volume was higher in patients with Engel I outcome (3.93 cm3) compared to Engel II-IV outcome (1.02 cm3). The proportion of ablation to insula volume was lowest in patients with Engel II-IV outcome (25.09%). The mean energy requirement to create a unit volume of ablation in the insula is 1205.86 J. A linear trend was noted between thermal ablation energy and ablation volume (R2 = 0.884). Over a mean follow-up period of 104 days, three patients were seizure-free (Engel I), and one patient saw significant improvement in seizure frequency (Engel III). CONCLUSIONS: The proportion of insula ablated, as well as the volume of ablation, are related to seizure outcome with increasing ablation volumes corresponding to improved seizure control. Further analysis of insula laser ablation thermal dynamics and volumes is needed.

An initial cost-effectiveness analysis of intraoperative magnetic resonance imaging (iMRI) in pediatric epilepsy surgery.

PURPOSE: Previous studies have illustrated the clinical utility of the addition of intraoperative magnetic resonance imaging (iMRI) to conventional microsurgical resection. While iMRI requires initial capital cost investment, long-term reduction in costly follow-up management and reoperation costs may prove economically efficacious. The objective of this study is to investigate the cost-effectiveness of the addition of iMRI utilization versus conventional microsurgical techniques in focal cortical dysplasia (FCD) resection in pediatric patients with medically refractory epilepsy. METHODS: We retrospectively reviewed the medical records of pediatric subjects who underwent surgical resection of FCD at the Children's National Health System between March 2005 and April 2015. Patients were assigned to one of three cohorts: iMRI-assisted resection, conventional resection with iMRI-assisted reoperation, or conventional resection. Direct costs included preoperative, operative, postoperative, long-term follow-up, and antiepileptic drug (AED) costs. The cost-effectiveness was calculated as the sum total of all direct medical costs over the quality-adjusted life years (QALYs). We also performed sensitivity analysis on numerous variables to assess the validity of our results. RESULTS: Fifty-six consecutive pediatric patients underwent resective surgery for medically intractable FCD. Ten patients underwent iMRI-assisted resection; 7 underwent conventional resection followed by iMRI-assisted reoperation; 39 patients underwent conventional microsurgical resection. Taken over the lifetime of the patient, the cumulative discounted QALY of patients in the iMRI-assisted resection cohort was about 2.91 years, versus 2.61 years in the conventional resection with iMRI-assisted reoperation cohort, and 1.76 years for the conventional resection cohort. Adjusting for inflation, iMRI-assisted surgeries have a cost-effectiveness ratio of $16,179 per QALY, versus $28,514 per QALY for the conventional resection with iMRI-assisted reoperation cohort, and $49,960 per QALY for the conventional resection cohort. Sensitivity analysis demonstrated that no one single variable significantly altered cost-effectiveness across all three cohorts compared to the baseline results. CONCLUSION: The addition of iMRI to conventional microsurgical techniques for resection of FCD in pediatric patients with intractable epilepsy resulted in increased seizure freedom and reduction in long-term direct medical costs compared to conventional surgeries. Our data suggests that iMRI may be a cost-effective addition to the surgical armamentarium for epilepsy surgery.

Early outcomes of stereoelectroencephalography followed by MR-guided laser interstitial thermal therapy: a paradigm for minimally invasive epilepsy surgery.

