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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.

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.

Electrical stimulation mapping is a longstanding practice that aids in identification and delineation of eloquent cortex. Initially used to expand our understanding of the typical human cortex, it now plays a significant role in mapping cortical function in individuals with atypical structural and functional tissue organization undergoing epilepsy surgery. This review discusses the unique challenges that arise in the functional testing of the immature cortex of a child and the parameters of stimulation that optimize accurate results in conventional open implantation and in stereo-electroencephalography. The prerequisite baseline evaluation and preparation recommended to increase the yield from pediatric stimulation mapping sessions is described, as are ideal approaches to the mapping of the sensory, motor, language, and visual cortices.

Background: fMRI of mental phenomena is quite difficult to perform because lack of patient's cooperation or because the symptoms are stable. In some exceptional cases, however, fMRI and DTI are capable to provide insights on the anatomy of organic hallucinations. Methods: In this report we describe a 14-year-old boy with a left fronto-dorsal tumor who experienced chronic complex brief, frequent and repetitive complex visual and auditory hallucinations. His clinical picture included multiple and severe social and mood problems. During a presurgical fMRI mapping the patient complained of having the visual and auditory hallucinations. A block-design FMRI paradigm was obtained from the event timecourse. Deterministic DTI of the brain was obtained seeding the lesion as ROI. The patient underwent surgery and electrocorticography of the lesional area. Results: The fMRI of the hallucinations showed activation in the left inferior frontal gyrus (IFG) and the peri-lesional area. The tractography of the tumor revealed structural aberrant connectivity to occipital and temporal areas in addition to the expected connectivity with the IFG via the aslant fasciculus and homotopic contralateral areas. Intraoperative EEG demonstrated epileptic discharges in the tumor and neighboring areas. After resection, the patient's hallucinations stopped completely. He regained his normal social life and recover his normal mood. He remained asymptomatic for 90 days. Afterwards, hallucinations reappeared but with less intensity. Conclusions: To our knowledge, this is the first reported case of combined functional and structural connectivity imaging demonstrating brain regions participating in a network involved in the generation of complex auditory and visual hallucinations.

Background: Infantile spasms is a rare disease characterized by distinct seizures and hypsarrhythmia. Adrenocorticotropic hormone (ACTH) is available as a natural product (repository corticotropin injection, [RCI]; Acthar® Gel) and as synthetic analogs. RCI is a naturally-sourced complex mixture of purified ACTH analogs and other pituitary peptides approved by the United States Food and Drug Administration as a monotherapy for the treatment of infantile spasms. RCI is commonly used in the United States. Outside the United States, synthetic analogs of ACTH—synthetic ACTH1-24 (tetracosactide) and synthetic ACTH1-39 (corticotropin carboxymethyl-cellulose [CCMC])—are used. The efficacy of RCI may differ from that of synthetic ACTH treatments based on the structure of peptide; however, no head-to-head clinical trials have compared the efficacy of RCI and synthetic ACTH treatments. Objective: A systematic review and indirect treatment comparison of clinical trials was conducted to assess the comparative efficacy of RCI and synthetic ACTH treatments in infantile spasms. Methods: A search was conducted in MEDLINE, EMBASE, and Cochrane databases through September 30, 2020. Relevant clinical trials on RCI or synthetic ACTH therapy and reporting either cessation of spasms or resolution of hypsarrhythmia, separately or as a combined outcome were included. A Bayesian indirect treatment comparison using a fixed-effects model was used for comparative efficacy. Results: Of 473 citations screened, 21 studies were reviewed qualitatively. In the indirect treatment comparison of six eligible clinical trial studies, the odds of achieving efficacy outcomes were five to eight times greater with RCI than with tetracosactide and 14 to 16 times greater than CCMC. This translated to a risk reduction of 10% to 14% and 40% to 50% with RCI versus tetracosactide and CCMC, respectively. For every two to five patients treated, RCI improved efficacy outcomes in one additional patient compared to synthetic ACTH (adjusted number needed-to-treat). Conclusions: Based on the available limited evidence, results suggest RCI may be more efficacious for infantile spasms than synthetic ACTH treatments. Our findings provide a blueprint to inform the design of future prospective studies for the treatment of infantile spasms., A systematic review and indirect treatment comparison of clinical trials was conducted to assess the comparative efficacy of RCI and synthetic ACTH treatments in infantile spasms.

