Establishing criteria for pediatric epilepsy surgery center levels of care: Report from the ILAE Pediatric Epilepsy Surgery Task Force.

Presurgical evaluation and surgery in the pediatric age group are unique in challenges related to caring for the very young, range of etiologies, choice of appropriate investigations, and surgical procedures. Accepted standards that define the criteria for levels of presurgical evaluation and epilepsy surgery care do not exist. Through a modified Delphi process involving 61 centers with experience in pediatric epilepsy surgery across 20 countries, including low-middle- to high-income countries, we established consensus for two levels of care. Levels were based on age, etiology, complexity of presurgical evaluation, and surgical procedure. Competencies were assigned to the levels of care relating to personnel, technology, and facilities. Criteria were established when consensus was reached (≥75% agreement). Level 1 care consists of children age 9 years and older, with discrete lesions including hippocampal sclerosis, undergoing lobectomy or lesionectomy, preferably on the cerebral convexity and not close to eloquent cortex, by a team including a pediatric epileptologist, pediatric neurosurgeon, and pediatric neuroradiologist with access to video-electroencephalography and 1.5-T magnetic resonance imaging (MRI). Level 2 care, also encompassing Level 1 care, occurs across the age span and range of etiologies (including tuberous sclerosis complex, Sturge-Weber syndrome, hypothalamic hamartoma) associated with MRI lesions that may be ill-defined, multilobar, hemispheric, or multifocal, and includes children with normal MRI or foci in/abutting eloquent cortex. Available Level 2 technologies includes 3-T MRI, other advanced magnetic resonance technology including functional MRI and diffusion tensor imaging (tractography), positron emission tomography and/or single photon emission computed tomography, source localization with electroencephalography or magnetoencephalography, and the ability to perform intra- or extraoperative invasive monitoring and functional mapping, by a large multidisciplinary team with pediatric expertise in epilepsy, neurophysiology, neuroradiology, epilepsy neurosurgery, neuropsychology, anesthesia, neurocritical care, psychiatry, and nursing. Levels of care will improve safety and outcomes for pediatric epilepsy surgery and provide standards for personnel and technology to achieve these levels.

Epilepsy surgery near or in eloquent cortex in children-Practice patterns and recommendations for minimizing and reporting deficits.

OBJECTIVE: We aimed to investigate the current practices guiding surgical resection strategies involving epileptogenic zones (EZs) near or in eloquent cortex (EC) at pediatric epilepsy surgery centers worldwide. METHODS: A survey was conducted among 40 respondents from 33 pediatric epilepsy surgery centers worldwide on the weight assigned to diagnostic tests used to define the EZ and EC, how EC is viewed, and how surgeries are planned for foci near or in eloquent cortex. RESULTS: A descriptive analysis was performed that revealed considerable variation in the use of diagnostic tests and resective strategies toward EZ and EC. SIGNIFICANCE: The wide variation in strategies may contribute to undesirable outcomes characterized by poor seizure control with added deficits and underscores the need to establish best practices in pediatric epilepsy surgery. The survey data were used to formulate a set of recommendations to help minimize deficits and to report them consistently.

PET hypermetabolism in medically resistant childhood epilepsy: Incidence, associations, and surgical outcome.

OBJECTIVE: We observed several children with medically resistant epilepsy demonstrating focal positron emission tomography (PET) hypermetabolism, a finding rarely reported and of questionable significance. We therefore retrospectively reviewed the incidence of hypermetabolic PET, and its relationship to electroencephalography (EEG) and magnetic resonance imaging (MRI) findings, and to the outcome of epilepsy surgery. METHODS: We retrospectively reviewed 498 PET brain studies in patients with medically resistant childhood epilepsy for evidence of hypermetabolism. In patients with PET hypermetabolism, we correlated metabolic abnormality with the scalp EEG and MRI findings. In a subset of patients who underwent surgical resection, we further correlated the PET findings with histopathologic and surgical outcomes. RESULTS: Focal PET hypermetabolism was identified in 33 (6.6%) of 498 studies. The region of hypermetabolism correlated with a spike count of ≥10 per minute in 26 of 32 concomitant scalp EEG studies and 18 of 21 lesions evident on MRI. In 17 patients who underwent surgical resection, PET hypermetabolism further correlated with regions revealing almost continuous epileptiform discharges on the intracranial EEG and with histopathologically malformative tissue. At a minimum follow-up of 1 year postsurgery (median 33 months), 7 (50%) of 14 patients had Engel's class I outcome, 4 patients had class II, and 2 had class III outcome, whereas one patient was unchanged. At last follow-up, seizure freedom was noted in five of seven patients with focal PET hypermetabolism alone versus three of eight patients with PET hypometabolism. SIGNIFICANCE: Focal PET hypermetabolism is associated with high spike frequency on scalp EEG and can occur in the absence of ictal events during the peri-injection period. Correlation with intracranial EEG usually corroborates the highly epileptogenic pathophysiologic state. Cortical malformations constitute the most common pathologic substrate, and resection of the hypermetabolic PET region may facilitate favorable outcomes. These observations indicate that focal PET hypermetabolism is an important marker of the epileptogenic zone and may represent its epicenter.

