Pediatric Palliative Epilepsy Surgery: A Report From the Pediatric Epilepsy Research Consortium (PERC) Surgery Database.

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

Deep Brain Stimulation of Bilateral Centromedian Thalamic Nuclei in Pediatric Patients with Lennox-Gastaut Syndrome: An Institutional Experience.

BACKGROUND: Surgical management of pediatric patients with nonlesional, drug-resistant epilepsy, including patients with Lennox-Gastaut syndrome (LGS), remains a challenge given the lack of resective targets in most patients and shows seizure freedom rates <50% at 5 years. The efficacy of deep brain stimulation (DBS) is less certain in children than in adults. This study examined clinical and seizure outcomes for pediatric patients with LGS undergoing DBS targeting of the centromedian thalamic nuclei (CMTN). METHODS: An institutional review board-approved retrospective analysis was performed of patients aged ≤19 years with clinical diagnosis of LGS undergoing bilateral DBS placement to the CMTN from 2020 to 2021 by a single surgeon. RESULTS: Four females and 2 males aged 6-19 years were identified. Before surgery, each child experienced at least 6 years of refractory seizures; 4 children had experienced seizures since infancy. All took antiseizure medications at the time of surgery. Five children had previous placement of a vagus nerve stimulator and 2 had a previous corpus callosotomy. The mean length of stay after DBS was 2 days. No children experienced adverse neurologic effects from implantation; the mean follow-up time was 16.3 months. Four patients had >60% reduction in seizure frequency after surgery, 1 patient experienced 10% reduction, and 1 patient showed no change. No children reported worsening seizure symptoms after surgery. CONCLUSIONS: Our study contributes to the sparse literature describing CMTN DBS for children with drug-resistant epilepsy from LGS. Our results suggest that CMTN DBS is a safe and effective therapeutic modality that should be considered as an alternative or adjuvant therapy for this challenging patient population. Further studies with larger patient populations are warranted.

A multi-center comparison of surgical techniques for corpus Callosotomy in pediatric drug-resistant epilepsy.

OBJECTIVES: Corpus callosotomy (CC) is used to reduce seizures, primarily in patients with generalized drug-resistant epilepsy (DRE). The invasive nature of the procedure contributes to underutilization despite its potential superiority to other palliative procedures. The goal of this study was to use a multi-institutional epilepsy surgery database to characterize the use of CC across participating centers. METHODS: Data were acquired from the Pediatric Epilepsy Research Consortium (PERC) Surgery Database, a prospective observational study collecting data on children 0-18 years referred for surgical evaluation of DRE across 22 U.S. pediatric epilepsy centers. Patient, epilepsy, and surgical characteristics were collected across multiple CC modalities. Outcomes and complications were recorded and analyzed statistically. RESULTS: Eighty-three patients undergoing 85 CC procedures at 14 participating epilepsy centers met inclusion criteria. Mean age at seizure onset was 2.3 years (0-9.4); mean age for Phase I evaluation and surgical intervention were 9.45 (.1-20) and 10.46 (.2-20.6) years, respectively. Generalized seizure types were the most common (59%). Complete CC was performed in 88%. The majority of CC procedures (57%) were via open craniotomy, followed by laser interstitial thermal therapy (LiTT) (20%) and mini-craniotomy/endoscopic (mc/e) (22%). Mean operative times were significantly longer for LiTT, whereas mean estimated blood loss was greater in open cases. Complications occurred in 11 cases (13%) and differed significantly between surgical techniques (p < .001). There was no statistically significant difference in length of postoperative stay across approaches. Mean follow-up was 12.8 months (range 1-39). Favorable Engel outcomes were experienced by 37 (78.7%) of the patients who underwent craniotomy, 10 (58.8%) with LiTT, and 12 (63.2%) with mc/e; these differences were not statistically significant. SIGNIFICANCE: CC is an effective surgical modality for children with DRE. Regardless of surgical modality, complication rates are acceptable and seizure outcomes generally favorable. Newer, less-invasive, surgical approaches may lead to increased adoption of this efficacious therapeutic option for pediatric DRE.