Objective: 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. Methods: 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. Results: 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. Significance: 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.

This paper presents a theoretical elaboration aimed to explain the correlation found between a new rs-fMRI modality and electrophysiology and nuclear medicine neuroimaging, performed to localize epileptogenic brain areas. We present in detail the clinical history, and electrophysiological and neuroimaging results of one child with intractable epilepsy, who was submitted for Phase-1 work-up as candidate for epilepsy surgery. The patient underwent a thorough workup including video-telemetry, ictal and interictal nuclear medicine imaging, resting-state fMRI, EEG-fMRI, intracranial electroencephalography (ECoG), deep electrode implantation, and resective surgery. Electrophysiology and neuroimaging findings were concordant with findings provided by the resting-state mean signal. The patient became seizure-free after the resection of the target area. A theoretical discussion is provided that considers the presence of a stable BOLD effect explaining the findings of the observed resting-state mean signal. This stable BOLD is linked to low regional metabolism usually present in the epileptogenic area during interictal periods, coupled with low oxygen extraction. Low oxygen extraction leaves more oxygen for the draining venule and consequently increases the BOLD signal.

Background Patients with autism spectrum disorder and developmental delay or encephalopathy rarely demonstrate no or negligible hair and nail growth, suggesting a biotin-responsive clinical disorder. Methods A ten-year-old girl presented with features of autism spectrum disorder, isolated headaches, and episodes of headaches and limb shaking. Her medical history revealed that her hair and nails did not grow. Administration of biotin restored her nail and hair growth and improved intellectual ability and school performance. Her episodes of headaches, single limb shaking, and loss of consciousness responded to administration of acetazolamide, and her school performance and social skills further improved. Results A de novo c.1091 C > T, p.T364M pathogenic variant was found in the ATP1A2 gene by whole-exome sequencing, but a genetic etiology in the biotin-responsive metabolic pathways was not identified. Conclusions The combination of biotin and acetazolamide treatment was successful in restoring normal mental function and school performance. Poor or no clinical nail and hair growth in any child with a developmental delay-autism spectrum disorder presentation should be considered as evidence for a biotin-responsive genetic disorder even when exome testing is negative.

SummaryObjective Evaluate the seizure-reduction response and safety of brain-responsive stimulation in adults with medically intractable partial-onset seizures of neocortical origin. Methods Patients with partial seizures of neocortical origin were identified from prospective clinical trials of a brain-responsive neurostimulator (RNS System, NeuroPace). The seizure reduction over years 2–6 postimplantation was calculated by assessing the seizure frequency compared to a preimplantation baseline. Safety was assessed based on reported adverse events. Additional analyses considered safety and seizure reduction according to lobe and functional area (e.g., eloquent cortex) of seizure onset. Results There were 126 patients with seizures of neocortical onset. The average follow-up was 6.1 implant years. The median percent seizure reduction was 70% in patients with frontal and parietal seizure onsets, 58% in those with temporal neocortical onsets, and 51% in those with multilobar onsets (last observation carried forward [LOCF] analysis). Twenty-six percent of patients experienced at least one seizure-free period of 6 months or longer and 14% experienced at least one seizure-free period of 1 year or longer. Patients with lesions on magnetic resonance imaging (MRI; 77% reduction, LOCF) and those with normal MRI findings (45% reduction, LOCF) benefitted, although the treatment response was more robust in patients with an MRI lesion (p = 0.02, generalized estimating equation [GEE]). There were no differences in the seizure reduction in patients with and without prior epilepsy surgery or vagus nerve stimulation. Stimulation parameters used for treatment did not cause acute or chronic neurologic deficits, even in eloquent cortical areas. The rates of infection (0.017 per patient implant year) and perioperative hemorrhage (0.8%) were not greater than with other neurostimulation devices. Significance Brain-responsive stimulation represents a safe and effective treatment option for patients with medically intractable epilepsy, including adults with seizures of neocortical onset, and those with onsets from eloquent cortex.

