OBJECTIVES: The purpose of this paper was to investigate the contributions of sociodemographic, neurologic, and neuropsychological variables to health-related quality of life (HRQoL) in children with epilepsy and high seizure burden. Focus was placed on the relationship between memory and HRQoL, which has not been previously investigated.
METHODS: Ninety children with epilepsy receiving clinical care at a tertiary-level children’s hospital were retrospectively identified. Primary assessment measures were verbal memory (California Verbal Learning Test–Children’s Version) and HRQoL. Other neuropsychological variables included intellectual function, executive function, emotional and behavioral function, and adaptive function. Sociodemographic and neurologic variables were extracted from chart review.
RESULTS: No significant correlations were found between HRQoL and sociodemographic or neurologic variables. Moderate correlations were found between neuropsychological variables and HRQoL. Emotional function (Child Behavior Checklist) and verbal memory (California Verbal Learning Test–Children’s Version) emerged as significant predictor variables of HRQoL. Low verbal memory was associated with a twofold risk of low HRQoL, emotional and behavioral difficulty with a 10-fold risk, and the combination of emotional and behavioral difficulty and low verbal memory with a 17-fold risk.
CONCLUSIONS: Verbal memory and emotional and behavioral difficulty are associated with increased risk of low HRQoL, even when other important variables are considered in children with high seizure burden. The results reinforce the importance of neuropsychological assessment in clinical care in pediatric epilepsy and suggest important areas of focus for psychological intervention.
- quality of life
- executive function
- ACH —
- Alberta Children’s Hospital
- AED —
- antiepileptic drug
- CI —
- confidence interval
- CVLT-C —
- California Verbal Learning Test–Children’s Version
- HRQoL —
- health-related quality of life
- ICI —
- Impact of Childhood Illness Scale
- LDFR —
- long delay free recall
- OR —
- odds ratio
What’s Known on This Subject:
Research has suggested children with epilepsy are at risk for low health-related quality of life (HRQoL), which may be related to sociodemographic, neurologic, and neuropsychological variables. The role of memory has not been previously investigated.
What This Study Adds:
We investigated memory and HRQoL in pediatric epilepsy. Memory and emotional/behavioral difficulty were related to low HRQoL, even when other variables were considered. Results reinforce the importance of neuropsychological assessment and suggest areas of psychological intervention.
Health-related quality of life (HRQoL) is an aspect of the broader construct of quality of life that refers to an individual’s subjective perception of his/her health status.1 The relationship between memory and HRQoL in pediatric epilepsy has not been investigated. This is an important area of investigation because memory is frequently vulnerable to the effects of epilepsy, and cognitive effects of epilepsy are cited by patients as one of their most troubling concerns.2–6 Previous research indicates memory difficulty is related to lower HRQoL in adults with epilepsy.7,8
In children, memory difficulties may exert even greater interference with quality life than in adults, given the importance placed on learning and acquisition of new knowledge in academic, leisure, and social contexts.9 Given the relationship between memory difficulty and important functional outcomes, such as HRQoL in adults, children with epilepsy with comorbid memory difficulty may be at particularly high risk for low HRQoL when they are adults. Given the frequency of memory difficulty and the importance of memory in everyday life, the purpose of this article was to investigate the relationship between memory and HRQoL in children with epilepsy, in the context of other important sociodemographic, neurologic, and neuropsychological variables.
Previous research has suggested that there are a number of neurologic, cognitive, and psychosocial factors that contribute to HRQoL. Sociodemographic factors (eg, age, gender, socioeconomic status) may also relate to HRQoL, although mixed results have been reported.10–12 Neurologic factors, such as neurologic comorbidities, number of antiepileptic drugs (AEDs), and seizure severity, have been shown to place children with epilepsy at higher risk for reduced quality of life.10,13,14
Recently, neuropsychological variables have emerged as particularly strong predictors of quality of life, even when neurologic factors such as AEDs, age of onset, and seizure frequency are taken into account. These factors include executive function,15 attention,11 depression and anxiety,16 and adaptive function.17 Neuropsychological difficulties are common in children with epilepsy evaluated at tertiary care centers. A large proportion of children with epilepsy seen in tertiary care settings have lower levels of intellectual function than typically developing children (∼57% with IQ scores <80 standard score points18), clinically significant attention and executive function difficulty (up to 60% in some studies,11,19–21 30% in others22), higher rates of depressive and anxiety disorders (23% and 35%, respectively23), and greater social difficulty.24–27 Therefore, children with high seizure burden seen at epilepsy centers would be particularly vulnerable to the negative effects of neuropsychological function on HRQoL.