OBJECTIVE Stereoelectroencephalography (sEEG) and MR-guided laser interstitial thermal therapy (MRgLITT) have both emerged as minimally invasive alternatives to open surgery for the localization and treatment of medically refractory lesional epilepsy. Although some data are available about the use of these procedures individually, reports are almost nonexistent on their use in conjunction. The authors' aim was to report early outcomes regarding efficacy and safety of sEEG followed by MRgLITT for localization and ablation of seizure foci in the pediatric population with medically refractory lesional epilepsy. METHODS A single-center retrospective review of pediatric patients who underwent sEEG followed by MRgLITT procedures was performed. Demographic, intraoperative, and outcome data were compiled and analyzed. RESULTS Four pediatric patients with 9 total lesions underwent sEEG followed by MRgLITT procedures between January and September 2017. The mean age at surgery was 10.75 (range 2-21) years. Two patients had tuberous sclerosis and 2 had focal cortical dysplasia. Methods of stereotaxy consisted of BrainLab VarioGuide and ROSA robotic guidance, with successful localization of seizure foci in all cases. The sEEG procedure length averaged 153 (range 67-235) minutes, with a mean of 6 (range 4-8) electrodes and 56 (range 18-84) contacts per patient. The MRgLITT procedure length averaged 223 (range 179-252) minutes. The mean duration of monitoring was 6 (range 4-8) days, and the mean total hospital stay was 8 (range 5-11) days. Over a mean follow-up duration of 9.3 (range 5.1-16) months, 3 patients were seizure free (Engel class I, 75%), and 1 patient saw significant improvement in seizure frequency (Engel class II, 25%). There were no complications. CONCLUSIONS These early data demonstrate that sEEG followed by MRgLITT can be used safely and effectively to localize and ablate epileptogenic foci in a minimally invasive paradigm for treatment of medically refractory lesional epilepsy in pediatric populations. Continued collection of data with extended follow-up is needed.

MR-Guided Laser Interstitial Thermal Therapy for Medically Refractory Lesional Epilepsy in Pediatric Patients: Experience and Outcomes.

INTRODUCTION: MR-guided laser interstitial thermal therapy (MRgLITT) has emerged as a safe and effective treatment option for the ablation of epileptic foci. Its minimally invasive nature makes it attractive due to decreased morbidity and hospital stay. OBJECTIVE: To report the efficacy and safety of MRgLITT as a minimally invasive procedure for the ablation of epileptic foci in the pediatric population of medically refractory lesional epilepsy. METHODS: A retrospective review of patients who underwent MRgLITT via Visualase laser ablation at a single pediatric center was performed. Demographic and outcome data were compiled and analyzed. RESULTS: Twelve pediatric patients with a total 18 lesions underwent MRgLITT procedures between December 2013 and September 2017. Mean age at surgery was 11.1 years. Surgical substrates included 4 hypothalamic hamartomas, 3 periventricular heterotopias, 2 deep focal cortical dysplasias, 2 tuberous sclerosis, and 1 mesial temporal sclerosis. Methods of stereotaxis used included Leksell frame, BrainLab VarioGuide, ROSA robot guidance, and ClearPoint navigation. Mean procedure length was 250 min, and mean length of stay was 1.3 days. After treatment, 8 patients were seizure free (Engel I, 66.7%), 2 patients demonstrated significant improvement (Engel II, 16.7%), and 2 patients showed worthwhile improvement (Engel III, 16.7%). One patient developed a left superior quadrantanopsia postoperatively. Mean follow-up duration was 10 months. CONCLUSION: This study contributes to the sparse literature in this field by demonstrating the high efficacy and low morbidity of MRgLITT as a minimally invasive method of ablation of epileptic foci in the pediatric population of medically refractory lesional epilepsy.

Temporal lobe epilepsy and focal cortical dysplasia in children: A tip to find the abnormality.