ESES is a developmental epileptic disorder directly responsible for progressive encephalopathy and neurocognitive regression. The natural history, indications for surgical intervention, and predictors for favorable seizure and neuropsychological outcome remain unclear. We performed a retrospective review of children who underwent resective or disconnective surgery for ESES between January 2009 and July 2016 at a large tertiary pediatric center. Information on the patients' demographics, seizure semiology, radiographic and electrographic findings, and surgical management was collected. The primary outcome was seizure freedom at last follow-up visit, and secondary outcomes were neuropsychological improvement and electrographic ESES resolution. We identified 11 children who underwent surgery for ESES. The mean ages were 3.2 years for seizure onset, 7.1 years for formal ESES diagnosis, and 9.4 years for surgery. Seizure etiologies included cortical malformations (four patients), encephalomalacia and gliosis from prior hemorrhage or tumor resections (three patients), developmental porencephaly (one patient), and Rasmussen's encephalitis (one patient); the etiology was unknown in two children. Preoperatively, nine children had motor deficits, seven had speech and language delay, and three had visual field defects. All children had seizures and neuropsychological regression prior to surgical consideration. Focal cortical resections were performed in seven children, and hemispherectomies in four. Post-operatively, nine children experienced decreased seizure frequency, eight had neuropsychological improvement, and nine had resolution of electrographic ESES. Patients with poor surgical outcomes had more significant pre-operative comorbidities, in addition to bilateral ESES activity. In this case series, surgery for a carefully selected group of children with ESES is safe and feasible, yielding rates of seizure freedom and neuropsychological improvement that compare favorably with previous reports for antiepileptic drugs, benzodiazepines, and steroids. As we gain greater understanding into the management of ESES, surgery is an increasingly useful tool for patients with mild or moderate neurodevelopmental delay, focal epileptogenic foci, and hemi-ESES electrographic findings.

A more complete understanding of the epileptic aura represents an important challenge for localizing the epileptogenic zone and understanding brain networks. This review re-visits the localizing value of the epileptic aura, focusing on clinical pitfalls in epileptogenic zone detection and the importance of defining functional connectivity. We review the role of network node activation or alteration and its relationship to hub activation.

Infants with West Syndrome and underlying structural pathology typically experience persistent symptomatic focal seizures and intellectual disability. We performed a retrospective case review of 84 patients with West Syndrome evaluated at one institution between 1990 and 2013. From this group we identified three patients with West syndrome and congenital hemiplegia who later developed genetic epilepsy features and had normal intellectual development. This outcome is highly unusual and raises important questions about the relationship and possible influence of genetic epilepsy in patients with pre-existent West Syndrome and brain injury.

OBJECTIVE Seizure onset in the insular cortex as a cause of refractory epilepsy is underrepresented in the pediatric population, possibly due to difficulties localizing seizure onset in deep anatomical structures and limited surgical access to the insula, a complex anatomical structure with a rich overlying vascular network. Insular seizure semiology may mimic frontal, temporal, or parietal lobe semiology, resulting in false localization, incomplete resection, and poor outcome. METHODS The authors retrospectively reviewed the records of all pediatric patients who underwent insular cortical resections for intractable epilepsy at Miami Children's Hospital from 2009 to 2015. Presurgical evaluation included video electroencephalography monitoring and anatomical/functional neuroimaging. All patients underwent excisional procedures utilizing intraoperative electrocorticography or extraoperative subdural/depth electrode recording. RESULTS Thirteen children (age range 6 months–16 years) with intractable focal epilepsy underwent insular-opercular resection. Seven children described symptoms that were suggestive of insular seizure origin. Discharges on scalp EEG revealed wide fields. Four patients were MRI negative (i.e., there were no insular or brain abnormalities on MRI), 4 demonstrated insular signal abnormalities, and 5 had extrainsular abnormalities. Ten patients had insular involvement on PET/SPECT. All patients underwent invasive investigation with insular sampling; in 2 patients resection was based on intraoperative electrocorticography, whereas 11 underwent surgery after invasive EEG monitoring with extraoperative monitoring. Four patients required an extended insular resection after a failed initial surgery. Postoperatively, 2 patients had transient hemiplegia. No patients had new permanent neurological deficits. At the most recent follow-up (mean 43.8 months), 9 (69%) children were seizure free and 1 had greater than 90% seizure reduction. CONCLUSIONS Primary insular seizure origin should be considered in children with treatment-resistant focal seizures that are believed to arise within the perisylvian region based on semiology, widespread electrical field on scalp EEG, or insular abnormality on anatomical/functional neuroimaging. There is a reasonable chance of seizure freedom in this group of patients, and the surgical risks are low.

