OBJECTIVE:This study was undertaken to understand the circumstances surrounding pediatric sudden unexpected death in epilepsy (SUDEP) and identify clinical factors that may be associated with SUDEP in childhood. METHODS:A retrospective case series was conducted. Pediatric SUDEP cases were collected across Canada from the Ontario Forensic Pathology Service, Canadian Pediatric Surveillance Program, and Canadian Pediatric Epilepsy Network. Demographics, epilepsy history, comorbidities, and circumstances surrounding death were analyzed. RESULTS:Forty-nine children with pediatric SUDEP were analyzed; 25 (51%) were females, and the median age at death was 8 years. Six children (12%) were <2 years of age at the time of death. Information on seizure types 6 months before death was known in 35 children. Twenty-two had tonic-clonic seizures within the last 6 months prior to death (63%). Seven children (18%) had no tonic-clonic seizures in their lifetime. Two thirds of children were treated with ≥2 antiseizure medications. Genetic etiologies were most common (55%). Data on global developmental delay (GDD) was known in 46 children; 12 children (26%) had no impairment, and 34 were globally delayed (74%). Children with GDD had earlier age at seizure onset (p < .001); however, epilepsy duration was similar to those without GDD (p = .170). Similar to adult cohorts, death was often unwitnessed (n = 41/46, 89%). Information on recent infection before death was known in 37 children. Seventeen children (46%) had a recent infection. SIGNIFICANCE:Our study represents the largest pediatric SUDEP case series to date. SUDEP occurred in children of all ages, including infants, with a spectrum of epilepsies with and without neurodevelopmental impairment. The circumstances around death (i.e., timing of death, witnessed/unwitnessed) were similar to previous SUDEP cohorts. A recent infection was often observed, which could decrease seizure threshold and trigger a terminal seizure and may suggest that times of increased seizure risk could warrant heightened surveillance for SUDEP. However, further research is needed to determine the significance of this finding.

IntroductionSudden Unexpected Death in Epilepsy (SUDEP) is the leading epilepsy-related cause of death, affecting approximately 1 per 1,000 individuals with epilepsy per year. Genetic variants that affect autonomic function, such as genes associated with cardiac arrhythmias, may predispose people with epilepsy to greater risk of both sudden cardiac death and SUDEP. Advances in next generation sequencing allow for the exploration of gene variants as potential biomarkers.MethodsGenetic testing for the presence of cardiac arrhythmia and epilepsy gene variants was performed via genetic panels in 39 cases of SUDEP identified via autopsy by the Ontario Forensic Pathology Service. Variants were summarized by in-silico evidence for pathogenicity from 4 algorithms (SIFT, PolyPhen-2, PROVEAN, Mutation Taster) and allele frequencies in the general population (GnomAD). A maximum credible population allele frequency of 0.00004 was calculated based on epilepsy prevalence and SUDEP incidence to assess whether a variant was compatible with a pathogenic interpretation.ResultsMedian age at the time of death was 33.3 years (range: 2, 60). Fifty-nine percent (n=23) were male. Gene panels detected 62 unique variants in 45 genes: 19 on the arrhythmia panel and 26 on the epilepsy panel. At least one variant was identified in 28 (72%) of decedents. Missense mutations comprised 57 (92%) of the observed variants. At least three in silico models predicted 12 (46%) cardiac arrhythmia panel missense variants and 20 (65%) epilepsy panel missense variants were pathogenic. Population allele frequencies were <0.00004 for 11 (42%) of the cardiac variants and 10 (32%) of the epilepsy variants. Together, these metrics identified 13 SUDEP variants of interest.DiscussionNearly three-quarters of decedents in this SUDEP cohort carried variants in comprehensive epilepsy or cardiac arrhythmia gene panels, with more than a third having variants in both panels. The proportion of decedents with cardiac variants aligns with recent studies of the disproportionate cardiac burden the epilepsy community faces compared to the general population and suggests a possible cardiac contribution to epilepsy mortality. These results identified 13 priority targets for future functional studies of these genes potential role in sudden death and demonstrates the necessity for further exploration of potential genetic contributions to SUDEP.

