Contents

Up to one third of the epilepsy population consists of children with cryptogenic localization related epilepsy (CLRE). Unfortunately, the effect of CLRE on the development is still unclear. Behavioral and academic problems have been reported, but no conclusive study concerning the impact of CLRE on neuropsychological functioning is yet published.

This study was a systematic cross-sectional open clinical and nonrandomized investigation, which included 68 children with CLRE. Several neuropsychological tests were analyzed and age-related normative values were used as reference. Differences between CLRE and reference values were tested with Paired-Samples t-tests. Z scores were computed to compare the different neuropsychological tests and to inspect whether a characteristic neuropsychological profile exists for CLRE. The Independent-Samples t-test was used to explore which epilepsy factors (seizure type, seizure frequency, age at onset, duration of epilepsy, and drug load) were influencing the cognitive profile of CLRE.

There seems to be a characteristic cognitive profile for children with CLRE; children with CLRE experience cognitive difficulties on a wide range of areas—in particular, alertness, mental speed, and memory. Seizure type, seizure frequency, duration of epilepsy, and drug load do not influence this neuropsychological profile. Age at onset was an important risk factor; the earlier the age at onset, the worse the cognitive performance. In spite of the influence of age at onset, the revealed profile can be seen as a stable, independent of temporary factors, neuropsychological profile for children with CLRE.     

The WISC-V in children and adolescents with epilepsy

Despite its popularity in the neuropsychological evaluation of children, the utility of the Wechsler Intelligence Scale for Children – Fifth Edition (WISC-V) has not yet been investigated in children with epilepsy. Eighty clinically referred children and adolescents with epilepsy were administered the WISC-V as part of a comprehensive assessment and scores were compared to matched controls from the WISC-V standardization sample. T tests compared WISC-V indices and subtests between patients and controls and Chi-square analyses compared the rates of low scores. Correlational analyses assessed the relationships between epilepsy severity variables (e.g., age of onset, duration of epilepsy, number of antiepileptic drugs, seizure frequency). All WISC-V composites and subtests were significantly lower in patients versus controls and the rate of low scores was higher in patients than controls for all composites and subtests with the exception of Figure Weights. The Working Memory Index and Processing Speed Index were most sensitive to impairment, while the Verbal Comprehension Index and Fluid Reasoning Index were least sensitive. Of the epilepsy severity variables, age of seizure onset and number of antiepileptic drugs were strong predictors of deficits, whereas seizure frequency was the weakest predictor. Importantly, no significant differences were seen in children with right hemisphere epilepsy versus left on the five WISC-V composites, though a trend was seen towards a lower Visual-Spatial Index in those with right-sided focal seizures.     

Peer Difficulties in Children with Epilepsy: Association with Seizure,Neuropsychological, Academic,and Behavioral Variables

Purpose/Objective: A developmental psychopathology framework was used to examine variables associated with peer problems in children with epilepsy (CWE). Variables commonly associated with peer difficulties in typically developing children, such as inattentive behavior, anxious behavior, and academic achievement were investigated. Neuropsychological functioning, age at epilepsy onset, and seizure status were also examined.

Research Method/Design: Participants were 173 CWE, ages 8–15. Structural equation modeling (SEM) was used to determine which variables predicted peer problems in CWE and to test hypothesized interrelations among variables.

Results: The SEM revealed that anxious behavior mediated relations between neuropsychological functioning and peer difficulties and seizure status and peer difficulties. Inattentive behavior mediated the association between neuropsychological functioning and peer difficulties. Neuropsychological functioning mediated the relation between age at epilepsy onset and inattentive behavior, anxious behavior, and academic achievement.

Conclusions/Implications: As seen with typically developing children, inattentive and anxious behaviors are related to peer difficulties in CWE. Neuropsychological functioning, age at epilepsy onset, and seizure status are indirectly associated with peer difficulties; therefore, these variables are important to examine in CWE who are experiencing peer problems.     

A clinical comparative study evaluating the effect of epilepsy versus ADHD on timed cognitive tasks in children.