Clinical outcomes of pediatric hemispherectomy following unsuccessful subhemispheric resection for refractory epilepsy: a case review study.

OBJECTIVE: Epilepsy surgery remains one of the most underutilized procedures in epilepsy despite its proven superiority to other available therapies. This underutilization is greater in patients in whom initial surgery fails. This case series examined the clinical characteristics, reasons for initial surgery failure, and outcomes in a cohort of patients who underwent hemispherectomy following unsuccessful smaller resections for intractable epilepsy (subhemispheric group [SHG]) and compared them to those of a cohort of patients who underwent hemispherectomy as the first surgery (hemispheric group [HG]). The objective of this paper was to determine the clinical characteristics of patients in whom a small, subhemispheric resection failed, who went on to become seizure free after undergoing a hemispherectomy. METHODS: Patients who underwent hemispherectomy at Seattle Children's Hospital between 1996 and 2020 were identified. Inclusion criteria for SHG were as follows: 1) patients ≤ 18 years of age at the time of hemispheric surgery; 2) initial subhemispheric epilepsy surgery that did not produce seizure freedom; 3) hemispherectomy or hemispherotomy after the subhemispheric surgery; and 4) follow-up for at least 12 months after hemispheric surgery. Data collected included the following: patient demographics; seizure etiology; comorbidities; prior neurosurgeries; neurophysiological studies; imaging studies; and surgical details-plus surgical, seizure, and functional outcomes. Seizure etiology was classified as follows: 1) developmental, 2) acquired, or 3) progressive. The authors compared SHG to HG in terms of demographics, seizure etiology, and seizure and neuropsychological outcomes. RESULTS: There were 14 patients in the SHG and 51 patients in the HG. All patients in the SHG had Engel class IV scores after their initial resective surgery. Overall, 86% (n = 12) of the patients in the SHG had good posthemispherectomy seizure outcomes (Engel class I or II). All patients in the SHG who had progressive etiology (n = 3) had favorable seizure outcomes, with eventual hemispherectomy (1 each with Engel classes I, II, and III). Engel classifications posthemispherectomy between the groups were similar. There were no statistical differences in postsurgical Vineland Adaptive Behavior Scales Adaptive Behavior Composite scores or postsurgical full-scale IQ scores between groups when accounting for presurgical scores. CONCLUSIONS: Hemispherectomy as a repeat surgery after unsuccessful subhemispheric epilepsy surgery has a favorable seizure outcome, with stable or improved intelligence and adaptive functioning. Findings in these patients are similar to those in patients who had hemispherectomy as their first surgery. This can be explained by the relatively small number of patients in the SHG and the higher likelihood of hemispheric surgeries to resect or disconnect the entire epileptogenic lesion compared to smaller resections.

Epilepsy surgery in children with genetic etiologies: A prospective evaluation of current practices and outcomes.

OBJECTIVE: This study assesses current practices and outcomes of epilepsy surgery in children with a genetic etiology. It explores the pre-surgical workup, types of surgeries, and post-surgical outcomes in a broad array of disorders. METHODS: Patients ≤18 years who completed epilepsy surgery and had a known genetic etiology prior to surgical intervention were extrapolated from the Pediatric Epilepsy Research Consortium (PERC) surgery database, across 18 US centers. Data were assessed univariably by neuroimaging and EEG results, genetic group (structural gene, other gene, chromosomal), and curative intent. Outcomes were based on a modified International League Against Epilepsy (ILAE) outcome score. RESULTS: Of 81 children with genetic epilepsy, 72 % had daily seizures when referred for surgery evaluation, which occurred a median of 2.2 years (IQR 0.3, 5.2) after developing drug resistance. Following surgery, 68 % of subjects had >50 % seizure reduction, with 33 % achieving seizure freedom [median follow-up 11 months (IQR 6, 17). Seizure freedom was most common in the monogenic structural group, but significant palliation was present across all groups. Presence of a single EEG focus was associated with a greater likelihood of seizure freedom (p=0.02). SIGNIFICANCE: There are meaningful seizure reductions following epilepsy surgery in the majority of children with a genetic etiology, even in the absence of a single structural lesion and across a broad spectrum of genetic causes. These findings highlight the need for expedited referral for epilepsy surgery and support of a broadened view of which children may benefit from epilepsy surgery, even when the intent is palliative.