AIMS:For the first time, to our knowledge, in a clinical sample with alcohol use disorder (AUD), this study compared the effects of two versions of alcohol-specific inhibition training (Alc-IT) on drinking outcomes and on experimental parameters assessing two possible working mechanisms: stimulus devaluation and inhibitory enhancement. DESIGN:Multi-centre, double-blind, three-arm clinical RCT with 3-, 6- and 12-month follow-up comparing standard Alc-IT, improved Alc-IT and an active control condition. SETTING:Three specialized AUD treatment centres in Switzerland. PARTICIPANTS:A total of 242 detoxified, recently abstinent patients with severe AUD (18-60 years; 29.8% female). INTERVENTION AND COMPARATOR:Both interventions [standard Alc-IT (n = 84) and improved Alc-IT (n = 79)] and the comparator [unspecific inhibition training (n = 79)] consisted of six sessions of a modified inhibitory task (Go/NoGo task) with alcohol-related and neutral stimuli. Both versions of Alc-IT required response inhibition in alcohol-related trials but differed in Go/NoGo ratios (standard: 50/50; improved: 75/25), with improved Alc-IT posing higher inhibitory demands. The control condition, an unspecific inhibition training, featured alcohol-related pictures in Go as well as NoGo trials. MEASUREMENTS:The primary outcome, percentage of days abstinent, was assessed at 3-month follow-up with a time-line follow-back interview. FINDINGS:The group receiving improved Alc-IT showed a significantly higher percentage of days abstinent at 3-month follow-up compared with the control group [γcontrol  = 74.30; γimproved  = 85.78; β = 11.48, 95% confidence interval (CI) = 2.57, 20.40, P = 0.012, adjusted r2  = 0.062], while for standard Alc-IT no effect significantly different from zero was detected (γstandard  = 70.95; β = -3.35, 95% CI = -12.20, 5.50, P = 0.457, adjusted r2  = -0.04). CONCLUSIONS:Alcohol-specific inhibition training with high inhibitory demands increased days abstinent at 3-month follow-up in patients with severe alcohol use disorder. Such an improved, inhibitory-demanding, alcohol-specific inhibition training outperformed the standard version of alcohol-specific inhibition training, suggesting an inhibitory working mechanism.

ABSTRACT We hypothesized that children receiving medium-chain triglyceride ketogenic diet (MCTKD) experience similar seizure reduction despite lower ketosis compared with classic ketogenic diet (CKD). Children initiating CKD or MCTKD were enrolled in a prospective observational study. Forty-five children completed 6 months of KD (n = 17 MCTKD, n = 28 CKD). The proportion achieving ≥50% seizure reduction was 71% CKD group and 59% MCTKD group; ≥90% reduction was 32% and 36% in CKD and MCTKD groups, respectively. CKD had higher urine ketones (≥8 mmol/L: 79% vs. 36%, p = 0.005). Children receiving MCTKD experience similar seizure control to CKD despite lower urine ketone measures.

Objective Sudden unexpected death in epilepsy (SUDEP) is a diagnosis of exclusion; the definition includes individuals with epilepsy who die suddenly without an identifiable toxicological or anatomical cause of death. Limited data suggest underidentification of SUDEP as the cause of death on death certificates. Here, we evaluate the autopsy-reported cause of death in a population-based cohort of SUDEP cases. Methods Case summaries of forensic autopsies conducted in Ontario, Canada between January 2014 and June 2016 were retrospectively screened using a language processing script for decedents with a history of epilepsy or seizures. After manual review for potential SUDEP cases, two neurologists independently examined the autopsy reports and classified deaths by Nashef criteria. Demographic characteristics and consideration by the forensic pathologist of the role of epilepsy, seizure, and SUDEP in death were summarized. Results One hundred and eight Definite, 34 Definite Plus, and 22 Possible SUDEP cases were identified. Seventy-five percent of Definite/Definite Plus SUDEP cases identified by the neurologists were attributed to SUDEP, epilepsy, or seizure disorder in the autopsy report. There was a significant association between the proportion of cases listed in the autopsy report as SUDEP, epilepsy, or seizure disorder and neurologists' SUDEP classification (86% of Definite, 38% of Definite Plus, 0% of Possible). Age was significantly associated with SUDEP classification; Definite cases were younger than Definite Plus, which were younger than Possible SUDEP cases. Significance Most SUDEP cases identified by neurologists were classified concordantly by forensic pathologists in Ontario, Canada; however, concordance decreased with increased case complexity. Although the role of epilepsy/seizures was considered in most Definite/Definite Plus cases, this study highlights the need for autopsy report review of potential SUDEP cases in research studies and assessments of the public health burden of SUDEP. The relationship between age and SUDEP classification has important public health implications; SUDEP incidence may be underappreciated in older adults.