The diagnostic utility of 3D-ESI rotating and moving dipole methodology in the pre-surgical evaluation of MRI-negative childhood epilepsy due to focal cortical dysplasia.

OBJECTIVE: This study investigates whether a combined rotating dipole (RD) and moving dipole (MD) solution enhances three-dimensional electroencephalography (EEG) source imaging (3D-ESI) localization in magnetic resonance imaging (MRI)-negative pediatric patients with focal cortical dysplasia (FCD). METHODS: We retrospectively selected 14 MRI-negative patients with FCD from a cohort of 60 pediatric patients previously used to evaluate the diagnostic utility of 3D-ESI in epilepsy surgery. Patients were younger than 18 years at time of surgery and had at least 1 year of outcome data. RD and MD models were constructed for each interictal spike or sharp wave, and it was determined whether each inverse algorithm localized within the surgical resection cavity (SRC). We also compared the 3D-ESI findings and surgical outcome with positron emission tomography (PET) and ictal single photon emission computed tomography (iSPECT). RESULTS: RD analyses revealed a high concordance with the SRC (78.6%), particularly for temporal lobe resection (100.0%), and showed superior localization compared to PET and iSPECT, with the highest correlation in FCD type I and temporal lobe resection. Furthermore, the RD method was superior to iSPECT in FCD type II cases and to PET in extratemporal resections. RD and MD results were comparable, but in 18.2% of patients with FCD type I with localizing RDs, the MD solution was only partially within the SRC; in all of these patients 3D-ESI also correlated with superior surgical outcome compared to PET and iSPECT, especially when RD and MD solutions were analyzed together. SIGNIFICANCE: 3D-ESI in MRI-negative cases showed superior localization compared to iSPECT or PET, especially in FCD type I and temporal lobe epilepsy, and correlated with superior surgical outcome compared to iSPECT and PET at 1 year and 2 years postoperatively, especially when RD and MD solutions were analyzed together. These findings suggest that 3D-ESI based on a combined RD-MD solution improves surgical accuracy in MRI-negative patients with FCD.

The diagnostic utility of 3D electroencephalography source imaging in pediatric epilepsy surgery.

OBJECTIVE: The aim of this study was to investigate the utility of three-dimensional electroencephalography source imaging (3D-ESI) with low-resolution electroencephalographic data in the pediatric noninvasive presurgical evaluation, and to compare the findings with positron emission tomography (PET) and ictal single-photon emission computed tomography (iSPECT). METHODS: We retrospectively selected 60 patients from a database of 594 patients who underwent excisional surgery for drug-resistant epilepsy. Patients were <18 years at time of surgery, had at least one presurgical volumetric brain magnetic resonance imaging (MRI), and at least 1 year of outcome data. 3D-ESI was performed with NeuroScan software CURRY V.7.0. For each patient the surgical resection was planned utilizing 3D-ESI as an adjunctive tool to supplement MRI and electrocorticographic data. Our analyses addressed three critical variables: pathology (focal cortical dysplasia vs. other pathologies), imaging (MRI negative vs. positive cases), and surgery (temporal resection vs. extratemporal and multilobar resections). We also compared the localizing utility and surgical outcome of 3D-ESI findings with PET, iSPECT, and the colocalized surgical resection. Statistical analyses were performed using the Statistical Package for the Social Sciences, Version 20. RESULTS: Mean age at surgery was 11.18 years (range 1-18 years). 3D-ESI showed a strong correlation with the surgical resection cavity (65.0%), particularly within the temporal lobe. 3D-ESI demonstrated better localization in MRI-negative cases (78.6%), which was not statistically significant. 3D-ESI also correlated with a superior surgical outcome profile compared to PET and iSPECT. SIGNIFICANCE: Our findings demonstrate that 3D-ESI data obtained with low-resolution electroencephalography achieves reasonably accurate noninvasive localization of epileptic spikes in pediatric focal epilepsy, especially in temporal lobe and MRI-negative cases, and is comparable to iSPECT and PET. Given its lesser expense and lack of radiation exposure, 3D-ESI is a useful and efficient tool for evaluating surgical candidacy in pediatric epilepsy surgery centers, particularly if PET and iSPECT are unavailable.

