Acquired visual agnosia as an uncommon presentation of epileptic encephalopathy in a 6-year-old boy with CSWS.

BACKGROUND: Acquired visual agnosia in the context of continuous spikes and waves during slow sleep (CSWS) is rarely described. We present a case of an almost 7-year-old boy who lost his ability to name pictures and recognize familiar faces. Initial encephalography (EEG) revealed sleep induced epileptiform activity with a spike-wave index (SWI) of 100%, predominanting in the left posterior head region. METHODS: Serial neuropsychological testing with concomitant EEG was done during the first 18 months of treatment with intravenous methylprednisolone. We administered intelligence scales, verbal tasks (memory, fluency), visual tasks (drawings, search, face recognition), and tasks requiring visual-verbal integration (picture naming, visual closure). ANALYSES: Neuropsychological recovery studied with reliable cognitive change cut-offs and 95% confidence intervals. RESULTS: With treatment, there was an improvement of the EEG pattern (SWI reduction to 45%), followed by a relapse (SWI 82%). Neuropsychological measures in part synchronized with improvement, stability, and fluctuating values. Significant increases were seen on Verbal Comprehension Index and semantic memory. Visual Spatial Index remained unchanged (67 to 73). Naming pictures showed only limited change. Interpreting degraded pictures remained extremely difficult. DISCUSSION: Acquired visual agnosia may be seen in children with CSWS. Early recognition, prompt accurate treatment and tailored neuropsychological assessment remain crucial.

Neurocognition after prenatal levetiracetam, lamotrigine, carbamazepine or valproate exposure.

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.

Exposure to antiepileptic drugs in pregnancy: The need for a family factor framework.

PURPOSE: Children exposed to antiepileptic drugs (AEDs) in utero are at risk for developmental problems. Maternal epilepsy, its impact on the family system, and other family factors may also contribute. We reviewed the possible associations between family factors and developmental outcome in children who had been exposed to AED during pregnancy. METHODS: We conducted a narrative review and searched MEDLINE, Embase, Google Scholar, and PsycINFO on the following terms: in utero exposure, pregnancy outcome, and AEDs. A family factor framework (the ABCX model) served as the basis to review distinct family factors in children who were exposed to AEDs in pregnancy. RESULTS: Few studies have investigated these factors. Mothers with epilepsy have problems caring for themselves and for the child and experience more parenting stress. There is a paucity of studies of the possible impact of family factors on the neurocognitive and behavioral development of children of mothers with epilepsy. DISCUSSION: Further work is required to ascertain which family factors are associated with child development in addition to the effects of AED exposure and their potential interaction. As epilepsy may have considerable impact on intrafamily factors and as children are especially vulnerable to such effects, study designs incorporating family factors should be encouraged.

Development of verbal short-term memory and working memory in children with epilepsy: Developmental delay and impact of time-related variables. A cross-sectional study.

While short-term memory (STM) and working memory (WM) are understood as being crucial for learning, and children with epilepsy often experience learning difficulties, little is known about the age-related development of memory span tasks in children with epilepsy. Short-term memory and WM, operationalized as digit span forwards (DSF) or digit span backwards (DSB), respectively, were studied. Participants were 314 children with epilepsy and 327 typically developing children in ages between 5 and 15years and full scale intelligence quotient (FS-IQ)≥75. Cross-sectional analyses of the data were done with analyses of variance and analyses of covariance ((M)ANCOVAs) and generalized linear analyses. The analyses revealed that STM problems in epilepsy were mediated by age-related gains in WM as well as by differences in IQ. Working memory developed at a quick pace in the younger children, the pace slowed down to some extent in the later primary school years and resumed again later on. Working memory problems prevailed in epilepsy, independent of IQ and development of STM. Timing of the epilepsy in terms of age at onset and duration determined memory development. The youngest children with epilepsy showed age-appropriate development in STM but were the most vulnerable in terms of WM development. Later in the course of the epilepsy, the WM problems of the young children attenuated. In later onset epilepsy, WM problems were smaller but persisted over time.

Complex SCN8A DNA-abnormalities in an individual with therapy resistant absence epilepsy.