Both children with epilepsy and children with ADHD may be characterized by slowing on reaction-time measurement. This is of particular interest, as neuropsychological assessment is often requested in the differential diagnosis between children with short non-convulsive epileptic seizures and children with ADHD. In this study we attempt to identify patterns of impairment on timed tasks that are specific for epilepsy, relative to ADHD. This study was an open, controlled parallel-group clinical investigation which included two groups of patients: 60 children with ADHD and 60 children with epilepsy. These children were compared with a control group (n=30) on two types of timed cognitive tasks: tasks with low information load (simple reaction-time measurement) and tasks with high information load (multiple decision reaction-time measurement). The simple reaction-time measurements show significant differences between ADHD and controls (all except for visual RT non-dominant hand) and between epilepsy and controls (only one test). No significant differences were found between epilepsy and ADHD. The two tests with high information load show significant slowing compared with the controls for epilepsy on the Binary Choice Reaction-Time Test and for ADHD on the Visual Searching Test. On both tests also the differences between epilepsy and ADHD are significant. The two tests in combination have a relatively satisfactory potential to classify the children with ADHD (75% correct classification) and the children with epilepsy (55% correct classification). We may conclude that complex reaction-time tests (i.e., timed tasks with high information load) have potential for assessing the differential impact of ADHD and epilepsy on attentional function. These tasks specifically reveal general slowing for children with epilepsy and slowing as an effect of failures of inhibitory self control on unstructured tasks for ADHD.     

A Clinical Comparative Study Evaluating the Effect of Epilepsy Versus Adhd on Timed Cognitive Tasks in Children

Both children with epilepsy and children with ADHD may be characterized by slowing on reaction-time measurement. This is of particular interest, as neuropsychological assessment is often requested in the differential diagnosis between children with short non-convulsive epileptic seizures and children with ADHD. In this study we attempt to identify patterns of impairment on timed tasks that are specific for epilepsy, relative to ADHD. This study was an open, controlled parallel-group clinical investigation which included two groups of patients: 60 children with ADHD and 60 children with epilepsy. These children were compared with a control group (n =30) on two types of timed cognitive tasks: tasks with low information load (simple reaction-time measurement) and tasks with high information load (multiple decision reaction-time measurement). The simple reaction-time measurements show significant differences between ADHD and controls (all except for visual RT non-dominant hand) and between epilepsy and controls (only one test). No significant differences were found between epilepsy and ADHD. The two tests with high information load show significant slowing compared with the controls for epilepsy on the Binary Choice Reaction-Time Test and for ADHD on the Visual Searching Test. On both tests also the differences between epilepsy and ADHD are significant. The two tests in combination have a relatively satisfactory potential to classify the children with ADHD (75% correct classification) and the children with epilepsy (55% correct classification). We may conclude that complex reaction-time tests (i.e., timed tasks with high information load) have potential for assessing the differential impact of ADHD and epilepsy on attentional function. These tasks specifically reveal general slowing for children with epilepsy and slowing as an effect of failures of inhibitory self control on unstructured tasks for ADHD.     

Cognitive estimations as a measure of executive dysfunction in childhood epilepsy

Children and adolescents with epilepsy are known to demonstrate executive function deficits. Despite prior work that has shown that cognitive estimation tasks are sensitive to executive dysfunction in children, such tasks have not been studied in children with epilepsy. This is particularly important given the fact that executive tasks have heretofore shown poor ecological validity, and it has been speculated that estimation tasks may show stronger ecological validity than other executive tests. One hundred and thirteen clinically referred children and adolescents with epilepsy were included. The Biber Cognitive Estimations Test was sensitive to cognitive dysfunction, with about half showing impairments on this task in comparison to age-matched normative data; the most frequently impaired subscales were quantity estimation and time estimation. Moreover, the Biber Cognitive Estimation Test showed moderate correlations with not only overall intellectual functions and academic achievement but also other commonly administered tests of executive functions, including digit span, Trailmaking, and the Tower of London but not with the contingency naming test. Cognitive estimations were also modestly correlated with age of epilepsy onset but not other epilepsy-severity variables such as number of antiepilepsy drugs (AEDs) or seizure frequency. Unfortunately, the hypothesis that the Biber Cognitive Estimation Test would show strong ecological validity was not supported, as it showed weak relations with parent-reported executive function deficits. The significance and limitations of this investigation are discussed.     