Prognostic Value of Preoperative and Postoperative Electroencephalography Findings in Pediatric Patients Undergoing Hemispheric Epilepsy Surgery.

OBJECTIVE: The seizure outcomes after hemispheric epilepsy surgery have been excellent, with 54%-90% of patients achieving long-term freedom from seizures. Similarly, the neuropsychological outcomes have been favorable. The prognostic value of pre- and postoperative electroencephalography (EEG) has not been well-studied. In the present study, we characterized the value of the pre- and postoperative EEG findings for predicting the seizure and neuropsychological outcomes for pediatric patients undergoing hemispherectomy. METHODS: A total of 22 children who had undergone functional hemispherectomy at our institution from 2010 to 2020 were included. The ictal and interictal findings were categorized as ipsilateral to the operated hemisphere, independently arising from the contralateral hemisphere, and/or generalized. The seizure outcomes were classified using the Engel scale. All neuropsychological evaluations were performed in accordance with our institution's protocol. The relationship between the EEG findings and outcomes was analyzed. RESULTS: Of the 22 patients, 19 (86%) were seizure free (Engel class IA) at the latest follow-up (mean, 4.2 years). On the preoperative EEGs, 9 had had seizures, all had had ipsilateral interictal discharges, and 9 had had contralateral interictal discharges. On the postoperative EEGs, obtained a median of 1 year after surgery, 3 had had seizures, 16 had had ipsilateral interictal discharges, and 5 had had contralateral interictal discharges. Of the 3 patients with seizures found on the postoperative EEG, all were clinically free of seizures. The patients who had not achieved Engel class IA were not significantly more likely to have abnormalities found on the EEG. The neuropsychological scores were stable from before to after surgery, with no evidence of EEG abnormalities having predictive value. CONCLUSIONS: The seizure and neuropsychology outcomes after hemispherectomy were excellent in our study, with 86% of our cohort achieving freedom from seizures. The presence, lateralization, and evolution of pre- and postoperative EEG abnormalities were not predictive of the outcomes.

Magnetic resonance imaging features of isolated periventricular heterotopia in pediatric epilepsy: a comparative study

Objective: Periventricular nodular heterotopia is a neurodevelopmental disorder in which neurons fail to migrate to the cortical surface, forming discrete areas of grey matter adjacent to the lateral ventricles. Given that periventricular nodular heterotopia is seen as an incidental finding in patients without epilepsy, causality between periventricular nodular heterotopia and epilepsy cannot be assumed. Furthermore, the structural characteristics of periventricular nodular heterotopia in patients with epilepsy are poorly defined and can be misleading. In this article, we investigate whether structural radiological characteristics of heterotopia can predict epileptogenicity in pediatric patients. Methods: Pediatric patients with periventricular nodular heterotopia, but no other epilepsy-associated cortical abnormalities on magnetic resonance imaging, were identified and divided into two groups: with epilepsy and without epilepsy. Radiological characteristics of laterality, regionalization, largest dimension and number of nodules were compared between the two groups. Results: Only periventricular nodular heterotopia spreading across several regions was associated with a statistically higher chance of epilepsy. Other features including laterality, individual region, number and largest dimension did not reliably predict epileptogenicity. Significance: Most radiological characteristics of periventricular nodular heterotopia are similar in patients with and without epilepsy. The involvement of multiple periventricular regions with heterotopia was the only feature that inferred a higher risk of epilepsy. Periventricular nodular heterotopia requires a comprehensive work-up and should be interpreted in the context of each individual patient and not assumed to be directly causative of epilepsy, nor unrelated to it. Therefore, further studies using additional structural and functional imaging modalities are needed to determine the radiological features of epileptogenic periventricular nodular heterotopia.

Precision medicine in pediatric temporal epilepsy surgery: optimization of outcomes through functional MRI memory tasks and tailored surgeries.

