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Objective: To determine whether automated, electronic alerts increased referrals for epilepsy surgery. Methods: We conducted a prospective, randomized controlled trial of a natural language processing–based clinical decision support system embedded in the electronic health record (EHR) at 14 pediatric neurology outpatient clinic sites. Children with epilepsy and at least two prior neurology visits were screened by the system prior to their scheduled visit. Patients classified as a potential surgical candidate were randomized 2:1 for their provider to receive an alert or standard of care (no alert). The primary outcome was referral for a neurosurgical evaluation. The likelihood of referral was estimated using a Cox proportional hazards regression model. Results: Between April 2017 and April 2019, at total of 4858 children were screened by the system, and 284 (5.8%) were identified as potential surgical candidates. Two hundred four patients received an alert, and 96 patients received standard care. Median follow‐up time was 24 months (range: 12–36 months). Compared to the control group, patients whose provider received an alert were more likely to be referred for a presurgical evaluation (3.1% vs 9.8%; adjusted hazard ratio [HR] = 3.21, 95% confidence interval [CI]: 0.95–10.8; one‐sided p =.03). Nine patients (4.4%) in the alert group underwent epilepsy surgery, compared to none (0%) in the control group (one‐sided p =.03). Significance: Machine learning–based automated alerts may improve the utilization of referrals for epilepsy surgery evaluations. [ABSTRACT FROM AUTHOR]

Objectives: Epilepsy surgery is underutilized. Automating the identification of potential surgical candidates may facilitate earlier intervention. Our objective was to develop site‐specific machine learning (ML) algorithms to identify candidates before they undergo surgery. Materials & Methods: In this multicenter, retrospective, longitudinal cohort study, ML algorithms were trained on n‐grams extracted from free‐text neurology notes, EEG and MRI reports, visit codes, medications, procedures, laboratories, and demographic information. Site‐specific algorithms were developed at two epilepsy centers: one pediatric and one adult. Cases were defined as patients who underwent resective epilepsy surgery, and controls were patients with epilepsy with no history of surgery. The output of the ML algorithms was the estimated likelihood of candidacy for resective epilepsy surgery. Model performance was assessed using 10‐fold cross‐validation. Results: There were 5880 children (n = 137 had surgery [2.3%]) and 7604 adults with epilepsy (n = 56 had surgery [0.7%]) included in the study. Pediatric surgical patients could be identified 2.0 years (range: 0–8.6 years) before beginning their presurgical evaluation with AUC =0.76 (95% CI: 0.70–0.82) and PR‐AUC =0.13 (95% CI: 0.07–0.18). Adult surgical patients could be identified 1.0 year (range: 0–5.4 years) before beginning their presurgical evaluation with AUC =0.85 (95% CI: 0.78–0.93) and PR‐AUC =0.31 (95% CI: 0.14–0.48). By the time patients began their presurgical evaluation, the ML algorithms identified pediatric and adult surgical patients with AUC =0.93 and 0.95, respectively. The mean squared error of the predicted probability of surgical candidacy (Brier scores) was 0.018 in pediatrics and 0.006 in adults. Conclusions: Site‐specific machine learning algorithms can identify candidates for epilepsy surgery early in the disease course in diverse practice settings. [ABSTRACT FROM AUTHOR]

Objective: Delay to resective epilepsy surgery results in avoidable disease burden and increased risk of mortality. The objective was to prospectively validate a natural language processing (NLP) application that uses provider notes to assign epilepsy surgery candidacy scores. Methods: The application was trained on notes from (1) patients with a diagnosis of epilepsy and a history of resective epilepsy surgery and (2) patients who were seizure‐free without surgery. The testing set included all patients with unknown surgical candidacy status and an upcoming neurology visit. Training and testing sets were updated weekly for 1 year. One‐ to three‐word phrases contained in patients' notes were used as features. Patients prospectively identified by the application as candidates for surgery were manually reviewed by two epileptologists. Performance metrics were defined by comparing NLP‐derived surgical candidacy scores with surgical candidacy status from expert chart review. Results: The training set was updated weekly and included notes from a mean of 519 ± 67 patients. The area under the receiver operating characteristic curve (AUC) from 10‐fold cross‐validation was 0.90 ± 0.04 (range = 0.83‐0.96) and improved by 0.002 per week (P <.001) as new patients were added to the training set. Of the 6395 patients who visited the neurology clinic, 4211 (67%) were evaluated by the model. The prospective AUC on this test set was 0.79 (95% confidence interval [CI] = 0.62‐0.96). Using the optimal surgical candidacy score threshold, sensitivity was 0.80 (95% CI = 0.29‐0.99), specificity was 0.77 (95% CI = 0.64‐0.88), positive predictive value was 0.25 (95% CI = 0.07‐0.52), and negative predictive value was 0.98 (95% CI = 0.87‐1.00). The number needed to screen was 5.6. Significance: An electronic health record–integrated NLP application can accurately assign surgical candidacy scores to patients in a clinical setting. [ABSTRACT FROM AUTHOR]

• Stimulation within auditory cortex produced facial expressions and perioral motor responses in approximately one-third of patients. • Cortical sites with motor and language responses within transverse temporal gyrus and adjacent cortex (TGG+) showed different yet overlapping neurophysiologic characteristics. • TTG+ likely participates in non-verbal responses to low-level auditory and/or emotional cues during a communicative discourse. We investigated the role of transverse temporal gyrus and adjacent cortex (TTG+) in facial expressions and perioral movements. In 31 patients undergoing stereo-electroencephalography monitoring, we describe behavioral responses elicited by electrical stimulation within the TTG+. Task-induced high-gamma modulation (HGM), auditory evoked responses, and resting-state connectivity were used to investigate the cortical sites having different types of responses on electrical stimulation. Changes in facial expressions and perioral movements were elicited on electrical stimulation within TTG+ in 9 (29%) and 10 (32%) patients, respectively, in addition to the more common language responses (naming interruptions, auditory hallucinations, paraphasic errors). All functional sites showed auditory task induced HGM and evoked responses validating their location within the auditory cortex, however, motor sites showed lower peak amplitudes and longer peak latencies compared to language sites. Significant first-degree connections for motor sites included precentral, anterior cingulate, parahippocampal, and anterior insular gyri, whereas those for language sites included posterior superior temporal, posterior middle temporal, inferior frontal, supramarginal, and angular gyri. Multimodal data suggests that TTG+ may participate in auditory-motor integration. TTG+ likely participates in facial expressions in response to emotional cues during an auditory discourse. [ABSTRACT FROM AUTHOR]

Racial disparities in the utilization of epilepsy surgery are well documented, but it is unknown whether a natural language processing (NLP) algorithm trained on physician notes would produce biased recommendations for epilepsy presurgical evaluations. To assess this, an NLP algorithm was trained to identify potential surgical candidates using 1097 notes from 175 epilepsy patients with a history of resective epilepsy surgery and 268 patients who achieved seizure freedom without surgery (total N = 443 patients). The model was tested on 8340 notes from 3776 patients with epilepsy whose surgical candidacy status was unknown (2029 male, 1747 female, median age = 9 years; age range = 0‐60 years). Multiple linear regression using demographic variables as covariates was used to test for correlations between patient race and surgical candidacy scores. After accounting for other demographic and socioeconomic variables, patient race, gender, and primary language did not influence surgical candidacy scores (P > .35 for all). Higher scores were given to patients >18 years old who traveled farther to receive care, and those who had a higher family income and public insurance (P < .001,.001,.001, and.01, respectively). Demographic effects on surgical candidacy scores appeared to reflect patterns in patient referrals. [ABSTRACT FROM AUTHOR]

Transcranial Magnetic Stimulation (TMS) has emerged as a viable non-invasive method for mapping language networks. Little is known about the tolerability of transcranial magnetic stimulation language mapping in children. Children aged 5–18 years underwent bilateral language mapping using repetitive transcranial magnetic stimulation (rTMS) to target 33 sites/hemisphere. Stimulation was delivered at 5 Hz, in 1–2 second bursts, during visual naming and auditory verb generation. Pain unpleasantness and pain intensity were assessed using an unpleasantness visual analog scale (VAS). 49 participants tolerated motor mapping and had repetitive transcranial magnetic stimulation. 35/49 (71%) completed visual naming and 26/49 (53%) completed both visual naming and verb generation. Mean electrical field per participant was 115 V/m. Young age and lower language ability were associated with lower completion. Visual analogue scale scores were significantly higher (6.1 vs. 2.8) in participants who withdrew early compared to those who completed at least visual naming. Pain measured by VAS was a major contributor to early withdrawal. However, a complete bilateral map was obtained with one paradigm in 71% of participants. Future studies designed to reduce pain during repetitive transcranial magnetic stimulation over language cortex will boost viability. This study represents the first attempt to characterize tolerability of bilateral repetitive transcranial magnetic stimulation language mapping in healthy children. • The first prospective study of language mapping using repetitive TMS in healthy children. • Most (71%) of children completed stimulation bilaterally during object naming. • Discomfort related to stimulation was the major factor associated with withdrawal. [ABSTRACT FROM AUTHOR]

