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Background: Hippocampal sclerosis (HS) is a common surgical substrate in adult epilepsy surgery cohorts but variably reported in various pediatric cohorts., Objective: We aimed to study the epilepsy phenotype, radiological and pathological variability, seizure and neurocognitive outcomes in children with drug-resistant epilepsy and hippocampal sclerosis (HS) with or without additional subtle signal changes in anterior temporal lobe who underwent surgery., Methods: This retrospective study enrolled children with drug-resistant focal epilepsy and hippocampal sclerosis with or without additional subtle T2-Fluid Attenuated Inversion Recovery (FLAR)/Proton Density (PD) signal changes in anterior temporal lobe who underwent anterior temporal lobectomy with amygdalohippocampectomy. Their clinical, EEG, neuropsychological, radiological and pathological data were reviewed and summarized., Results: Thirty-six eligible patients were identified. The mean age at seizure onset was 3.7 years; 25% had daily seizures at time of surgery. Isolated HS was noted in 22 (61.1%) cases and additional subtle signal changes in ipsilateral temporal lobe in 14 (38.9%) cases. Compared to the normative population, the group mean performance in intellectual functioning and most auditory and visual memory tasks were significantly lower than the normative sample. The mean age at surgery was 12.3 years; 22 patients (61.1%) had left hemispheric surgeries. ILAE class 1 outcomes was seen in 28 (77.8%) patients after a mean follow up duration of 2.3 years. Hippocampal sclerosis was noted pathologically in 32 (88.9%) cases; type 2 (54.5%) was predominant subtype where further classification was possible. Additional pathological abnormalities were seen in 11 cases (30.6%); these had had similar rates of seizure freedom as compared to children with isolated hippocampal sclerosis/gliosis (63.6% vs 84%, p=0.21). Significant reliable changes were observed across auditory and visual memory tasks at an individual level post surgery., Conclusions: Favourable seizure outcomes were seen in most children with isolated radiological hippocampal sclerosis. Patients with additional pathological abnormalities had similar rates of seizure freedom as compared to children with isolated hippocampal sclerosis/gliosis., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Purpose: To investigate the utility of Low Density (LD) Electrical Source Imaging (ESI) to model the ictal onset zone (IOZ) for the surgical work up of children with medically refractory epilepsy., Methods: This was a retrospective review of 12 patients from a district and regional pediatric epilepsy center, who underwent focal resections between 2014 and 2019. ESI was generated using the Curry 8 software, incorporating T1 Magnetic Resonance Imaging (MRI) scans and scalp electroencephalogram (EEG) recordings. Concordance of the ictal LD-ESI localizations to the epileptogenic zone was assessed by comparing the location of the ictal LD-ESI to the focal resection margins on neuroimaging and noting the post-operative outcomes at one year. Localizations determined by ictal LD-ESI were also compared to interictal LD-ESI, positron emission tomography (FDG-PET) and interictal magnetoencephalography (MEG)., Results: Ictal ESI correctly localized the ictal onset zone in 4/6 patients, with all four being seizure free at one year. Similarly, interictal ESI localized the irritative zone in 7/9 patients with focal resections, with 6/7 being seizure free at one year. Additionally, we observed ictal ESI to be concordant to interictal ESI in 5/6 patients. Ictal ESI and interictal ESI were concordant to interictal MEG in 3/6 patients. Ictal ESI was concordant with FDG-PET in 6/7 cases., Conclusion: IOZ source localization through LD-ESI is a promising complementary method of assessing the epileptogenic focus in children. These findings may support the inclusion of ictal LD-ESI within the pre-surgical evaluation of children to supplement current diagnostic tools., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Purpose: In patients with medically refractory epilepsy and normal magnetic resonance imaging (MRI), high-resolution dedicated MRI may identify cryptic lesions. The aim of this study was to assess improvement in lesion detection and its impact on clinical management, using additional high-resolution dedicated 3T MRI in children with medically refractory epilepsy who had normal 3T epilepsy protocol MRI., Materials and Methods: Children who had resective epilepsy surgery and suspected focal cortical dysplasia (FCD) or normal 3T epilepsy protocol MRI were included. Those with other diagnosis on MRI including tumor and hippocampal sclerosis were excluded. Patients who had normal MRI on 3T epilepsy protocol underwent dedicated high-resolution 3T MRI through the epileptogenic zone, guided by video EEG, Magnetoencephalography and FDG-PET data., Results: 101 patients with at least 1 year follow-up were included. Twenty-nine of 44 (66%) patients who had normal epilepsy protocol MRI had a lesion identified on dedicated high-resolution MRI. The addition of dedicated high-resolution MRI to standard epilepsy protocol increased sensitivity from 53.1% (95%CI: 40%-66%) to 85.9% (95%CI: 75%-93%). Identified lesions were concordant to surgical resection in all patients and guided depth/strip electrode insertion in 20/25 (80%) patients who underwent staged resection. Dedicated MRI detected small deep seated lesions in 10/20 (50%), and guided depth electrodes placement, without which it would not be feasible, as the lobar location of epileptogenic zone from other non-invasive tests were not sufficiently precise., Conclusion: Patients with non-lesional epilepsy on standard epilepsy protocol MR may benefit from high-resolution dedicated MRI to aid identification of an underlying lesion, which could impact surgical management and improve seizure control., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Introduction: The diagnosis and surgical management of pediatric patients with insular epilepsy is challenging due to variable and indistinct seizure semiology arising within the insular cortex. In addition, surgical approaches are associated with potential morbidity given the regional neurosurgical and vascular anatomy. Our institutional experience in evaluation and surgical management of insular epilepsy patients is presented. Diagnostic evaluation, surgical treatment and seizures outcomes are highlighted., Methods: The institutional database for all pediatric surgical epilepsy patients was reviewed over a period of 15 years (2000-2015). Study subjects were defined as patients who had undergone surgical resection of the epileptogenic zone involving the insular cortex. Diagnostic imaging, electrophysiological studies and surgical records were assessed., Results: Six (n = 6) patients with insular epilepsy were identified with a mean follow up of 2.8 years (range: 0.8-6.8 years). Mean age at surgical resection was 9.5 ± 2.5 years (range: 2.5-16 years). Majority of patients (n = 4/6, 67%) underwent more than 1 surgical procedure. Magnetoencephalography (MEG) identified insular cortex involvement presurgically in all cases. MEG cluster localization was useful in guiding invasive EEG monitoring in 5 patients and was concordant with identification of epileptogenic zone through intracranial monitoring in all 5 patients. Surgical resection of the epileptogenic zone, as delineated through MEG spike sources and invasive EEG monitoring, was associated with favorable seizure outcome in 4 of 6 patients (67%; Engel Class I). Cortical dysgenesis was identified on histopathology in 4 cases., Conclusion: Diagnostic evaluation through invasive and noninvasive electrophysiological studies is critical to identify pediatric patients with insular epilepsy. Our findings suggest that MEG may help with identifying the epileptogenic zone within the insular cortex, which could be confirmed with invasive intracranial monitoring., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Objective: We hypothesized that the extensive epileptic network in patients with tuberous sclerosis complex (TSC) manifests as clustered and scattered distributions of magnetoencephalography spike sources (MEGSS)., Methods: We retrospectively analyzed pre-surgical MEG in 15 patients with TSC. We performed