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Purpose: Up to half of the children undergoing epilepsy surgery will continue to have seizures (szs) despite a cortical resection or ablation. Functional connectivity has shown promise in better identifying the epileptogenic zone. We hypothesized that cortical areas showing high information outflow during interictal epileptiform discharges are part of the epileptogenic zone., Methods: We identified 22 children with focal epilepsy who had undergone stereo electroencephalography, surgical resection or ablation, and had ≥1 year of postsurgical follow-up. The mean phase slope index, a directed measure of functional connectivity, was calculated for each electrode contact during interictal epileptiform discharges. The positive predictive value and negative predictive value for a sz-free outcome were calculated based on whether high information outflow brain regions were resected., Results: Resection of high outflow (z-score ≥ 1) and very high outflow (z-score ≥ 2) electrode contacts was associated with higher sz freedom (high outflow: χ 2 statistic = 59.1; P < 0.001; very high outflow: χ 2 statistic = 31.3; P < 0.001). The positive predictive value and negative predictive value for sz freedom based on resection at the electrode level increased at higher z-score thresholds with a peak positive predictive value of 0.86 and a peak negative predictive value of 0.9., Conclusions: Better identification of the epileptogenic zone has the potential to improve epilepsy surgery outcomes. If the surgical plan can be modified to include these very high outflow areas, more children might achieve sz freedom. Conversely, if deficits from resecting these areas are unacceptable, ineffective surgeries could be avoided and alternative therapies offered., (Copyright © 2021 by the American Clinical Neurophysiology Society.)

Importance: It is currently unknown how often and in which ways a genetic diagnosis given to a patient with epilepsy is associated with clinical management and outcomes., Objective: To evaluate how genetic diagnoses in patients with epilepsy are associated with clinical management and outcomes., Design, Setting, and Participants: This was a retrospective cross-sectional study of patients referred for multigene panel testing between March 18, 2016, and August 3, 2020, with outcomes reported between May and November 2020. The study setting included a commercial genetic testing laboratory and multicenter clinical practices. Patients with epilepsy, regardless of sociodemographic features, who received a pathogenic/likely pathogenic (P/LP) variant were included in the study. Case report forms were completed by all health care professionals., Exposures: Genetic test results., Main Outcomes and Measures: Clinical management changes after a genetic diagnosis (ie, 1 P/LP variant in autosomal dominant and X-linked diseases; 2 P/LP variants in autosomal recessive diseases) and subsequent patient outcomes as reported by health care professionals on case report forms., Results: Among 418 patients, median (IQR) age at the time of testing was 4 (1-10) years, with an age range of 0 to 52 years, and 53.8% (n = 225) were female individuals. The mean (SD) time from a genetic test order to case report form completion was 595 (368) days (range, 27-1673 days). A genetic diagnosis was associated with changes in clinical management for 208 patients (49.8%) and usually (81.7% of the time) within 3 months of receiving the result. The most common clinical management changes were the addition of a new medication (78 [21.7%]), the initiation of medication (51 [14.2%]), the referral of a patient to a specialist (48 [13.4%]), vigilance for subclinical or extraneurological disease features (46 [12.8%]), and the cessation of a medication (42 [11.7%]). Among 167 patients with follow-up clinical information available (mean [SD] time, 584 [365] days), 125 (74.9%) reported positive outcomes, 108 (64.7%) reported reduction or elimination of seizures, 37 (22.2%) had decreases in the severity of other clinical signs, and 11 (6.6%) had reduced medication adverse effects. A few patients reported worsening of outcomes, including a decline in their condition (20 [12.0%]), increased seizure frequency (6 [3.6%]), and adverse medication effects (3 [1.8%]). No clinical management changes were reported for 178 patients (42.6%)., Conclusions and Relevance: Results of this cross-sectional study suggest that genetic testing of individuals with epilepsy may be materially associated with clinical decision-making and improved patient outcomes.