Background: Electrographic status epilepticus in slow sleep or continuous spike and waves during slow-wave sleep is an epileptic encephalopathy characterized by seizures, neurocognitive regression, and significant activation of epileptiform discharges during nonrapid eye movement sleep. There is no consensus on the diagnostic criteria and evidence-based optimal treatment algorithm for children with electrographic status epilepticus in slow sleep.Patient Description: We describe a 12-year-old girl with drug-resistant electrographic status epilepticus in slow wave sleep that was successfully treated with vagus nerve stimulation. Her clinical presentation, presurgical evaluation, decision-making, and course after vagus nerve stimulator implantation are described in detail.Findings: After vagus nerve stimulator implantation, the girl remained seizure free for more than a year, resolved the electrographic status epilepticus in slow sleep pattern on electroencephalography, and exhibited significant cognitive improvement.Conclusion: Vagus nerve stimulation may be considered for electrographic status epilepticus in slow sleep. [ABSTRACT FROM AUTHOR]

Purpose There is wide variation in clinical practice regarding the role of electrocorticography immediately after resection (post-resection ECoG) for pediatric epilepsy surgery. Results can guide further resection of potentially epileptogenic tissue. We hypothesized that post-resection ECoG spiking represents a biomarker of the epileptogenic zone and predicts seizure outcome in children undergoing epilepsy surgery. Methods We retrospectively identified 124 children with post-resection ECoG performed on the margins of resection. ECoG records were scored in a blinded fashion based on presence of frequent spiking. For patients identified as having additional resection based on clinical post-resection ECoG interpretation, these “second-look” ECoG results were re-reviewed for ongoing discharges or completeness of resection. Frequent spike populations were grouped using a standard scoring system into three ranges: 0.1–0.5 Hz, 0.5–1 Hz, >1 Hz. Seizure outcomes were determined at minimum 12-month followup. Results Of 124 patients who met inclusion criteria, 60 (48%) had an identified spike population on post-resection ECoG. Thirty (50%) of these had further resection based on clinical interpretation. Overall, good outcome (ILAE 1) was seen in 56/124 (45%). Completeness of resection of spiking (absence of spiking on initial post-resection ECoG or resolution of spiking after further resection) showed a trend toward good outcome (OR 2.03, p = 0.099). Patients with completeness of resection had good outcome in 41/80 (51%) of cases; patients with continued spikes had good outcome in 15/44 (35%) of cases. Conclusions Post-resection ECoG identifies residual epileptogenic tissue in a significant number of children. Lower frequency or absence of discharges on initial recording showed a trend toward good outcome. Completeness of resection demonstrated on final ECoG recording did not show a significant difference in outcome. This suggests that post-resection discharges represent a prognostic marker rather than a remediable biomarker of the epileptogenic zone in all patients. Resecting residual spike-generating cortex may be beneficial in selected patients, including children with tumors. [ABSTRACT FROM AUTHOR]

Objective The predictive value of intraoperative electrocorticography ( ECoG) in pediatric epilepsy surgery is unknown. In a population of children undergoing ECoG followed typically by invasive extraoperative monitoring ( IEM) and resection, we aimed to determine the relationship between frequent ECoG abnormalities and the seizure onset zone and outcome after resection. Methods We retrospectively identified 103 children with preresection ECoG of sufficient technical quality. ECoG records were scored based on electrode location and frequency, blinded to the seizure-onset zone and outcome. Electrographic seizure and spike locations were identified. Locations of seizures and spike populations were then compared to the location of seizure-onset zone defined by IEM using subdural electrodes and resection margin. Results Electrographic seizures were identified in 11 (11%) of 103 patients. A spike population of one or more was noted in 79 (77%) of 103 patients. In 50 (63%) of 79 patients, spike populations correlated with seizure-onset zone location. The overall surgical outcome was good ( ILAE 1 to 3) in 53 (52%) of 101 patients. Outcome was good in seven (78%) of nine patients when electrographic seizure location was resected. The best outcomes were obtained with resection of both the seizure-onset zone and ECoG abnormalities to include seizures and spike locations (22/33 good outcome, 67%, p = 0.008). There was a significantly better outcome in children with complete resection of ECoG-identified spike populations (14/26, 62% good outcome) compared to when none were resected (4/14, 29%, p = 0.043). Significance Electrographic seizures and frequent spikes are frequently seen on pre-resection ECoG in children. The brain locations corresponding to these discharges are highly concordant with the seizure-onset zone; resection of these regions is correlated with good seizure outcome. Further research is needed to design interventions that increase the reliability of ECoG prediction of the epileptogenic zone and obviate the need for IEM. [ABSTRACT FROM AUTHOR]

The primary objectives of this study were to determine the prevalence of nonconvulsive seizures and nonconvulsive status epilepticus in patients with abusive head trauma who underwent electroencephalography (EEG) monitoring and to describe predictive factors for this population. Children with a diagnosis of abusive head trauma were studied retrospectively to determine the rate of EEG monitoring, the rate of nonconvulsive seizures and nonconvulsive status epilepticus, and the associated neuroimaging findings. Over 11 years, 73 of 199 (36.8%) children with abusive head trauma had electroencephalography monitoring performed. Of these, 20 (27.4%) had nonconvulsive seizures and 3 (4.1%) had nonconvulsive status epilepticus. The presence of subarachnoid hemorrhage and cortical T2 / fluid-attenuated inversion recovery signal abnormalities were both significantly associated with the presence of nonconvulsive seizures / nonconvulsive status epilepticus. Nonconvulsive seizures are relatively common in abusive head trauma and may go unrecognized. Specific neuroimaging characteristics increase the likelihood of nonconvulsive seizures on EEG. [ABSTRACT FROM AUTHOR]

It has been postulated that mitochondrial dysfunction may be an important factor in epileptogenesis of intractable epilepsy. The current study tests the hypothesis that mitochondrial Complex IV (CIV) or cytochrome c oxidase dysfunction is associated with the seizure onset zone (SOZ) in patients with focal cortical dysplasia (FCD). Subjects were selected based on: age <19y; epilepsy surgery between May, 2010 and October, 2011; pathological diagnosis of isolated focal cortical dysplasia Type I (FCDI) or Type II (FCDII); and sufficient residual cortical tissue to conduct analysis of electron transport chain complex (ETC) activity in SOZ and adjacent cortical regions. In this retrospective study, patients were identified who had sufficient unfixed, frozen brain tissue for biochemical analysis in tissue homogenates. Specimens were subtyped using ILAE classification for FCD, and excluded if diagnosed with FCD Type III or dual pathology. Analysis of ETC activity in resected tissues was conducted independently and without knowledge of the identity, diagnosis, or clinical status of individual subjects. Seventeen patients met the inclusion criteria, including 6 FCDI and 11 FCDII. Comparison of adjacent cortical resections showed decreased CIV activity in the SOZ of the FCDII group ( P = 0.003), but no significant CIV difference in adjacent tissues of the FCDI group. Because of the importance of CIV as the terminal and rate-limiting complex in the mitochondrial electron transport chain, these authors conclude that 1) a deficit of CIV is associated with the SOZ of patients with FCDII; 2) CIV deficiency may contribute to the spectrum of FCD neuropathology; and 3) further investigation of CIV in FCD may lead to the discovery of new targets for neuroprotective therapies for patients with intractable epilepsy. [ABSTRACT FROM AUTHOR]

This study explored predictors of response to vagus nerve stimulation in childhood-onset epilepsy. This retrospective chart review included all patients with new vagus nerve stimulator insertion between January 1, 2006, and December 31, 2011. Primary outcome was change in seizure frequency classified on the International League Against Epilepsy scale. Overall, 67.4% (95% confidence limits 53.3%-81.6%) of the patients had outcome of class 4 or better, and 4 patients (9.3%, 95% confidence interval 0.5%-18.1%) achieved complete seizure freedom (mean follow-up 3.5 y). Absence of magnetic resonance imaging (MRI) lesion (odds ratio 6.068, 95% confidence interval 1.214-30.329, P = .028) and duration of epilepsy before implantation (odds ratio 1.291, 95% confidence interval 1.015-1.642, P = .038) were found to be statistically significant predictors of good outcome and provided a sufficient fit to the data (area under the receiver operating characteristic curve .80, Hosmer-Lemeshow goodness of fit P = .92). This study provides preliminary evidence that nonlesional patients are significantly more likely to have better outcome with vagus nerve stimulation. [ABSTRACT FROM PUBLISHER]