OBJECTIVES:The objectives were to investigate the relationship between ketogenic diet therapy and neutropenia in children with epilepsy.METHODS:A retrospective chart review of children who initiated ketogenic diet at the Hospital for Sick Children between January 1, 2000, and May 1, 2018 was performed. Factors associated with the development of neutropenia during ketogenic diet therapy were evaluated and the relationship between development of a significant or suspected infection and neutrophil count was analyzed.RESULTS:One hundred two children met inclusion criteria and were followed on the diet for up to 24 months. Thirteen of 102 (13%) children were neutropenic at diet initiation. In the remaining 89 children, 27 developed neutropenia. Developing neutropenia was significantly associated with the ketogenic diet at 6 (13%), 12 (23%), and 24 (25%) months follow-up. Developing neutropenia was associated with higher urinary ketones (OR = 4.26, 95% CI: 1.27, 14.15) and longer duration of ketogenic diet therapy (OR = 3.29, 95% CI: 1.42, 7.96). There was no significant association between development of a clinically significant infection and neutropenia.CONCLUSION:Ketogenic diet therapy is associated with neutropenia in children with epilepsy, however, it does not have a significant clinical impact. Concern regarding neutropenia should not discourage the use of the ketogenic diet in children.

OBJECTIVE:This study investigates neurophysiological correlates of general and alcohol-specific inhibitory control in patients with Alcohol Use Disorder (AUD), focusing on its association with individual craving levels and with relapse at three-month follow-up.METHODS:59 abstinent AUD patients and 20 healthy controls performed a Go/NoGo task incorporating alcohol-related and neutral stimuli during 64-channel electroencephalography (EEG) recording, yielding four event-related potentials (ERP) per participant (NoGo-Alcohol, Go-Alcohol, NoGo-Neutral, Go-Neutral). Whole-scalp randomization-based statistics assessed effects of the factors group (patients/controls or relapsers/abstainers), craving level, response type (NoGo/Go) and picture type (alcohol/neutral) on topography and signal strength of the ERP components N2 and P3.RESULTS:No differences on group level were observed between patients and controls. However, analyses incorporating individual craving indicated that the topographic difference between alcohol-related and neutral NoGo-N2 components increased with craving. Moreover, topographic differences in the alcohol-related and neutral NoGo-P3 component allowed for differentiation between relapsers and abstainers.CONCLUSIONS:In alcohol-related contexts, the response inhibition conflict reflected in the NoGo-N2 seems enhanced in patients with high craving. The inhibition-sensitive NoGo-P3 varies in relapsers but not in abstainers between neutral and alcohol-related contexts.SIGNIFICANCE:In AUD patients, neurophysiological correlates of inhibition vary with alcohol-related contexts and craving, and might be indicative of relapse risk.