Diagnostic utility of invasive EEG for epilepsy surgery: Indications, modalities, and techniques.

Many patients with medically refractory epilepsy now undergo successful surgery based on noninvasive diagnostic information, but intracranial electroencephalography (IEEG) continues to be used as increasingly complex cases are considered surgical candidates. The indications for IEEG and the modalities employed vary across epilepsy surgical centers; each modality has its advantages and limitations. IEEG can be performed in the same intraoperative setting, that is, intraoperative electrocorticography, or through an independent implantation procedure with chronic extraoperative recordings; the latter are not only resource intensive but also carry risk. A lack of understanding of IEEG limitations predisposes to data misinterpretation that can lead to denying surgery when indicated or, worse yet, incorrect resection with adverse outcomes. Given the lack of class 1 or 2 evidence on IEEG, a consensus-based expert recommendation on the diagnostic utility of IEEG is presented, with emphasis on the application of various modalities in specific substrates or locations, taking into account their relative efficacy, safety, ease, and incremental cost-benefit. These recommendations aim to curtail outlying indications that risk the over- or underutilization of IEEG, while retaining substantial flexibility in keeping with most standard practices at epilepsy centers and addressing some of the needs of resource-poor regions around the world.

A probabilistic approach for pediatric epilepsy diagnosis using brain functional connectivity networks.

BACKGROUND: The lives of half a million children in the United States are severely affected due to the alterations in their functional and mental abilities which epilepsy causes. This study aims to introduce a novel decision support system for the diagnosis of pediatric epilepsy based on scalp EEG data in a clinical environment. METHODS: A new time varying approach for constructing functional connectivity networks (FCNs) of 18 subjects (7 subjects from pediatric control (PC) group and 11 subjects from pediatric epilepsy (PE) group) is implemented by moving a window with overlap to split the EEG signals into a total of 445 multi-channel EEG segments (91 for PC and 354 for PE) and finding the hypothetical functional connectivity strengths among EEG channels. FCNs are then mapped into the form of undirected graphs and subjected to extraction of graph theory based features. An unsupervised labeling technique based on Gaussian mixtures model (GMM) is then used to delineate the pediatric epilepsy group from the control group. RESULTS: The study results show the existence of a statistically significant difference (p < 0.0001) between the mean FCNs of PC and PE groups. The system was able to diagnose pediatric epilepsy subjects with the accuracy of 88.8% with 81.8% sensitivity and 100% specificity purely based on exploration of associations among brain cortical regions and without a priori knowledge of diagnosis. CONCLUSIONS: The current study created the potential of diagnosing epilepsy without need for long EEG recording session and time-consuming visual inspection as conventionally employed.

The diagnostic utility of intracranial EEG monitoring for epilepsy surgery in children.

OBJECTIVE: There are limited data on the indications for the use of chronic invasive electroencephalography (EEG) monitoring (IEM) for pediatric epilepsy surgery. METHODS: We retrospectively studied 102 children who underwent intracranial monitoring to map critical cortex, localize the epileptogenic region, or resolve divergent findings. We assessed IEM utility based on changes to the resection plan following analysis of noninvasive data. RESULTS: IEM was judged useful in 87% of cases and had greatest utility for resolving discordant data and localizing extratemporal and multilobar epileptogenic zones. IEM data were least useful for seizure onset in the temporal lobe and had little utility for direct cortical stimulation mapping unless functional magnetic resonance imaging (fMRI) revealed atypical language representation or the epileptogenic zone was in proximity to critical cortex. SIGNIFICANCE: IEM utility was demonstrated for a majority of cases with well-defined indications. The method of assessing utility will facilitate multicentric studies toward developing future consensus and practice guidelines.