The primary objective of this article was to investigate the relationship between memory and HRQoL in children with epilepsy and high seizure burden. Because previous literature has indicated associations between HRQoL and other variables, it was important to evaluate the contribution of memory to HRQoL in the context of other important sociodemographic, neurologic, and neuropsychological variables. On the basis of previous literature, hypotheses were that neurologic and neuropsychological variables would relate to HRQoL, but sociodemographic variables would not, given inconsistent relations between HRQoL and these variables in the literature. Furthermore, it was expected that memory would predict HRQoL even when other important variables were considered.
Participants (Retrospective Cohort)
Data collection was retrospective, with variables identified from a chart review of children who completed neuropsychological assessment as part of routine clinical care at Alberta Children’s Hospital (ACH), a tertiary-level children’s hospital. Patients were included as part of a study approved by the ethics committee at ACH. Data were included if patients met the following criteria: (1) epilepsy (as diagnosed by an epileptologists at ACH), (2) no previous epilepsy surgery, (3) availability of memory (as measured by the California Verbal Learning Test–Children’s Version [CVLT-C28]) and HRQoL (as measured by the Impact of Childhood Illness [ICI]29) data (routinely collected as part of neuropsychological assessment), and (4) no previous testing with the CVLT-C and ICI. Six children in the sample were older than 16 years and 11 months of age (age range, 17–20 years), and these participants completed the CVLT—Second Edition. Neuropsychological assessment was completed as part of routine clinical care, typically for medical and educational planning purposes as requested by the child’s epileptologist at ACH. Fourteen percent of the children in our sample subsequently underwent epilepsy surgery.
Ninety patients were identified by retrospective review of the clinical neuropsychology database at ACH. An a priori power analysis (GPOWER30,31) assuming a moderate effect size, an α level of 0.05, and power of 0.8 for association analyses (eg, correlation and regression) suggested a sample size requirement of 55 to 67 participants; therefore, our sample size was adequate for sufficient power. Although data for each demographic, neurologic, and neuropsychological variable were not available for all children in the sample, no children who met the criteria were excluded.
The CVLT-C indices have good to adequate reliability, have good evidence of validity, and have been widely used in clinical populations.33 The variable reflecting recall after the long (ie, 20 minutes) delay was used as the primary memory measure in this study. Delayed verbal recall has been used previously in the measurement of memory function in epilepsy.34,35 As children are often required to retrieve information after a delay in everyday contexts (eg, school), an index reflecting memory after a delay was chosen. A single measure from the CVLT-C, rather than multiple measures, was chosen to limit the number of statistical comparisons. Sociodemographic, neurologic, and neuropsychological variables were extracted from chart review.
Descriptive Statistics: Sociodemographic, Neurologic, and Neuropsychological Variables
Patient characteristics are provided in Tables 2 and 3. In summary, both genders were equally represented. Most children were white (82%), right-handed (81%), in middle childhood, had parents who were college or university educated (65%), and had specialized learning programs at school (58%). Many children had bilateral and multifocal findings on EEG (51% and 66%, respectively), were nonlesional on MRI (56%), and had seizures beginning before 5 years of age (46%). Approximately half of children had epilepsy for at least half of their lives at the time of neuropsychological assessment (48%). Seizure frequency varied, with many children having fewer than 1 seizure the month before neuropsychological assessment (37%) and other children having seizures more than once a day (15%). Most children were on an initial trial (88% of the sample had not taken previous AEDs) of 1 to 2 AEDs (61% of the sample was taking 1 to 2 AEDs at the time of assessment). Overall, the sample was characterized by features of severe epilepsy, including early age of onset, long duration of epilepsy, high seizure burden, and polytherapy.
Neuropsychological variables of interest and descriptive statistics are presented in Table 4. The mean score on HRQoL was within 1 SD of the range of children with seizures reported previously,29 and with SDs similar to previous research, suggesting a similar level of variability in response distribution. Mean ICI scores in our sample were approximately 1 SD lower than the validation sample, with somewhat less variability in our sample (validation sample mean = 63.8, SD = 3029; our sample mean = 36.34, SD = 21.6). Group means suggested verbal memory was low average overall (27th percentile), intellectual function was in the “borderline range,” adaptive function was average (34th percentile), and executive dysfunction and behavioral difficulties were elevated overall.
