Neuropsychological group rehabilitation on neurobehavioral comorbidities in children with epilepsy

YEBEH-06386; No of Pages 7 Epilepsy & Behavior xxx (xxxx) xxx

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Neuropsychological group rehabilitation on neurobehavioral comorbidities in children with epilepsy Kati Rantanen a,b,⁎, Elina Vierikko b, Kai Eriksson c,d, Pirkko Nieminen b a

Tampere University Hospital, Department of Pediatrics, Finland Tampere University, Faculty of Social Sciences, Finland Tampere Center for Child Health Research, Faculty of Medicine and Health Technology, Tampere University, Finland d Department of Pediatric Neurology, Tampere University Hospital, Finland b c

a r t i c l e

i n f o

Article history: Received 1 May 2019 Revised 14 June 2019 Accepted 17 June 2019 Available online xxxx Keywords: Attention Executive functions Epilepsy ADHD Children Neuropsychological Group intervention Neuropsychological intervention

a b s t r a c t Neurobehavioral comorbidities, particularly attention-deficits, are common in children with epilepsy (CWE). Neurobehavioral problems are manifested in school performance, peer relations, and social competence. Although the high prevalence of these comorbid behavioral problems is fully recognized, there remains to be a lack of studies on the interventions targeted for CWE. A manualized neuropsychological group intervention, Rehabilitation of EXecutive Function and ATtention (EXAT) has been developed for school-aged children (aged 6–12 years) with executive function (EF) and attention-deficits. This study aimed to explore the effects of EXAT on parent- and teacher-rated attention and behavior problems in CWE compared with children with the diagnosis of attention-deficit hyperactivity disorder (ADHD) and children with no formal diagnosis but prominent deficits in EF and attention. Forty-two children attending in neuropsychological group rehabilitation EXAT between the years 2006 and 2017 participated in this retrospective registry study. The CWE group consisted of 11 children, the ADHD group with 16 children, and EF/attention group consisted of 15 children with EF attention and/or problems without diagnosis of ADHD. The CWE group did not differ from the other two study groups (ADHD and no formal diagnosis) before the EXAT intervention. This indicates that attention problems in CWE are similar to those with diagnosed ADHD. The results were promising for applying structured multilevel intervention for CWE and neurobehavioral comorbidities. Lack of group differences between the groups participating EXAT suggests similar intervention effects between CWE, ADHD, and those with less severe EF and attention problems. In parent ratings, intervention effects were higher in hyperactivity and oppositional behavior for children with attention problems and without epilepsy. Parents in the CWE group reported no effects except for one subscale related to hyperactivity. However, teachers reported consistently positive intervention effects for both inattention and hyperactivity–impulsivity along with anxiety and emotional lability. The results suggest that neurobehavioral comorbidities in CWE could be targeted in neuropsychological group intervention. In conclusion, CWE seem to benefit from interventions and behavior modification techniques first developed for children with ADHD. © 2019 Elsevier Inc. All rights reserved.

1. Introduction 1.1. Neurobehavioral comorbidities in CWE Neurobehavioral comorbidities are common in children with epilepsy (CWE). These problems have long-term psychosocial outcomes [1] by affecting children's overall social competence [2] and academic success [3] and by compromising overall quality of life [4,5]. Clinical studies [1] have demonstrated that in particular, deficits in executive functions (EFs) and ⁎ Corresponding author at: Tampere University Hospital, Department of Pediatrics, PO Box 2000, 33521 Tampere, Finland. E-mail address: kati.rantanen@tuni.fi (K. Rantanen).

attention are common in CWE regardless of epilepsy or seizure type. Executive function is defined as a control system [6] necessary for regulation of one's thoughts and behaviors [7], goal-directed behavior, including planning, organized search, and attention control [8]. Core components of EF include inhibitory control, working memory (updating), and shifting [7], which contribute to the performance of more complex-level EF, such as problem-solving and strategy use [9]. The development of EF continues throughout childhood until early adulthood [10], reflecting the maturation of frontal lobe, prefrontal cortex in particular, and myelinization of subcortical brain structures [11]. Although underlying structural or functional pathology causing seizures often explains cognitive and behavioral comorbidities [1], adverse effects may be further increased by active epilepsy during childhood years of ongoing cognitive development.