OBJECTIVE: The goal of epilepsy surgery is both seizure cessation and maximal preservation of function. In temporal lobe (TL) cases, the lack of functional MRI (fMRI) tasks that effectively activate mesial temporal structures hampers preoperative memory risk assessment, especially in children. This study evaluated pediatric TL surgery outcome optimization associated with tailored resection informed by an fMRI memory task. METHODS: The authors identified focal onset TL epilepsy patients with 1) TL resections; 2) viable fMRI memory scans; and 3) pre- and postoperative neuropsychological (NP) evaluations. They retrospectively evaluated preoperative fMRI memory scans, available Wada tests, pre- and postoperative NP scores, postoperative MRI scans, and postoperative Engel class outcomes. To assess fMRI memory task outcome prediction, the authors 1) overlaid preoperative fMRI activation onto postoperative structural images; 2) classified patients as having "overlap" or "no overlap" of activation and resection cavities; and 3) compared these findings with memory improvement, stability, or decline, based on Reliable Change Index calculations. RESULTS: Twenty patients met the inclusion criteria. At a median of 2.1 postoperative years, 16 patients had Engel class IA outcomes and 1 each had Engel class IB, ID, IIA, and IID outcomes. Functional MRI activation was linked to NP memory outcome in 19 of 20 cases (95%). Otherwise, heterogeneity characterized the cohort. CONCLUSIONS: Functional MRI memory task activation effectively predicted individual NP outcomes in the context of tailored TL resections. Patients had excellent seizure and overall good NP outcomes. This small study adds to extant literature indicating that pediatric TL epilepsy does not represent a single clinical syndrome. Findings support individualized surgical intervention using fMRI memory activation to help guide this precision medicine approach.

Surgical evaluation in children <3 years of age with drug-resistant epilepsy: Patient characteristics, diagnostic utilization, and potential for treatment delays.

OBJECTIVE: Drug-resistant epilepsy (DRE) occurs at higher rates in children <3 years old. Epilepsy surgery is effective, but rarely utilized in young children despite developmental benefits of early seizure freedom. The present study aims to identify unique patient characteristics and evaluation strategies in children <3 years old who undergo epilepsy surgery evaluation as a means to assess contributors and potential solutions to health care disparities in this group. METHODS: The Pediatric Epilepsy Research Consortium Epilepsy Surgery Database, a multicentered, cross-sectional collaboration of 21 US pediatric epilepsy centers, collects prospective data on children <18 years of age referred for epilepsy surgery evaluation. We compared patient characteristics, diagnostic utilization, and surgical treatment between children <3 years old and those older undergoing initial presurgical evaluation. We evaluated patient characteristics leading to delayed referral (>1 year) after DRE diagnosis in the very young. RESULTS: The cohort included 437 children, of whom 71 (16%) were <3 years of age at referral. Children evaluated before the age of 3 years more commonly had abnormal neurological examinations (p = .002) and daily seizures (p = .001). At least one ancillary test was used in 44% of evaluations. Fifty-nine percent were seizure-free following surgery (n = 34), with 35% undergoing limited focal resections. Children with delayed referrals more often had focal aware (p < .001) seizures and recommendation for palliative surgeries (p < .001). SIGNIFICANCE: There are relatively few studies of epilepsy surgery in the very young. Surgery is effective, but may be disproportionally offered to those with severe presentations. Relatively low utilization of ancillary testing may contribute to reduced surgical therapy for those without evident lesions on magnetic resonance imaging. Despite this, a sizeable portion of patients have favorable outcome after focal epilepsy surgery resections.

A clinically applicable functional MRI memory paradigm for use with pediatric patients.