Background: Conditioned food cues (e.g., smell, sight) can affect intake of foods associated with those cues, regardless of homeostatic need. As such, altering automatic associations with food cues could support weight loss or maintenance efforts by affecting the salience of those cues and the effort required to resist consumption., Objectives: This study investigated neuronal and behavioral effects of an implicit priming (IP) intervention, in which negatively valenced images were paired with high-calorie foods and positively valenced images with low-calorie foods. Priming images were presented immediately before food images, but below conscious perception (20 ms). We hypothesized that this evaluative conditioning approach could alter food cue responses by modifying affective associations., Methods: The final sample included 41 adults with BMI ≥25 kg/m2 (n = 22, active IP; n = 19, control IP). In control IP, food images were primed with neutral, scrambled images. Participants completed a visual food cue task during fMRI, both before and after IP. To determine the replicability of prior behavioral findings, food image ratings were completed before and after IP as a secondary outcome., Results: In a whole-brain analysis, reduced dorsolateral prefrontal cortex (dlPFC) response to high-calorie foods was observed after active compared with control IP (t = 4.93, P = 0.033). With a region of interest analysis, reduced response to high-calorie foods in active compared with control IP was also observed in the striatum (t = 2.40, P = 0.009) and insula (t = 2.38, P = 0.010). Active compared with control IP was associated with reduced high-calorie food ratings (F = 4.70, P = 0.038)., Conclusions: Reduced insula and striatum response to high-calorie foods after active compared with control IP suggests effectiveness of IP in altering food cue salience. Reduced dlPFC response to high-calorie foods after active compared with control IP may reflect fewer attentional resources being directed to those images and reduced engagement of inhibitory processes.This trial was registered at clinicaltrials.gov as NCT02347527., (Published by Oxford University Press on behalf of the American Society for Nutrition 2022.)

The neurobiology of autism spectrum disorder remains poorly understood. The present study addresses this knowledge gap by examining the relationship between functional brain connectivity and Autism Diagnostic Observation Schedule (ADOS) scores using publicly available data from the Autism Brain Imaging Data Exchange (ABIDE) database (N = 107). This relationship was tested across all brain voxels, without a priori assumptions, using a novel statistical approach. ADOS scores were primarily associated with decreased connectivity to right temporoparietal junction, right anterior insula, and left fusiform gyrus (p < 0.05, corrected). Seven large-scale brain networks influenced these associations. Findings largely encompassed brain regions involved in processing socially relevant information, highlighting the importance of these processes in autism spectrum disorder.

Functional connectivity is providing new insights into the network nature of epilepsy with growing clinical applications. Our objective was to validate a novel magnetoencephalography-based method to non-invasively measure the epileptic network. We retrospectively identified pediatric and adult patients with refractory focal epilepsy who underwent pre-surgical magnetoencephalography with subsequent intracranial electrographic monitoring. Magnetoencephalography tracings were visually reviewed, and interictal epileptiform discharges ("spikes") were individually marked. We then evaluated differences in whole-brain connectivity during brief epochs preceding the spikes and during the spikes using the Network-Based Statistic to test differences at the network level. In six patients with statistically-significant network differences, we observed substantial overlap between the spike-associated networks and electrographically active areas identified during intracranial monitoring (the spike-associated network was 78% and 83% sensitive for intracranial electroencephalography-defined regions in the irritative and seizure onset zones, respectively). These findings support the neurobiological validity of the spike-associated network method. Assessment of spike-associated networks has the potential to improve surgical planning in epilepsy surgery patients by identifying components of the epileptic network prior to implantation.

Our objective was to summarize and evaluate the rapidly expanding body of literature studying functional connectivity in childhood epilepsy. In the self-limited childhood epilepsies, awareness of cognitive comorbidities has been steadily increasing, and recent advances in our understanding of the network effects of these disorders promise insights into the underlying neurobiology. We reviewed publications addressing functional connectivity in children with epilepsy with an emphasis on studies of children with self-limited childhood epilepsies. The majority of studies have been published in the past 10 years and predominantly examine childhood epilepsy with centrotemporal spikes and childhood absence epilepsy. Cognitive network alterations are commonly observed across the childhood epilepsies. Some of these effects appear to be nonspecific to epilepsy syndrome or even to category of neurological disorder. Other patterns, such as changes in the connectivity of cortical language areas in childhood epilepsy with centrotemporal spikes, provide clues to the underlying cognitive deficits seen in affected children. The literature to date is dominated by general observations of connectivity patterns without a priori hypotheses. These data-driven studies build an important foundation for hypothesis generation and are already providing useful insights into the neuropathology of the childhood epilepsies. Future work should emphasize hypothesis-driven approaches and rigorous clinical correlations to better understand how the knowledge of network alterations can be applied to guidance and treatment for the children in our clinics., (Wiley Periodicals, Inc. © 2019 International League Against Epilepsy.)