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Please cite this article as: K. Rantanen, E. Vierikko, K. Eriksson, et al., Neuropsychological group rehabilitation on neurobehavioral comorbidities in children with epilepsy, Epilepsy & Behavior, https://doi.org/10.1016/j.yebeh.2019.06.030

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K. Rantanen et al. / Epilepsy & Behavior xxx (xxxx) xxx

Executive function dysfunctions are most often encountered in focal frontal lobe epilepsies and generalized epilepsies [1], and are manifested as global problems in behavioral ratings of EF [12], along with problems in initiation and cognitive flexibility and slowing of cognitive processing in psychological tests [13]. A major manifestation of EF dysfunction is impaired attention or more severe problems fulfilling the diagnostic criteria of attention-deficit hyperactivity disorder (ADHD), which is overrepresented in CWE. Over half of children are estimated to have attention problems with varying severity, and prevalence of the diagnosis of ADHD is about 30% [14] (ranging from 12 to 70%) [1, 15] whereas in general population, the prevalence varies between 7% and 9%. Both inattention, hyperactivity, and impulsive behavior are reported in CWE [1,15], although predominantly inattentive presentation is suggested to be more prevalent [16,17]. In CWE, behavioral problems are evident early in the course of epilepsy or at the time of the onset of seizures [1]. Behavior problems are not regarded as epilepsy syndrome specific [18]. Rather, they are more related to the activity of epilepsy [19]. Behavioral comorbidities are manifested in both internalizing and externalizing problems, such as thought problems, and social problems [20]. Also, anxiety is reported in 15–36% of CWE [21]. Comparable with healthily or typically developing children, inattentive and anxious behaviors are related to peer difficulties [22], poorer social skills, and lower assertiveness in CWE [23]. It seems that peer or social problems are mediated by neuropsychological functioning and learning disability and indirectly related to epilepsy-related variables (e.g., age at seizure onset, seizure status) [22,23]. Familyrelated factors, such as lower parent–child relationship quality, parental stress or anxiety, and problems with family functioning may further increase behavioral problems in CWE [24]. 1.2. Neuropsychological and cognitive rehabilitation in CWE While recognizing the high prevalence of comorbid attention-deficits and behavioral problems, and a higher risk for poor long-term social outcome in pediatric epilepsy, there remains a paucity of studies on the interventions targeted for CWE. Systematic reviews and meta-analyses of neuropsychological and cognitive interventions for children with central nervous system disorders or neurodevelopmental disorders [25] and executive dysfunctions [26] indicated that populations consisted of mostly those with ADHD, and some with traumatic brain injury (TBI), but none of the studies reviewed consisted of CWE. Moreover, studies with populations with epilepsy [27,28] on the effects of neuropsychological and cognitive rehabilitation did not include children. Most intervention studies conducted on CWE have focused on psychosocial interventions targeting, e.g., improving epilepsy knowledge and self-management skills or health-related quality of life [29]. Recently, a growing interest has been paid to intensive short-term computerized cognitive training in CWE targeting, e.g., working memory [30] and attention [31]. Despite positive improvements reported after intensive cognitive training (e.g., in complex attention and tracking) in CWE [31], and in children with ADHD [32], meta-analyses have consistently shown small effect sizes for attention and EF [33,34]. Further, the gains do not seem to generalize to other skills [35] or to improve academic, behavioral, or cognitive functioning [32]. Thus, the clinical relevance of cognitive training has been questioned, and a holistic or multilevel approach is recommended to overcome the limitations of focused drill-based cognitive training. In adults with epilepsy, a holistic rehabilitation approach is reported to be more useful than selective interventions targeting memory and attention problems [27]. Before epilepsy-specific intervention strategies are available, behavioral and psychosocial interventions, including parent training and teacher consultation targeted at children with ADHD or other patient groups, are suggested to be applied in CWE [36,37] provided that epilepsy-related factors are to be taken into account and the applicability of the methods is examined [37]. An advantage of holistic intervention approach is that it addresses both cognitive and behavioral