PURPOSE:To further define the epilepsy phenotype in a cohort of children with 15q13.3 microdeletion syndrome.METHODS:We retrospectively reviewed the phenotypic spectrum of all children aged < 18 years with epilepsy and 15q13.3 microdeletion syndrome.RESULTS:Thirteen children were included, 69% were female. The median age of children in the cohort was 12 years (age range: 3 years-15 years). Median age at seizure onset was 4 years. Eleven children (85%) had intellectual disability. Nine of 13 children (69%) had a history of typical absence seizures with median age of onset at 5 years (2 had absence status epilepticus). Thirty-one percent (4/13) had focal with impaired awareness non-motor onset seizures. ILAE recognized absence epilepsy syndromes were diagnosed in 6/13 (46%). The remainder were classified as having genetic generalized epilepsies with overlap clinical features, combined or focal epilepsies. Electroencephalogram in the cohort showed generalized (85%) and focal epileptiform discharges (62%) and posterior dominant rhythm slowing (33%). One child had electrical status epilepticus of sleep. Neuroimaging was performed in 5 children (38%) and revealed abnormal findings in 3. Seizures were drug resistant in a third of the cohort. Valproate resulted in seizure freedom in 5 (42%). Oxcarbazepine caused clinical worsening in one child with combined seizure types. Two children tried cannabidiol and one tried the ketogenic diet; neither was effective.CONCLUSIONS:The epilepsy phenotype in children with 15q13.3 microdeletion syndrome is defined by childhood onset absence seizures, and may have atypical features such as, early onset absences, persistence into adolescence, status epilepticus, intellectual disability and treatment resistance. Focal seizures and focal EEG findings may be observed and should be treated cautiously, given the possibility of combined seizure types. Valproate appeared effective, although other treatments must be explored further.

Abstract Objective To characterize SUDEP discussion practices of child neurologists approximately 6 and 12 months after publication of the American Academy of Neurology SUDEP Clinical Practice Guideline and explore factors associated with discussion practice. Methods Child Neurology Society members (~2450) were electronically surveyed in November 2017 and May 2018 regarding their practice of discussing SUDEP with patients with epilepsy or their caregivers. Multivariable proportional odds ordinal logistic regression evaluated factors associated with discussing SUDEP with a greater proportion of epilepsy patients/caregivers. Reasons for changing practice were described. Results Among the 369 child neurologist respondents, 36% reported discussing SUDEP with at least half of their epilepsy patients/caregivers including 12% who discuss with all or almost all (>90%) of their epilepsy patients/families. Those who discussed SUDEP with an increased proportion of their patients were more likely to agree that they knew enough to talk about SUDEP, agree that healthcare providers have an ethical obligation to discuss SUDEP, and disagree that there is not enough time to talk about SUDEP. Those who agreed SUDEP could provoke excessive anxiety or worry were less likely to discuss SUDEP with an increased proportion of their patients. Reading the SUDEP Clinical Practice Guideline was a frequently cited reason among respondents who reported a recent change in discussion practice. Significance Most child neurologists do not follow the current SUDEP Clinical Practice Guideline regarding SUDEP discussion. Feeling sufficiently knowledgeable and ethically obligated to discuss SUDEP were associated with increased discussion practice, suggesting an educational intervention may be effective at increasing SUDEP discussion rates.

Background Neuroscientific models of alcohol use disorders (AUDs) postulate an imbalance between automatic, implicit, and controlled (conscious) processes. Implicit associations towards alcohol indicate the automatically attributed appeal of alcohol‐related stimuli. First, behavioral studies indicate that negative alcohol associations are less pronounced in patients compared to controls, but potential neurophysiological differences remain unexplored. This study investigates neurophysiological correlates of implicit alcohol associations in recently abstinent patients with AUD for the first time, including possible gender effects. Methods A total of 62 patients (40 males and 22 females) and 21 controls performed an alcohol valence Implicit Association Test, combining alcohol‐related pictures with positive (incongruent condition) or negative (congruent condition) words, while brain activity was recorded using 64‐channel electroencephalography. Event‐related potentials (ERPs) for alcohol‐negative and alcohol‐positive trials were computed. Microstate analyses investigated the effects of group (patients, controls) and condition (incongruent, congruent); furthermore, possible gender effects in patients were analyzed. Significant effects were localized with standardized low‐resolution brain electromagnetic topography analysis. Results Although no behavioral group differences were found, ERPs of patients and controls were characterized by distinct microstates from 320 ms onwards. ERPs between conditions differed only in patients with higher signal strength during incongruent trials. Around 600 ms, controls displayed higher signal strength than patients. A gender effect mirrored this pattern with enhanced signal strength in females as opposed to male patients. Around 690 ms, a group‐by‐valence interaction indicated enhanced signal strength in congruent compared to incongruent trials, which was more pronounced in controls. Conclusions For patients with AUD, the pattern, timing, and source localization of effects suggest greater effort regarding semantic and self‐relevant integration around 400 ms during incongruent trials and attenuated emotional processing during the late positive potential timeframe. Interestingly, this emotional attenuation seemed reduced in female patients, thus corroborating the importance of gender‐sensitive research and potential treatment of AUD.