Diagnostic methods and treatment options for focal cortical dysplasia.

Our inability to adequately treat many patients with refractory epilepsy caused by focal cortical dysplasia (FCD), surgical inaccessibility and failures are significant clinical drawbacks. The targeting of physiologic features of epileptogenesis in FCD and colocalizing functionality has enhanced completeness of surgical resection, the main determinant of outcome. Electroencephalography (EEG)-functional magnetic resonance imaging (fMRI) and magnetoencephalography are helpful in guiding electrode implantation and surgical treatment, and high-frequency oscillations help defining the extent of the epileptogenic dysplasia. Ultra high-field MRI has a role in understanding the laminar organization of the cortex, and fluorodeoxyglucose-positron emission tomography (FDG-PET) is highly sensitive for detecting FCD in MRI-negative cases. Multimodal imaging is clinically valuable, either by improving the rate of postoperative seizure freedom or by reducing postoperative deficits. However, there is no level 1 evidence that it improves outcomes. Proof for a specific effect of antiepileptic drugs (AEDs) in FCD is lacking. Pathogenic mutations recently described in mammalian target of rapamycin (mTOR) genes in FCD have yielded important insights into novel treatment options with mTOR inhibitors, which might represent an example of personalized treatment of epilepsy based on the known mechanisms of disease. The ketogenic diet (KD) has been demonstrated to be particularly effective in children with epilepsy caused by structural abnormalities, especially FCD. It attenuates epigenetic chromatin modifications, a master regulator for gene expression and functional adaptation of the cell, thereby modifying disease progression. This could imply lasting benefit of dietary manipulation. Neurostimulation techniques have produced variable clinical outcomes in FCD. In widespread dysplasias, vagus nerve stimulation (VNS) has achieved responder rates >50%; however, the efficacy of noninvasive cranial nerve stimulation modalities such as transcutaneous VNS (tVNS) and noninvasive (nVNS) requires further study. Although review of current strategies underscores the serious shortcomings of treatment-resistant cases, initial evidence from novel approaches suggests that future success is possible.

Diagnostic test utilization in evaluation for resective epilepsy surgery in children.

Epilepsy surgery is highly successful in achieving seizure freedom in carefully selected children with drug-resistant focal epilepsy. Advances in technology have aided presurgical evaluation and increased the number of possible candidates. Many of the tests employed are resource intense, and in specific cases they may be unhelpful or have adverse effects. Some standardization of the evaluation process is thus considered timely. Given the lack of class 1 or 2 evidence defining the relative utility of each test in specific clinicopathologic cohorts, a set of expert recommendations was attempted using consensus among members of the Pediatric Epilepsy Surgery Task Force of the International League Against Epilepsy (ILAE) Commissions of Pediatrics and Diagnostics These recommendations aim to limit fringe over or underutilization of use while retaining substantial flexibility in the use of various tests, in keeping with most standard practices at established pediatric epilepsy centers. A PowerPoint slide summarizing this article is available for download in the Supporting Information section here.

Localizing value of ictal SPECT is comparable to MRI and EEG in children with focal cortical dysplasia.

PURPOSE: To assess the predictive value of ictal single-photon emission computed tomography (SPECT) for outcome after excisional epilepsy surgery in a large population of children with focal cortical dysplasia (FCD). METHODS: One hundred seventy-three ictal SPECT studies in 106 children with histologically proven FCD were retrospectively analyzed. The extent and location of ictal hyperperfusion and completeness of surgical removal were assessed. Completeness of resection of epileptogenic regions defined by ictal SPECT, electroencephalography (EEG), and magnetic resonance imaging (MRI) were compared and correlated with postoperative seizure outcome. In addition, subcortical activation of the cerebellum, basal ganglia, and thalamus were analyzed. KEY FINDINGS: The extent of hyperperfusion was focal or lobar in 58%, whereas multilobar activations occurred in only 32%; hemispheric or bilateral findings were rare. Favorable postsurgical seizure outcome was achieved in 67% patients with nonlocalized SPECT findings, 45% with nonresected ictal hyperperfusion, 36% with partially resected ictal hyperperfusion, and 86% when the zone of ictal hyperperfusion was completely resected (p = 0.000198). The favorable postsurgical outcome after complete removal of the SPECT hyperperfusion zone surpassed the 75% rate of seizure freedom in patients with removal of MRI/EEG-defined epileptogenic region. A similar predictive value of ictal SPECT for seizure outcome was found in nonoperated patients and subjects who were undergoing reoperation. Subcortical activation conferred no predictive value. SIGNIFICANCE: Ictal SPECT helps to define the epileptogenic zone in a high proportion of children with FCD undergoing surgical evaluation. Complete removal of both SPECT and MRI/EEG-defined regions is a strong predictor of surgical success and has important implications for surgical planning.