problems related to psychosocial disabilities [27]. Holistic rehabilitation programs applied for children with EF deficits include typically an individually varying combination of cognitive rehabilitation, psychoeducation, psychosocial support, and behavior management [26,38,39]. As far as we know, a holistic intervention approach has not been considered before for CWE. Thus, the current study contributes to our knowledge by investigating the potential of the holistic approach and its suitability for the application of multilevel group intervention developed for children with deficits in EF and attention for CWE. 1.3. The EXAT intervention model A manualized neuropsychological group intervention, Rehabilitation of EXecutive Function and ATtention (EXAT) [40,41] has been developed at the Psychology Clinic of the Tampere University. It is a structured group intervention model aiming to reinforce EF, particularly, behavior and emotion regulation, and social competence, and foster children's positive self-esteem. The EXAT is based on the principles of neuropsychological rehabilitation integrated with an evidence-based behavioral modification approach. As a multilevel intervention model, it comprises intervention groups for children and parents, along with meetings with teachers. The EXAT was designed for school-aged children (aged 6–12 years) with EF and attention-deficits regardless of specific diagnosis for whom learning support provided in basic education has proven insufficient. Thus, EF deficits in children eligible for entry to EXAT can be related either to neurodevelopmental or neurological disorders. The EXAT is implemented by 2–3 licensed clinical neuropsychologists or psychologists, who have completed formal training for EXAT and attended supervisory meetings during the intervention to ensure treatment fidelity and quality. Specific individual rehabilitation goals are defined with the parents and teachers, and a unique program for each group is tailored according to the manifestation of the participants' EF deficits, and their unique patterns of strengths and weaknesses. Children's intervention group consists of 4–5 children participating weekly in 90-minute sessions for ten months. Highly structured sessions and the activities are determined depending on children's age, functional level, and rehabilitation goals. Individual guidance, use of visual aids, and feedback and reinforcement system are applied. An example of session program, objectives, and activities are presented in Table 1. Parent intervention groups are organized monthly. Teacher collaboration includes typically 2–3 meetings aiming to strengthen the generalization of the learned skills to the school environment (e.g., classroom behavior and interaction with peers). The effects of EXAT in children with developmental deficits in attention and EF have first been piloted in academic theses with simple intervention study designs, small sample sizes, and varying methods (for a review, see [40]). Positive intervention effects on children's behavior regulation skills by decreasing impulsivity and restless behavior were recently reported in a study of 86 school-aged children attending EXAT [41]. This current study aimed to explore whether the EXAT model is applicable to CWE. The purpose was to investigate the effects of EXAT on attention and behavior problems in the CWE group compared with the intervention effects of children who fulfill the diagnostic criteria of ADHD and those with similar attention and/or EF deficits or problems without fulfilling all the formal diagnostic criteria of ADHD. This study was part of a larger ongoing clinical intervention study at the Psychology Clinic of the Tampere University, which was assessed by the Ethics Committee of University of Tampere. This registry study was also approved by the Tampere University Hospital, Pirkanmaa Hospital District. 2. Materials and measures 2.1. Participants Total sample consisted of 42 children with mean age of 8.8 years (standard deviation (SD): 1.3) attending EXAT. Thirty-five boys and

Please cite this article as: K. Rantanen, E. Vierikko, K. Eriksson, et al., Neuropsychological group rehabilitation on neurobehavioral comorbidities in children with epilepsy, Epilepsy & Behavior, https://doi.org/10.1016/j.yebeh.2019.06.030

K. Rantanen et al. / Epilepsy & Behavior xxx (xxxx) xxx Table 1 Example of session activities and objectives. Session activity

Objectives and activities

1. Programme

Anticipation and planning Visual and written schedule Discussion: ‘What is our plan for the session?’ Inhibition, turn-taking, and listening skills Discussion of events from children's week Turn-taking, inhibition, and role-taking The ‘Simon says’ game On-task behavior (i.e., planning, executing, monitoring, evaluating a single task) Connect the dots and color the picture Free discussion and taking social roles Participants are encouraged to interact with one another during the break. Turn-taking, planning, emotion regulation, inhibition, and working memory Junior Labyrinth Learning calming down strategies Deep breathing, counting to 10 Evaluation of the execution of the session plan ‘Did we do all what we planned?’, ‘How did I do?’