Hintergrund Die erhohte automatische Anreizwirkung auf Alkoholreize ist bedeutend fur die Entstehung und Aufrechterhaltung von Alkoholkonsumstorungen (AUD). Implizite Alkoholassoziationen sind ein Indikator dieser Anreizwirkung. Laut behavioralen Studien weisen sowohl Gesunde als auch Patient_innen mit AUD negative implizite Alkoholassoziationen auf, Patient_innen haben aber einen schwacheren negativen Bias. Studien zur Neurophysiologie bei Patient_innen mit einer AUD im Vergleich zu Gesunden erganzen und erweitern bisherige Reaktionszeitanalysen. Methoden Die Hirnstrome von 63 Patient_innen mit AUD und 21 Gesunden werden wahrend der Durchfuhrung eines Impliziten Assoziationstests (IAT) mit einem 64-Kanal-EEG abgeleitet. Darauf werden ereignisbezogene Potentiale (Alkohol-positiv und Alkohol-negativ) berechnet. Mittels Microstates werden quasi-stabile topografische Zustande von 0-1000ms nach Stimulus identifiziert. Innerhalb dieser wird analysiert, ob sich Patient_innen und Gesunde in der Verarbeitung positiver und negativer Alkoholzuordnungen unterscheiden. Ergebnisse/Diskussion Laut ersten Analysen weisen Patient_innen und Gesunde um 400ms nach Stimulus unterschiedliche Microstates mit divergenten zugrundeliegenden Netzwerken auf. Bei Patient_innen zeigen sich beim Vergleich der Alkohol-positiven mit den Alkohol-negativen ERPs eine signifikante Differenz in der Amplitude (meanGFP, p=0.002) sowie Trends in Dauer und Schwerpunkt. Gesunde unterscheiden sich nicht signifikant hinsichtlich der Alkohol-Valenz-Bedingung. Schlussfolgerung Anders als bei Gesunden wird bei Patient_innen in der Verarbeitung positiver Alkoholassoziationen rund 400ms nach Stimulus mehr Gehirnaktivitat benotigt als bei negativen Zuordnungen. Bisherige Forschung verband hohere Amplituden in diesem Zeitfenster (N400) mit Mehraufwand in der semantischen Verarbeitung. So konnte bei Patient_innen wahrend der Verarbeitung positiver Alkoholassoziationen hohere semantische Inkongruenz vorliegen.

Children with neurodevelopmental disorders (NDDs) exhibit a shared phenotype that involves executive dysfunctions including impairments in mental flexibility (MF). It is of interest to understand if this phenotype stems from some shared neurobiology. To investigate this possibility, we used magnetoencephalography (MEG) neuroimaging to compare brain activity in children (n = 88; 8–15 years) with autism spectrum disorders (ASD), attention deficit hyperactivity disorder (ADHD) and obsessive-compulsive disorder (OCD), as they completed a set-shifting/mental flexibility task. Neuroimaging results revealed a similar parietal activation profile across the NDD, groups suggesting a link to their shared phenotype. Differences in frontal activity differentiated the three clinical groups. Brain-behaviour analyses showed a link with repetitive behaviours suggesting shared dysfunction in the associative loop of the corticostriatal system. Our study supports the notion that NDDs may exist along a complex phenotypic/biological continuum. All NDD groups showed a sustained parietal activity profile suggesting that they share a strong reliance on the posterior parietal cortices to complete the mental flexibility task; future studies could elucidate whether this is due to delayed brain development or compensatory functioning. The differences in frontal activity may play a role in differentiating the NDDs. The OCD group showed sustained prefrontal activity that may be reflective of hyperfrontality. The ASD group showed reduced frontal activation suggestive of frontal dysfunction and the ADHD group showed an extensive hypoactivity that included frontal and parietal regions. Brain-behaviour analyses showed a significant correlation with repetitive behaviours which may reflect dysfunction in the associative loop of the corticostriatal system, linked to inflexible behaviours.

