Executive functioning in childhood epilepsy: parent-report and cognitive assessment

Transcription

1 Executive functioning in childhood epilepsy: parent-report and cognitive assessment Joy Parrish MS; Elizabeth Geary MS, Department of Psychology, Rosalind Franklin University of Medicine and Science, North Chicago, IL; Jana Jones PhD; Raj Seth MD; Bruce Hermann PhD, Department of Neurology, University of Wisconsin, Madison, WI; Michael Seidenberg* PhD, Department of Psychology, Rosalind Franklin University of Medicine and Science, North Chicago, IL, USA. *Correspondence to last author at Department of Psychology, Rosalind Franklin University of Medicine and Science, 3333 Green Bay Road, North Chicago, Illinois 60064, USA. There is considerable interest in the assessment of executive function (EF) in pediatric clinical populations but only a few well-standardized measures exist. We examined EF in 53 children aged 8 to 18 years with recent onset epilepsy (31 males, 22 females) and 50 control children (23 males, 27 females) using the Behavior Rating Inventory of Executive Function (BRIEF) and the Delis-Kaplan Executive Function System (D-KEFS). Thirty children had localization-related epilepsy and 23 had idiopathic generalized epilepsy; average duration of 10 months (SD 4y 1mo) and onset age of 11 years 6 months (SD 3y 6mo). The study sample was characterized by good seizure control, with 40 participants taking one antiepileptic drug (AED), one taking two AEDs, and 12 not treated pharmacologically. Children with epilepsy showed greater executive difficulties on both measures than children in the control group. The BRIEF and D-KEFS were significantly correlated, and an at-risk group identified from the BRIEF was more significantly impaired on the D-KEFS than a low risk group. The BRIEF was also a better predictor of performance on the D-KEFS than the Child Behavior Checklist. These findings indicate that children with recent onset epilepsy show significant difficulties in EF, and demonstrate the utility of parent ratings (BRIEF) in the assessment of EF. See end of paper for list of abbreviations. Cognitive impairment is common in childhood epilepsy and considerable attention has been devoted to identify related seizure characteristics. 1,2 In recent years there has been considerable interest in the study of executive function (EF) and its status in various childhood clinical populations including childhood epilepsy. 3 6 From a neuropsychological perspective, EF is an umbrella term used to identify a set of selfregulatory processes encompassing behaviors such as initiation, planning, organization, purposive actions, self-monitoring, and self-regulation, viewed as critical skills that are associated with successful day-to-day functioning. 7 One of the difficulties in studying EF has been the relative dearth of specific standardized assessment tools developed for this specific purpose, particularly with children. Delis et al. 8 developed a test battery (Delis-Kaplan Executive Function System [D-KEFS]) intended specifically to assess EF. The D-KEFS is the first nationally standardized set of objective cognitive measures to evaluate EF. Several studies have demonstrated the sensitivity of the D-KEFS for evaluating EF in a variety of both adult and child clinical populations. 9 From a clinical assessment perspective, particularly with children, it is also useful to have available reliable and valid parent rating measures of childhood behavior. Paper and pencil measures provide a quick, direct, and ecologically valid method to evaluate a child s behavior. The Behavior Rating Inventory of Executive Function (BRIEF) 10 was developed as a standardized parent-rated measure intended to assess eight domains of EF. The BRIEF has been used to assess EF in several pediatric samples, including traumatic brain injury, 11,12 attention-deficit hyperactivity disorder (ADHD), 13 hydrocephalus, 14 and autism. 15,16 The BRIEF differs from other parent and teacher report measures, such as the Achenbach Child Behavior Checklist (CBCL) which is a frequently used parent-report measure of both broad (e.g. internalizing, externalizing) and narrow dimensions (e.g. aggression, anxiety) of child behavior, 17 in that the BRIEF was developed specifically to assess the domain of EF. A recent study with adults found that the D-KEFS differentiated patients with frontal lobe epilepsy from control participants, 18 and children with epilepsy have also been shown to receive parentrated scores that were elevated on the BRIEF. 