OBJECTIVE: Clinically employable functional MRI (fMRI) memory paradigms are not yet established for pediatric patient epilepsy surgery workups. Seeking to establish such a paradigm, we evaluated the effectiveness of memory fMRI tasks we developed by quantifying individual activation in a clinical pediatric setting, analyzing patterns of activation relative to the side of temporal lobe (TL) pathology, and comparing fMRI and Wada test results. METHODS: We retrospectively identified 72 patients aged 6.7-20.9 years with pathology (seizure focus and/or tumor) limited to the TL who had attempted memory and language fMRI tasks over a 9-year period as part of presurgical workups. Memory fMRI tasks required visualization of autobiographical memories in a block design alternating with covert counting. Language fMRI protocols involved verb and sentence generation. Scans were both qualitatively interpreted and quantitatively assessed for blood oxygenation level dependent (BOLD) signal change using region of interest (ROI) masks. We calculated the percentage of successfully scanned individual cases, compared 2 memory task activation masks in cases with left versus right TL pathology, and compared fMRI with Wada tests when available. Patients who had viable fMRI and Wada tests had generally concordant results. RESULTS: Of the 72 cases, 60 (83%), aged 7.6-20.9 years, successfully performed the memory fMRI tasks and 12 (17%) failed. Eleven of 12 unsuccessful scans were due to motion and/or inability to perform the tasks, and the success of a twelfth was indeterminate due to orthodontic metal artifact. Seven of the successful 60 cases had distorted anatomy that precluded employing predetermined masks for quantitative analysis. Successful fMRI memory studies showed bilateral mesial temporal activation and quantitatively demonstrated: (1) left activation (L-ACT) less than right activation (R-ACT) in cases with left temporal lobe (L-TL) pathology, (2) nonsignificant R-ACT less than L-ACT in cases with right temporal lobe (R-TL) pathology, and (3) lower L-ACT plus R-ACT activation for cases with L-TL versus R-TL pathology. Patients who had viable fMRI and Wada tests had generally concordant results. SIGNIFICANCE: This study demonstrates evidence of an fMRI memory task paradigm that elicits reliable activation at the individual level and can generally be accomplished in clinically involved pediatric patients. This autobiographical memory paradigm showed activation in mesial TL structures, and cases with left compared to right TL pathology showed differences in activation consistent with extant literature in TL epilepsy. Further studies will be required to assess outcome prediction.

Epilepsy Surgery: Special Circumstances.

Epilepsy surgery has proven to be very effective in treating refractory focal epilepsies in children, producing seizure freedom or partial seizure control well beyond any other medical or dietary therapies. While surgery is mostly utilized in certain clinical phenotypes, either based on the location such as temporal lobe epilepsy, or based on the presence of known epileptogenic lesions such as focal cortical dysplasia, tumors or hemimegalencephaly, there is a growing body of evidence to support the role of surgery in other patients' cohorts that were classically not thought of as surgical candidates. These include patients with rare genetic disorders, electrical status epilepticus in sleep, status epilepticus and the very young patients. Furthermore, epilepsy surgery is not considered as a "last resort" as seizure and cognitive outcomes of surgery are considerably better when done earlier rather than later in relation to the time of onset of epilepsy and age of surgery especially in the context of known focal cortical dysplasia. This article examines the accumulating evidence of the utility of epilepsy surgery in these special circumstances.

Pediatric hemispherectomy outcome: Adaptive functioning, intelligence, and memory.