Summary 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

Aims. To assess the localizing value of ictal SPECT in very young epilepsy surgery candidates when cerebral haemodynamic responses are known to be immature. Methods. We retrospectively studied 13 infants with intractable focal epilepsy caused by focal cortical dysplasia (FCD). Completeness of resection of the (1) ictal SPECT hyperperfusion zone and (2) cerebral cortex with prominent ictal and interictal abnormalities on intracranial EEG (ECoG or long-term invasive monitoring) and the MRI lesion, when present, were correlated with postoperative seizure outcome. Results. All five patients with complete resection of the ictal SPECT hyperperfusion zone were seizure-free compared to only one of eight patients with incomplete or no excision of hyperperfusion zones (p=0.00843). Similar results were noted for the MRI/iEEG-defined epileptogenic region; five of six patients with complete removal were seizure-free, whereas only one of seven incompletely resected patients was seizure-free (p=0.02914). All four patients who underwent complete resection of both regions were seizure-free compared to none of the six with incomplete resection (p=0.01179). Conclusion. Despite age-related differences in cerebral perfusion, ictal SPECT provides useful localization data in infants with FCD. Complete resection of the hyperperfused regions is a strong predictor of favourable outcome. The added information may alleviate the need for invasive EEG evaluations in some patients.

The pharmacotherapy of epilepsy in children must account for a number of specific issues. The nature of epileptic disorders found in children differs from that in adults. For example, epilepsies of childhood are more likely to be developmentally or genetically based than those found in adults. Children also differ from adults in indications for antiepileptic drugs. Indeed, some types of childhood epilepsy do not require specific pharmacological treatment since prognosis is often excellent without therapy. This is especially true for children who are neurologically nonnal and those with benign epilepsy syndromes that have a characteristic electroclinical presentation, such as febrile seizures. In contrast, children with evidence of brain damage or those with serious epilepsy syndromes must be treated promptly.Once it has been decided that treatment is necessary, the choice of treatment should be based on a comparison of efficacy and tolerability of individual antiepileptic agents. The spectrum of toxicity is often different in younger patients from that in adults, and adverse effects that are acceptable in adults may be cause for discontinuation of therapy in children. Intellectual, cognitive and behavioural toxicity are particularly unacceptable.Establishing sustained therapeutic serum concentrations in children also requires specific attention. Rapid gastrointestinal transit times and interactions with milk and infant formulas may pose special management problems. Toxic metabolites of antiepileptic drugs are frequently produced in children. This can lead to drug hypersensitivity and other possible conditions, such as valproic acid (sodium valproate)-induced hepatotoxicity.Unless specific paediatric data are obtained, recommendations for the treatment of epilepsies in children will continue to be based on studies in adults and on anecdotal observations. Given the high prevalence and significant morbidity of childhood epilepsies, further studies of treatments are urgently needed.

SummaryObjective 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.

We describe a patient with medically refractory focal epilepsy who presented with divergent non-invasive data, with MRI revealing hippocampal sclerosis and EEG indicating involvement of the occipital lobe. A localized corticectomy over the occipital convexity was performed based on intracranial EEG recording. The patient was seizure-free after four years of follow-up. Electroclinical hypotheses and challenges of defining the epileptogenic network are discussed.

Summary 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.