Objective: Children suffering from epilepsy with suspected low-grade tumors may benefit from a surgical approach that considers the epileptogenic zone, which can be more extensive than the tumor region. This study aimed to determine the prevalence of epilepsy in children undergoing supratentorial tumor resection and the factors predictive of postoperative seizure freedom in children with low-grade tumors. Methods: Subjects 3 months to 21 years undergoing supratentorial brain tumor resection between 2007 and 2011 were included in this retrospective study. Children with supratentorial, cortically based tumors and a preoperative diagnosis of epilepsy were considered epilepsy surgery candidates. Pre- and postoperative MRI were reviewed and scored for extent of resection, adjacent dysplasia, and remaining abnormal cortex postoperatively. Results: The prevalence of seizures in all cases of supratentorial tumors was 46/87 (53 %). Eighteen were epilepsy surgery candidates. Eight of 18 (44 %) were seizure-free postoperatively with a mean follow-up of 39 months. Children who were seizure free postoperatively had tried fewer anticonvulsants than those with continued seizures (1.7 v. 2.9, p = 0.01). Presurgical evaluation was nonstandardized, and a more extensive workup and resection were performed in children who continued to have seizures postoperatively. Conclusions: All epilepsy surgery candidates had low-grade tumors on histological evaluation, indicating that a surgical approach that takes into consideration the epileptogenic zone is reasonable in this population. Gross total resection should be the goal, with additional attention to resection of the epileptogenic zone when located in the noneloquent cortex. [ABSTRACT FROM AUTHOR]

Purpose: Determine if blood messenger RNA (mRNA) expression patterns in children with newly diagnosed untreated idiopathic epilepsy are different from those in healthy controls. Determine the differential expression patterns between epilepsy patients with generalized onset or partial onset seizures compared to healthy controls. Methods: Whole blood was obtained from otherwise healthy pediatric patients with newly diagnosed untreated idiopathic epilepsy along with healthy pediatric controls. mRNA was isolated and hybridized to Affymetrix HGU 133 2.0+ microarrays. Analysis was performed using Genespring. Differentially expressed gene lists resulted from comparison of (1) epilepsy and control groups and (2) seizure type subgroups with controls. Tissue expression and gene ontology analysis was performed using DAVID. Key Findings: Thirty-seven epilepsy patients and 28 controls were included. Overall, 575 genes were differentially expressed in subjects with epilepsy compared to controls. The generalized seizure subgroup versus control (GvC) gene list and the partial seizure subgroup versus control (PvC) gene list were different (p < 0.05). Tissue expression analysis identified almost half of the genes in GvC and PvC as brain based. Functional group analysis identified several biologically relevant pathways. In GvC, these included mitochondria and lymphocyte activation. In PvC, we identified apoptosis, inflammatory defense, and cell motion pathways. Significance: A unique, biologically meaningful mRNA expression pattern is detectable in whole blood of pediatric subjects with new-onset and untreated epilepsy. This analysis finds many similar pathways to those identified in brain studies examining lesional intractable epilepsy. Blood mRNA expression patterns show promise as a target for biomarker development in pediatric epilepsy. [ABSTRACT FROM AUTHOR]

Purpose: Intracranial electroencephalography (EEG) is performed as part of an epilepsy surgery evaluation when noninvasive tests are incongruent or the putative seizure-onset zone is near eloquent cortex. Determining the seizure-onset zone using intracranial EEG has been conventionally based on identification of specific ictal patterns with visual inspection. High-frequency oscillations (HFOs, >80 Hz) have been recognized recently as highly correlated with the epileptogenic zone. However, HFOs can be difficult to detect because of their low amplitude. Therefore, the prevalence of ictal HFOs and their role in localization of epileptogenic zone on intracranial EEG are unknown. Methods: We identified 48 patients who underwent surgical treatment after the surgical evaluation with intracranial EEG, and 44 patients met criteria for this retrospective study. Results were not used in surgical decision making. Intracranial EEG recordings were collected with a sampling rate of 2,000 Hz. Recordings were first inspected visually to determine ictal onset and then analyzed further with time-frequency analysis. Forty-one (93%) of 44 patients had ictal HFOs determined with time-frequency analysis of intracranial EEG. Key Findings: Twenty-two (54%) of the 41 patients with ictal HFOs had complete resection of HFO regions, regardless of frequency bands. Complete resection of HFOs (n = 22) resulted in a seizure-free outcome in 18 (82%) of 22 patients, significantly higher than the seizure-free outcome with incomplete HFO resection (4/19, 21%). Significance: Our study shows that ictal HFOs are commonly found with intracranial EEG in our population largely of children with cortical dysplasia, and have localizing value. The use of ictal HFOs may add more promising information compared to interictal HFOs because of the evidence of ictal propagation and followed by clinical aspect of seizures. Complete resection of HFOs is a favorable prognostic indicator for surgical outcome. [ABSTRACT FROM AUTHOR]

Summary: Purpose: Magnetoencephalography (MEG) has been shown a useful diagnostic tool for presurgical evaluation of pediatric medically intractable partial epilepsy as MEG source localization has been shown to improve the likelihood of seizure onset zone (SOZ) sampling during subsequent evaluation with intracranial EEG (ICEEG). We investigated whether ictal MEG onset source localization further improves results of interictal MEG in defining the SOZ. Methods: We identified 20 pediatric patients with one habitual seizure during MEG recordings between October 2007 and April 2011. MEG was recorded with sampling rates of 600Hz and 4000Hz for 10 and 2min respectively. Continuous head localization (CHL) was applied. Source localization analyses were applied using multiple algorithms, both at the beginning of ictal onset and for interictal MEG discharges. Ictal MEG onsets were identified by visual inspection and power spectrum using short-time Fourier transform (STFT). Source localizations were compared with ICEEG, surgical procedure and outcome. Key findings: Eight patients met all inclusion criteria. Five of the 8 patients (63%) had concordant ictal MEG onset source localization and interictal MEG discharge source localizations in the same lobe, but the source of ictal MEG onset was closer to the SOZ defined by ICEEG. Significance: Although the capture of seizures during MEG recording is challenging, the source localization for ictal MEG onset proved to be a useful tool for presurgical evaluation in our pediatric population with medically intractable epilepsy. [Copyright &y& Elsevier]

Abstract: To determine vigabatrin’s effectiveness and the prevalence of symptomatic visual impairment (i.e., impairment affecting the ability to perform everyday activities) associated with its therapy in pediatric epilepsy, we retrospectively reviewed medical records of 156 patients receiving vigabatrin at Cincinnati Children’s Medical Center from 1998-2010. In addition to demographics and vigabatrin dosing information, data included seizure type/frequency at presentation and subsequent follow-up. Of 156 patients, we excluded 35 because their medical records were insufficient to permit verification of the exact duration or timing of vigabatrin treatment. To evaluate efficacy (n = 121/135), we used a 5-point scale (0-4) to compare seizure frequency at several time points. To evaluate visual impairment (n = 63), we reviewed serial ophthalmologic evaluations at baseline and during treatment for patients in whom they were clinically indicated. Mean age at treatment initiation was 1.8 years (range, 0.1-29.2 years). Treatment duration ranged from 0.7-101.0 months, with an estimated average daily dose of 79 mg/kg/day. Tuberous sclerosis complex was the commonest seizure etiology (83%). Partial-onset seizure, alone or with infantile spasms, was the commonest seizure type (84%). Seizure frequency decreased from 3.7 ± 0.6 S.D. at baseline to 1.8 ± 1.7 S.D. at 6 months (P < 0.001). Responses to vigabatrin did not differ by tuberous sclerosis complex or nontuberous sclerosis complex etiology, and were sustained for 5 years. Sixty-three patients (∼50% of all patients evaluated) underwent clinically indicated ophthalmologic assessments during the review period. In our clinical judgment, no cases of clinically relevant vigabatrin-associated visual impairment occurred. Vigabatrin was effective for refractory childhood partial-onset epilepsy, and was not associated with symptomatic vision loss. [Copyright &y& Elsevier]

Introduction: Rotational vertebral artery occlusion (RVAO), sometimes known as 'Bow hunter syndrome,' is an important and diagnostically challenging cause of posterior circulation stroke in children. It is caused by impingement of osseous and/or ligamentous structures on the vertebral artery. Discussion: We review the differential diagnosis and recommended workup for posterior circulation stroke in children. The anatomical cause for pediatric RVAO is most commonly an anomalous bone formation of the rostral vertebral column. Many bony anomalies have been associated with RVAO, including the 'ponticulus posticus,' a common anomaly of the C1 vertebrae. The definitive diagnosis of RVAO is made with dynamic angiography, and surgical decompression of the vertebral artery prevents recurrent strokes. Illustrative case: We report a 15-year-old boy with recurrent posterior circulation ischemic strokes caused by an anomalous ossification of the C1 vertebrae. Three-dimensional (3D) and multiplanar reconstructed CT images showed the anomalous C1 ossification, and cervicocerebral digital subtraction angiography (DSA) revealed an associated vertebral artery (VA) dissection. The patient was initially managed by head immobilization in a hard collar and anticoagulation for 3 months. After healing of the dissection that was confirmed angiographically, dynamic DSA demonstrated reversible occlusion of the VA during contralateral head turn. Surgical decompression of the VA was performed and confirmed by intra-operative DSA with head turning. Conclusions: RVAO is an important diagnosis in children with posterior circulation stroke. Our case demonstrates the need for high clinical suspicion and careful analysis of 3D cervical spine CT images in children with posterior circulation stroke. [ABSTRACT FROM AUTHOR]