2. Discussion 3. Play 4. Paper–pencil task

5. Break/group snack

6. Game

7. Relaxation/calming down 8. Evaluation and feedback

seven girls participated in the study. For study purposes, children were divided into CWE group (n = 11), ADHD group (n = 16), and a group of children with attention and/or EF problems without diagnosis of ADHD (n = 15) (Table 2). Mean Intelligence Quotient (IQ) of the total sample was 91.4, and there were no differences between the groups, although epilepsy group had the lowest mean IQ (85.0). There were no differences between the groups on other background variables either. Fifteen children received general support for learning, 13 received intensified, and 14 with special educational support. This distribution reflects the Finnish school system, in which everyone is entitled to general learning support without formal medical diagnosis (Basic Education Act, 1998). Support provided within school system is systematically organized and gradually intensified based on pedagogical assessments and statements. If general support turns out to be insufficient, the need for intensified support or later special support is assessed and provided for those in need. All children in the CWE group had good seizure control during the study period; nine of them were or had been totally seizure-free for years, two of them had only occasional, brief, self-limiting seizures with the maximum frequency of one per month. Seven children were still on antiepileptic medication (AED) at the time of intervention, and four children did not have AEDs or any other medications. Twelve children with ADHD were on psychostimulant or other medication. 2.2. Procedure This is a retrospective registry study with children participating in neuropsychological group rehabilitation EXAT between years 2006 and 2017. All children attended a ten-month EXAT group intervention. Licensed neuropsychologists or psychologists determined participants of each intervention group on the basis of the manifestation of children's EF deficits, and their unique patterns of strengths and weaknesses. Thus, the intervention is not diagnosis-specific, and children with CWE, ADHD, and attention or EF problems without formal ADHD diagnosis were in mixed groups during intervention. For the study, inclusion criteria for the epilepsy group were earlier confirmed diagnosis of epilepsy made by experienced pediatric neurologist in the pediatric neurology department of Tampere University Hospital according to the clinical guidelines of epilepsy diagnostics and treatment. For the ADHD group, the diagnosis of ADHD according to national diagnostic criteria was required, and those with other psychiatric problems (e.g., depression) were excluded. The third study group consisted of children with no formal diagnosis but with prominent deficits in EF and attention assessed at referral by local psychologists. All children were within the age range of 6–12 years. Only those children with parent and/or

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Table 2 Demographic and medical background data.

N Gender (boy/girl) Age, mean (SD) IQ, mean (SD) Mother's age, mean (SD) Father's age, mean (SD) Mother's education 9–12 years 12–15 years 16 or more Unknown Father's education 9–12 years 12–15 years 16 or more Unknown Medication No Yes (ADHD) Yes (epilepsy) Learning support at school General support Intensified support Special support

All

Epilepsy group

ADHD group

EF/attention group

42 35/7 8.8 (1.3) 91.4 (15.1) 40.4 (6.0) 44.0 (6.1)

11 9/2 8.6 (1.2) 85.0 (6.6)

15 11/4 8.4 (0.9) 95.8 (15.3)

41.8 (8.4) 45.2 (9.2)

16 15/1 9.3 (1.5) 92.5 (18.4) 40.5 (4.2) 44.5 (4.5)

16 17 9 0

3 6 2 0

7 5 4 0

6 6 3 0

21 10 8 3

4 4 2 1

8 4 3 1

9 2 3 1

23 12 7

4 0 7

4 12 0

15 0 0

15 13 14

2 3 6

7 4 5

6 6 3

39.4 (6.1) 42.5 (4.8)

teacher-completed behavior ratings before and after the EXAT were included in the analyses. 2.3. Measures Demographic data and developmental and medical history were obtained from the Psychology Clinic records based on structured interviews with the parents and information given at referrals by local psychologists. Children's background variables included gender, age, diagnosis, medication, IQ assessed with the Wechsler Scales (e.g., [42]), and learning support at school. Family background variables included the mother's and father's age and education. For intervention purposes, all participants in the study group were assessed with parent and teacher rating scales before and after the EXAT intervention. The wellvalidated and in both clinical and research practice commonly used Conners' Rating Scales — Revised (CRS-R) [43] were used to assess a broad range of behavior problems and the effects of EXAT. The raw scores of the subscales were individually converted into T-scores. Because of a lack of nonlocal data, original normative data provided in the manual were used. The mean T-score is 50, and the SD is 10. The above-average cutoff level for problems is a T-score N 65 (SD: 1.5), indicating problems within clinical range in this study. 2.4. Statistical analysis The IBM® SPSS® Statistics software (version 23.0) was used for the statistical analyses. Prior to the analysis, all item responses were examined for missing values. Missing data were minimal, comprising max 2.5% and 3.4% of the parent and teacher ratings, respectively. Individual-mean imputation was used to replace missing items to overcome underestimation of raw scores and T-scores [43]. T-scores of the CRS-R subscales were used for the comparisons between the intervention and control groups. Because of the small number of subjects and abnormally distributed data, nonparametric tests (Mann–Whitney, Kruskal–Wallis, Wilcoxon signed-rank test) were used for the group comparisons and the intervention effects. Spearman's rank correlation coefficients were used to study the associations between background variables and intervention effects. p values less than .05 were considered statistically significant. The effect size was calculated from the

Please cite this article as: K. Rantanen, E. Vierikko, K. Eriksson, et al., Neuropsychological group rehabilitation on neurobehavioral comorbidities in children with epilepsy, Epilepsy & Behavior, https://doi.org/10.1016/j.yebeh.2019.06.030

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pffiffiffiffi formula: r = Z / N [44]. The number of observations (N) was calculated over the two time points in the Wilcoxon signed-rank test.