Childhood Epilepsy and Autism Spectrum Disorders: Psychiatric Problems, Phenotypic Expression, and Anticonvulsants

Epilepsy and autism spectrum disorders (ASDs) frequently co-occur during childhood, however, the characteristics of psychiatric or behavioural problems in these children remains largely unknown. This article contributes to these discussions by reporting on the prevalence and presentation of psychiatric or behavioural problems in children with epilepsy and ASDs, as well as on the use of anticonvulsants in these children. The current evidence suggests that children with epilepsy and ASDs may present with a distinct clinical profile, with a greater number of developmental difficulties, and a more severe expression of the ASD phenotype that can not solely be accounted for by level of intellectual functioning. Positive effects of anticonvulsants on behavioural symptoms associated with ASDs were also reported, though pharmacoresistance and a lack of clear treatment guidelines may contribute to an elevated risk of adverse side effects. In relation to clinical presentation and management there is a need for careful consideration of potential interaction effects between disorder specific factors (e.g., age of seizure onset/ASD diagnosis), cognitive characteristics (e.g., intellectual functioning, memory), and psychosocial variables (e.g., coping strategies). Ultimately however, many conclusions are tentative and this review highlights the need for more empirically validated research on children with epilepsy and ASDs.     

Everyday executive function in focal onset pediatric epilepsy on the parent-report BRIEF2

Executive function (EF) difficulties are a core neuropsychological feature of pediatric epilepsy, and parent-report measures of EF concerns are an important complement to task-based EF measures. The Behavior Rating Inventory of Executive Function (BRIEF) has shown sensitivity to parent-reported EF concerns in epilepsy and other pediatric populations. We compared profiles of parent-reported EF concerns using the BRIEF and its revision, the BRIEF2, in 117 pediatric patients with focal onset epilepsy to examine the clinical utility of the revised scale. We then compared BRIEF2 profiles between patients and age- and gender-matched healthy controls. Among patients, profiles on the BRIEF did not globally differ from the BRIEF2, and agreement was very good across scales. Patients and controls differed significantly on the BRIEF2, with patients showing higher EF difficulties reported by parents across most scales. High rates of clinical elevation among patients emerged on the Task Monitor, Plan/Organize, Working Memory, and Shift scales. Younger age of epilepsy onset, chronic epilepsy, and right hemisphere seizure focus were associated with higher parent-reported EF concerns. Findings suggest that the BRIEF2 demonstrates similar performance to the BRIEF among pediatric patients with focal onset epilepsy who are most at risk in the areas of task monitoring, working memory, planning and organization, and flexibility. These findings are informative when comparing literature across versions and provide additional insight into the nature of parent-reported EF difficulties among children with focal onset epilepsy.     

Classroom performance and adaptive skills in children with epilepsy

The relationships of age at onset, seizure syndrome, seizure type, and seizure frequency, respectively, to the classroom performance and adaptive skills of 131 children with epilepsy were studied. The Teacher Report Form of the Child Behavior Checklist was completed by the children's teachers. Hierarchical multiple regression analyses were conducted on ratings of academic subject areas and overall adaptive skills. Significant results were obtained for English/Language, Reading, Mathematics, overall School Performance, Learning, Happy, and Total Adaptive skills. Epilepsy syndrome and frequency of seizures were significantly related to some of these analyses, with amounts of variance accounted for ranging from 11% to 23%. Children with secondary generalized epilepsy performed significantly worse than children with other epilepsy syndromes. The results suggest that a seizure disorder associated with a diffuse or multifocal brain insult can produce problems in achievement and school adaptation as manifested on a day-to-day basis. Suggestions for future research are presented.     

The impact of age at seizure onset on the likelihood of atypical language representation in children with intractable epilepsy

Studies have suggested that early postnatal lesions are associated with a greater likelihood of atypical speech representation than lesions acquired later in life. Comparison groups have been defined differently across studies, with age typically being treated as a dichotomous (i.e., early versus late lesion onset) rather than continuous variable. Thus, little is known about the age at which children become less likely to exhibit atypical representation following a brain insult. This study examined the likelihood of typical versus atypical speech representation in children with intractable epilepsy (n = 75). Age of seizure onset was treated as a continuous variable to examine whether there was a naturally occurring cut-off point after which the rate of atypical speech representation decreased. A much higher proportion of children with seizure onset prior to the fifth year showed atypical speech representation as compared to children whose seizures began after 5 years of age.     

Cognitive development in absence epilepsy during long-term follow-up

Absence epilepsy (AE) has been associated with lower than average cognitive functioning, which are clinically relevant in some and may predispose to problems later in life. This study aimed to assess cognitive development during long-term follow-up in children with AE. Thirty-one children with AE, who had undergone two neuropsychological assessments between 2010 and 2017 were analyzed retrospectively. Cognitive measurements were 1.7 ± 0.95 years apart. The difference in neurocognitive test scores was assessed on a group level and on an individual level using reliable change methodology. Results show that sustained attention was lower at the first measurement compared to the normative mean. Sustained attention improved during follow-up and 7 out of 14 children showed improvement after correction for practice effects. Receptive vocabulary showed a decline over time, but did not differ from the normative mean. Significant lower mean group scores were present for performance IQ, perceptual organization, processing speed, simple reaction times, and visual motor integration, while being stable over time in the majority of children. Cognitive development was not associated with seizure freedom. Mild-to-severe academic underachievement was present in 65% and comorbidities that might affect learning in 38%. This study in children with AE showed improvement in sustained attention during long-term follow-up while other cognitive weaknesses persisted over time, regardless of seizure freedom.     