This study evaluated language organization in children with intractable epilepsy caused by temporal lobe focal cortical dysplasia (FCD) alone or dual pathology (temporal lobe FCD and hippocampal sclerosis, HS). We analyzed clinical, neurological, fMRI, neuropsychological, and histopathologic data in 46 pediatric patients with temporal lobe lesions who underwent excisional epilepsy surgery. The frequency of atypical language representation was similar in both groups, but children with dual pathology were more likely to be left-handed. Atypical receptive language cortex correlated with lower intellectual capacity, verbal abstract conceptualization, receptive language abilities, verbal working memory, and a history of status epilepticus but did not correlate with higher seizure frequency or early seizure onset. Histopathologic substrate had only a minor influence on neuropsychological status. Greater verbal comprehension deficits were noted in children with atypical receptive language representation, a risk factor for cognitive morbidity.

Performing epilepsy surgery on children with non-lesional brain MRI often results in large lobar or multilobar resections. The aim of this study was to determine if smaller resections result in a comparable rate of seizure freedom.We reviewed 25 children who had undergone focal corticectomies restricted to one aspect of a single lobe or the insula at our institution within a 5.5-year period. Data collected in the comprehensive non-invasive pre-surgical evaluation (including scalp video-EEG, volumetric MRI, functional MRI, EEG source localization, and SPECT and PET), as well as from invasive recordings performed in each patient, was reviewed. Data from each functional modality was identified as convergent or divergent with the epileptogenic zone using image coregistration. Specific biomarkers (from extra-operative and invasive testing) previously indicated to be indicative of focal epileptogenicity were used to further tailor each resection to an epileptogenic epicentre. Tissue pathology and postoperative outcomes were obtained from all 25 patients.Two years postoperatively, 15/25 (60%) children were seizure-free, three (12%) experienced90% reduction in seizure frequency, two (8%) had a 50-90% reduction in seizure frequency, and the remaining five (20%) had no change in seizure burden. There was no significant difference in outcome based on numerous pre- and postoperative factors including location of resection, the number of preoperative functional tests providing convergent data, and tissue pathology.In MRI-negative children with focal epilepsy, an epileptogenic epicentre within a larger epileptogenic zone can be identified when specific biomarkers are recognized on non-invasive and invasive testing. When such children undergo resection of a small, well-defined epileptogenic epicentre, favourable outcomes can be achieved.

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.

Summary Objective To report the feasibility, safety, and clinical outcomes of an exploratory study of MR-guided Laser Interstitial Thermal Therapy (MRgLITT) as a minimally invasive surgical procedure for the ablation of epileptogenic foci in children with drug-resistant, lesional epilepsy. Methods Retrospective chart review of all MRgLITT procedures at a single tertiary care center. All procedures were performed using a U.S. Food and Drug Administration (FDA)–cleared surgical laser ablation system (Visualase Thermal Therapy System). Predefined clinical and surgical variables were extracted from archived medical records. Results Seventeen patients underwent 19 MRgLITT procedures from May 2011 to January 2014. Mean age at seizure onset was 7.1 years (range 0.1–14.8 years). Mean age at surgery was 15.3 years (range 5.9–20.6 years). Surgical substrates were mixed but mainly composed of focal cortical dysplasia (n = 11). Complications occurred in four patients. Average length of hospitalization postsurgery was 1.56 days. Mean follow-up was 16.1 months (n = 16; range 3.5–35.9 months). Engel class I outcome was achieved in seven patients (7/17; 41%), Engel class II in one (1/17; 6%), Engel class III in three (3/17; 18%), and Engel class IV in six (6/17; 35%). Three patients (3/8; 38%) with class I and II outcomes and five patients (5/9; 56%) with class III and IV outcomes had at least one prior resection. Fisher's exact test was not statistically significant for the association between Engel class outcome and previous resection (p = 0.64). Significance This study provides descriptive results regarding the use of MRgLITT in a mixed population of pediatric, lesional, drug-resistant epilepsy cases. The ability to classify case-specific outcomes and reduce technical complications is anticipated as experience develops. Further multicenter, prospective studies are required to delineate optimal candidates for MRgLITT, and larger cohorts are needed to more accurately define outcome and complication rates.

Summary 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.