Objective: We evaluated changes in cognitive domains after neurosurgical lesioning of cortical sites with significant high‐gamma power modulations (HGM) during a visual naming task, although these sites were found language‐negative on standard‐of‐care electrical stimulation mapping (ESM). Methods: In drug‐resistant epilepsy patients who underwent resection/ablation after stereo‐electroencephalography (SEEG), we computed reliable change indices (RCIs) from a battery of presurgical and 1‐year postsurgical neuropsychological assessments. We modeled RCIs as a function of lesioning even one HGM language site, number of HGM language sites lesioned, and the magnitude of naming‐related HGM. The analyses were adjusted for 1‐year seizure freedom, operated hemispheres, and the volumes of surgical lesions. Results: In 37 patients with 4455 SEEG electrode contacts (1839 and 2616 contacts in right and left hemispheres, respectively), no ESM language sites were lesioned. Patients with lesioning of even one HGM language site showed significantly lower RCIs for Peabody Picture Vocabulary Test (PPVT), working memory, and verbal learning immediate (VLI) scores. RCI declines with higher number of HGM language sites lesioned were seen in PPVT (slope [β] = −.10), working memory (β = −.10), VLI (β = −.14), and letter–word identification (LWI; β = −.14). No neuropsychological domains improved after lesioning of HGM language sites. Significant effects of the HGM magnitude at lesioned sites were seen on working memory (β = −.31), story memory immediate (β = −.27), verbal learning recognition (β = −.18), LWI (β = −.16), spelling (β = −.49), and passage comprehension (β = −.33). Because working memory was significantly affected in all three analyses, patients with maximal working memory decline were examined post hoc, revealing that all such patients had HGM naming sites lesioned in the posterior quadrants of either hemisphere. Significance: HGM language mapping should be used as an adjunct to ESM in clinical practice and may help counsel patients/families about postsurgical cognitive deficits. [ABSTRACT FROM AUTHOR]

• Primary hub was significantly closer to the stereotactic EEG-defined seizure onset zone compared to the center of ECD cluster. • Both ECD cluster and network analyses suggested that spatially restricted region correlate with better seizure outcomes. • Our findings suggest that magnetoencephalography network analysis could be a valuable complement to the conventional ECD method. To clinically validate the connectivity-based magnetoencephalography (MEG) analyses to identify seizure onset zone (SOZ) with comparing to equivalent current dipole (ECD). The ECD cluster was quantitatively analyzed by calculating the centroid of the cluster and maximum distance (the largest distance between all dipoles). The "primary hub" was determined by the highest eigencentrality. The distribution of nodes in the top 5% of eigenvector centrality values was quantified by generating the convex hull between each node. Thirty-one patients who underwent MEG, stereotactic-EEG, and focal surgery were included. The primary hub was significantly closer to the sEEG-defined SOZ compared to ECD (p = 0.009). The seizure freedom positive and negative predictive values of complete ECD cluster and primary hub resections did not significantly differ, although complete resection of the primary hub showed slightly better negative predictive value (ECD: 50.0% NPV, hub: 64.7% NPV). Both quantitative ECD and functional connectivity analyses suggested that spatially restricted dipole distributions and higher connectivity in a smaller region correlate with better seizure outcomes. Our findings suggest that MEG network analysis could be a valuable complement to the ECD methods. The results of this study are an important step towards using non-invasive neurophysiologic recordings to accurately define the epileptic network. [ABSTRACT FROM AUTHOR]

A left perisylvian network is known to support language in healthy adults. Low-beta (13–23 Hz) event-related desynchrony (ERD) has been observed during verb generation, at approximately 700–1200 ms post-stimulus presentation in past studies; the signal is known to reflect increased neuronal firing and metabolic demand during language production. In contrast, concurrent beta event-related synchrony (ERS) is thought to reflect neuronal inhibition but has not been well studied in the context of language. Further, while low-beta ERD for expressive language has been found to gradually shift from bilateral in childhood to left hemispheric by early adulthood, developmental lateralization of ERS has not been established. We used magnetoencephalography to study low beta ERS lateralization in a group of children and adolescents (n = 78), aged 4 to less than 19 years, who performed covert verb generation. We found that the youngest children had bilateral ERD and ERS. By adolescence, low-beta ERD was predominantly left lateralized in perisylvian cortex (i.e., Broca's and Wernicke's regions), while beta ERS was predominantly right lateralized. Increasing lateralization was significantly correlated to age for both ERD (Spearman's r = 0.45, p < 0.01) and ERS (Spearman's r = − 0.44, p < 0.01). Interestingly, while ERD lateralized in a linear manner, ERS lateralization followed a nonlinear trajectory, suggesting distinct developmental trajectories. Implications to early-age neuroplasticity and neuronal inhibition are discussed. [ABSTRACT FROM AUTHOR]

Language comprehension is a complex process involving an extensive brain network. Brain regions responsible for prosodic processing have been studied in adults; however, much less is known about the neural bases of prosodic processing in children. Using magnetoencephalography (MEG), we mapped regions supporting speech envelope tracking (a marker of prosodic processing) in 80 typically developing children, ages 4–18 years, completing a stories listening paradigm. Neuromagnetic signals coherent with the speech envelope were localized using dynamic imaging of coherent sources (DICS). Across the group, we observed coherence in bilateral perisylvian cortex. We observed age-related increases in coherence to the speech envelope in the right superior temporal gyrus (r = 0.31, df = 78, p = 0.0047) and primary auditory cortex (r = 0.27, df = 78, p = 0.016); age-related decreases in coherence to the speech envelope were observed in the left superior temporal gyrus (r = − 0.25, df = 78, p = 0.026). This pattern may indicate a refinement of the networks responsible for prosodic processing during development, where language areas in the right hemisphere become increasingly specialized for prosodic processing. Altogether, these results reveal a distinct neurodevelopmental trajectory for the processing of prosodic cues, highlighting the presence of supportive language functions in the right hemisphere. Findings from this dataset of typically developing children may serve as a potential reference timeline for assessing children with neurodevelopmental hearing and speech disorders. [ABSTRACT FROM AUTHOR]

Objective: Electrical stimulation mapping (ESM) is the clinical standard for functional localization with subdural electrodes (SDE). As stereoelectroencephalography (SEEG) has emerged as an alternative option, we compared functional responses, afterdischarges (ADs), and unwanted ESM‐induced seizures (EISs) between the two electrode types. Methods: Incidence and current thresholds for functional responses (sensory, motor, speech/language), ADs, and EISs were compared between SDE and SEEG using mixed models incorporating relevant covariates. Results: We identified 67 SEEG ESM and 106 SDE ESM patients (7207 and 4980 stimulated contacts, respectively). We found similar incidence of language and motor responses between electrode types; however, more SEEG patients reported sensory responses. ADs and EISs occurred less commonly with SEEG than SDE. Current thresholds for language, face motor, and upper extremity (UE) motor responses and EIS significantly decreased with age. However, they were not affected by electrode type, premedication, or dominant hemispheric stimulation. AD thresholds were higher with SEEG than with SDE. For SEEG ESM, language thresholds remained below AD thresholds up to 26 years of age, whereas this relationship was inverse for SDE. Also, face and UE motor thresholds fell below AD thresholds at earlier ages for SEEG than SDE. AD and EIS thresholds were not affected by premedication. Significance: SEEG and SDE have clinically relevant differences for functional brain mapping with electrical stimulation. Although evaluation of language and motor regions is comparable between SEEG and SDE, SEEG offers a higher likelihood of identifying sensory areas. A lower incidence of ADs and EISs, and a favorable relationship between functional and AD thresholds suggest superior safety and neurophysiologic validity for SEEG ESM than SDE ESM. [ABSTRACT FROM AUTHOR]

Objectives This meta-analysis was performed to determine if acute postoperative seizures (APOS) predict epilepsy surgery outcomes. Additionally, we estimated pooled prevalence for APOS and explored if certain APOS characteristics predict surgical outcomes. Methods A systematic literature search was performed for studies reporting seizure outcomes after epilepsy surgery in patients with and without APOS. APOS were defined as seizure(s) occurring within 30 days of surgery. After data extraction, pooled Mantel-Haenszel odds ratio (OR) with 95% confidence intervals (CI) was calculated for 1-year seizure-free outcome in patients with and without APOS using random-effects meta-analysis. Sub-group meta-analysis for pediatric studies, time of occurrence, and APOS semiology were also performed. A meta-regression was performed to explore source(s) of heterogeneity. Results Seventeen studies were included in the final synthesis. Pooled prevalence of APOS was found to be 22.58%. A significantly higher proportion of patients without APOS within 30 days of surgery (73.49%) were seizure-free at ≥1-year (OR 4.20, 95% CI 2.97–5.93, p < 0.0001) compared to those with APOS (38.96%). Among the pediatric studies (n = 6) 77.14% of patients without APOS were seizure-free at ≥1-year, compared to 35.94% of those with APOS (OR 5.71, 95% CI 3.32–9.80, p < 0.0001). Patients having APOS within 24 h of surgery and APOS semiology different from habitual pre-surgical seizures were more likely to achieve seizure-free outcomes, but these results failed to achieve statistical significance. Conclusions APOS reliably predict 1-year seizure outcomes after epilepsy surgery. This information should help counsel patients and families. [ABSTRACT FROM AUTHOR]