single moving dipole analysis to localize and classify clustered and scattered MEGSS. We compared the number of electrodes within the resected area (RA) and the proportions of clustered and scattered MEGSS within RA with the seizure outcome., Results: The number of electrodes within RA ranged from 29 to 83 (mean=51). The MEGSS were distributed over multiple lobes (3-8; mean=5.9) and bilaterally in 14 patients. Clusters of MEGSS ranged from 1 to 4 (mean=1.4). The number of MEGSS ranged in total from 28 to 139 (mean=70); in the clusters, 10-128 (mean=49); and in the scatters, 0-45 (mean=21). Four patients achieved an Engel class I surgical outcome, four, a class II outcome; five, a class III outcome; and two, a class IV outcome. The proportion of MEGSS ranged in total from 0 to 92% (mean=57%) within RA; 0-100% (mean=67%) in the resection hemisphere; 0-100% (mean=63%) in the clusters; and 0-81% (mean=28%) in the scatters. Univariate ordinal logistic regression analyses showed that the proportion of scattered MEGSS within RA (p=0.049) significantly correlated with seizure outcomes. Multivariate analyses using three covariates (number of electrodes, proportions of clustered and scattered MEGSS within RA) showed that only the proportion of scattered MEGSS within RA significantly correlated with seizure outcomes (p=0.016)., Significance: MEG data showed a wide distribution of multilobar MEGSS in patients with TSC. The seizure outcome was not related to the clustered MEGSS within RA, since the grids were essentially planned to cover and resect the clustered MEGSS surrounding tubers. The maximal possible resection of scattered MEGSS correlated with improved seizure outcome in TSC. Some parts of the epileptogenic zone disrupted by multiple tubers did not have a sufficiently large area to produce clustered MEGSS. Although the wide distribution of scattered MEGSS is not interpreted as epileptogenic, they might be interrelated with clustered MEGSS to project a complex epilepsy network and be part of the extensive epileptogenic zones found in TSC., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background: The aims of this systematic review and meta-analysis were to assess (i) estimates of good neurodevelopmental outcome in infantile spasms (IS), (ii) if neurodevelopmental outcome has changed since the publication of the first guideline on medical treatment of IS in 2004 and (iii) effect of lead time to treatment (LTTT)., Methods: The Medline, Embase, Cochrane, PsycINFO, Web of Science and Scopus databases, and reference lists of retrieved articles were searched. Studies inclusion criteria were: (i) >5 patients with IS, (ii) mean/median follow-up of >6 months, (iii) neurodevelopmental outcome, and (iv) randomized and observational studies. The data extracted included proportion of good neurodevelopmental outcome, year of publication, cryptogenic or symptomatic IS and LTTT., Results: Of the 1436 citations screened, 55 articles were included in final analysis, with a total of 2967 patients. The pooled estimate for good neurodevelopmental outcome was 0.236 (95% CI: 0.193-0.286). There was no difference between the proportions of good neurodevelopmental outcome for the 21 studies published after 2004 [0.264 (95% CI: 0.197-0.344)] compared to the 34 studies published before 2004 [0.220 (95% CI: 0.168-0.283)] (Q value=0.862, p=0.353). The pooled estimate of good neurodevelopmental outcome for cryptogenic IS [0.543 (95% CI: 0.458-0.625)] was higher than symptomatic IS [0.125 (95% CI: 0.09-0.171)] (Q value=69.724, p<0.001). Risk ratio of LTTT <4weeks relative to >4weeks for good neurodevelopmental outcome of 8 studies was 1.519 (95% CI: 1.064-2.169)., Conclusion: Neurodevelopmental outcome was overall poor in patients with IS and has not changed since the publication of first guideline on IS. Although cryptogenic IS has better prognosis than symptomatic IS, the outcome for cryptogenic IS remained poor. There was heterogeneity in neurodevelopmental outcome ascertainment methods, highlighting the need for a more standardized and comprehensive assessment of cognitive, behavioural, emotional and functional outcomes., (Copyright © 2014 Elsevier B.V. All rights reserved.)