Predictors of seizure-free outcome after epilepsy surgery for pediatric tuberous sclerosis complex.

PURPOSE: Variable predictors of postsurgical seizure outcome have been reported in children with tuberous sclerosis complex (TSC). We analyzed a large surgical series of pediatric TSC patients in order to identify prognostic factors crucial for selection of subjects for epilepsy surgery. METHODS: Thirty-three children with TSC who underwent excisional epilepsy surgery at Miami Children's Hospital were retrospectively reviewed. A total of 29 clinical, neuropsychological, electroencephalography (EEG), magnetic resonance imaging (MRI), and surgical variables were analyzed and related to seizure outcomes. Univariate Barnard's exact test, Wilcoxon's rank-sum test, and multivariate statistical Cox's model were used to examine the significance of associations between the variables and seizure outcome. KEY FINDINGS: Eighteen patients (55%) have been seizure-free 2 years after (final) surgery; postoperative complications occurred in five subjects (15%). Complete removal of epileptogenic tissue detected by both MRI and intracranial EEG, regional scalp interictal EEG patterns, and agreement of interictal and ictal EEG localization were the most powerful predictors of seizure-free outcome. Other significant predictors included occurrence of regional scalp ictal EEG patterns, fewer brain regions affected by tubers, presence of preoperative hemiparesis, and one-stage surgery. Remaining factors such as age at seizure onset, incidence of infantile spasms or other seizure types, duration of epilepsy, seizure frequency, mental retardation, as well as types and extent of resections did not influence outcome. SIGNIFICANCE: Perioperative features rather than preoperative variables are the most important determinants of postsurgical seizure outcome in patients with TSC. Our findings may assist in the surgical management of these patients.

Predictive factors of ictal SPECT findings in paediatric patients with focal cortical dysplasia.

AIMS: To identify variables that influence the extent of ictal single-photon emission computed tomography (SPECT) findings in paediatric patients with focal cortical dysplasia (FCD). METHODS: We visually evaluated 98 ictal SPECT studies from 67 children treated surgically for intractable epilepsy caused by FCD. SPECT findings were classified as "non-localised", "well-localised", and "extensive" and compared with parameters of injected seizures (seizure type and duration, injection time, and scalp EEG ictal pattern), presence of structural pathology on MRI, type of surgery performed after SPECT study, and histological findings. RESULTS: A shorter injection time and duration of injected seizure was associated with more localised SPECT hyperperfusion. SPECT findings were not significantly influenced by type of injected seizure. Widespread ictal scalp EEG patterns were associated with extensive SPECT findings. Larger zones of hyperperfusion were more common in patients with lesional MRI and patients undergoing multilobar resections. SPECT studies demonstrating good localisation were more common in patients with mild malformations of cortical development. CONCLUSION: Early ictal SPECT radiotracer injection is crucial for successful localisation of the epileptogenic zone. Seizure duration, type of scalp EEG findings, and presence of structural pathology on MRI may influence the extent of ictal SPECT hyperperfusion, which was associated with certain types of epilepsy surgery as well as histopathological findings.

Graph neural networks in EEG spike detection.

OBJECTIVE: This study develops new machine learning architectures that are more adept at detecting interictal epileptiform discharges (IEDs) in scalp EEG. A comparison of results using the average precision (AP) metric is made with the proposed models on two datasets obtained from Baptist Hospital of Miami and Temple University Hospital. METHODS: Applying graph neural networks (GNNs) on functional connectivity (FC) maps of different frequency sub-bands to yield a novel architecture we call FC-GNN. Attention mechanism is applied on a complete graph to let the neural network select its important edges, hence bypassing the extraction of features, a model we refer to as CA-GNN. RESULTS: On the Baptist Hospital dataset, the results were as follows: Vanilla Self-Attention →0.9029±0.0431, Hierarchical Attention →0.8546±0.0587, Vanilla Visual Geometry Group (VGG) →0.92±0.0618, Satelight →0.9219±0.046, FC-GNN →0.9731±0.0187, and CA-GNN →0.9788±0.0125. In the same order, the results on the Temple University Hospital dataset are 0.9692, 0.9113, 0.97, 0.9575, 0.963, and 0.9879. CONCLUSION: Based on the good results they yield, GNNs prove to have a strong potential in detecting epileptogenic activity. SIGNIFICANCE: This study opens the door for the discovery of the powerful role played by GNNs in capturing IEDs, which is an essential step for identifying the epileptogenic networks of the affected brain and hence improving the prospects for more accurate 3D source localization.