Resective epilepsy surgery can improve seizures when the epileptogenic zone (EZ) is limited to a well-defined region. High frequency oscillations (HFO) have been recognized as having a high association with the seizure onset zone. Therefore, we retrospectively identified ictal HFOs and determined their relationship to specific intracranial features of cortical tubers in children with TSC who underwent resective surgery. We identified 14 patients with drug resistant epilepsy secondary to TSC who underwent subdural grid and strip implantation for presurgical evaluation and subsequent resection with adequate post-surgical follow-up. We aimed to determine the relationship between ictal HFOs, post-resection outcome and neuroimaging features in this population. The largest tuber was identified in all 14 patients (100%). Four patients (29%) had unusual tubers. HFOs were observed at ictal onset in all 14 patients. Seven of 10 patients with complete resection of HFOs were seizure free. The better seizure outcome (ILAE = 1–3) was achieved with complete HFO resection regardless of the unique TSC structural features (p = 0.0140). Our study demonstrates the presence of ripple and fast ripple range HFOs at ictal onset in children with TSC. Our study showed that complete HFO resection led to the better surgical outcome, independent of MR imaging findings. [ABSTRACT FROM AUTHOR]

Background: Cortical dysplasia is the most common cause of pediatric refractory epilepsy. MRI detection of epileptogenic lesion is associated with good postsurgical outcome. Additional electrophysiological information is suggested to be helpful in localization of cortical dysplasia. Educational measures were taken to increase the awareness of cortical dysplasia at our institution in the context of a recent International League Against Epilepsy (ILAE 2011) classification of cortical dysplasia.Objective: To determine changes in the rate of prospective identification of cortical dysplasia on an initial radiology report and also evaluate the benefit of MRI review as part of a multidisciplinary epilepsy conference in identifying previously overlooked MRI findings.Materials and Methods: We retrospectively evaluated surgically treated children with refractory epilepsy from 2007 to 2014 with cortical dysplasia on histopathology. We analyzed the initial radiology report, preoperative MRI interpretation at multidisciplinary epilepsy conference and subsequent retrospective MRI review with knowledge of the resection site. We recorded additional electrophysiological data and the presence of lobar concordance with the MRI findings.Results: Of 78 children (44 MRI lesional) evaluated, 18 had initially overlooked MRI findings. Comparing 2007-2010 to 2011-2014, there was improvement in the rate of overlooked findings on the initial radiology report (54% vs. 13% of lesional cases, respectively; P = 0.008). The majority (72%) were identified at a multidisciplinary conference with lobar concordance of findings with at least one additional electrophysiological investigation in 89%.Conclusion: Awareness of current classification schemes of cortical dysplasia and image review in the context of a multidisciplinary conference can lead to improved MRI detection of cortical dysplasia in children. [ABSTRACT FROM AUTHOR]

Objective: We describe the development and evaluation of a system that uses machine learning and natural language processing techniques to identify potential candidates for surgical intervention for drug-resistant pediatric epilepsy. The data are comprised of free-text clinical notes extracted from the electronic health record (EHR). Both known clinical outcomes from the EHR and manual chart annotations provide gold standards for the patient’s status. The following hypotheses are then tested: 1) machine learning methods can identify epilepsy surgery candidates as well as physicians do and 2) machine learning methods can identify candidates earlier than physicians do. These hypotheses are tested by systematically evaluating the effects of the data source, amount of training data, class balance, classification algorithm, and feature set on classifier performance. The results support both hypotheses, with F-measures ranging from 0.71 to 0.82. The feature set, classification algorithm, amount of training data, class balance, and gold standard all significantly affected classification performance. It was further observed that classification performance was better than the highest agreement between two annotators, even at one year before documented surgery referral. The results demonstrate that such machine learning methods can contribute to predicting pediatric epilepsy surgery candidates and reducing lag time to surgery referral. [ABSTRACT FROM AUTHOR]

Ninety percent of tuberous sclerosis complex (TSC) patients have seizures, with ∼50 % developing drug refractory epilepsy. Surgical intervention aims to remove the seizure onset zone (SOZ). This retrospective study investigated the relationship of SOZ size, ictal pattern, and extent of resection with surgical outcomes. TSC patients undergoing resective/ablative surgery with >1-year follow-up and adequate imaging were included. Preoperative iEEG data were reviewed to determine ictal pattern and SOZ location. For outcomes, an ILAE score of 1–3 was defined as good and 4–6 as poor. Forty-four patients were included (age 117.4 ± 110.8 months). Of these, 59.1 % achieved a good outcome, while 40.9 % had a poor outcome. Size of SOZ was a significant factor (p = 0.009), with the poor outcome group having a larger SOZ (11.9 ± 6.7 electrode contacts) than the good outcome group (7.3 ± 7.2). SOZ number was significant (p = 0.020); >1 SOZ was associated with poor outcome. These results demonstrate extent of SOZ as a predictor of seizure freedom following epilepsy surgery in a mostly pediatric TSC cohort. We hypothesize that these features represent biomarkers of focality of the epileptogenic zone and can be used to sharpen prognosis for epilepsy surgery outcomes in this cohort. • Pediatric TSC epilepsy surgery outcomes were determined in 44 patients. • Good outcomes were observed in 59 % of cases. • Smaller seizure onset zone based on intracranial EEG was a predictor of good outcome. • This information can be used to select best candidates for TSC surgery. [ABSTRACT FROM AUTHOR]

Microarray testing has revolutionized clinical cytogenetics, as it provides a significantly higher resolution and greater clinical yield than karyotype analysis. This study assessed the clinical utility of single-nucleotide polymorphism microarray in patients with epilepsy. Study subjects were patients between the ages of birth to 23 years who were diagnosed with epilepsy and had a microarray performed at Cincinnati Children’s Hospital Medical Center. Statistical analysis explored the association of microarray results and brain magnetic resonance imaging (MRI), seizure type, and structural malformations. Approximately 17.7% (26/147) of participants had an abnormal microarray as defined by laboratory guidelines. There were no differences in frequency of abnormal brain MRI or seizure type between the abnormal and normal microarray groups. There was a higher prevalence of musculoskeletal malformations (P < .0035) and cardiovascular malformations (P < .0081) in subjects with abnormal microarrays. Clinicians should consider microarray analysis in individuals who have epilepsy, especially in combination with musculoskeletal malformation or cardiovascular malformation. [ABSTRACT FROM AUTHOR]

• During visual naming, high-gamma modulation occurs in a posteroanterior sequential pattern with overlapping temporal profiles. • Cortical activations during visual naming represent cognitive sub-components with different relative contributions from the left and right cerebral hemispheres. • Post-surgical neuropsychological deficits correlated with the location of resected parcels within the visual naming network. Cerebral spatiotemporal dynamics of visual naming were investigated in epilepsy patients undergoing stereo-electroencephalography (SEEG) monitoring. Brain networks were defined by Parcel-Activation-Resection-Symptom matching (PARS) approach by matching high-gamma (50–150 Hz) modulations (HGM) in neuroanatomic parcels during visual naming, with neuropsychological outcomes after resection/ablation of those parcels. Brain parcels with >50% electrode contacts simultaneously showing significant HGM were aligned, to delineate spatiotemporal course of naming-related HGM. In 41 epilepsy patients, neuroanatomic parcels showed sequential yet temporally overlapping HGM course during visual naming. From bilateral occipital lobes, HGM became increasingly left lateralized, coursing through limbic system. Bilateral superior temporal HGM was noted around response time, and right frontal HGM thereafter. Correlations between resected/ablated parcels, and post-surgical neuropsychological outcomes showed specific regional groupings. Convergence of data from spatiotemporal course of HGM during visual naming, and functional role of specific parcels inferred from neuropsychological deficits after resection/ablation of those parcels, support a model with six cognitive subcomponents of visual naming having overlapping temporal profiles. Cerebral substrates supporting visual naming are bilaterally distributed with relative hemispheric contribution dependent on cognitive demands at a specific time. PARS approach can be extended to study other cognitive and functional brain networks. [ABSTRACT FROM AUTHOR]