Cognitive outcomes of pediatric stroke

A limited number of longitudinal studies have investigated long-term neuropsychological development in the pediatric stroke population. This study retrospectively examines cognitive outcomes in 41 children with a history of stroke, with reference to age at stroke, laterality, region and mechanism of stroke. In the course of recovery, neuropsychological measures of intellectual functioning and memory were administered at two time points, whilst executive functioning, attention and academic skills were administered at one time point. As predicted, children with stroke performed significantly worse compared to normative expectations on all neuropsychological measures. Up to two thirds of children scored in the borderline impaired and impaired ranges on at least one domain of cognition. Performance on intellectual and memory assessment remained relatively stable over time. Younger age at stroke was found to be associated with poorer intellectual functioning. No effects of laterality of stroke on neuropsychological performance over time were found. Children with subcortical stroke demonstrated a greater improvement in immediate memory over time than children with cortical stroke. These findings reveal that children with stroke display long-term cognitive difficulties that typically remain stable over time. Attention and academic skills are particularly vulnerable to impairment. Further evidence that age at stroke is a significant factor in terms of cognitive outcome is provided, in support of the “early vulnerability” position.     

Factors Involved in Learning Problems and Educational Delay in Children with Epilepsy

Educational delay was assessed in a group of children with epilepsy and co-morbid learning problems, and compared with a matched group of children with learning problems, but without epilepsy. In addition, delay in the academic skills reading/spelling and arithmetic was compared for the two groups. Moreover, the differential contribution for the development of learning problems of each of the following epileptic factors was inspected: type of epilepsy, seizure type, seizure frequency and type of AED-treatment. The ‘Groninger School Onderzoek’ (G.S.O.) was used to yield an objective measurement of school achievement. The first 24 children with a reconfirmed diagnosis of epilepsy and with co-morbid learning problems who were referred to our outpatient department for ‘epilepsy and learning disabilities’ were included in the study. Each child was matched to a control subject (children with learning problems, but without epilepsy). Matching was carried out for the potential confounding factors age, school-type, school-grade and intelligence. The measure for school achievement showed no significant differences between the two groups with a delay in both groups of approximately a half year. Also, no statistically significant difference was found with respect to achievement on the academic skills reading/spelling and arithmetic. The impact of several epileptic factors on the measurement of school achievement were analyzed. The analysis of type of epilepsy showed significant lower school achievement scores for the patients with idiopathic generalized epilepsy compared to the patients with localisation-related epilepsy. Further evaluation of this result shows that most of the patients, classified as idiopathic generalized epilepsy have a recent onset epilepsy, a high seizure frequency and are not yet satisfactorily controlled with antiepileptic therapy. The key factor contributing to learning problems in children with epilepsy is an ‘uncontrolled’ epilepsy, i.e., an epilepsy with high seizure frequency.     

Memory outcome after pediatric epilepsy surgery: objective and subjective perspectives.

Memory was investigated in 27 children and adolescents in a longitudinal study before and at one and two years after epilepsy surgery. A comparison group with intractable epilepsy (n = 15), matched in age, sex, age of seizure onset, and IQ, was studied at comparable points in time. Methods included administration of standardized measures of story recall and face recognition, and qualitative interviews to probe the participants' perceptions of their memory function over time. There was no significant change over time in either group on the standardized measures. Site and laterality of excision, age at surgery, and seizure outcome were not predictive of change within the surgical group. The narratives revealed facets of memory that were problematic in daily life. The objective and subjective results showed low concordance regarding change, possibly due to limitations in the objective measures for capturing semantic and autobiographical memory.     

Performance of children with epilepsy and normal age-matched controls on the WISC-III.