Purpose: Our objective was to use semiautomatic methods for calculating the spike-wave index (SWI) in electrical status epilepticus in slow-wave sleep (ESES) and to determine whether this calculation is noninferior to human experts (HEs)., Methods: Each HE marked identical 300-second epochs for all spikes and calculated the SWI in sleep EEGs of patients diagnosed with ESES. Persyst 13 was used to mark spikes (high sensitivity setting) in the same 300-second epochs marked by HEs. The spike-wave index was calculated. Pairwise HE differences and pairwise Persyst 13 (P13)-HE differences for the SWI were calculated. Bootstrap resampling (BCa, N = 3,000) was performed to better estimate mean differences and their 95% confidence bounds between HE and P13-HE pairs. Potential noninferiority of P13 to HEs was tested by comparing the 95% confidence bounds of the mean differences between pairs for the SWI., Results: Twenty EEG records were analyzed. Each HE marked 100 minutes of EEG. HEs 1, 2, 3, and 4 marked 10,075, 8,635, 9,710, and 9,898 spikes, respectively. The highest and lowest 95% confidence bound of the mean difference in the SWI between HE pairs was: High: 10.3%; Low: -10.2%. Highest and lowest 95% confidence bound of the mean difference in the SWI between P13 and HE pairings was as follows: high, 9.5% and low, -6.7%. The lack of a difference between P13 and HEs supports that the algorithm is not inferior to HEs., Conclusions: Persyst 13 is noninferior to HEs in calculating the SWI in ESES, thus suggesting that an automated approach to SWI calculation may be a useful clinical tool.

Objective: To investigate the common thinking, as reinforced by the International Classification of Headache Disorders, 3rd edition (beta), that occipital headaches in children are rare and suggestive of serious intracranial pathology., Methods: We performed a retrospective chart review cohort study of all patients ≤18 years of age referred to a university child neurology clinic for headache in 2009. Patients were stratified by headache location: solely occipital, occipital plus other area(s) of head pain, or no occipital involvement. Children with abnormal neurologic examinations were excluded. We assessed location as a predictor of whether neuroimaging was ordered and whether intracranial pathology was found. Analyses were performed with cohort study tools in Stata/SE 13.0 (StataCorp, College Station, TX)., Results: A total of 308 patients were included. Median age was 12 years (32 months-18 years), and 57% were female. Headaches were solely occipital in 7% and occipital-plus in 14%. Patients with occipital head pain were more likely to undergo neuroimaging than those without occipital involvement (solely occipital: 95%, relative risk [RR] 10.5, 95% confidence interval [CI] 1.4-77.3; occipital-plus: 88%, RR 3.7, 95% CI 1.5-9.2; no occipital pain: 63%, referent). Occipital pain alone or with other locations was not significantly associated with radiographic evidence of clinically significant intracranial pathology., Conclusions: Children with occipital headache are more likely to undergo neuroimaging. In the absence of concerning features on the history and in the setting of a normal neurologic examination, neuroimaging can be deferred in most pediatric patients when occipital pain is present., (© 2017 American Academy of Neurology.)

Background: Chorioamnionitis is a risk factor for cerebral palsy. The relationship between extra-amniotic infections and cerebral palsy is less well studied. We examined maternal intra-amniotic and extra-amniotic infections and risk of cerebral palsy in the child., Methods: Among a retrospective cohort of 6 million Californian births, 1991-2001, we analyzed administrative maternal and newborn hospital discharge abstracts linked to records of all children receiving services for cerebral palsy at the California Department of Developmental Services. We identified maternal hospital diagnoses of intra-amniotic (chorioamnionitis) and extra-amniotic (other genitourinary and respiratory) infections occurring up to 12 months before delivery. Using multivariable logistic regression, we determined the independent association between maternal infections and cerebral palsy, adjusting for infant sex, maternal age, race, education, socioeconomic status, and obesity., Results: About 5.5% of mothers had a hospital discharge diagnosis of at least one of the following: chorioamnionitis (2.0%), other genitourinary (3.1%), and respiratory infection (0.6%). An infection diagnosis was more common in mothers of the 8473 infants with cerebral palsy than in mothers of unaffected children (13.7% vs 5.5%, P < 0.001). All three types of maternal infections (chorioamnionitis, odds ratio [OR] 3.1, 95% confidence interval [CI] 2.9-3.4; other genitourinary infection, OR 1.4, 95% CI 1.3-1.6; and respiratory infection, OR 1.9, 95% CI 1.5-2.2) were associated with cerebral palsy in multivariable analyses. Maternal extra-amniotic infections, whether diagnosed during prenatal or birth hospitalizations, conferred an increased risk of cerebral palsy., Conclusions: Maternal extra-amniotic infections diagnosed in the hospital during pregnancy are associated with a modestly increased risk of cerebral palsy in the child., (Copyright © 2016 Elsevier Inc. All rights reserved.)