Correlations: Relations Between HRQoL and Sociodemographic, Neurologic, and Neuropsychological Variables
No significant correlations were observed between HRQoL and sociodemographic or neurologic variables (ie, age, gender, parental education: r = −0.049 to 0.11, P > .05; age of onset, current or previous AEDs, seizure frequency: r = −0.12 to 0.15, P > .05). In contrast, moderate correlations were observed between HRQoL and neuropsychological variables, suggesting worse HRQoL is related to lower verbal memory, lower intellectual function, greater executive dysfunction, greater behavioral/emotional difficulty, and lower adaptive behavior (CVLT-C: r = −0.36, P ≤ .001; Wechsler Intelligence Scale for Children Fourth Edition: r = −0.43, P ≤ .001; Behavior Rating Inventory of Executive Function: r = 0.31, P ≤ .01; Child Behavior Checklist: r = 0.41, P ≤ .001; Scales of Independent Behavior—Revised: r = −0.37, P ≤ .01).
Multiple Regression Analyses: Predictors of HRQoL
Multiple regression was performed to evaluate how much variance in HRQoL was accounted for by memory in comparison with other neuropsychological variables. The regression model using neuropsychological variables was significant (F(5, 54) = 4.83, P ≤ .001), with a moderate effect size (R2 = 0.31, adjusted R2 = 0.25, P ≤ .001). As summarized in Table 5, only verbal memory (CVLT-C long delay free recall [LDFR]) and emotional and behavioral function (CBCL total score) emerged as significant unique predictors of HRQoL (ICI total score). This indicated verbal memory and emotional and behavioral function accounted for a unique amount of variance in HRQoL when common variance was controlled for.
Logistic Regression and Odds Ratio Analyses: Predictors of HRQoL
Primary outcome variables and previously identified significant predictors were dichotomized based on clinical cutoffs, as summarized in Table 6. Results indicated that 75% of patients were correctly classified in terms of presence/absence of low HRQoL when the predictors of verbal memory (CVLT-C LDFR) and emotional and behavioral function (CBCL total score) were entered (χ2 = 21.39, P < .001). The presence of low verbal memory (CVLT-C LDFR) was associated with a twofold risk of low HRQoL (odds ratio [OR] = 2.0; 95% confidence interval [CI] = 0.85–4.77), emotional and behavioral difficulty (CBCL total score) was associated with a 10-fold risk of low HRQoL (OR = 10.44; 95% CI = 2.83–38.56), and both emotional/behavioral and memory difficulty were associated with a 17-fold risk of lower HRQoL (OR = 17.14; 95% CI = 3.06–95.94).
Given the salience of memory to patients, relationship of memory to HRQoL in adults, and the importance of memory in children’s day to day lives, understanding memory’s contribution to HRQoL in pediatric epilepsy is essential. In this study, we examined relationships between HRQoL and sociodemographic, neurologic, and neuropsychological factors that previous literature suggested relate to HRQoL. Importantly, we included memory in our investigation, which had not been previously examined. In this study, sociodemographic and neurologic variables were not related to HRQoL. In contrast, neuropsychological variables (ie, verbal memory, IQ, executive function, emotional and behavioral function, adaptive behavior) were significantly related to HRQoL. When examining the relative contribution of these neuropsychological variables to HRQoL, memory and emotional/behavioral function emerged as unique significant predictors of HRQoL. The presence of clinically significant emotional and behavioral difficulty was associated with a 10-fold risk of low HRQoL, low verbal memory with a twofold risk of low HRQoL, and both low verbal memory and clinically significant emotional and behavioral difficulty with a 17-fold risk of low HRQoL.
Although a prominent characteristic of epilepsy is recurrent seizures, neurobiological, cognitive, psychological, and social features are also essential to the definition and understanding of epilepsy.36 Previous research has suggested children with epilepsy have higher rates of psychosocial difficulty, both compared with typically developing children and children with other chronic illnesses, such as asthma.13,37 The finding that the CBCL predicted HRQoL (as measured by the ICI) reinforces the notion that clinically referred children with epilepsy are at risk for a variety of psychosocial difficulties, which translate into reduced HRQoL.17 Memory was also found to be a risk factor for low HRQoL. This finding highlights the importance of memory to everyday life in children with epilepsy, even in the context of other neuropsychological variables.
