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Children with epilepsy commonly have comorbid neurocognitive impairments that severely affect their psychosocial well‐being, education, and future career prospects. Although the provenance of these deficits is multifactorial, the effects of interictal epileptiform discharges (IEDs) and anti‐seizure medications (ASMs) are thought to be particularly severe. Although certain ASMs can be leveraged to inhibit IED occurrence, it remains unclear whether epileptiform discharges or the medications themselves are most deleterious to cognition. To examine this question, 25 children undergoing invasive monitoring for refractory focal epilepsy performed one or more sessions of a cognitive flexibility task. Electrophysiological data were recorded to detect IEDs. Between repeated sessions, prescribed ASMs were either continued or titrated to <50% of the baseline dose. Hierarchical mixed‐effects modeling assessed the relationship between task reaction time (RT), IED occurrence, ASM type, and dose while controlling for seizure frequency. Both presence (β ± SE = 49.91 ± 16.55 ms, p =.003) and number of IEDs (β ± SE = 49.84 ± 12.51 ms, p <.001) were associated with slowed task RT. Higher dose oxcarbazepine significantly reduced IED frequency (p =.009) and improved task performance (β ± SE = −107.43 ± 39.54 ms, p =.007). These results emphasize the neurocognitive consequences of IEDs independent of seizure effects. Furthermore, we demonstrate that inhibition of IEDs following treatment with select ASMs is associated with improved neurocognitive function. [ABSTRACT FROM AUTHOR]

Objective: The theory of transient cognitive impairment in epilepsy posits that lapses in attention result from ephemeral disruption of attentional circuitry by interictal events. Eye movements are intimately associated with human attention and can be monitored in real time using eye‐tracking technologies. Here, we sought to characterize the associations between interictal epileptiform discharges (IEDs), gaze, and attentional behavior in children with epilepsy. Methods: Eleven consecutive children undergoing invasive monitoring with stereotactic electrodes for localization‐related epilepsy performed an attentional set‐shifting task while tandem intracranial electroencephalographic signals and eye‐tracking data were recorded. Using an established algorithm, IEDs were detected across all intracranial electrodes on a trial‐by‐trial basis. Hierarchical mixed‐effects modeling was performed to delineate associations between trial reaction time (RT), eye movements, and IEDs. Results: Hierarchical mixed‐effects modeling revealed that both the presence of an IED (β ± SE = 72.74 ± 24.21 ms, p =.003) and the frequency of epileptiform events (β ± SE = 67.54 ± 17.30 ms, p <.001) were associated with prolonged RT on the attentional set‐shifting task. IED occurrence at the time of stimulus presentation was associated with delays in gaze initiation toward the visual targets (p =.017). Significance: The occurrence of epileptiform activity in close temporal association with stimulus presentation is associated with delays in target‐directed gaze and prolonged response time, hallmarks of momentary lapses in attention. These findings provide novel insights into the mechanisms of transient impairments in children and support the use of visual tracking as a correlate of higher order attentional behavior. [ABSTRACT FROM AUTHOR]

Objective: Working memory deficits are prevalent in childhood epilepsy. Working memory processing is thought to be supported by the phase of hippocampal neural oscillations. Disruptions in working memory have previously been linked to the occurrence of transient epileptic activity. This study aimed to resolve the associations between oscillatory neural activity, transient epileptiform events, and working memory in children with epilepsy. Methods: Intracranial recordings were acquired from stereotactically implanted electrodes in the hippocampi, epileptogenic zones, and working memory‐related networks of children with drug‐resistant epilepsy during a 1‐back working memory task. Interictal epileptic activity was captured using automated detectors. Hippocampal phase and interregional connectivity within working memory networks were indexed by Rayleigh Z and the phase difference derivative, respectively. Trials with and without transient epileptiform events were compared. Results: Twelve children (mean age = 14.3 ± 2.8 years) with drug‐resistant epilepsy were included in the study. In the absence of transient epileptic activity, significant delta and theta hippocampal phase resetting occurred in response to working memory stimulus presentation (Rayleigh z‐score = 9, Rayleigh z‐score = 8). Retrieval trials that were in phase with the preferred phase angle were associated with faster reaction times (p =.01, p =.03). Concurrently, delta and theta coordinated interactions between the hippocampi and working memory‐related networks were enhanced (phase difference derivative [PDD] z‐scores = 6–11). During retrieval trials with pre‐encoding or pre‐retrieval transient epileptic activity, phase resetting was attenuated (Rayleigh z‐score = 5, Rayleigh z‐score = 1), interregional connectivity was altered (PDD z‐scores = 1–3), and reaction times were prolonged (p =.01, p =.03). Significance: This work highlights the role of hippocampal phase in working memory. We observe poststimulus hippocampal phase resetting coincident with enhanced interregional connectivity. The precision of hippocampal phase predicts optimal working memory processing, and transient epileptic activity prolongs working memory processing. These findings can help guide future treatments aimed at restoring memory function in this patient population. [ABSTRACT FROM AUTHOR]

Objective: Through international collaboration, we evaluated the phenotypic aspects of a multiethnic cohort of KCNT1‐related epilepsy and explored genotype‐phenotype correlations associated with frequently encountered variants. Methods: A cross‐sectional analysis of children harboring pathogenic or likely pathogenic KCNT1 variants was completed. Children with one of the two more common recurrent KCNT1 variants were compared with the rest of the cohort for the presence of particular characteristics. Results: Twenty‐seven children (15 males, mean age = 40.8 months) were included. Seizure onset ranged from 1 day to 6 months, and half (48.1%) exhibited developmental plateauing upon onset. Two‐thirds had epilepsy of infancy with migrating focal seizures (EIMFS), and focal tonic seizures were common (48.1%). The most frequent recurrent KCNT1 variants were c.2800G>A; p.Ala934Thr (n = 5) and c.862G>A; p.Gly288Ser (n = 4). De novo variants were found in 96% of tested parents (23/24). Sixty percent had abnormal magnetic resonance imaging (MRI) findings. Delayed myelination, thin corpus callosum, and brain atrophy were the most common. One child had gray‐white matter interface indistinctness, suggesting a malformation of cortical development. Several antiepileptic drugs (mean = 7.4/patient) were tried, with no consistent response to any one agent. Eleven tried quinidine; 45% had marked (>50% seizure reduction) or some improvement (25%‐50% seizure reduction). Seven used cannabidiol; 71% experienced marked or some improvement. Fourteen tried diet therapies; 57% had marked or some improvement. When comparing the recurrent variants to the rest of the cohort with respect to developmental trajectory, presence of EIMFS, >500 seizures/mo, abnormal MRI, and treatment response, there were no statistically significant differences. Four patients died (15%), none of sudden unexpected death in epilepsy. Significance: Our cohort reinforces common aspects of this highly pleiotropic entity. EIMFS manifesting with refractory tonic seizures was the most common. Cannabidiol, diet therapy, and quinidine seem to offer the best chances of seizure reduction, although evidence‐based practice is still unavailable. [ABSTRACT FROM AUTHOR]

Summary: Objective: Polymicrogyria (PMG) is a common malformation of cortical development. Many patients with PMG will have medically refractory epilepsy but the role of epilepsy surgery is unclear. The objective of this study was to assess the efficacy of surgical resection/disconnection in achieving seizure control in pediatric patients with PMG. Methods: A retrospective review of children undergoing epilepsy surgery for PMG between 2002 and 2017 at The Hospital for Sick Children in Toronto, Canada, was performed. Results: A total of 12 children aged 6 months to 17.8 years (median 8.8 years) underwent resective surgery (7 children) or functional hemispherectomy (5 children). Gross total resection or complete disconnection of PMG was carried out in 7 of 12 children. Follow‐up duration was between 1 and 9 years (median 2.1 years). Nine children remained seizure‐free at last follow‐up. Complete resection or disconnection of PMG led to seizure freedom in 6 of 7 patients (86%), whereas subtotal resection produced seizure freedom in 3 of 5 patients (60%). Significance: We present one of the largest surgical series of pediatric PMG patients. Seizure outcomes were best with complete resection/disconnection of PMG. However, tailored resections based on electroclinical and neuroradiologic data can produce good outcomes and remain an appropriate strategy for patients with extensive PMG. [ABSTRACT FROM AUTHOR]