Epilepsy

ADHD

EF/Attention

80

T-Score

70

3. Results The main aim of the study was to explore the effects of EXAT on parent- and teacher-rated attention and behavior problems in CWE compared with children with the diagnosis of ADHD and children with no formal diagnosis but prominent deficits in EF and attention. The CWE group did not differ from the other two study groups (ADHD and no formal diagnosis) in the Conners' Parent Rating Scales — Revised (CPRS-R) or Conners' Teacher Rating Scales — Revised (CTRS-R) subscales before the EXAT intervention (Figs. 1 and 2). This indicates that attention problems in CWE are similar with the other study groups. The only exception was the subscale for Psychosomatic complaints in the CPRS-R where the CWE group scored significantly higher than the other two groups (χ2 (2) = 6.46, p = .04), with a mean rank score of 28.55 for CWE, 21.41 for ADHD, and 16.43 for EF/attention group. The subscale mean T-scores ranged between normal and clinical level problems in all groups before the EXAT intervention. Although there were no significant statistical differences between the groups in the CPRS-R or CTRS-R subscales, the relative proportion of parent reported within clinical range problems was high in CWE group. For example, within clinical range problems in Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) Total subscale were reported in parent ratings in 72.7% in CWE group, 56.3% in ADHD group, and 20.0% in EF/attention group, and in teacher ratings 18.2%, 25.0%, and 40.0%, respectively. As seen in Figs. 3 and 4, nearly all difference scores in the CPRS-R and the CTRS-R subscales indicated positive change after the EXAT intervention. The study groups did not differ in the difference scores suggesting that changes during the intervention were similar in all groups. Subgroup analyses on the intervention effects revealed that in CWE group, teachers reported larger changes in attention and behavior after the intervention compared with parents (Appendix A). In parent ratings, only the overall score for attention problems (the Conners' Global Index (CGI) Total scale) decreased statistically significantly. In teacher ratings, statistically significant changes with moderate to large effect sizes after intervention were found in the overall scores and several CTRS-R subscales for inattention, hyperactivity–impulsivity, and emotional lability. Positive change with moderate effect size was also found for anxiety/ shyness.

60 50 40

Fig. 2. Preintervention T-scores of the Conners' Teacher Rating Scales — Revised in the study groups.

In ADHD and EF/attention groups, the parent-rated problems decreased statistically significantly in the CPRS-R subscales for hyperactive–impulsive and oppositional behavior and total scores. In addition, in ADHD group, parents reported significant changes in inattention, social problems, and anxiety and shyness, and in EF/attention group, in restlessness. Effect sizes were moderate except for Oppositional subscale in the EF/attention group, which had a large effect size. In teacher ratings, no statistically significant changes were found in ADHD group, and only oppositional behavior and emotional lability decreased in EF/ attention group. The proportion of clinically significant problems decreased in all study groups during the EXAT intervention both in parent and teacher ratings. For example, the number of children within clinical range in the parent-rated DSM-IV Total score decreased from 72,7% to 54,4% in CWE group, from 56,3% to 25,0% in ADHD group, and from 20,0% to 13,3% in EF/attention group. Similar decrease, although smaller, was

Epilepsy

ADHD

EF/Attention

DSM Total DSM-IV Hyperactivity-Impulsivity DSM-IV Inattention CGI:Total

Epilepsy

ADHD

EF/Attention

80

CGI:Emotional Lability CGI:Restless ADHD Index

T-Score

70 60

Hyperactivity Cognitive problems / Inattention Oppositional

50 40

Psychosomatic Problems Social Problems Perfectionism Anxious/Shy -6

-4

-2

negative change

Fig. 1. Preintervention T-scores of the Conners' Parent Rating Scales — Revised in the study groups.

0

2

4

6

8

10

positive change

Fig. 3. Difference scores in Conners' Parent Rating Scale — Revised. A positive difference score indicates a positive change after the EXAT intervention.