OBJECTIVE: To demonstrate an association between magnetic resonance imaging (MRI) findings and pathologic characteristics in children who had surgery for medically refractory epilepsy due to focal cortical dysplasia (FCD). METHODS: We retrospectively studied 110 children who had epilepsy surgery. Twenty-seven patients with FCD were included. Thirteen had temporal lobe epilepsy (TLE) and 14 had extra-temporal lobe epilepsy (ETLE). Three patients had associated mesial temporal sclerosis. Preoperative 3T MRIs interleaved with nine controls were blindly re-reviewed and categorized according to signal alteration. Pathologic specimens were classified according to the 2011 International League Against Epilepsy (ILAE) classification and compared to MRI studies. RESULTS: Rates of pathology subtypes differed between TLE and ETLE (χ2 (3) = 8.57, p = 0.04). FCD type I was more frequent in TLE, whereas FCD type II was more frequent in ETLE. In the TLE group, nine patients had temporal tip abnormalities. They all exhibited gray-white matter blurring with decreased myelination and white matter hyperintense signal. Blurring involved the whole temporal tip, not just the area of dysplasia. These patients were less likely to demonstrate cortical thickening compared to those without temporal tip findings (χ2 (1) = 9.55, p = 0.002). Three of them had FCD Ib, three had FCD IIa, two had FCD IIIa, and one had FCD IIb; MRI features could not entirely distinguish between FCD subtypes. TLE patients showed more pronounced findings than ETLE on MRI (χ2 (1) = 11.95, p = 0.003, odds ratio [OR] 18.00). In all cases of FCD, isolated blurring was more likely to be associated with FCD II, whereas blurring with decreased myelination was seen with FCD I (χ2 (6) = 13.07, p = 0.042). SIGNIFICANCE: Our study described associations between MRI characteristics and pathology in children with FCD and offered a detailed analysis of temporal lobe tip abnormalities and FCD subtypes in children with TLE. These findings may contribute to the presurgical evaluation of patients with refractory epilepsy.

Considerations in deep brain stimulation (DBS) for pediatric secondary dystonia.

PURPOSE: There is a paucity of effective long-term medication treatment for secondary dystonias. In situations where significantly impairing secondary dystonias fail to respond to typical enteral medications and intrathecal (or even intraventricular) baclofen, consideration should be given to the use of deep brain stimulation (DBS). While Level I evidence and long-term follow-up clearly demonstrate the efficacy of DBS for primary dystonia, the evidence for secondary dystonia remains mixed and unclear. In this study, we report our experience with pediatric subjects who have undergone DBS for secondary dystonia. METHODS: We discuss the indications and outcomes of DBS procedures completed at our center. We also present a detailed discussion of the considerations in the management of these patients as well as a literature review. RESULTS: Of the four cases retrospectively examined here, all subjects experienced reductions in the severity of their dystonia (ranging from 0 to 100% on both the Barry-Albright Dystonia (BAD) and Burke-Fahn-Marsden Dystonia Rating Scale-Motor (BFMDRS-M) scales). CONCLUSIONS: Pallidal DBS should be considered among children with functionally debilitating, medication-resistant secondary dystonia. Patients without fixed skeletal deformities who have experienced a short duration of symptoms are most likely to benefit from this intervention.

Resective surgery for focal cortical dysplasia in children: a comparative analysis of the utility of intraoperative magnetic resonance imaging (iMRI).

PURPOSE: Seizure freedom following resection of focal cortical dysplasia (FCD) correlates with complete resection of the dysplastic cortical tissue. However, difficulty with intraoperative identification of the lesion may limit the ability to achieve the surgical objective of complete extirpation of these lesions. Intraoperative magnetic resonance imaging (iMRI) may aid in FCD resections. The objective of this study is to compare rates of postoperative seizure freedom, completeness of resection, and need for reoperation in patients undergoing iMRI-assisted FCD resection versus conventional surgical techniques. METHODS: We retrospectively reviewed the medical records of pediatric subjects who underwent surgical resection of FCD at Children's National Medical Center between March 2005 and April 2015. RESULTS: At the time of the last postoperative follow-up, 11 of the 12 patients (92 %) in the iMRI resection group were seizure free (Engel Class I), compared to 14 of the 42 patients (33 %) in the control resection group (p = 0.0005). All 12 of the iMRI patients (100 %) achieved complete resection, compared to 24 of 42 patients (57 %) in the control group (p = 0.01). One (8 %) patient from the iMRI-assisted resection group has required reoperation, compared to 17 (40 %) patients in the control resection group. CONCLUSION: Our results suggest that the utilization of iMRI during surgery for resection of FCD results in improved postoperative seizure freedom, completeness of lesion resection, and reduction in the need for reoperation.