Research findings regarding the effects of childhood epilepsy on general intelligence have produced variable results. The aim of this study was to investigate the effects of epilepsy, age of seizure onset, and Antiepileptic Drugs (AED) on intellectual ability as assessed by the Wechsler Intelligence Scale for Children, 3rd Edition (WISC-III; Wechsler, 1991). This study included children with epilepsy assessed with the WISC-III who achieved either a Full Scale, Verbal Scale, or Performance Scale IQ score >or= 70. A clinical sample of children diagnosed with epilepsy (n = 32) were age- and gender-matched with subjects from the normative standardization sample for the WISC-III, yielding a total sample of 64 subjects. Comparison using a MANOVA revealed significant differences across WISC-III Index standard scores (p = 0.0005) and subtest scaled scores (p = 0.0013), with control participants performing better than epileptic participants. Secondary analyses were also conducted considering monotherapy (n = 14) versus polytherapy (n = 11), and age of seizure onset (<6 years, n = 12; 6 > years, n = 15). MANOVA comparisons revealed no significant differences between groups across WISC-III Index standard scores.     

Memory Outcome After Pediatric Epilepsy Surgery: Objective and Subjective Perspectives

Memory was investigated in 27 children and adolescents in a longitudinal study before and at one and two years after epilepsy surgery. A comparison group with intractable epilepsy (n = 15), matched in age, sex, age of seizure onset, and IQ, was studied at comparable points in time. Methods included administration of standardized measures of story recall and face recognition, and qualitative interviews to probe the participants’ perceptions of their memory function over time. There was no significant change over time in either group on the standardized measures. Site and laterality of excision, age at surgery, and seizure outcome were not predictive of change within the surgical group. The narratives revealed facets of memory that were problematic in daily life. The objective and subjective results showed low concordance regarding change, possibly due to limitations in the objective measures for capturing semantic and autobiographical memory.     

Rhythm and Melody in Children and Adolescents after Left or Right Temporal Lobectomy

Rhythm (a pattern of onset times and duration of sounds) and melody (a pattern of sound pitches) were studied in 22 children and adolescents several years after temporal lobectomy for intractable epilepsy. Left and right lobectomy groups discriminated rhythms equally well, but the right lobectomy group was poorer at discriminating melodies. Children and adolescents with right lobectomy, but not those with left temporal lobectomy, had higher melody scores with increasing age. Rhythm but not melody was related to memory for the right lobectomy group. In neither group was melody related to age at onset of non-febrile seizures, time from surgery to music tests, or the linear amount of temporal lobe resection. Pitch and melodic contour show different patterns of lateralization after temporal lobectomy in childhood or adolescence.     

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.     

Neuropsychological Features of Lesion-related Epilepsy in Adults: An Overview

Lesional epilepsy is thought to be a direct consequence of focal brain lesions of dysgenetic, neoplastic, vascular, or traumatic origin. It has been estimated that at least half of all epilepsies are the result of such lesions. The current discussion includes an overview of the cognitive and behavioral presentations in adults with epilepsy secondary to focal pathology. The neuropsychological presentation in this population is influenced by many factors, including the location and nature of the underlying lesion, seizure characteristics, the effects of treatment, and patient variables. Few studies attempt to disentangle the specific contributions of these variables to cognitive performance. However, where available studies examining the separable effects of seizure-related variables on cognitive functioning in individuals with lesional epilepsy are also reviewed. This overview includes a discussion of focal malformations of cortical and vascular development and select foreign tissue and acquired lesions.     

Cognitive function of youths born to mothers with opioid and poly-substance abuse problems during pregnancy

Previous research has provided inconclusive evidence regarding the neuropsychological difficulties of children born to mothers partaking in opioid or poly-drug use during pregnancy. Little is known about how these children fare as they get older. The present longitudinal study includes follow-up data on 45 children born to mothers who used heroin and poly-drugs and a group of 48 children without prenatal drug exposure. Most of the drug-exposed youths were placed in permanent foster or adoptive homes before one year of age. The youths (ages 17 to 21) were administered 10 neuropsychological tests. The drug-exposed youths had cognitive and fine motor functions within the normal range compared to population norms but performed significantly worse than the non-exposed group. There were indications of generally lower cognitive functions rather than specific problems with executive functioning. Lower mean birthweight in the risk group (619 grams mean difference, p < .001) only partially mediated the group differences in cognitive functioning. There was a tendency for youths who had few and early changes in their caregivers or who were born to mothers who had used the least number of different drugs during pregnancy to have the best cognitive scores. The study indicates that youths born to mothers who used multiple drugs during pregnancy are vulnerable relative to their peers within a wide range of cognitive functions. The vulnerability seems to be related not only to the mother’s drug use during pregnancy but also to factors such as birthweight and unstable parental care during infancy.