OBJECTIVE: Our purpose was to characterize neuropsychological evaluation (NP) outcome following functional hemispherectomy in a large, representative cohort of pediatric patients. METHODS: We evaluated seizure and NP outcomes and medical variables for all post-hemispherectomy patients from Seattle Children's Hospital epilepsy surgery program between 1996 and 2020. Neuropsychological evaluation outcome tests used were not available on all patients due to the diversity of patient ages and competency that is typical of a representative pediatric cohort; all patients had at least an adaptive functioning or intelligence measure, and a subgroup had memory testing. RESULTS: A total of 71 hemispherectomy patients (37 right; 34 females) yielded 66 with both preoperative (PREOP) plus postoperative (POSTOP) NPs and 5 with POSTOP only. Median surgery age was 5.7 (IQR 2-9.9) years. Engel classification indicated excellent seizure outcomes: 59 (84%) Class I, 6 (8%) Class II, 5 (7%) Class III, and 1 (1%) Class IV. Medical variables - including seizure etiology, surgery age, side, presurgical seizure duration, unilateral or bilateral structural abnormalities, secondarily generalized motor seizures - were not associated with either Engel class or POSTOP NP scores, though considerable heterogeneity was evident. Median PREOP and POSTOP adaptive functioning (PREOP n = 45, POSTOP n = 48) and intelligence (PREOP n = 29, POSTOP n = 36) summary scores were exceptionally low and did not reveal group decline from PREOP to POSTOP. Fifty-five of 66 (85%) cases showed stability or improvement. Specifically, 5 (8%) improved; 50 (76%) showed stability; and 11 (16%) declined. Improve and decline groups showed clinically interesting, but not statistical, differences in seizure control and age. Median memory summary scores were low and also showed considerable heterogeneity. Overall median PREOP to POSTOP memory scores (PREOP n = 16, POSTOP n = 24) did not reveal declines, and verbal memory scores improved. Twenty six percent of intelligence and 33% of memory tests had verbal versus visual-spatial discrepancies; all but one favored verbal, regardless of hemispherectomy side. SIGNIFICANCE: This large, single institution study revealed excellent seizure outcome in 91% of all 71 patients plus stability and/or improvement of intelligence and adaptive functioning in 85% of 66 patients who had PREOP plus POSTOP NPs. Memory was similarly stable overall, and verbal memory improved. Medical variables did not predict group NP outcomes though heterogeneity argues for further research. This study is unique for cohort size, intelligence plus memory testing, and evidence of primacy of verbal over visual-spatial development, despite hemispherectomy side. This study reinforces the role of hemispherectomy in achieving good seizure outcome while preserving functioning.

Determination of language dominance in pediatric patients with epilepsy for clinical decision-making: Correspondence of intracarotid amobarbitol procedure and fMRI modalities.

Identification of the language dominant hemisphere is an essential part of the evaluation of potential pediatric epilepsy surgery patients. Historically, language dominance has been determined using the intracarotid amobarbitol procedure (IAP), but use of functional Magnetic Resonance Imaging (fMRI) scanning is becoming more common. Few studies examine the correspondence between fMRI and IAP in pediatric samples. The current study examined the agreement of hemispheric lateralization as determined by fMRI and IAP in a consecutive sample of 10 pediatric patients with epilepsy evaluated for epilepsy surgery. Data showed a strong correlation between IAP and fMRI lateralilty indices (r=.91) and 70% agreement in determination of hemispheric dominance, despite increased demonstration of bilateral or atypical language representation in this pediatric sample. Clinical implications and interpretation challenges are discussed.

Language regression, hemichorea and focal subclinical seizures in a 6-year-old girl with GLUT-1 deficiency.

•A 6 year old girl with progressive speech difficulties, new abnormal movements, olfactory hallucinations•Choreiform movement of her right hemibody along with her face and tongue•Seizures were noted during sleep without clinical correlate, progressing to awake subclinical seizures.

Multiple hippocampal transections for refractory pediatric mesial temporal lobe epilepsy: seizure and neuropsychological outcomes.

OBJECTIVE: Temporal lobe epilepsy (TLE) is the most common focal epilepsy across adult and pediatric age groups. It is also the most amenable to surgery, with excellent long-term seizure outcome. Most TLE cases have an epileptogenic zone in the mesial temporal structures, namely the hippocampus. Resecting the dominant hippocampus has been shown to be associated with significant verbal memory deficits, especially in patients with intact verbal memory scores presurgically. Multiple hippocampal transection (MHT) is a relatively new surgical technique designed to interrupt the longitudinal hippocampal circuitry involved in seizure propagation yet preserve the circular fibers involved in memory function. This technique has been used to treat mesial TLE in both dominant- and nondominant-hemisphere cases, almost exclusively in adults. It has been applied to normal and sclerotic hippocampi. METHODS: In this study, information on 3 pediatric patients who underwent MHT for mesial TLE at Children's Wisconsin between 2017 and 2018 is included. Clinical, electroencephalographic, and neuropsychological features and outcomes are described in detail. RESULTS: MRI revealed a tumor in the amygdala with a normal hippocampus in 1 patient and hippocampal sclerosis in 2 patients. All patients underwent stereoelectroencephalography confirming the involvement of the hippocampus in seizure onset. MHTs were completed under intraoperative monitoring, with amygdala and temporal tip resection in all patients due to early spread to these regions. All patients had excellent seizure outcomes at 1 year, and 2 of the 3 patients remain seizure free at last follow-up (range 20-36 months), all with stable or improved neuropsychological profiles, including verbal memory. CONCLUSIONS: MHT is a relatively new surgical procedure designed to preserve essential memory circuitry while disrupting seizure propagation pathways in the hippocampus. A growing body of literature shows good seizure and neuropsychological results, but mainly in adults. This is the first series of MHTs used exclusively in children at one medical center, showcasing excellent seizure control and preservation of neuropsychological functioning. One of the patients is also the first described to have MHT in the setting of an amygdalar tumor abutting the hippocampus, further expanding the pathological setting in which MHT can be used effectively.