Objective To determine the incidence of sudden unexpected death in epilepsy (SUDEP) in children in Ontario, Canada. Methods Cases of suspected pediatric SUDEP occurring between January 1, 2014, and December 31, 2015, in Ontario, Canada, were eligible for inclusion. Potential cases were identified through 3 sources: a national pediatrician surveillance program, child neurologist report, and screening of provincial forensic autopsies. Cases were classified as definite, definite plus, probable, possible, and near/near plus according to criteria described by Nashef et al. (Epilepsia 2012). Overall crude pediatric SUDEP incidence and the incidence of definite or probable pediatric SUDEP were calculated using estimates of the prevalence of pediatric epilepsy in Canada drawn from government survey data and the number of children living in Ontario. Capture-recapture analysis was used to estimate the number of missing cases and determine an adjusted definite/probable SUDEP incidence. Results Seventeen cases of pediatric SUDEP resulted in an overall incidence of 1.17 (95% confidence interval 0.68-1.88) per 1,000 pediatric epilepsy person-years. The definite/probable incidence, including definite (n = 11), definite plus (n = 2), or probable (n = 3) SUDEP cases, was 1.11 (0.63-1.79). Capture-recapture analysis indicated an estimated 21 (16-39) definite/probable SUDEP cases occurred during the study period, giving an adjusted incidence of definite/ probable SUDEP of 1.45 (0.90-2.22) per 1,000 pediatric epilepsy person-years. Conclusion SUDEP may be more common in children than widely reported, with the incidence rate of definite/probable SUDEP in children being similar to rates reported in adults.

OBJECTIVES:The risk of drowning is reported to be 15-19 times greater in people with epilepsy compared to the general population. Despite this disproportionate burden, there is limited data about the circumstances surrounding drowning deaths in people with epilepsy. This population-based case series characterizes drowning deaths in people with epilepsy.METHODS:Postmortem data from coroner-ordered autopsies conducted in Ontario between 2014 and 2016 were screened for cases of drowning in people with a history of seizures. Demographic information, epilepsy characteristics, and circumstances surrounding death were extracted from post mortem reports. The incidence of drowning in people with epilepsy was calculated using government estimates of the Ontario population and the number of people with epilepsy.RESULTS:Twenty-five people with epilepsy drowned during the three-year study period, giving an estimated incidence of 1.5 per 10,000 epilepsy person-years (95% CI: 0.98, 2.23). Decedents were mostly young (mean age 36 years) and without physical or developmental disability. Approximately one-third had psychiatric comorbidities. Epilepsy severity ranged from well-controlled to drug refractory. Only 3 people had alcohol or illicit drugs detected on toxicological analysis. Forty-four percent of deaths were the result of an unwitnessed drowning in a bathtub.CONCLUSIONS:This population-based case series confirms people with epilepsy drown at a rate nearly ten times greater than the general population (1.5 per 10,000 epilepsy person-years compared to the estimated provincial average of 0.13 per 10,000). Drowning deaths in people with epilepsy most often occur in the bathtub. These deaths are only rarely associated with intoxication. People with epilepsy should receive counseling on the increased risk of drowning, including information regarding the significant risk associated with bathtub use, the potential protective roles of anti-epileptic drug (AED) adherence and supervision when in or around water, and the fact that all people with epilepsy remain at an increased risk of drowning regardless of their apparent seizure control.

