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Purpose: The presence of specific neurocognitive deficits may help explain why school achievement and psychosocial functioning are often worse in children with epilepsy than would be predicted by their global intellectual functioning. This study compared children with two forms of epilepsy: localization-related epilepsy with complex partial seizures (CPS) and childhood absence epilepsy (CAE), to determine whether they display distinct neurocognitive profiles.
Methods: Fifty-one children with CPS, 31 children with CAE, and 51 controls underwent neuropsychological testing assessing verbal memory, visual memory, and executive functioning. Groups were compared in these cognitive domains. Within-group analyses were also conducted to examine seizure-related factors that may be related to neuropsychological test performance.
Key Findings: When compared to controls, children with CPS showed a mild generalized cognitive deficit, whereas children with CAE did not. When we controlled for intelligent quotient (IQ), both epilepsy groups showed poorer performance relative to controls in the domain of verbal memory. When the epilepsy groups were compared to one another, the CPS group performed significantly poorer than the CAE group on a test of generalized cognitive functioning. However, in the specific domains of executive functioning, verbal memory, and visual memory the epilepsy groups did not differ when compared to one another.
Significance: Neurocognitive deficits present in the context of grossly intact global intellectual functioning highlight the importance of neuropsychological screening in both children with CPS and children with CAE.
Although a significant proportion of children with severe forms of epilepsy score below average on intelligence tests, the majority of children with epilepsy have intellectual functioning within the average range (Berg et al., 2008). Despite their mostly intact global intellectual functioning, however, children with epilepsy as a group are at high risk for poor academic functioning (Sillanpaa, 2004; Aldenkamp et al., 2005; Fastenau et al., 2008) and negative psychosocial outcomes (Wirrell et al., 1997; Sillanpaa et al., 1998). Researchers have therefore highlighted the importance of neuropsychological testing in children with epilepsy, positing that specific cognitive deficits in domains other than general intelligence may help explain why school achievement and psychosocial functioning are often worse than would be predicted by their intelligence scores alone (Nolan et al., 2004; Jocic-Jakubi & Jovic, 2006; Fastenau et al., 2008).
Past research has indicated that children with epilepsy display specific cognitive weaknesses, with a number of studies demonstrating deficits in the domains of memory and executive functioning (Jambaque et al., 1993; Bailet & Turk, 2000; Lassonde et al., 2000; Pavone et al., 2001; Culhane-Shelburne et al., 2002; Nolan et al., 2004; Henkin et al., 2005; Hoie et al., 2005; Borden et al., 2006; Hermann et al., 2006; Hommet et al., 2006; Jocic-Jakubi & Jovic, 2006; MacAllister & Schaffer, 2007; Parrish et al., 2007; Seidenberg et al., 2007; Hermann et al., 2008; Pulsipher et al., 2009). However, the question of whether children with different types of seizures or epilepsy syndromes show distinct cognitive profiles has yet to be resolved in the literature. Most studies to date looking at cognitive functioning in children with epilepsy have compared children with epilepsy to a healthy control group or standard scores. The epilepsy groups in these studies have been heterogeneous, limiting the conclusions that can be drawn in terms of delineating distinct cognitive profiles. Although several recent studies have directly compared children with different types of seizures and epilepsy syndromes, findings have been mixed with regard to whether there are differences among epilepsy groups. In addition, children have been grouped together using different criteria in terms of type of seizure and epilepsy syndrome, making comparisons across studies difficult.
For example, some studies have compared children with generalized seizures to children with focal epilepsies and found that children with focal epilepsies perform poorer on tests of memory (Jambaque et al., 1993; Nolan et al., 2004). Other studies comparing children with localization-related epilepsies to children with generalized seizures have not found significant differences in memory functioning (Williams et al., 1998, 2001; Hermann et al., 2006). In the domain of executive functioning, some studies comparing children with localization-related epilepsy to children with idiopathic generalized epilepsy have found no or small differences between the groups (Hermann et al., 2006; Parrish et al., 2007). Similarly, a study comparing children with absence seizures to children with complex partial seizures found no differences among the groups in executive functioning (Williams et al., 1998). In contrast, a study comparing children with juvenile myoclonic epilepsy (JME) to children with benign childhood epilepsy with centrotemporal spikes (BCETS) found children with JME to have significant executive dysfunction, whereas children with BCECTS did not show the same pattern (Pulsipher et al., 2009).
In addition to seizure type and epilepsy syndrome, a number of other seizure-related variables have been identified as contributing to variability in cognitive outcomes for children with epilepsy. Age at onset of epilepsy has been shown to predict later cognitive ability, with younger age of onset associated with poorer cognitive outcomes (Jambaque et al., 1993; Schoenfeld et al., 1999; Pavone et al., 2001; Nolan et al., 2004; Hoie et al., 2006; Jocic-Jakubi & Jovic, 2006). Other disease-related factors such as longer duration of illness (Nolan et al., 2004), greater numbers of seizures (Hoie et al., 2006; Jocic-Jakubi & Jovic, 2006; Fastenau et al., 2009), and treatment with one or more antiepileptic drugs (AEDs) (Schoenfeld et al., 1999; Nolan et al., 2004; Fastenau et al., 2009) have also been associated with increased cognitive difficulties.