19 However, to date there is no study in childhood epilepsy that has concurrently examined the D-KEFS and the BRIEF. The objectives of the present study were to: (1) compare EF in children with newly diagnosed epilepsy with children in the control group utilizing both the BRIEF and subtests from the D-KEFS; (2) examine the association between the parent-rated BRIEF and performance on the D-KEFS; and (3) determine whether the BRIEF or CBCL is a stronger predictor of performance on the D-KEFS. Method PARTICIPANTS Study participants were recruited from pediatric neurology clinics at two large Midwestern outpatient medical centers. Research participants included children with new onset epilepsy (n=53) and healthy first degree cousin controls (n=50) aged 8 to18 years. Criteria for the patients with epilepsy included: (1) diagnosis of epilepsy in the past 12 months; (2) chronological age between 8 to 18 years; (3) no other developmental disabilities (e.g. autism, developmental delay); and (4) no other neurological disorder. In the epilepsy 412 Developmental Medicine & Child Neurology 2007, 49:

2 group, the average duration of epilepsy was 10 months (SD 4.1), and the average age of onset was 11 years 6 months (SD=3y 6mo). The epilepsy group consisted of 30 patients diagnosed with a localization-related epilepsy (LRE) and 23 diagnosed with idiopathic generalized epilepsy (IGE). Overall, the epilepsy group was characterized by good seizure control. They have recent onset diagnosis of epilepsy and the vast majority had few seizures. Antiepileptic drugs (AEDs) were used by 77% of the sample: 40 participants were taking one AED, one participant was on two AEDs, and 12 patients were not being treated with an AED at time of testing. Participants in the control group were first cousins, aged 8 to 18 years. Criteria for inclusion in the control group were no history of: (1) an initial precipitating event (e.g. simple or complex febrile seizures); (2) a seizure or seizurelike episode; (3) diagnosed neurological disease; (4) loss of consciousness greater than five minutes; or (5) other family history of a first degree relative with epilepsy or febrile convulsions. First degree cousins were used as controls because: (1) first degree cousins, sharing only one-eigth of their genes with the participants with epilepsy, were expected to be less predisposed than siblings to genetic factors that underlie anomalies in brain structure, psychiatric status, and cognition; (2) there were a greater number of available first degree cousins than siblings in the target age range; and (3) the important family link was anticipated to facilitate participant recruitment and retention over time. Due to the fact that a first degree cousin matching in sex and age was not available for each participant, matching was achieved across patient families. The epilepsy group and control group did not differ on age (t(101)=0.076, p=0.94), sex distribution (χ 2 =1.14, p>0.05), and education (i.e. grade; t(101)=0.05, p=0.96; see Table I). The study was approved by the Institutional Review Boards at the University of Wisconsin and Rosalind Franklin University of Medicine and Science. PROCEDURES On the day of study participation, families and children gave informed consent or assent for participation and underwent several procedures including comprehensive neuropsychological testing and completion of behaviorally-oriented questionnaires by parents. The focus of this paper is on EF as measured by the D-KEFS 8 and BRIEF. 10 For safety reasons, the research assistants were aware of each participant s epilepsy status and group membership. All tests were administered in a standardized fashion. Delis-Kaplan Executive Function System (D-KEFS) The D-KEFS 8 is a battery of nine tests examining EF, including problem solving, thinking flexibility, fluency, planning, and deductive reasoning in both spatial and verbal modalities for ages 8 to 89 years. For the current study we selected scores reflective of performance on three subtests, the sorting test (free sorting description), verbal fluency test (category switching accuracy), and the color-word interference test (inhibition), from the D-KEFS to examine EF. These indices are commonly used in the clinical and research literature as measures of EF, and the D-KEFS technical manual specifies that Table I: Group demographics and intellectual functioning Epilepsy patients Healthy controls Age 12.7 (3.3) 12.7 (2.9) Sex 31 M, 22 F 23 M, 27 F Full-scale IQ (13.0) a (10.0) Verbal IQ (11.8) a (11.6) Performance IQ (15.7) b (10.5) Age at onset (mo) (7.2) Duration (mo) (0.64) a p=0.01; b p=0.03. Table II: BRIEF and CBCL scores for epilepsy and control groups Epilepsy Controls p a Difference of means (95% confidence n=53 n=50 interval ) b BRIEF Behavioral regulation index 52.6 (12.8) 45.8 (8.6) ( to 2.59) Inhibit 52.3 (12.2) 48.0 (9.5) ( 8.59 to 0.02) Shift 52.0 (13.6) 44.7 (8.8) ( to 2.79) Emotional control 52.4 (12.3) 45.8 (8.8) ( to 2.40) Metacognition index 57.3 (13.5) 47.2 (8.9) ( to 5.54) Initiate 56.4 (14.1) 47.7 (8.8) ( to 4.11) Working memory 58.5 (13.8) 47.6 (9.4) ( to 6.22) Plan/organize 55.3 (13.2) 47.1 (9.2) ( to 3.68) Organization of materials 54.3 (10.2) 48.4 (8.7) ( 9.65 to 2.20) Monitor 53.7 (13.0) 46.5 (11.4) ( to 2.43) Child Behavior Checklist (CBCL) Externalizing problems 52.2 (13.2) 46.6 (10.3) ( to 0.96) Internalizing problems 56.6 (12.1) 48.5 (9.4) ( to 3.85) Total problems 55.2 (13.6) 46.1 (12.1) ( to 4.00) a Independent samples t-test of means, epilepsy vs controls; b Epilepsy vs controls. BRIEF, Behaviour Rating Inventory of Executive Function. Executive Function in Childhood Epilepsy Joy Parrish et al. 413

3 each test can be used as a stand-alone measure or administered as part of the larger battery. 8 The sorting test evaluates problem-solving and flexibility of thinking with 16 different sorting concepts (formerly known as the California card sorting test). The verbal fluency test evaluates phonemic and semantic fluency, as well as the ability to shift between two categories (e.g. fruit and furniture) during an oral fluency task, the color-word interference test examines verbal inhibition (naming printed colors of incongruous color words), similar to the Stroop color word test. Psychometric findings (e.g. test retest reliability, internal consistency) for the D- KEFS measures are considered to be good. Behavior Rating Inventory of Executive Function (BRIEF) The BRIEF 10 is an 86-item parent questionnaire. It consists of two summary index scores, an overall general index score, and eight subscales intended to capture the basic components of EF. The subscales of inhibit, shift, and emotional control make up the summary Behavioral Regulation Index (BRI), while the Metacognition Index (MCI) is comprised of initiate, working memory, plan/organize, organizations, and monitor subscales. Scores are standardized based on a normal distribution with a mean of 50 and SD of 10. In this study, we examined scores on both the BRI and MCI. Reliability studies show high internal consistency, and test retest reliability. Convergent validity was established with other measures of inattention, impulsivity, and learning skills in clinical ADHD populations. 10 Table III: Pearson s correlation coefficients between BRIEF and D-KEFS Behavior regulation index Metacognition index Free sorting description a Category switching accuracy b Color-word inhibition b a p=0.05; b p=0.02. BRIEF, Behavior Rating Inventory of Executive Function; D-KEFS, Delis-Kaplan Executive Function System. Table IV: Demographic and seizure variables for epilepsy subgroups based on BRIEF MCI scores ( at-risk and low risk ) At-risk epilepsy group Low-risk epilepsy group Age (y:mo) 12:11 (3:5) 12:7 (3:2) a Sex (M/F) 12/7 19/5 b Duration (mo) 9.4 (3.8) 10.4 (4.2) c Number of AEDs (0/1/2) 3/20/1 9/20/0 b Seizure type (LRE/IGE) 11/8 14/10 b a Independent sample t-tests at-risk versus low risk metacognition (MCI) groups, p=0.64; b χ 2 analyses at-risk versus low risk MCI groups, p>0.05; c Independent sample t-tests at-risk versus lowrisk MCI groups, p=0.07. BRIEF, Behavior Rating Inventory of Executive Function; MCI, metacognition index; AED, antiepileptic drug; LRE, localization-related epilepsy; IGE, idiopathic generalized epilepsy. Achenbach Child Behavior Checklist (CBCL) The CBCL 20 is a parent-rated instrument assessing problem behaviors in children aged 4 to 18 years. It consists of 120 items related to problem behaviors in several areas that have occurred in the past 6 months, which are rated by parents on a 3-point Likert scale. Similar to the BRIEF, the ratings are used to obtain T scores (mean 50, SD 10). There are eight individual scales from which three composite scores are derived, including externalizing problems, internalizing problems, and total problems, and these will be the focus of the current study. Test retest reliability, interrater reliability, and internal consistency are excellent. Statistical analyses Independent sample t-tests were used to compare the epilepsy group with the control group on age, education, intellectual functioning, D-KEFS performance, BRIEF, and CBCL scores. Independent sample t-tests were also used to compare performance between epilepsy groups; children with localized and generalized seizures, and groups with at-risk and low risk scores on the BRIEF. χ 2 analyses were