Examining the Utility of Resective Epilepsy Surgery in Children With Electrical Status Epilepticus in Sleep: Long Term Clinical and Electrophysiological Outcomes.

Background: Electrical Status Epilepticus in Sleep (ESES) is an epileptic encephalopathy syndrome characterized by infrequent clinical seizures and prominent interictal burden during slow wave sleep associated with cognitive deficits and behavioral dysfunction. Medical treatment with anti-epileptic drugs is often unsuccessful. Resective surgery may be a valuable option in carefully selected patients. This case series aims to describe the indications, long term results and utility of resective surgery for ESES. Methods: Information on 14 patients who underwent surgery for epilepsy and ESES at the Children's Hospital of Wisconsin between 2007 and 2017 is included. Clinical, electrographic and neuropsychological features and outcomes are described in detail. Results: The most common pathology was encephalomalacia due to perinatal middle cerebral artery stoke (5/14). Twelve patients had imaging findings of perinatal pathologies; however, two patients had normal magnetic resonance imaging. Surgery was performed to control refractory epilepsy in eight patients. Six patients had no clinical seizures for 1-6 years prior to surgery, one of which had no known clinical seizures at all. All showed cognitive declines (6/14) or impairment (8/14) on neuropsychological assessments, and surgery was suggested to minimize further cognitive declines. The most common surgical procedure was hemispherotomy (10/14). Temporo-parieto-occipital disconnection, frontal lobectomy, parieto-occipital resection, and limited corticectomy were also used, with good outcomes for the first three procedures. Clinical follow up mean was 4.4 years and 12 patients had excellent seizure outcome. Electroencephalography (EEG) follow up mean was 3 years and ESES resolved in 12/14 patients. All patients completed post-surgical neuropsychological evaluation with mean follow-up of 17.46 months. Conclusions: Resective surgery is an effective treatment for selected cases of ESES, producing long term seizure freedom, resolution of ESES and stabilization of cognitive and behavioral functioning in most patients. Our case series is the largest single center cohort description addressing resective surgery for ESES. Outcomes in this sample suggest that good long-term seizure, EEG and cognitive/behavioral outcomes can be achieved in patients with normal brain imaging and in limited lobar or multi-lobar resections. Moreover, patients with ESES and very infrequent clinical seizures can benefit from surgery with stabilization of cognitive and behavioral functioning.

Stereotactic laser ablation for nonlesional cingulate epilepsy: case report.

Stereotactic laser ablation (SLA) is being increasingly used to treat refractory focal epilepsy, especially mesial temporal lobe epilepsy. However, emerging evidence suggests it can be used for extratemporal lobe epilepsy as well.The authors report the case of a 17-year-old male who presented with refractory nocturnal seizures characterized by bilateral arms stiffening or rhythmic jerking lasting several seconds. Semiology suggested an epileptogenic zone close to one of the supplementary sensory motor areas. Electroencephalography showed seizures arising from the central region without consistent lateralization. Brain imaging showed no abnormality. An invasive evaluation using bilateral stereoelectroencephalography (SEEG) was utilized in 2 steps, first to establish the laterality of seizures, and second to further cover the mesial cingulate region of the right hemisphere. Seizures arose from the middle portion of the right cingulate gyrus. Extraoperative electrical mapping revealed that the seizure onset zone was adjacent to eloquent motor areas. SLA targeting the right midcingulate gyrus was performed. The patient has remained seizure free since immediately after the procedure with no postoperative deficits (follow-up of 17 months).This case highlights the utility of SEEG in evaluating difficult-to-localize, focal epilepsy. It also demonstrates that the use of SLA can be extended to nonlesional, extratemporal epilepsies.