The purpose of the present study was to compare neurocognitive functioning in children with localization-related epilepsy with complex partial seizures (CPS), usually thought to involve cognitive impairment (particularly memory), and children with childhood absence epilepsy (CAE), often regarded as a benign disorder without cognitive or other comorbidities. Children with general cognitive functioning in the average range were compared on neuropsychological measures of verbal memory, visual memory, and executive functioning. We also investigated the effects of clinical variables on neurocognitive functioning in this population, including age at seizure onset, duration of illness, seizure frequency, number of AEDs, as well as lateralization and localization of epileptic activity on EEG. The current study included a larger sample size than in most previous studies of neurocognitive functioning in children with epilepsy, a healthy control group, and groups with comparable demographic variables. If patterns specific to epilepsy group and clinical seizure variables can be identified, this could aid in the early identification of children at risk of developing cognitive problems and in tailoring interventions that address their specific needs.
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The present study is one of few that compare neurocognitive functioning in relatively large samples of children with different types of epilepsy with comparable demographic variables. When compared to each other, the CPS and CAE group differed significantly in generalized cognitive functioning, but not in the specific cognitive domains of executive functioning, verbal memory, and visual memory. Compared to controls, children with CPS showed a mild generalized cognitive deficit reflected by a mean Full Scale IQ of 94 (SD = 15), whereas children with CAE did not (mean Full Scale IQ = 102, SD = 16). Relative to controls, both groups showed poorer performances in the domains of executive functioning and verbal memory, with the CPS group showing poorer across a greater range of tests. This is consistent with a study of children with CPS, which found a pattern of relatively diffuse and generalized cognitive dysfunction in children with CPS (Schoenfeld et al., 1999).
To determine whether neuropsychological testing could help identify specific neurocognitive weaknesses in children with CPS and CAE above and beyond what would be predicted by their general intellectual functioning, we also compared our study groups controlling for IQ. After controlling for IQ, no differences were found between the epilepsy groups and the controls in the domain of executive functioning. However, both the CPS and CAE groups demonstrated mild verbal memory deficits that were not associated with deficits in generalized cognitive functioning. Specifically, controlling for IQ, the CPS group performed poorer than the controls on delayed verbal memory tasks (memory for word lists and memory for stories), and the CAE performing poorer than the control group on story memory tasks (both immediate and delayed). The present study is among the few to document cognitive impairments in children with CAE. CAE has historically been considered a “benign” disorder, with little effect on neurocognitive functioning. However, increasing evidence suggests that this may not be the case. In a prospective study with 39 children with generalized absence seizures, children with absence seizures performed more poorly on tests of attention/executive functioning/construction than controls (Fastenau et al., 2009). Although we found intact nonverbal memory skills with mild verbal memory deficits in children with CAE, two other studies found the reverse pattern of mild nonverbal memory problems, with intact verbal memory skills (Pavone et al., 2001; Nolan et al., 2004). These inconsistencies in findings may be partially due to small sample sizes and subsequent lack of power to detect differences. Varying degrees of seizure control in the study populations and differences across studies in instruments used to assess verbal and visual memory may also partially account for these discrepant findings. More research is needed to better characterize the factors that account for within-group variability in cognitive functioning among children with CAE. Nonetheless, these findings, along with studies showing language impairments (Caplan et al., 2009) in children with CAE suggest that CAE is a syndrome that affects multiple cognitive functions.
The literature is somewhat inconclusive regarding the relationship between seizure variables and cognitive functioning in children with epilepsy, with some studies finding relationships and others not (Schoenfeld et al., 1999; Williams et al., 2001; Nolan et al., 2004; Hermann et al., 2006; Jocic-Jakubi & Jovic, 2006; Fastenau et al., 2009; Austin & Fastenau, 2010; see Jambaque et al., 1993). In our sample, seizure frequency was associated with cognitive test performance in the CPS group, but not in the CAE group. Younger age of onset was associated with poorer performance on cognitive tests for the CAE group, but not the CPS group. It may be that the relationship between age of seizure onset and frequency and neurocognitive performance differs depending on type of epilepsy and involved brain regions. However, the literature does not adequately address this question, and further exploration of the mechanisms underlying the association between these factors and neurocognitive functioning or lack thereof is needed. In particular, large prospective studies initiated close after the onset of epilepsy will be useful in characterizing the course of neuropsychological functioning over time and in determining the relative contributions of seizures variables on neuropsychological impairment (Hermann et al., 2006; Fastenau et al., 2009; Austin & Fastenau, 2010).
Along with the cross-sectional design of this study and the lack of power to detect differences in the visual memory domain, other limitations should be noted. The study was not population-based, which limits the generalizability of the findings. Although the control group was well-matched to the epilepsy group on demographic variables, the control group performed better than average on many of the neuropsychological tests. In addition, information on lateralization and localization of the EEG findings of the CPS group was limited because it was based on reports of EEG recordings done at the time of the diagnosis of epilepsy.
Despite its limitations, the present study demonstrates that although children with CPS and CAE may look similar in terms of their academic and behavioral problems (Caplan et al., 2004, 2008; Fastenau et al., 2008; Caplan et al., 2009), the cognitive underpinnings of their functional deficits may be distinct, with the CPS group showing more diffuse cognitive impairment. In addition, the present study demonstrated verbal memory deficits in children with CAE and CPS in the context of intact global intellectual functioning. Although the deficits were mild in magnitude for many of the children studied, it is important to note that, overall, a disproportionate number of children with CPS and CAE fell more than one standard deviation below controls, even when controlling for IQ. There is clearly a subset of children who are at risk for academic and functional difficulties due to memory problems. More research is needed to determine whether these memory difficulties may be present in the nonverbal domain, as the present study was underpowered to detect visual memory differences. Because neuropsychological testing is costly in terms of both time and financial resources, findings may be useful for designing more targeted memory screenings of children with epilepsy.