BACKGROUND: De novo SCN8A missense mutations have been identified as a rare dominant cause of epileptic encephalopathy. We described a person with epileptic encephalopathy associated with a mosaic deletion of the SCN8A gene. METHODS: Array comparative genome hybridization was used to identify chromosomal abnormalities. Next Generation Sequencing was used to screen for variants in known and candidate epilepsy genes. A single nucleotide polymorphism array was used to test whether the SCN8A variants were in cis or in trans. RESULTS: We identified a de novo mosaic deletion of exons 2-14 of SCN8A, and a rare maternally inherited missense variant on the other allele in a woman presenting with absence seizures, challenging behavior, intellectual disability and QRS-fragmentation on the ECG. We also found a variant in SCN5A. CONCLUSIONS: 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.

Pediatric epilepsy and comorbid reading disorders, math disorders, or autism spectrum disorders: Impact of epilepsy on cognitive patterns.

INTRODUCTION: In pediatric epilepsy, comorbidities are reported to be frequent. The present study focusedon the cognitive patterns of children with isolated epilepsy, children with isolated neurodevelopmental disorders (reading disorders, math disorders, autism spectrum disorders), and children with epilepsy and these neurodevelopmental disorders as comorbidities. METHODS: Based on two samples of referred children, one with epilepsy, reading disorders, math disorders, or ASDs occurring in "isolation" (n=117) and one with reading disorders, math disorders, and ASDs occurring comorbid with epilepsy (n=171), cognitive patterns were compared. The patterns displayed by verbal and nonverbal abilities from the WISC series were studied with repeated measures ANOVA. Thereafter, an exploratory 2∗3∗2 factorial analysis was done to study the independent contribution of the type of comorbidity and of the presence or absence of epilepsy to the VIQ-PIQ pattern. RESULTS: 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.

Duration of epilepsy and cognitive development in children: a longitudinal study.

OBJECTIVE: To study the pattern of cognitive development in relation to duration of epilepsy. METHODS: Participants were 113 children with epilepsy referred because of concerns about their cognitive development and tested at least twice at tertiary epilepsy settings. Verbal, Performance, and Full Scale IQ were measured with Wechsler Intelligence Scales. Various epilepsy and demographic variables were included. Change over time was modeled with multilevel analysis for longitudinal data with variable measurement occasion. RESULTS: The Verbal and Full Scales could be fitted best as a downward progressing function. Earlier in time, decline was likely to be largest; later in time, decline followed a continuous, dwindling course. A similar trend was seen for the Performance Scale. Initially, Verbal IQ was higher than Performance IQ but this discrepancy decreased over time. Later onset of epilepsy was associated with an attenuated decline of the Verbal Scale. None of the other epilepsy variables were related to the course of cognitive development. Higher parental education was associated with higher IQ, but was not protective against decline. CONCLUSIONS: 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.

Differential effect of lesion side on intra-individual variability in children with focal lateralized epilepsy.

A differential impact of hemispheric side (left vs right) on cognitive measures, specifically Verbal and Performance IQ, has been described previously for both focal onset seizures and lateralized brain lesions. This study revealed a differential effect on intra-individual variability, measured as subtest scaled-score range, on the Dutch WISC-R and WISC-III, in children with epilepsy. The presence of documented brain lesion was associated with elevated variability on the Verbal Scale for the left hemisphere seizure group and with decreased variability on the Verbal and Full Scales for the right hemisphere seizure group.

Intra-individual subtest variability on the Dutch Wechsler Intelligence Scales for Children-Revised (WISC-R(NL)) for children with learning disabilities, psychiatric disorders, and epilepsy.

It is common practice to look at disparities among subtest scores ("scatter") on an intelligence test to establish if a score is deviant. However, it remains unclear whether subtest scatter reflects primarily normal variation within individuals or is clinically meaningful. The present study explored this issue based on data from 467 children with developmental disabilities tested on the Dutch WISC-R(NL). Of these children, 132 had learning disabilities, 178 had psychiatric disorders, and 157 had epilepsy. Subtest scatter was defined as scaled-score range (highest minus lowest scaled score). When contrasted with "normal scatter," the overall sample revealed higher ranges on the Performance Scale and Full Scale, although effect sizes were small. Analysis of the data for the three separate clinical samples revealed unusual scatter only for the sample of children with psychiatric disorders. When comparing the clinical samples, scaled-score range was larger for the sample of children with psychiatric disorders than for those with epilepsy. Two distinct subsamples revealed elevated ranges with moderate effect sizes: children with autistic spectrum disorders and children with left hemisphere seizures. These results suggest that elevated subtest scaled-score range might characterize specific clinical samples rather than denoting an overall sign of pathology.