Please cite this article as: K. Rantanen, E. Vierikko, K. Eriksson, et al., Neuropsychological group rehabilitation on neurobehavioral comorbidities in children with epilepsy, Epilepsy & Behavior, https://doi.org/10.1016/j.yebeh.2019.06.030

K. Rantanen et al. / Epilepsy & Behavior xxx (xxxx) xxx

Epilepsy

ADHD

EF/Attention

DSM Total DSM-IV Hyperactivity-Impulsivity DSM-IV Inattention CGI:Total CGI:Emotional Lability CGI:Restless ADHD Index Hyperactivity Cognitive problems Oppositional

Social Problems Perfectionism Anxious/Shy -6

-4

-2

negative change

0

2

4

6

8

10

positive change

Fig. 4. Difference scores in Conners' Teacher Rating Scale — Revised. A positive difference score indicates a positive change after the EXAT intervention.

found in teacher-rated DSM-IV Total score in CWE group (35.8 vs. 33.8%) and in EF/attention group (41.2 vs. 35.3%). However, one-fourth of children in the ADHD group had the clinically significant problems in the DSM-IV Total score both before and after the EXAT intervention. Since no differences on the difference scores were found between the study groups, associations between intervention effects and background variables were studied by combining study groups in a larger sample of children participating EXAT. Correlations calculated for the combined groups yielded some significant but weak associations. In teacher ratings, association between higher intervention effect and child's younger age was found. Statistically significant negative correlations were found between age and difference scores for Anxious/ Shy (r = − 0.428, p = .005), Perfectionism (r = − 0.314, p = .043), ADHD Index (r = −0.338, p = .029), Emotional Lability (r = −0.305, p = .049), Conners' GI Total (r = − 0.314, p = .043), and DSM-IV Total (r = − 0.325, p = .036). Further, lower IQ was associated with higher difference score in the parent ratings for Emotional Lability (r = −0.384, p = .017). In addition, significant negative correlation was found between mother's younger age and the difference score for the parent-rated Hyperactivity (r = −0.345, p = .017). Learning support provided at school was associated with teacher-rated child's social problems: children at special support scored significantly higher at the subscale of Social Problems compared with children at general or intensified support (χ2 (2) = 9.84, p = .007), with a mean rank score of 21.30 for children at general support, 13.96 for children at intensified support, and 28.71 for children at special support.

4. Discussion The EXAT was developed for school-aged children with deficits in EF and attention related to neurodevelopmental impairments or neurological condition [41]. The present study aimed to investigate the intervention effects on attention and behavior problems in the CWE group compared with children with ADHD and those with similar attention and/or EF problems without fulfilling all the formal diagnostic criteria of ADHD.

5

Although based on a limited number of participants, the results are promising for applying structured multilevel intervention for CWE and neurobehavioral comorbidities. Lack of group differences between the groups participating EXAT suggests similar intervention effects between CWE, ADHD, and those with less EF and attention problems. In parent ratings, intervention effects were higher in hyperactivity and oppositional behavior for children with attention problems and without epilepsy. This result is consistent with earlier intervention study of EXAT [41] demonstrating positive effects on behavior control, impulse control, and compliancy. Similarly, the results on the positive effects concur with previous intervention studies on ADHD symptoms and behavior problems [38,45,46]. Interestingly, parents in the CWE group report positive intervention effects only for one subscale related to hyperactivity. Yet, teachers reported consistently positive intervention effects for both inattention and hyperactivity–impulsivity along with anxiety and emotional lability. For other children with EF and attention problems without epilepsy, positive intervention effects for decreasing oppositional behavior and emotional lability were reported only by teachers of EF/attention group. This result is consistent with the earlier observations, which showed that teachers report fewer changes compared with parents of children with developmental EF deficits [41]. The discrepancies between parent and teacher ratings may partly reflect environmental demands and contexts. It is also a common clinical finding and also wellrecognized in studies regarding agreement on ADHD symptoms in children [47–49]. Positive assessments of teachers in the CWE group were somewhat unanticipated and contrary to earlier findings of the effects of EXAT [41]. Higher intervention effects of the epilepsy group may reflect increasing teachers' knowledge of e.g., how to cope with EF and attention-deficits and other neurobehavioral comorbidities in classroom settings. This finding, while preliminary, suggests that there may be a need of teacher guidance targeting comorbidities related to pediatric epilepsy, in particular EF and behavioral management. The results presented here are also consistent with earlier observations [41] demonstrating that especially younger children and those with a lower IQ benefited from the EXAT intervention. Because of the small sample size, the associations between epilepsy-related variables and intervention effects could not be studied. It could be argued that the positive results were likely related to well-controlled seizures. Hence, the results must be interpreted with caution. Pediatric neuropsychologists are focusing mostly on assessment of neurocognitive and social functions, and up to now, far too little attention has been paid to the role of cognitive (yet along holistic) rehabilitation in CWE [28]. Although the findings reported here are preliminary in nature, they concur with the suggestions that programs and behavior modification techniques tailored for children with ADHD may be utilized also in CWE [36,37]. Problems in attention and EF in CWE could be targeted in neuropsychological group intervention. These encouraging findings support the conclusion by Triplett and coworkers [50] that CWE may indeed benefit from the use of incentives in cognitive remediation. Clinical retrospective studies based on registry data have inevitably some limitations. First, the small sample size may be regarded as a major limitation of the study. Second, CWE group represents children with good seizure control or in remission, and hence, the results may not be generalized to all epilepsy types. However, the study sample of CWE with good seizure control reflects the epilepsy care practices in epilepsy units, where neuropsychological intervention is not the first choice of treatment nor considered for those with poor seizure control. Further, intervention effects were assessed with behavioral ratings, which are justified as measures for behavioral manifestation of EF and attention-deficits. We recognize that the Conners' Rating Scale is a symptom scale and, as such, may not capture all essential features of EF problems in CWE group (e.g., slowed processing speed and cognitive flexibility). Intervention effects could also be overestimated because of the fact that those actively participating in the intervention, namely parents and teachers, did the assessments. Blinded assessment would have