Emotion regulation mediates socio‐cognitive functions and is essential for interactions with others. The capacity to automatically inhibit responses to emotional stimuli is an important aspect of emotion regulation; the underlying neural mechanisms of this ability have been rarely investigated. Forty adults completed a Go/No‐go task during magnetoencephalographic (MEG) recordings, where they responded rapidly to either a blue or purple frame which contained angry or happy faces. Subjects responded to the target color in an inhibition (75% Go trials) and a vigilance condition (25% Go trials). As expected, inhibition processes showed early, sustained activation (200–450 ms) in the right inferior frontal gyrus (IFG). Emotion‐related inhibition processes showed greater activity with angry faces bilaterally in the orbital‐frontal gyri (OFG) starting at 225 ms and temporal poles from 250 ms, with right hemisphere dominance. The presence of happy faces elicited earlier activity in the right OFG. This study demonstrates that the timing of inhibition processes varies with the emotional context and that there is much greater activation in the presence of angry faces. It underscores the importance of the right IFG for inhibition processes, but the OFG in automatic emotion regulation.

Objective: Limited evidence on the relationship between antiepileptic drug (AED) tapering and the likelihood of a seizure during an Epilepsy Monitoring Unit (EMU) admission is available, and no evidence specific to the pediatric population has been published. Our study sought to determine whether AED tapering leads to increased seizure likelihood in a pediatric EMU setting. Methods: We performed a retrospective chart review of children admitted to the pediatric EMU at the Hospital for Sick Children in Toronto between June 1, 2014 and June 1, 2016. Data collected included demographics, reason for EMU referral, and epilepsy and medical characteristics. Among those with nondaily seizures, Kaplan-Meier curves were fit to compare probability of EMU seizure in those who were tapered fully from at least one AED to those not tapered. A Cox proportional hazards model was fit to evaluate this relationship after adjustment for subject sex, distance traveled to hospital, epilepsy duration, seizure frequency, time since last seizure, whether EMU referral was part of presurgical planning, magnetic resonance imaging (MRI) findings, and number of prescribed AEDs. An interaction between medication taper and number of prescribed AEDs was also included. Terms not significant at p < 0.3 were removed from the model, and the reduced model was recomputed. Results: Of the 281 children included in the study, 159 had nondaily seizures. Kaplan-Meier curves indicated fully tapering at least one AED was associated with increased likelihood of seizure during EMU; however, after adjustment for confounding variables, this association was not preserved. Abnormal MRI findings, referral for presurgical evaluation, and shorter (<= 3 months) time since last seizure were associated with increased likelihood of seizure during EMU. Significance: Short-term AED tapering in pediatric patients may not be effective for increasing seizure likelihood in the EMU. (C) 2018 Elsevier Inc. All rights reserved.

During speech, how does the brain integrate information processed on different timescales and in separate brain areas so we can understand what is said? This is the language binding problem. Dynamic functional connectivity (brief periods of synchronization in the phase of EEG oscillations) may provide some answers. Here we investigate time and frequency characteristics of oscillatory power and phase synchrony (dynamic functional connectivity) during speech comprehension. Twenty adults listened to meaningful English sentences and non-sensical "Jabberwocky" sentences in which pseudo-words replaced all content words, while EEG was recorded. Results showed greater oscillatory power and global connectivity strength (mean phase lag index) in the gamma frequency range (30-80 Hz) for English compared to Jabberwocky. Increased power and connectivity relative to baseline was also seen in the theta frequency range (4-7 Hz), but was similar for English and Jabberwocky. High-frequency gamma oscillations may reflect a mechanism by which the brain transfers and integrates linguistic information so we can extract meaning and understand what is said. Slower frequency theta oscillations may support domain-general processing of the rhythmic features of speech. Our findings suggest that constructing a meaningful representation of speech involves dynamic interactions among distributed brain regions that communicate through frequency-specific functional networks.