The results of this study have clinical ramifications. First, findings reinforce the importance of neuropsychological assessment to identifying children and adolescents at risk for reduced HRQoL. Second, findings reinforce the clinical need for empirically supported rehabilitation and therapeutic options for children and adolescents with epilepsy who struggle with low HRQoL. The results of the current study suggest that in addition to the aforementioned features, an important aspect of intervention aimed at improving HRQoL may include memory rehabilitation. Memory rehabilitation strategies may include strategy training, domain-specific procedural training, rehearsal, priming, elaboration of a personal history, and external aids.38 These strategies may hold promise for improving the quality of life with youth with epilepsy and their families, particularly when strategies are carefully selected in the context of the child’s cognitive profile.
On the basis of research with epilepsy populations39–41 and empirically based interventions for children and adolescents,42 important aspects of psychosocial interventions for children with epilepsy are likely to include the following features: an interdisciplinary team approach, an emphasis on parental involvement, psychoeducation, cognitive/behavioral strategies, and fostering a repertoire of coping skills. A 6-week program for adolescents with epilepsy and their parents that incorporated many of these factors was associated with positive patient feedback and trends toward improvements in HRQoL.41
This study was important because the results identified memory and emotional function as important predictors of HRQoL. However, some limitations exist. First, the majority of children in our sample were taking at least 1 AED. As AEDs have been shown to negatively affect cognition43,44 the cognitive and behavioral functioning of our sample may have been affected to some extent by medication.
Second, these data were retrospectively extracted from a neuropsychology database. For this reason, some clinical variables were not available, such as the specific nature of EEG findings (eg, generalized slowing versus multifocal spike and wave activity), type of AEDs, and epilepsy syndrome. Examining the influence of these variables is an important direction of future research.
Third, although we found significant relations between memory, HRQoL, and emotional function, it should be noted that there is some similarity of item content between measures. For example, ICI and CBCL share some similarity of item content. However, the degree of similarity of item content is minimal and therefore is unlikely to wholly account for the significant findings.
Features of this study must be taken into account when generalizing to clinical practice. First, participants in the study were patients referred for neuropsychological assessment by neurologists at a tertiary care center. Although parents endorsed a better HRQoL on average than reported in previous research,11,15,29 our sample was characterized by features of severe epilepsy, including a high seizure burden, early age of onset, and polytherapy. Additionally, as in the previous literature,18 our sample had an intellectual level in the low range overall, with a significant number of children meeting criteria for intellectual disability. For these reasons, it is uncertain whether results would generalize to community-based practice or children who are not referred for neuropsychological assessment. Second, our sample was heterogeneous in terms of epilepsy characteristics. Examination of factors contributing to HRQoL in larger, more homogenous samples may yield different results. Finally, the parameters examined were those included as part of routine clinical care in our neuropsychology epilepsy service, and for this reason, it was not possible to examine other potentially important contributors to HRQoL, such as family or parental factors. These are important features of future research focused on examining contributions to HRQoL in pediatric epilepsy. Continued research and application of research findings relating to predictors of HRQoL is critical to informing clinical care and improving the HRQoL of children with epilepsy and their families.
- Accepted October 1, 2012.
- Address correspondence to Marianne Hrabok, PhD, Alberta Children’s Hospital, Neurosciences, 2888 Shaganappi Trail NW, Calgary, AB, Canada T3B 6A8. E-mail:
Dr Hrabok conceptualized and designed the study, completed the literature review, drafted the initial manuscript, carried out the analyses, revised the manuscript, and approved the manuscript for submission; Dr Sherman conceptualized and designed the study, supervised data collection, critically reviewed the manuscript, and approved the manuscript for submission; Dr Bello-Espinosa provided neurology consult for the paper and reviewed the manuscript; and Dr Hader provided conceptual and methodological contributions to the paper and reviewed the manuscript.
FINANCIAL DISCLOSURE: The authors have indicated they have no financial relationships relevant to this article to disclose.
FUNDING: No external funding.
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- Copyright © 2013 by the American Academy of Pediatrics