completed to compare the percentage of participants (epilepsy and controls) falling within the at-risk range on the BRIEF and to examine the distributions of categorical variables (e.g. sex, seizure type). All test results and significance levels reported are based on two-tailed analyses unless otherwise indicated. Finally, a simultaneous regression analysis examined the extent to which BRIEF and CBCL scores predicted scores on the cognitive measures of EF (D-KEFS). Results PARTICIPANT INTELLECTUAL FUNCTIONING Scores on measures of intellectual reasoning (Wechsler Abbreviated Scale of Intelligence [WASI]) were significantly lower for the newly diagnosed epilepsy group compared with the control group; F/Q (t(101)=2.73, p=0.01), V/Q (t(101)=2.49, p=0.01), and P/Q (t(101)=2.27, p=0.03). Nevertheless, the epilepsy group scored well within the average range on the IQ measures (see Table I). Within the epilepsy group, there were no significant differences between patient groups (LRE, IGE) on full-scale IQ (t(46)= 0.30, p=0.77), verbal IQ (t(46)= 0.49, p=0.63), or performance IQ (t(46)=0.15, p=0.89) scores of the WASI. BRIEF AND CBCL Comparisons on the BRIEF revealed significant group differences between epilepsy participants and controls on both summary index scores, BRI and MCI, and all subscale T scores. Parents of children in the epilepsy group endorsed more EF problems for their children than parents of children in the control group (see Table II). Similar group differences were also evident on the three summary scores of the CBCL, internalizing problems, externalizing problems, and total problems (see Table II). For both the BRIEF and CBCL, there was no significant difference between the LGE and IGE groups. D-KEFS The epilepsy group performed more poorly than the control group on two of the three D-KEFS measures of EF, free sorting description (z= 0.87, t(93)=2.68, p=0.009) and inhibition (z= 1.46, t(93)= 4.20, p<0.001), and there was 414 Developmental Medicine & Child Neurology 2007, 49:

4 a trend toward differences on the third, category switching accuracy (z= 0.42, t(92)=1.59, p=0.12). The LRE group performed more poorly than the IGE group on the inhibition measure (t(48)=2.20, p=0.03), but no significant group difference between patients with IGE or LRE was evident for the free sorting description (t(48)= 0.014, p=0.99), and category switching accuracy (t(48)=0.96, p=0.34) measures. RELATIONSHIP BETWEEN THE BRIEF AND D-KEFS For the entire epilepsy sample, we examined the association between the BRI and MCI scores from the BRIEF and performance on the D-KEFS measures of EF. Pearson s correlation analyses indicated a significant association between the MCI score and all three D-KEFS indices, with increased report of problems on the BRIEF related to poorer performance on D-KEFS measures. In contrast, the BRI score was not significantly correlated with any of the D-KEFS measures (see Table III). AT-RISK PARTICIPANTS A significantly higher percentage of the epilepsy group (48%) compared with the control group (8%) had t-scores greater than or equal to 60 ( at-risk ) on the two BRIEF summary scales: BRI (χ 2 =9.4, P<0.01) and MCI (χ 2 =33.3, P<0.001). Using the MCI, we split the epilepsy patients into two subgroups, an at-risk group (t-score>60, n=19) and a low risk group (t-score<60, n=34). The two groups did not differ significantly in age, sex distribution, distribution of LRE and IGE patients, or average number of AEDs (see Table IV). Comparisons between the groups showed significant differences on all three D-KEFS indices (see Fig. 1), with the at-risk group performing more poorly than the low risk group, free sorting description (t(48)=2.20, p=0.03), category switching accuracy (t(48)=2.02, p=0.049), and inhibition (t(48)= 2.31, p=0.02). COMPARISONS BETWEEN BRIEF AND CBCL Simultaneous regression analyses were conducted to determine the predictive value of the BRIEF MCI and the CBCL Total Problems Index (TPI) for performance on the three D- KEFS indices. The BRIEF MCI score was a stronger predictor than the CBCL TPI score on two of the D-KEFS subtest scores (free sorting description and inhibition), and there was a marginally significant effect in the same direction for category switching (see Table V). Discussion The results of this study are consistent with previous reports indicating that EF is a vulnerable domain of cognition among pediatric epilepsy patients regardless of epilepsy syndrome. 