Successful surgical management of New Onset Refractory Status Epilepticus (NORSE) presenting with gelastic seizures in a 3 year old girl.

Gelastic seizures (GS) are typically associated with hypothalamic hamartomas and present during childhood. However it is now known that GS can be found in focal epilepsies arising from other regions in the brain, including mesial and neocortical frontal, temporal and parietal regions. GS have rarely been described as the presenting manifestation of New Onset Refractory Status Epilepticus (NORSE). In this article we describe a previously healthy 3-year-old who presented with an explosive onset of GS that were refractory to multiple anti-seizure medications. These seizures arose from the right frontal region. An extensive metabolic and immunological evaluation was negative. Her brain magnetic resonance imaging (MRI) was negative, however the Positron Emission Tomography (PET) scan showed a hypermetabolic region in the right frontal inferior gyrus. She underwent a depth electrode evaluation that revealed a widespread irritative zone involving the PET "lesion" as well as mesial and neocortical regions in the right frontal lobe. The seizure onset zone was widespread and non-localizable. However the GS were associated with a clear ictal epileptiform discharge on invasive EEG arising from the depth of the superior frontal gyrus, which was not overlapping with the PET hypermetabolic region. She underwent a right frontal lobectomy sparing the primary motor region in the pre-central gyrus. She has remained seizure free for 15 months since. The pathological analysis showed focal cortical dysplasia type II in the region of the PET scan hypermetabolism. This case expands the clinical spectrum of GS to include cases of NORSE. Additionally the case highlights the role of resective surgery in GS presenting as NORSE and the potentially excellent outcome that can be achieved by early intervention.

Ictal motor sequences: Lateralization and localization values.

OBJECTIVE: To determine the lateralization and localization values of ictal motor sequences in the setting of focal epilepsy ending with a secondarily generalized motor seizure. METHODS: Retrospectively, the ictal motor sequences were analyzed in patients with focal epilepsy ending with a secondarily generalized motor seizure by three readers blinded to all clinical and electrographic data. One representative seizure per patient was selected. Prevalence, positive predictive value (PPV), and Fleiss Kappa for the following motor signs were calculated: version, unilateral limb tonic posturing, unilateral limb clonic seizure, figure-of-4, M2e, hand dystonia, clonic asymmetric ending, and Todd's paralysis. Sequences of signs with a PPV ≥ 80% were then analyzed to determine their lateralization and localization values. RESULTS: A total of 47 seizures were studied. The "reliable" motor signs with a robust lateralizing value (PPV > 80%) were version, unilateral tonic posturing, M2e, unilateral clonic seizure, asymmetric clonic ending, and Todd's paralysis. Figure-of-4 and hand dystonia had a relatively low PPV, and therefore were not included in the following sequence analysis, which included only 38 patients with two or more motor signs of high PPV. Multiple combinations of temporal progression of motor signs were seen in these 38 patients, with version being the most common initial motor sign (29 of 38 patients) usually followed by M2e (15 of 29 patients), and/or a focal tonic seizure (7 of 29 patients). Accurate lateralization of the epileptogenic zone (EZ) with a PPV of 100% can be predicted when two or more reliable motor signs point to the same side. However, the various sequences of reliable motor signs did not differentiate between temporal and extratemporal epilepsy. SIGNIFICANCE: The presence of reliable ictal motor signs in focal epilepsy is extremely valuable in lateralizing the EZ, but not in determining the localization of the EZ. This is especially useful when epilepsy surgery is indicated.