• An approach for analysis of task-related high-gamma modulation in stereo-EEG using distribution of power differential clusters is described. • Stereo-EEG high-gamma language mapping effectively localized reference neuroanatomy (Neurosynth). • Stereo-EEG high-gamma language mapping also adequately classified electrical stimulation mapping speech/language sites. A novel analytic approach for task-related high-gamma modulation (HGM) in stereo-electroencephalography (SEEG) was developed and evaluated for language mapping. SEEG signals, acquired from drug-resistant epilepsy patients during a visual naming task, were analyzed to find clusters of 50–150 Hz power modulations in time–frequency domain. Classifier models to identify electrode contacts within the reference neuroanatomy and electrical stimulation mapping (ESM) speech/language sites were developed and validated. In 21 patients (9 females), aged 4.8–21.2 years, SEEG HGM model predicted electrode locations within Neurosynth language parcels with high diagnostic odds ratio (DOR 10.9, p < 0.0001), high specificity (0.85), and fair sensitivity (0.66). Another SEEG HGM model classified ESM speech/language sites with significant DOR (5.0, p < 0.0001), high specificity (0.74), but insufficient sensitivity. Time to largest power change reliably localized electrodes within Neurosynth language parcels, while, time to center-of-mass power change identified ESM sites. SEEG HGM mapping can accurately localize neuroanatomic and ESM language sites. Predictive modelling incorporating time, frequency, and magnitude of power change is a useful methodology for task-related HGM, which offers insights into discrepancies between HGM language maps and neuroanatomy or ESM. [ABSTRACT FROM AUTHOR]

• Stereo-EEG sensorimotor mapping was prospectively compared with reference neuroanatomy. • Electrical stimulation mapping localized anatomic sensorimotor parcels with high accuracy. • Sensorimotor thresholds below after-discharge thresholds suggest safety of stereo-EEG ESM. We evaluated stereo-EEG electrical stimulation mapping (ESM) for localization of anatomic sensorimotor parcels in pediatric patients with drug-resistant epilepsy. We also analyzed sensorimotor and after-discharge thresholds, and the somatotopy of sensorimotor responses. ESM was performed with 50 Hz, biphasic, 2–3 s trains, using 1–9 mA current. Pre- and post-implant neuroimaging was co-registered and intersected with Neurosynth reference, to classify each electrode contact as lying within/outside an anatomic sensorimotor parcel. Indices of diagnostic performance were computed. Sensorimotor and after-discharge thresholds were analyzed using multivariable linear mixed models. In 15 patients (6 females), aged 5.5–21.2 years, ESM showed high accuracy (0.80), high specificity (0.86), and diagnostic odds ratio (11.4, p < 0.0001) for localization of sensorimotor parcels. Mean sensorimotor threshold (3.4 mA) was below mean after-discharge threshold (4.2 mA, p = 0.0004). Sensorimotor and after-discharge thresholds showed a significant decrease with increasing intelligence quotient. Somatotopy of sensorimotor responses was mapped to standardized brain parcels. We provide evidence for diagnostic validity and safety of stereo-EEG sensorimotor ESM. The somatotopy of sensorimotor responses elicited with electrical stimulation provide new insights into mechanisms of motor control and sensory perception. [ABSTRACT FROM AUTHOR]

Summary: Objective: We studied age‐related dynamics of information sharing among cortical language regions with electrocorticographic high‐gamma modulation during picture‐naming and story‐listening tasks. Methods: Seventeen epilepsy patients aged 4‐19 years, undergoing extraoperative monitoring with left‐hemispheric subdural electrodes, were included. Mutual information (MI), a nondirectional measure of shared information, between 16 pairs of cortical regions of interest, was computed from trial‐averaged 70–150 Hz power modulations during language tasks. Impact of age on pairwise MI between language regions and their determinants were ascertained with regression analysis. Results: During picture naming, significant increase in MI with age was seen between pairwise combinations of Broca's area, inferior precentral gyrus (iPreC), and frontal association cortex (FAC); Wernicke's area and posterior association cortex (PAC); and Broca's and Wernicke's areas. During story listening, significant age‐related increase in MI was seen between Wernicke's area and either Broca's area, FAC, or PAC; and between Broca's area and FAC. Significant impact of baseline intelligence quotient was seen on the relationship between age and MI for all pairs, except between Broca's area and iPreC. The mean MI was higher during naming compared to listening for pairs including iPreC with Broca's area, FAC, or PAC and was lower for pairs of Wernicke's area or PAC with anterior language regions. Significance: Information sharing matures with age "within" frontal and temporoparietal language cortices, and "between" Broca's and Wernicke's areas. This study provides evidence for distinct patterns of developmental plasticity within perisylvian language cortex and has implications for planning epilepsy surgery. [ABSTRACT FROM AUTHOR]

Highlights • Resection of HGM language sites is associated with worse neuropsychological outcomes. • Working memory was significantly worse in patients with resection of HGM naming sites. • Neuropsychological evaluation of children with epilepsy should include multiple cognitive and language domains. Abstract Background Language mapping with high-gamma modulation (HGM) has compared well with electrical cortical stimulation mapping (ESM). However, there is limited prospective data about its functional validity. We compared changes in neuropsychological evaluation (NPE) performed before and 1-year after epilepsy surgery, between patients with/without resection of cortical sites showing HGM during a visual naming task. Methods Pediatric drug-resistant epilepsy (DRE) patients underwent pre-surgical language localization with ESM and HGM using a visual naming task. Surgical decisions were based solely on ESM results. NPE difference scores were compared between patients with/without resection of HGM naming sites using principal component (PC) analysis. Follow-up NPE scores were modeled with resection group as main effect and respective pre-surgical score as a covariate, using analysis of covariance. Results Seventeen native English speakers (12 females), aged 6.5–20.2 years, were included. One year after epilepsy surgery, first PC score increased by (mean ± standard deviation) 14.4 ± 16.5 points in patients without resection, whereas it decreased by 7.6 ± 24.6 points in those with resection of HGM naming sites (p = 0.040). This PC score represented verbal comprehension, working memory, perceptual reasoning (Wechsler subscales); Woodcock-Johnson Tests of Achievement; and Peabody Picture Vocabulary Test. Subsequent analysis showed significant difference in working memory score between patients with/without resection of HGM naming sites (−15.2 points, 95% confidence limits −29.7 to −0.7, p = 0.041). Conclusion We highlight the functional consequences of resecting HGM language sites, and suggest that NPE of DRE patients should include comprehensive assessment of multiple linguistic and cognitive domains besides naming ability. [ABSTRACT FROM AUTHOR]

Objective We evaluated the impact of radiotracer injection latency and post-injection seizure duration on subtraction ictal SPECT co-registered to MRI (SISCOM) test performance in identifying the epileptogenic zone (EZ) in children with drug-resistant epilepsy who had undergone a resective epilepsy surgery. Methods SISCOM concordance with the EZ was retrospectively reviewed to evaluate its performance in 113 children. The impact of radiotracer injection latency and post-injection seizure duration was evaluated for their predictive value of SISCOM localization accuracy. Results The overall sensitivity and specificity of SISCOM in identifying an EZ was 64.8% (95%CI = 50.6–77.3) and 40.7% (95%CI = 28.1–54.3). The positive likelihood ratio and diagnostic odd ratio was 1.09 (95%CI = 0.80–1.48) and 1.26 (95%CI = 0.59–2.71), respectively. Logistic regression showed that injection latency and post-injection seizure duration did not significantly predict the probability of true positive SISCOM (p-value = 0.45 and 0.29, respectively). Conclusion Radiotracer injection latency and post-injection seizure duration were not shown to have a statistical significant impact on SISCOM performance in identifying the EZ. Significance This study demonstrates that further study of factors contributing to the performance of SISCOM in EZ identification in children is needed. [ABSTRACT FROM AUTHOR]

Summary: Objective: This prospective study compared the topography of high‐gamma modulation (HGM) during a story‐listening task requiring negligible patient cooperation, with the conventional electrical stimulation mapping (ESM) using a picture‐naming task, for presurgical language localization in pediatric drug‐resistant epilepsy. Methods: Patients undergoing extraoperative monitoring with subdural electrodes were included. Electrocorticographic signals were recorded during quiet baseline and a story‐listening task. The likelihood of 70‐ to 150‐Hz power modulation during the listening task relative to the baseline was estimated for each electrode and plotted on a cortical surface model. Sensitivity, specificity, accuracy, and diagnostic odds ratio (DOR) were estimated compared to ESM, using a meta‐analytic framework. Results: Nineteen patients (10 with left hemisphere electrodes) aged 4‐19 years were analyzed. HGM during story listening was observed in bilateral posterior superior temporal, angular, supramarginal, and inferior frontal gyri, along with anatomically defined language association areas. Compared to either cognitive or both cognitive and orofacial sensorimotor interference with naming during ESM, left hemisphere HGM showed high specificity (0.82‐0.84), good accuracy (0.66‐0.70), and DOR of 2.23 and 3.24, respectively. HGM was a better classifier of ESM language sites in the left temporoparietal cortex compared to the frontal lobe. Incorporating visual naming with the story‐listening task substantially improved the accuracy (0.80) and DOR (13.61) of HGM mapping, while the high specificity (0.85) was retained. In the right hemisphere, no ESM sites for aphasia were seen, and the results of HGM and ESM comparisons were not significant. Significance: HGM associated with story listening is a specific determinant of left hemisphere ESM language sites. It can be used for presurgical language mapping in children who cannot cooperate with conventional language tasks requiring active engagement. Incorporation of additional language tasks, if feasible, can further improve the diagnostic accuracy of language localization with HGM. [ABSTRACT FROM AUTHOR]