4 6 Impairment on indices of the D-KEFS measuring response inhibition and problem solving was evident, even very early in the course of the seizure disorder. In addition, a paper and pencil parent report scale (BRIEF) also differentiated the epilepsy group from the controls. The findings reported here are consistent with reports attesting to the utility of the BRIEF as a measure of EF. 10,13,15 Parent ratings revealed more EF problems in children with epilepsy than children in the control group. The BRIEF scales were significantly correlated with D-KEFS performance, and establishment of at-risk and low risk epilepsy groups, based on the BRIEF, pointed to substantial deficits in EF associated with a high level of problems reported on the BRIEF. The BRIEF MCI showed a more consistent and stronger pattern of association with the D-KEFS measures than the BRI score. This may be accounted for by the different behaviors measured by these two index scores. The MCI includes questions tapping working memory, planning, and the ability to monitor behavior, whereas the BRI includes questions related to emotional control. In addition, the MCI score was more strongly correlated with the D-KEFS measures than was the CBCL TPI scale, as would be expected if the BRIEF was specifically examining aspects of EF rather than broad-based behavioral domains of functioning. Obviously, there is a very important role for the CBCL in the broad-based assessment of childhood behavior and it has been frequently used in the pediatric epilepsy literature. 1,21 Nevertheless, the BRIEF appears to be a worthwhile complement by providing a standardized parent-report measure of EF. Impairment in EF was evident in children with epilepsy of recent onset (mean 10mo) on both the D-KEFS and the parent-rated BRIEF. These difficulties were noted despite the fact that the epilepsy group scored well within the average Table V: Simultaneous regression for prediction of D-KEFS performance Model variables a Free sorting Category Color-word description switching inhibition accuracy BRIEF, Metacognition Index R Standardized Beta (β) b Significance (p) a Child Behavior Checklist Total Problems Score statistically excluded from every model; b Standardized regression coefficient. D-KEFS, Delis-Kaplan Executive Functions System; BRIEF, Behaviour Rating Inventory of Executive Function. Z-scores Free sort Switch accuracy D-KEFS subtests Color-word inhibition MCI < 60 MCI > 60 Figure 1: Comparisons between metacognition at-risk and low risk epilepsy groups on Delis-Kaplan Executive Functions System (D-KEFS). MCI, Metacognition Index. Executive Function in Childhood Epilepsy Joy Parrish et al. 415

5 range on measures of intellectual functioning. Several recent reports have also reported the presence of behavioral and adaptive problems in childhood epilepsy very close (within 6mo) to the time of diagnosis. 22,23 Culhane-Shelburne et al. 3 found that measures of EF (e.g. Stroop and Tower of Hanoi) were the strongest cognitive predictors of adaptive functioning (e.g. communication, socialization, daily living) in a sample of children with epilepsy. In addition, adaptive functioning was impaired in children with epilepsy at the time of diagnosis and also declined with the duration of epilepsy, 24 particularly in children with uncontrolled epilepsy. 23 EF showed a very distinct pattern of developmental growth and it will be important to determine the longitudinal trajectory of EF in pediatric epilepsy. It is also important to determine if early identification of impairment in EF can help identify high risk children for developing significant difficulties in adaptive functioning in the course of their epilepsy. If so, this would provide the potential for earlier time points of management and intervention. Accepted for publication 4th January References 1. Schoenfeld J, Seidenberg M, Woodard A, Hecox K, Inglese C, Mack K, Hermann B. (1999) Neuropsychological and behavioral status of children with complex partial seizures. Dev Med Child Neurol 41: Williams J, Griebel M, Dykman R. (1998) Neuropsychological patterns in pediatric epilepsy. Seizure 7: Culhane-Shelburne K, Chapieski L, Hiscock M, Glaze D. (2002) Executive functions in children with frontal and temporal lobe epilepsy. J Int Neuropsychol Soc 8: Hernandez M, Sauerwein H, Jambaque I, De Guise E, Lussier F, Lortie A, Dulac O, Lassonde M. 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J Epilepsy 8: List of abbreviations AED BRI BRIEF CBCL D-KEFS EF IGE LRE MCI Antiepileptic drug Behavioral Regulation Index Behavior Rating Inventory of Executive Function Child Behavior Checklist Delis-Kaplan Executive Function System Executive function Idiopathic generalized epilepsy Localization-related epilepsy Metacognition Index 416 Developmental Medicine & Child Neurology 2007, 49: