Objective To examine neurocognitive functioning of children exposed prenatally to carbamazepine, lamotrigine, levetiracetam or valproate monotherapy. Methods In a prospective observational study, children aged 6 or 7 years, identified from the European Registry of Antiepileptic Drugs and Pregnancy database in The Netherlands, were assessed using the Wechsler Intelligence Scale for Children and the developmental neuropsychological assessment. Maternal IQ was measured using Wechsler Adult Intelligence Scale. Assessors were blinded to drug exposures. Results One hundred and sixty-one children (one set of twins and 21 sibling pairs) of 139 mothers were included. As a group, children achieved average scores on neurocognitive outcomes. Children exposed to valproate (n = 22) performed lower on all six neurocognitive domains, especially language, than those exposed to carbamazepine (n = 32), lamotrigine (n = 82) or levetiracetam (n = 25). After controlling for maternal IQ and drug dose, the verbal IQ of valproate-exposed children was on average 9.1 points lower than those exposed to carbamazepine (95% confidence interval [CI] 1.3-17.0; p = 0.023), 10.3 lower than lamotrigine-exposed children (CI 3.4-17.3; p = 0.004) and 13.4 lower than levetiracetam-exposed children (CI 5.2-21.6; p = 0.002). No significant dose-effect was found. Virtually no significant differences were found between lamotrigine and levetiracetam or lamotrigine and carbamazepine exposed children. Conclusions Consistent with previous research, valproate-exposed children experienced more problems compared to three other common antiepileptic drugs, while children exposed to lamotrigine, carbamazepine or levetiracetam revealed little to no problems. This illustrates the need for systematic follow-up of prenatally exposed children, to support pre-pregnancy counseling and treatment decisions in women of reproductive age.

Verbal IQ, though initially spared, drops. The Performance IQ, which may have shown its vulnerability earlier in the course of the epilepsy, shows overall smaller changes. It is suggested that seizures impact synergistically on an affected brain, which leads to progressive cognitive decline. Earlier onset of epilepsy is associated with relatively higher VIQ, larger VIQ > PIQ discrepancies and more decline.

Introduction Increasing interest is seen for early and late memory consolidation and accelerated forgetting, but little is known about these phenomena in children with epilepsy. The present study analysed the trajectory of learning and retention in typically developing children and children with epilepsy on a story learning test. Methods 285 children, 126 typically developing children and 159 children with epilepsy, in ages between 4 and 10 years and Full-Scale IQs ≥ 75, were given a specifically designed story learning test (iter-SEIN). The learning phase included Initial reading and a Free Recall trial with 10 Questions, and up to three repetition trials with Questions. Trials of Delayed Free Recall and Questions followed after half an hour, the next day and 1 week later. With several repeated measures analyses of variance, level of performance and gains or losses over time were analysed. Results Age-dependent learning was seen after repetitions. On the Questions, typically developing children outperformed children with epilepsy increasingly, due to smaller gains after the second trial. Learned information was similarly preserved. Free Recall showed similar performance for both groups up to day 2. A week later, a conspicuous loss of information was observed in the children with epilepsy, whilst typically developing children retained the information. On index scores, reliable cognitive loss of information was seen in epilepsy in 24.5% of the children. Semantic neuropsychological tasks and severity measures of epilepsy were associated with level of performance. Discussion The results provided evidence for early decelerated learning and late accelerated forgetting in children with epilepsy.

The combination of a rare missense variant with a de novo mosaic deletion of a large part of the SCN8A gene suggests that other possible mechanisms for SCN8A mutations may cause epilepsy; loss of function, genetic modifiers and cellular interference may play a role. This case expands the phenotype associated with SCN8A mutations, with absence epilepsy and regression in language and memory skills.

In isolated epilepsy, a VIQ>PIQ pattern was found, which was not seen in the other disorders. When epilepsy and another disorder co-occurred, patterns were altered. They resembled partly the pattern seen in isolated epilepsy and partly the pattern seen in the isolated neurodevelopmental disorder. In comorbid reading disorders, the VIQ>PIQ pattern was mitigated; in comorbid math disorders, it was exacerbated. In comorbid ASDs, no clear pattern emerged. In the presence of epilepsy, patterns characteristic of isolated disorders appeared systematically shifted toward relatively lowered performance abilities or relatively spared verbal abilities. The similar "impact" exerted by epilepsy on the patterns of the various conditions suggested shared mechanisms.