Initial experience with magnetic resonance-guided focused ultrasound stereotactic surgery for central brain lesions in young adults.

OBJECTIVE: Magnetic resonance-guided focused ultrasound (MRgFUS) is an incisionless procedure capable of thermoablation through the focus of multiple acoustic beams. Although MRgFUS is currently approved for the treatment of tremor in adults, its safety and feasibility profile for intracranial lesions in the pediatric and young adult population remains unknown. METHODS: The long-term outcomes of a prospective single-center, single-arm trial of MRgFUS at Nicklaus Children's Hospital in Miami, Florida, are presented. Patients 15-22 years of age with centrally located lesions were recruited, clinically consistent with WHO grade I tumors that require surgical intervention. This cohort consisted of 4 patients with hypothalamic hamartoma (HH), and 1 patient with tuberous sclerosis complex harboring a subependymal giant cell astrocytoma (SEGA). RESULTS: In each case, high-intensity FUS was used to target the intracranial lesion. Real-time MRI was used to monitor the thermoablations. Primary outcomes of interest were tolerability, feasibility, and safety of FUS. The radiographic ablation volume on intra- and postoperative MRI was also assessed. All 5 patients tolerated the procedure without any complications. Successful thermoablation was achieved in 4 of the 5 cases; the calcified SEGA was undertreated due to intratumor calcification, which prevented attainment of the target ablation temperature. The HHs underwent target tissue thermoablations that led to MR signal changes at the treatment site. For the patients harboring HHs, FUS thermoablations occurred without procedure-related complications and led to improvement in seizure control or hypothalamic hyperphagia. All 5 patients were discharged home on postoperative day 1 or 2, without any readmissions. There were no cases of hemorrhage, electrolyte derangement, endocrinopathy, or new neurological deficit in this cohort. CONCLUSIONS: This experience demonstrates that FUS thermoablation of centrally located brain lesions in adolescents and young adults can be performed safely and that it provides therapeutic benefit for associated symptoms.

In vivo optical properties of cortical tubers in children with tuberous sclerosis complex (TSC): a preliminary investigation.

PURPOSE: Medically refractory epilepsy caused by cortical tubers resulting from tuberous sclerosis complex (TSC) often requires surgical intervention. The locations of cortical tubers generally are determined by preoperative magnetic resonance imaging (MRI). In this pilot study, we explored the feasibility of using the optical characteristics of cortical tubers as a potential means to guide their resection intraoperatively. METHODS: Optical characteristics of normal cortex and cortical tubers were measured intraoperatively using diffuse reflectance spectroscopy in three children undergoing epilepsy surgery for drug-resistant seizures. Unique diffuse reflectance spectroscopic features of cortical tubers were identified and their physiologic associations determined. KEY FINDINGS: Diffuse reflectance spectra revealed several features that distinguish cortical tubers from normal cortex. In tubers, diffuse reflectance intensities at oxy- and deoxyhemoglobin isobestic points, like 500, 530, and 570 nm, were consistently higher than those in normal cortex. According to the profile of diffuse reflectance spectra from 520-580 nm, hemoglobin oxygenation in tubers often was lower than in normal cortex. SIGNIFICANCE: Albeit preliminary, our findings suggest that the optical characteristics of cortical tubers differ from intervening normal cortex, likely reflecting the lower cerebral blood volumes and reduced hemoglobin oxygenation of cortical tubers. The results of this study can be used to design biomedical instruments that aid tuberectomies.

Early vagus nerve stimulator implantation as a main predictor of positive outcome in pediatric patients with epileptic encephalopathy.

We describe a multicenter experience with VNS implantation in pediatric patients with epileptic encephalopathy. Our goal was to assess VNS efficacy and identify potential predictors of favorable outcome. This was a retrospective study. Inclusion criteria were: ≤18 years at the time of VNS implantation and at least one year of follow-up. All patients were non-candidates for excisional procedures. Favorable clinical outcome and effective VNS therapy were defined as seizure reduction >50%. Outcome data were reviewed at one, two, three and five years after VNS implantation. Fisher's exact test, Kaplan-Meier and multiple logistic regression analysis were employed. Twenty-seven patients met inclusion criteria. Responder rate (seizure frequency reduction ≥ 50%) at one-year follow-up was 25.9%, and 15.3% at last follow-up visit. The only variable significantly predicting favorable outcome was time to VNS implantation, with the best outcome achieved when VNS implantation was performed within five years of seizure onset (overall response rate of 83.3% at one year of follow-up and 100% at five years). In total, 63% of patients evidenced improved QOL at last follow-up visit. Only one patient exited the study due to an adverse event at two years from implantation. Early VNS implantation within five years of seizure onset was the only predictor of favorable clinical outcome in pediatric patients with epileptic encephalopathy. Improved QOL and a very low incidence of adverse events were observed.

Early Implantation as a Main Predictor of Response to Vagus Nerve Stimulation in Childhood-Onset Refractory Epilepsy.

OBJECTIVE: We describe a multicenter experience with vagus nerve stimulator implantation in pediatric patients with drug-resistant epilepsy. Our goal was to assess vagus nerve stimulation efficacy and identify potential predictors of favorable outcome. METHODS: This is a retrospective study. Inclusion criteria: ≤18 years at time of vagus nerve stimulator implantation, at least 1 year of follow-up. All patients were previously found to be unsuitable for an excisional procedure. Favorable clinical outcome and effective vagus nerve stimulation therapy were defined as seizure reduction >50%. Outcome data were reviewed at 1, 2, 3, and 5 years after vagus nerve stimulator implantation. Fisher exact test and multiple logistic regression analysis were employed. RESULTS: Eighty-nine patients met inclusion criteria. Responder rate (seizure frequency reduction >50%) at 1-year follow-up was 25.8% (4.5% seizure-free). At last follow-up, 31.5% had a favorable outcome and 5.2% were seizure free. The only factor significantly predicting favorable outcome was time to vagus nerve stimulator implantation, with the best outcome achieved when vagus nerve stimulator implantation was performed within 3 years of seizure onset. Implantation between 3 and 5 years after epilepsy onset correlated with better long-term seizure freedom (13.3% at T5). Overall, 65.2% of patients evidenced improved quality of life at last follow-up. However, 12.4% had adverse events, but most were mild and disappeared after 3-4 months. CONCLUSIONS: Early vagus nerve stimulator implantation within 5 years of seizure onset was the only predictor of favorable clinical outcome in pediatric patients. Improved quality of life and a low incidence of significant adverse events were observed.

Medically intractable epilepsy in Sturge-Weber syndrome is associated with cortical malformation: implications for surgical therapy.

PURPOSE: Anecdotal reports have described cortical malformations in epileptic patients with Sturge-Weber syndrome (SWS). No data are available regarding the prevalence and significance of this association. METHODS: We reviewed retrospectively the clinical profile, preoperative magnetic resonance imaging (MRI) studies, and pathology reports of all patients with SWS and medically intractable epilepsy evaluated in our epilepsy surgery program between 1979 and 2006. RESULTS: Twelve patients (male/female = 7/5) were identified. Mean age at seizure onset was 11.1 +/- 16.7 months. Seizures occurred daily in seven patients and weekly in five patients. A facial port-wine stain was noted in 10 cases. Eleven patients evidenced developmental delay and eight were hemiparetic. Eight patients underwent excisional surgery for epilepsy (mean age 10.3 +/- 6.5 year), including hemispherectomy (n = 4) and focal cortical resection (n = 4). Tissue was available for neuropathology in six operated cases and revealed polymicrogyria (n = 3) and cortical dysplasia (n = 4). Polymicrogyria was associated with cortical dysplasia in one child. Brain MRIs were reviewed in 10 of 12 patients and were consistent with cortical malformations in all cases. CONCLUSIONS: We conclude that cortical malformations are frequent in patients with medically intractable epilepsy and Sturge-Weber-syndrome and may be the primary cause of epilepsy.