Purpose We studied the effect of fosphenytoin (FOS) pre-medication on the incidence and thresholds of after-discharges (ADs), seizures, and functional responses during electrical stimulation mapping (ESM). Methods As individualized by the attending epileptologist, FOS was given intravenously at 2 mg-phenytoin-equivalents (PE)/kg/min or 150 mg-PE/min (whichever slower). Patients who received and did not receive FOS were compared for the incidence and thresholds of ADs, seizures, and functional responses. Results Before ESM, 40 and 82 patients respectively were pre-medicated/not pre-medicated with FOS. The incidence of ESM-induced seizures was significantly lower in FOS pre-medicated patients (22.5% vs. 42.7%, p = 0.044), whereas temporal language threshold was higher (9.2 vs. 6.5 mA, p = 0.032). FOS was more efficacious in preventing ESM-induced seizures in patients with symptomatogenic zone ipsilateral to the side of ESM. Although FOS dose had no significant effect on minimum language, minimum motor, or AD thresholds; seizure and temporal language thresholds showed trends approaching significance, intersecting at 12.2 mg-PE/kg. The incidence of ESM-induced seizures was significantly lower in those who received FOS at a dose of ≤12 mg/kg (9.1%) compared to those who did not receive any FOS (42.7%, p = 0.046), while the temporal language thresholds were not significantly different (6.3 vs. 6.5 mA, p = 0.897). Conclusions This study provides class III evidence that FOS pre-medication before ESM decreases the incidence of ESM-induced seizures, but increases temporal language threshold. FOS pre-medication may thus be considered before ESM. Future studies should prospectively verify these observations and characterize dose-response relationships. [ABSTRACT FROM AUTHOR]

Objective This study examined the incidence, thresholds, and determinants of electrical cortical stimulation (ECS)-induced after-discharges (ADs) and seizures. Methods Electrocorticograph recordings were reviewed to determine incidence of ECS-induced ADs and seizures. Multivariable analyses for predictors of AD/seizure occurrence and their thresholds were performed. Results In 122 patients, the incidence of ADs and seizures was 77% (94/122) and 35% (43/122) respectively. Males (odds ratio [OR] 2.92, 95% CI 1.21–7.38, p = 0.02) and MRI-negative patients (OR 3.69, 95% CI 1.24–13.7, p = 0.03) were found to have higher odds of ECS-induced ADs. A significant trend for decreasing AD thresholds with age was seen (regression co-efficient −0.151, 95% CI −0.267 to −0.035, p = 0.011). ECS-induced seizures were more likely in patients with lateralized functional imaging (OR 6.62, 95% CI 1.36–55.56, p = 0.036, for positron emission tomography) and presence of ADs (OR 3.50, 95% CI 1.12–13.36, p = 0.043). Conclusions ECS is associated with a high incidence of ADs and seizures. With age, current thresholds decrease and the probability for AD/seizure occurrence increases. Significance ADs and seizures during ECS brain mapping are potentially hazardous and affect its functional validity. Thus, safer method(s) for brain mapping with improved neurophysiologic validity are desirable. [ABSTRACT FROM AUTHOR]

Objective To examine current thresholds and their determinants for language and motor mapping with extra-operative electrical cortical stimulation (ECS). Methods ECS electrocorticograph recordings were reviewed to determine functional thresholds. Predictors of functional thresholds were found with multivariable analyses. Results In 122 patients (age 11.9 ± 5.4 years), average minimum, frontal, and temporal language thresholds were 7.4 (± 3.0), 7.8 (± 3.0), and 7.4 (± 3.1) mA respectively. Average minimum, face, upper and lower extremity motor thresholds were 5.4 (± 2.8), 6.1 (± 2.8), 4.9 (± 2.3), and 5.3 (± 3.3) mA respectively. Functional and after-discharge (AD)/seizure thresholds were significantly related. Minimum, frontal, and temporal language thresholds were higher than AD thresholds at all ages. Minimum motor threshold was higher than minimum AD threshold up to 8.0 years of age, face motor threshold was higher than frontal AD threshold up to 11.8 years age, and lower subsequently. UE motor thresholds remained below frontal AD thresholds throughout the age range. Conclusions Functional thresholds are frequently above AD thresholds in younger children. Significance These findings raise concerns about safety and neurophysiologic validity of ECS mapping. Functional and AD/seizure thresholds relationships suggest individual differences in cortical excitability which cannot be explained by clinical variables. [ABSTRACT FROM AUTHOR]

Objectives To determine the prevalence of epilepsy and drug-resistant epilepsy in pediatric patients with focal cortical dysplasia (FCD) identified by magnetic resonance imaging (MRI). To determine clinical and imaging differences between those with drug-resistant epilepsy, drug-responsive epilepsy, and no epilepsy among children with MRI-identified FCD. Methods A keyword search of a hospital radiology database identified 97 study participants for inclusion in this retrospective study. Participants were included if they were under 18 years of age at time of database query and had an MRI between 2004 and 2013 showing FCD. Exclusion was based on imaging and clinical characteristics. Data was gathered using a chart review and supplemental questionnaire. Results In this cohort of patients with imaging findings compatible with FCD, 29% had not developed epilepsy. The prevalence of epilepsy and drug-resistant epilepsy was 71.13% (95% C.I. = 61.05–79.89%) and 32.99% (95% C.I. = 23.78–43.27%), respectively. Patients with epilepsy were more likely to have temporal ( p = 0.029) or frontal ( p = 0.044) lobe lesions and a family history of seizures ( p = 0.003) than those without epilepsy. Age of seizure onset was later in those with drug-responsive epilepsy than those with drug-resistant epilepsy ( p = 0.0002). A later age of seizure onset (OR = 1.22, p = 0.0441, 95% C.I. = 1.00–1.486) and absence of developmental delay (OR = 3.624, p = 0.0497, 95% C.I. = 1.002–13.110) predicted a less severe epilepsy phenotype. Conclusions Previous studies have only assessed patient cohorts with FCD and epilepsy, limiting the data on “asymptomatic” or “atypically presenting” FCD. Identifying a surprisingly large, novel cohort of children with FCD that had not developed epilepsy helps define prognosis and inform clinical management of children with FCD on imaging. [ABSTRACT FROM AUTHOR]

Invasive electroencephalographic monitoring with implantable subdural electrodes and intraparenchymal depth electrodes has become a basic tenet of epilepsy surgery. Improved localization of epileptic foci justifies the secondary procedure and monitoring period in many patients. Informed use of invasive monitoring in conjunction with imaging and functional studies makes epilepsy surgery a smaller, safer, and more effective endeavor. Herein we review the history, indications, implementation, and foreseeable future of grid, strip, and depth electrode use. [ABSTRACT FROM AUTHOR]

Objective This prospective study compared presurgical language localization with visual naming-associated high-γ modulation ( HGM) and conventional electrical cortical stimulation ( ECS) in children with intracranial electrodes. Methods Patients with drug-resistant epilepsy who were undergoing intracranial monitoring were included if able to name pictures. Electrocorticography ( ECoG) signals were recorded during picture naming (overt and covert) and quiet baseline. For each electrode the likelihood of high-γ (70-116 Hz) power modulation during naming task relative to the baseline was estimated. Electrodes with significant HGM were plotted on a three-dimensional (3D) cortical surface model. Sensitivity, specificity, and accuracy were calculated compared to clinical ECS. Results Seventeen patients with mean age of 11.3 years (range 4-19) were included. In patients with left hemisphere electrodes (n = 10), HGM during overt naming showed high specificity (0.81, 95% confidence interval [ CI] 0.78-0.85), and accuracy (0.71, 95% CI 0.66-0.75, p < 0.001), but modest sensitivity (0.47) when ECS interference with naming (aphasia or paraphasic errors) and/or oral motor function was regarded as the gold standard. Similar results were reproduced by comparing covert naming-associated HGM with ECS naming sites. With right hemisphere electrodes (n = 7), no ECS-naming deficits were seen without interference with oral-motor function. HGM mapping showed a high specificity (0.81, 95% CI 0.78-0.84), and accuracy (0.76, 95% CI 0.71-0.81, p = 0.006), but modest sensitivity (0.44) compared to ECS interference with oral-motor function. Naming-associated ECoG HGM was consistently observed over Broca's area (left posterior inferior-frontal gyrus), bilateral oral/facial motor cortex, and sometimes over the temporal pole. Significance This study supports the use of ECoG HGM mapping in children in whom adverse events preclude ECS, or as a screening method to prioritize electrodes for ECS testing. [ABSTRACT FROM AUTHOR]

Central nervous system comorbidities have been identified in patients with epilepsy. Several of these comorbidities have been correlated with poor surgery outcomes in patient cohorts. The authors sought to determine if prevalence of comorbidities in pediatric epilepsy surgery patients and their families correlate with long-term seizure outcome in a cross-sectional analysis. Three-generation pedigrees were elicited to compare family history of epilepsy, ADHD, anxiety, autism, bipolar disorder, cognitive disability, depression, migraine, and motor disability to surgery outcomes in 52 patients. Proportions of affected patients and relatives were compared to general population comorbidity rates and the patients' most recent seizure outcome classification. Patients and families had significantly higher rates of comorbidities than the general population. Poorer long-term seizure outcomes following resective surgery were associated with autism or cognitive disability in patients. Together these data support evidence for a common pathophysiological mechanism between epilepsy and central nervous system comorbidities. [ABSTRACT FROM AUTHOR]