Please cite this article as: K. Rantanen, E. Vierikko, K. Eriksson, et al., Neuropsychological group rehabilitation on neurobehavioral comorbidities in children with epilepsy, Epilepsy & Behavior, https://doi.org/10.1016/j.yebeh.2019.06.030

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increased objectivity of determining the intervention effects [51]. Evidently, there are many moderating and confounding factors affecting effectiveness of intervention. Future studies with solid study designs are needed to address these issues. 5. Clinical contribution Comorbidities related to CWE, rather than epilepsy, often determine the need for learning and psychosocial support. Despite the limited number of participants in our study, the results make an interesting

contribution by indicating positive intervention effects in CWE. Thus, CWE may well benefit from interventions and behavior modification techniques first developed for children with ADHD. At best, holistic intervention approach with cognitive training and psychoeducation for the management of the neurobehavioral comorbidities for parents and teachers may result in supportive social and learning environment. Declaration of Competing Interest None.

Appendix A. Parent and teacher ratings of EF-related behavior, pre- and post-EXAT Epilepsy group

Parent ratings CPRS-R: ADHD Index

ADHD group

Pre-EXAT

Post-EXAT

Md Range

Md Range

Za

p

61.0 47.0–80.0 58.0 45.0–75.0 57.0 47.0–68.0 58.0 47.0–75.0 64.0 47.0–84.0 59.0 44.0–76.0 67.0 46.0–79.0 51.0 41.0–63.0 49.0 40.0–64.0 65.0 49.0–90.0 48.0 42.0–90.0

−0.845

.398 0.18

−1.693

.091 0.36

−1.524

.128 0.32

−2.139

.032 0.46

52.0 45.0–69.0 55.0 45.0–67.0 48.0 43.0–74.0 51.0 44.0–69.0 53.0 43.0–73.0 50.0 44.0–75.0 52.0 46.0–76.0 58.0 44.0–67.0 49.0 42.0–69.0 55.0 45.0–66.0 56.0 45.0–73.0 50.0 42.0–78.0 59.0 53.0–87.0

68.0 54.0–81.0 CGI: Restless 63.0 50.0–84.0 CGI: Emotional Lability 68.0 41.0–79.0 CGI: Total 65.0 57.0–82.0 DSM-IV Inattention 69.0 55.0–81.0 DSM-IV 63.0 Hyperactivity–Impulsivity 50.0–81.0 DSM-IV Total 68.0 58.0–83.0 Anxious/Shy 51.0 41.0–65.0 Perfectionism 60.0 41.0–80.0 Social Problems 59.0 45.0–84.0 Psychosomatic Problems 56.0 43.0–82.0 Teacher ratings CTRS-R Oppositional 62.0 45.0–87.0 Cognitive 57.0 Problems/Inattention 48.0–70.0 Hyperactivity 55.0 43.0–82.0 ADHD Index 59.0 43.0–79.0 CGI: Restless 59.0 45.0–83.0 CGI: Emotional Lability 61.0 44.0–90.0 CGI: Total 58.0 46.0–90.0 DSM-IV Inattention 62.0 47.0–67.0 DSM-IV 56.0 Hyperactivity–Impulsivity 42.0–79.0 DSM-IV Total 59.0 45.0–72.0 Anxious/Shy 58.0 48.0–86.0 Perfectionism 52.0 42.0–81.0 Social Problems 64.0 50.0–87.0