In frontal lobe epilepsy (FLE), interictal discharges and seizures are more likely to spread to contralateral hemisphere and become secondarily generalized. The aim of this study was to assess white matter (WM) integrity in children with FLE using diffusion tensor imaging (DTI). Children with FLE and normal MRI, and healthy controls with no neurological or psychiatric disorders underwent DTI on 3T MRI. Whole brain fractional anisotropy (FA) and mean diffusivity (MD) maps were compared between right and left FLE with controls. 43 children with FLE, consisting of 28 left and 15 right FLE, and 44 healthy controls were recruited. Patients with left FLE had significant FA reductions in left (p=0.002) and right (p=0.003 and p=0.034) superior longitudinal fasciculi (SLF), genu/body (p=0.0002) and splenium (p=0.011) of corpus callosum. Patients with right FLE had significant FA reductions in left (p=0.016) and right (p=0.033) SLF, genu (p=0.001) and body of corpus callosum (p=0.001 and p=0.008), and significant MD elevation in right thalamus (p=0.032). There was no significant association between FA or MD and clinical seizure parameters. The abnormal WM both ipsilateral and contralateral to seizure focus may be due to seizure activity or abnormal brain development., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Purpose: Magnetoencephalography (MEG) provides source localization of interictal spikes. This study evaluated the inhibitory effects of propofol on MEG spike sources (MEGSSs) among different types of seizures in patients who underwent two separate MEG studies with and without total intravenous anesthesia (TIVA) using propofol., Methods: We studied 19 children (1-14 years; mean, 6.2 years) who had MEG with and without TIVA. TIVA was administered using propofol (0.03-0.06 mg/kg/min) to record MEG with simultaneous EEG. We analyzed number of spikes of MEG and MEGSSs comparing MEG studies done with and without TIVA., Results: Seizures were divided into nine focal seizure (FS) with/without secondary generalization, five epileptic spasm (ES), and five generalized seizure (GS). TIVA significantly decreased the number of MEG spikes/min (from 4.5 to 2.0) in five FS without secondary generalization (p<0.05). The number of MEG spikes/min was significantly lower (1.9) in FS than that in non-FS (ES+GS, 6.1) (p<0.01). MEGSSs without TIVA were clustered in 15 patients (6FS; 4ES; 5GS), scattered in four (3FS; 1ES). MEG under TIVA showed clusters in 10 patients (1FS; 4ES; 5GS), scatters in three (2FS; 1ES) and no MEGSS in six patients with FS. Under TIVA, nine (90%) of ten patients with non-FS showed MEGSSs clusters compared to one (11%) of nine patients with FS (p<0.01)., Conclusions: Reduction of MEGSSs occurred in patients with FS under TIVA. Diffuse/generalized spikes in non-FS are not affected by TIVA. Propofol may decrease focal spikes in the epileptic cortex in FS. Cortical hyperexcitability in non-FS group would be stronger or more extensive than that in the FS group of patients., (Copyright © 2013 Elsevier B.V. All rights reserved.)

The aim of this study was to use whole brain quantitative analysis to identify impaired white matter (WM) integrity using diffusion tensor imaging (DTI) in children with new-onset seizures. Thirty-five children with new-onset seizures and normal MRI were recruited. Twelve patients had generalized seizures, and 23 had partial seizures. Thirty-one healthy controls were also recruited. Whole brain fractional anisotropy (FA), apparent diffusion coefficient (ADC), radial diffusivity (RD) and axial diffusivity (AD) maps of patients were compared to controls, corrected for multiple comparisons. There was significantly reduced FA in left postcentral, elevated RD in left posterior cingulum and right external capsule, elevated AD in left middle temporal WM and left thalamus, and reduced AD in left anterior cingulum, left temporal, and right supramarginal WM in patients relative to controls. Patients with partial epilepsy showed elevated RD in bilateral posterior cingulum, increased AD in left middle frontal, reduced AD in left temporal, right parietal and right supramarginal WM. Patients with generalized epilepsy showed increased AD in right cerebellum, and reduced AD in left anterior cingulum and left middle temporal WM. The findings indicate that impaired WM integrity with abnormal myelin and axons is present in children with new-onset seizures., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Double-layered ternary-phase microparticles composed of a poly(D,L-lactide-co-glycolide) (50:50) (PLGA) core and a poly(L-lactide) (PLLA) shell impregnated with poly(caprolactone) (PCL) particulates were loaded with ibuprofen (IBU) and metoclopramide HCl (MCA) through a one-step fabrication process. MCA and IBU were localized in the PLGA core and in the shell, respectively. The aim of this study was to study the drug release profiles of these double-layered ternary-phase microparticles in comparison to binary-phase PLLA(shell)/PLGA(core) microparticles and neat microparticles. The particle morphologies, configurations and drug distributions were determined using scanning electron microscopy (SEM) and Raman mapping. The presence of PCL in the PLLA shell gave rise to an intermediate release rate of MCA between that of neat and binary-phase microparticles. The ternary-phase microparticles were also shown to have better controlled release of IBU than binary-phase microparticles. The drug release rates for MCA and IBU could be altered by changing the polymer mass ratios. Ternary-phase microparticles, therefore, provide more degrees of freedom in preparing microparticles with a variety of release profiles and kinetics., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Purpose: Due to differences in epilepsy types and surgery, economic evaluations of epilepsy treatment in adults cannot be extrapolated to children. We evaluated the cost-effectiveness of epilepsy surgery compared to medical treatment in children with intractable epilepsy., Method: Decision tree analysis was used to evaluate the cost-effectiveness of surgery relative to medical management. Fifteen patients had surgery and 15 had medical treatment. Cost data included inpatient and outpatient costs for the period April 2007 to September 2009, physician fee, and medication costs. Outcome measure was percentage seizure reduction at one-year follow-up. Incremental cost-effectiveness ratio (ICER) was assessed. Sensitivity analysis was performed for different probabilities of surgical and medical treatment outcomes and costs, and surgical mortality or morbidity., Results: More patients managed surgically experienced Engel class I and II outcomes compared to medical treatment at one-year follow-up. Base-case analysis yielded an ICER of $369 per patient for each percentage reduction in seizures for the surgery group relative to medical group. Sensitivity analysis showed robustness for the different probabilities tested., Conclusion: Surgical treatment resulted in greater reduction in seizure frequency compared to medical therapy and was a cost-effective treatment option in children with intractable epilepsy who were evaluated for epilepsy surgery and subsequently underwent surgery compared to continuing medical therapy. However, larger sample size and long-term follow-up are needed to validate these findings., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Purpose: To evaluate diffusion tensor imaging (DTI) indices of (i) cortical tubers and (ii) normal-appearing subcortical white matter adjacent to cortical tubers within the epileptogenic zone and non-epileptogenic zone., Methods: Twelve children with tuberous sclerosis complex underwent MRI, DTI and magnetoencephalography (MEG). Regions of interest (ROIs) were placed within cortical tubers and normal-appearing subcortical white matter adjacent to cortical tubers within MEG identified epileptogenic zone and non-epileptogenic zone. Fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (lambda(parallel)) and radial diffusivity (lambda(perpendicular)) were calculated., Results: 26 out of 104 cortical tubers were in the epileptogenic zone. FA of cortical tubers in the epileptogenic zone was significantly lower than non-epileptogenic zone (p=0.015). There were no significant differences between MD (p=0.896), lambda(parallel) (p=0.672) and lambda(perpendicular) (p=0.651) of cortical tubers in the epileptogenic and non-epileptogenic zone. In normal-appearing subcortical white matter within the epileptogenic zone, FA was lower (p=0.001) and lambda(perpendicular) (p=0.011) was higher than non-epileptogenic zone. There were no significant differences between MD (p=0.110) and lambda(parallel) (p=0.735) of normal-appearing subcortical white matter within the epileptogenic and non-epileptogenic zone., Conclusion: DTI changes in normal-appearing white matter within the epileptogenic zone could represent abnormal white matter related to MRI-occult dysplastic cortex or ictal/interictal activity., (Copyright 2010 Elsevier B.V. All rights reserved.)

Purpose: Hemimegalencephaly is an epileptic encephalopathy which presents during the neonatal period. Our aims are to analyze interictal fast oscillations and EEG patterns in neonates and infants with hemimegalencephaly., Methods: We collected scalp EEGs and applied multiple band frequency analysis (MBFA) to analyze frequency and power of interictal fast oscillations (FOs)., Results: We studied 18 scalp EEGs in 7 patients with catastrophic epilepsy secondary to hemimegalencephaly, between 3 days and 24 months of age. Maximum frequency of FOs (22-57 Hz; mean, 42 Hz) on the hemimegalencephalic side was significantly higher than those (8-27 Hz; mean, 18 Hz) in the unaffected side (p<0.05). Differences in maximum FOs remained within 1-8 Hz (mean, 3 Hz) across consecutive EEGs. We found four EEG patterns: (1) suppression burst pattern (7 EEGs, 6 patients), (2) continuous triphasic complex pattern (5 EEGs, 3 patients), (3) continuous high amplitude slow waves with spikes (3 EEGs, 2 patients) and (4) frequent spike and slow waves (3 EEGs, 2 patients). Five patients with multiple EEG recordings showed changing EEG patterns., Conclusion: We confirmed the interictal epileptogenic FOs in neonatal EEGs of patients with hemimegalencephaly. The frequency of epileptogenic FOs remains stable from the neonates through increasing age while the patterns of EEG changed during brain maturation.

Purpose: Cortical dysplasia (CD) has been classified as Taylor's focal cortical dysplasia (FCD type II) or other CD (FCD type I and mild malformation of cortical development) based on histological findings. The aims of this study were to determine whether MRI and magnetoencephalography (MEG) could distinguish between these two groups and to evaluate surgical outcomes., Methods: We evaluated the MRI features, MEG spike source (MEGSS) patterns (clusters or scatters) and postsurgical seizure outcomes of 27 children with CD., Results: Thirteen patients had Taylor's FCD and 14 had other CD. MRI showed visible lesion in 22 (81%) patients. Tapering of abnormal white matter signals to the ventricles and cortical thickening were more prevalent in Taylor's FCD; focal hypoplasia and white matter atrophy were more prevalent in other CD. MEG showed spike sources in 26 (96%) patients. Taylor's FCD showed clustered MEGSSs in 6, both clustered and scattered MEGSSs in 5 and scattered MEGSSs in 2; other CD demonstrated clusters in 2, cluster and scatter in 10 and scatter in 1. Eleven (85%) of 13 patients who had complete resection of clustered MEGSSs achieved Engel class I outcome, but 4 (44%) of 9 patients with incomplete resections achieved class I. Fifteen (88%) of 17 patients who had complete resection of MRI lesions achieved class I, but 1 (33%) of 3 patients with incomplete lesionectomy was class I. There was no difference in surgical outcomes between Taylor's FCD and other CD., Conclusions: Surgical outcome was the same in both groups following complete removal of areas containing clustered MEGSSs and MR lesions.

Purpose: Bilateral diffusion tensor imaging (DTI) abnormalities have been reported in the white matter associated to the hippocampus in adults with mesial temporal lobe epilepsy (TLE). In children with a shorter duration of epilepsy, such changes may not have yet emerged. The aim of this study was to investigate interictal changes in the temporal lobe white matter (TLWM) and cingulate gyrus white matter (CGWM) of children with TLE using DTI., Methods: DTI was performed in eight children with TLE and 10 healthy, age-matched controls. Fractional anisotropy (FA), trace, parallel (lambda(||)) and perpendicular (lambda( perpendicular)) diffusivity were calculated for a volume of interest in the TLWM and CGWM on the seizure focus side and the contralateral side. Data were compared for differences between sides for patients and between patients and controls., Results: There was no significant difference in FA, trace, lambda(||) and lambda( perpendicular) between TLWM and CGWM on the seizure focus side versus the contralateral side in TLE patients. Increased diffusivity, lambda(||) and lambda( perpendicular) within the TLWM and CGWM were found in TLE patients compared to controls, but no significant difference in FA was seen., Conclusions: Bilaterally increased diffusivity, lambda(||) and lambda( perpendicular) in the white matter in children with TLE may be related to seizure induced functional or structural changes. The preserved FA in our pediatric cohort is in contrast to the reduced FA in the white matter of adults with TLE and may relate to differences in the duration of epilepsy or in the vulnerability of white matter to seizures.