Summary Introduction This study describes development of a novel language mapping approach using high-γ modulation in electrocorticograph (ECoG) during spontaneous conversation, and its comparison with electrical cortical stimulation (ECS) in childhood-onset drug-resistant epilepsy. Methods Patients undergoing invasive pre-surgical monitoring and able to converse with the investigator were eligible. ECoG signals and synchronized audio were acquired during quiet baseline and during natural conversation between investigator and the patient. Using Signal Modeling for Real-time Identification and Event Detection (SIGFRIED) procedure, a statistical model for baseline high-γ (70–116 Hz) power, and a single score for each channel representing the probability that the power features in the experimental signal window belonged to the baseline model, were calculated. Electrodes with significant high-γ responses (HGS) were plotted on the 3D cortical model. Sensitivity, specificity, positive and negative predictive values (PPV, NPV), and classification accuracy were calculated compared to ECS. Results Seven patients were included (4 males, mean age 10.28 ± 4.07 years). Significant high-γ responses were observed in classic language areas in the left hemisphere plus in some homologous right hemispheric areas. Compared with clinical standard ECS mapping, the sensitivity and specificity of HGS mapping was 88.89% and 63.64%, respectively, and PPV and NPV were 35.29% and 96.25%, with an overall accuracy of 68.24%. HGS mapping was able to correctly determine all ECS+ sites in 6 of 7 patients and all false—sites (ECS+, HGS− for visual naming, n = 3) were attributable to only 1 patient. Conclusions This study supports the feasibility of language mapping with ECoG HGS during spontaneous conversation, and its accuracy compared to traditional ECS. Given long-standing concerns about ecological validity of ECS mapping of cued language tasks, and difficulties encountered with its use in children, ECoG mapping of spontaneous language may provide a valid alternative for clinical use. [ABSTRACT FROM AUTHOR]

• Three SISCOM patterns were seen in pediatric temporal lobe epilepsy and unilateral anterior hyperperfusion is most identified. • Type of focal cortical dysplasia and presence of hippocampal sclerosis were significant determinants of SISCOM patterns. • Lobar concordance of SISCOM and ictal and interictal scalp EEG significantly correlated with postoperative outcomes. • There was no significant correlation between SISCOM patterns and one-year postoperative outcomes. We evaluated SISCOM patterns and their relationship with surgical outcome in children with temporal lobe epilepsy (TLE) who had undergone a temporal lobe surgery. This was an observational study evaluating SISCOM patterns in 40 children with TLE. We classified SISCOM patterns into 4 categories; (i) unilateral anteromesial and/or anterolateral temporal pattern; (ii) unilateral anteromesial and/or anterolateral temporal plus posterior extension pattern; (iii) bilateral anteromesial and/or anterolateral temporal pattern; and (iv) atypical pattern. Determinants of SISCOM pattern and correlation between postoperative outcomes and SISCOM patterns were evaluated. Pattern (i), (ii), (iii), and (iv) were identified in 10 (25%), 14 (35%), 0 (0%), and 16 (40%) patients, respectively. There was no significant correlation between patterns and postoperative outcomes. SISCOM patterns significantly associated with the presence of hippocampal sclerosis and type of focal cortical dysplasia (p-value = 0.048 and 0.036, respectively). Patients with HS had 5 times the odds of having unilateral temporal pattern, compared to patients with other neuropathology (OR = 5, 95% CI 0.92 to 27.08). Patients with FCD type 2 had 9.71 times the odds of having atypical pattern, compared to patients with other types of FCD (OR = 9.71, 95% CI 0.92 to 103.04). Lobar concordance of SISCOM and ictal and interictal scalp EEG significantly correlated with postoperative outcomes (p-value = 0.018 and 0.013, respectively). Three SISCOM patterns were seen. Patients with HS had increased odds of having unilateral temporal pattern while patients with FCD type 2 had increased odds of having atypical pattern. However, there was no significant correlation between SISCOM patterns and postoperative outcomes. Lobar concordance of SISCOM and ictal and interictal scalp EEG significantly correlated with postoperative outcome. This study shows that the distribution of SISCOM patterns and their relationship with postoperative outcomes in children with TLE are different from adult population. Besides, SISCOM may add only limited diagnostic and prognostic information in children with drug-resistant TLE undergoing epilepsy surgery. Further evaluation to identify patient populations that may benefit from SISCOM is desirable. [ABSTRACT FROM AUTHOR]

[Display omitted] • Epileptic high frequency brain signals have significantly elevated kurtosis and skewness. • Sources of epileptic high frequency brain signals pinpoint to epileptogenic zones. • Magnetoencephalography can noninvasively localize epileptic high frequency activity. Neuromagnetic high frequency brain signals (HFBS, > 80 Hz) are a new biomarker for localization of epileptogenic zones (EZs) for pediatric epilepsy. Twenty three children with drug-resistant epilepsy and age/sex matched healthy controls were studied with magnetoencephalography (MEG). Epileptic HFBS in 80−250 Hz and 250−600 Hz were quantitatively determined by comparing with normative controls in terms of kurtosis and skewness. Magnetic sources of epileptic HFBS were localized and then compared to clinical EZs determined by invasive recordings and surgical outcomes. Kurtosis and skewness of HFBS were significantly elevated in epilepsy patients compared to healthy controls (p < 0,001 and p < 0.0001, respectively). Sources of elevated MEG signals in comparison to normative data were co-localized to EZs for 22 (22/23, 96 %) patients. The results indicate, for the first time, that epileptic HFBS can be noninvasively quantified by measuring kurtosis and skewness in MEG data. Magnetic source imaging based on kurtosis and skewness can accurately localize EZs. Source imaging of kurtosis and skewness of MEG HFBS provides a novel way for preoperative localization of EZs for epilepsy surgery. [ABSTRACT FROM AUTHOR]

• 26.7 % patients showed ≥1 McHugh class improvement after replacement with cardiac-based VNS device. • 50 % patients maintained their McHugh class at last follow up. • 36.7 % Patients showed >50 % seizure reduction after replacement. • 4 patients showed deterioration in behaviour after replacement. This study evaluated the seizure outcomes in children with drug-resistant epilepsy (DRE), having a pre-existing VNS device, after generator replacement with cardiac-based VNS device. This retrospective study enrolled 30 children with DRE from 2 centers with an existing VNS device nearing end-of-service who underwent generator replacement with cardiac-based VNS device and had at least 1 year follow up. Seizure outcomes and adverse effects were studied. The mean age at insertion of cardiac-based VNS device was 15.03 years. 26.7 % patients showed at least one class improvement at last follow up (mean 2.08 years) and half of the patients maintained their McHugh seizure-outcome class. Thirty-six percent of patients had > 50 % seizure reduction at last follow up. Ten patients reported improvement in ictal severity. Most of the patients tolerated the replacement well. Nearly one-third of patients with DRE showed additional improvement after replacement with cardiac based VNS device. Half of the patients maintained their seizure control. [ABSTRACT FROM AUTHOR]

We studied spatiotemporal dynamics of electrocorticographic (ECoG) high-gamma modulation (HGM) during visual naming. In 8 patients, aged 4–19 years, with left hemisphere subdural electrodes, propagation of ECoG HGM during overt visual naming was mapped with trial-averaged time-frequency analysis. Group-level synthesis was performed by transforming all electrodes to a standard space and assigning cortical parcels based on a reference atlas. After image display following cortical parcels were activated: inferior occipital, caudal angular, fusiform, and middle temporal gyri, and superior temporal sulcus [0–400 ms]; rostral pars triangularis (A45r), inferior frontal sulcus, caudal dorsolateral premotor cortex (A6cdl) [300–600 ms]; caudal ventrolateral premotor cortex (A6cvl), caudal pars triangularis (A45c), pars opercularis (A44) [400–800 ms]; primary sensorimotor cortex [600–1400 ms], with most prominent HGM in glossolaryngeal region (A4tl). Lastly, auditory cortex (A41/A42) and superior temporal gyrus (A22) were activated [900 ms–1.4 s]. After 1.5 s, HGM decreased globally, except in ventrolateral premotor cortex. During visual naming, ECoG HGM shows a sequential but overlapping spatiotemporal course through cortical regions. We provide neurophysiologic validation for a model of visual naming incorporating both modular and distributed cortical processing. This may explain cognitive deficits seen in some patients after surgery involving HGM naming sites outside perisylvian language cortex. • Sequential yet overlapping spatiotemporal course of cortical high-gamma modulation is seen during visual naming. • A neurophysiologic model for visual naming incorporating both modular and distributed cortical processing is formulated. • Cognitive deficits seen after epilepsy surgery involving high-gamma modulation language sites may be explained. [ABSTRACT FROM AUTHOR]