OBJECTIVES:The objective of this study was to review our experience with intra-operative "train of five" stimulation using subdural grid for motor mapping in children undergoing epilepsy surgery evaluation. METHODS:Twenty consecutive children below 18-years of age with drug-refractory epilepsy who underwent invasive-EEG monitoring using subdural-grid placement and intra-operative motor mapping using direct cortical stimulation by sub-dural grid electrodes (IODCS-SDG) at our institution between January-2016 and June-2017 were reviewed. Stimulation was delivered through the subdural-grid electrodes using a train-of-five pulses and muscle responses were recorded by motor-evoked-potentials (MEPs). Intra-operative direct cortical stimulation delivered through a ball-tipped probe (IODCS-probe) and extra-operative motor-mapping (EODCS-SDG) were also performed. RESULTS:IODCS-SDG was completed in 20 patients and subsequent EODCS-SDG was done in 17/20 patients. MEP responses were more commonly obtained in the deltoid (19/20), extensor-digitorum-communis (20/20) and first-dorsal-interosseus (19/20). The median thresholds varied between 40 V and 60 V for the six muscle groups. The respective IODCS-probe thresholds tended to be similar. No stimulation-provoked seizures or anaesthesia-related complications were noted during IODCS-SDG. EODCS-SDG could not be completed in 4/17 children and mapping data obtained was frequently inadequate. Nine patients demonstrated 100% concordance between IODCS-SDG and EODCS-SDG for the common mapped body regions. Stimulation-provoked seizures during EODCS-SDG were seen in 6/17 (35.3%) and after-discharges in 7/17 (41.2%) children. CONCLUSIONS:IODCS-SDG could be performed safely in children with drug refractory epilepsy undergoing invasive EEG monitoring. SIGNIFICANCE:IODCS-SDG may be a useful adjunct to EODCS-SDG in motor mapping for children.

Mental flexibility is a core property of cognitive executive functions, relying on an extended frontoparietal network in the brain. fMRI research comparing typically developing children and adults has found that children from an early age recruit the same "classic" brain areas associated with mental flexibility as adults; however, there is evidence that the timing of activation may be different. To investigate the temporal dynamics of brain activity associated with mental flexibility in children, we recruited 22 typically developing children (8-15 years) to complete a set-shifting task in the MEG. Our results showed that while the children relied on the same frontoparietal network of mental flexibility, there was a different emphasis on active brain regions, with children preferentially using their posterior parietal cortices. Additional areas such as the temporal pole and the premotor areas were also recruited, potentially playing a supporting role. Although children shared the same window of peak activity as adults, 75-350ms, we found a significant decrease in activation latency with increasing age, suggesting the presence of developmental differences in timing of brain activity in areas supporting mental flexibility during childhood.

Background and Purpose— Neurocognitive deficits are common among survivors of aneurysmal subarachnoid hemorrhage, even among those with good outcomes and no structural lesions. This study aims to probe the neurophysiological underpinnings of cognitive dysfunction among patients with ruptured intracranial aneurysms using magnetoencephalography (MEG). Methods— Thirteen patients who had undergone uncomplicated coiling for aneurysmal subarachnoid hemorrhage and 13 matched controls were enrolled. Neuropsychological tests were done before magnetoencephalography scans. Magnetoencephalography data were acquired in a 151-channel, whole-head magnetoencephalography system for resting state and 2 cognitive tasks (go-no-go and set-shifting). Mean time from treatment to test was 18.8 months. Results— Cognitive tasks of inhibition (go-no-go) indicated greater activation in the right anterior cingulate and inferior frontal gyrus, and cognitive set-shifting tasks (mental flexibility) indicated greater activity in the bilateral anterior cingulate cortex and right medial frontal gyrus among aneurysmal subarachnoid hemorrhage patients, with significantly different timing of activation between groups. Resting-state, beta-band connectivity of the anterior cingulate correlated negatively with Montreal Cognitive Assessment scores (left: r=−0.56; P<0.01 and right: r=−0.55; P<0.01): higher connectivity of this region was linked to poorer cognitive test performance. Conclusions— We have shown increased activation in areas of the anterior cingulate gyrus and frontobasal regions during the execution of more demanding tasks in good grade. The degree of activation in the anterior cingulate gyrus has a negative correlation with cognitive (Montreal Cognitive Assessment) scores. These subtle differences may be related to the common neurocognitive and behavioral complaints seen in this patient population.