Effect size

−0.1.122 .262 0.24 −0.980

.327 0.21

−1.423

.155 0.30

−0.818

.413 0.17

−1.911

.056 0.41

−0.562

.574 0.12

−1.020

.308 0.22

−1.601

.109 0.34

−1.794

.073 0.38

−1.899

.058 0.40

−2.710

.007 0.58

−2.675

.007 0.57

−2.392

.017 0.51

−2.668

.008 0.57

−2.670

.008 0.57

−2.201

.028 0.47

−2.504

.012 0.53

−2.113

.035 0.45

−1.895

.058 0.40

−0.970

.332 0.21

Attention/EF group

Pre-EXAT

Post-EXAT

Md Range

Md Range

Za

68.5 47.0–81.0 63.5 48.0–82.0 52.0 41.0–72.0 57.5 47.0–80.0 63.0 46.0–78.0 72.0 46.0–79.0 68.0 46.0–79.0 47.5 41.0–76.0 53.5 40.0–79.0 55.0 45.0–90.0 48.0 42.0–68.0

57.5 45.0–87.0 59.0 45.0–79.0 49.5 41.0–78.0 55.5 45.0–80.0 58.0 43.0–90.0 61.0 44.0–85.0 61.0 44.0–80.0 45.0 41.0–63.0 50.5 40.0–60.0 49.0 45.0–89.0 48.0 42.0–68.0

−1.854 .064 0.33

62.5 45.0–82.0 55.5 41.0–75.0 61.0 43.0–78.0 61.5 44.0–74.0 62.5 43.0–74.0 58.0 44.0–78.0 63.0 43.0–75.0 57.5 45.0–79.0 57.0 42.0–76.0 61.0 43.0–71.0 55.0 42.0–74.0 52.0 43.0–78.0 50.0 45.0–90.0

58.0 45.0–85.0 54.5 41.0–68.0 57.5 43.0–86.0 57.0 47.0–74.0 59.0 45.0–77.0 54.0 45.0–90.0 59.0 45.0–87.0 55.0 47.0–70.0 57.5 42.0–86.0 56.5 49.0–76.0 60.0 46.0–80.0 49.0 46.0–59.0 49.5 45.0–90.0

−1.037 .300 0.18

p

Effect size

−1.916 .055 0.34 −1.885 .059 0.33 −1.648 .099 0.29 −2.070 .038 0.37 −2.505 .012 0.44 −2.252 .024 0.40 −2.456 .014 0.43 −1.125 .260 0.20 −2.391 .017 0.42 −0.921 .357 0.16

−0.207 .836 0.04 −0.044 .965 0.01 −0.752 .452 0.13 −0.363 .717 0.06 −0.526 .599 0.09 −0.142 .887 0.03 −0.256 .798 0.05 −0.408 .683 0.07 −0.052 .959 0.01 −0.817 .414 0.14 −0.741 .459 0.13 −0.197 .844 0.03

Pre-EXAT

Post-EXAT

Md Range

Md Range

Za

60.0 47.0–73.0 62.0 45.0–77.0 51.0 41.0–84.0 58.5 43.0–82.0 57.0 43.0–75.0 60.0 45.0–90.0 62.0 43.0–80.0 51.0 42.0–67.0 47.0 40.0–69.0 55.0 45.0–83.0 43.0 42.0–73.0

55.0 42.0–75.0 54.0 43.0–73.0 43.0 41.0–70.0 52.0 42.0–70.0 55.0 43.0–76.0 56.0 44.0–74.0 55.0 43.0–72.0 48.0 41.0–58.0 44.0 40.0–63.0 53.0 45.0–77.0 43.0 42.0–90.0

−1.766 .077 0.32

67.0 45.0–90.0 59.0 41.0–68.0 66.0 47.0–90.0 67.0 55.0–76.0 68.0 55.0–80.0 63.0 45.0–90.0 69.0 52.0–87.0 64.0 47.0–70.0 65.0 44.0–90.0 64.0 55.0–80.0 58.0 45.0–82.0 53.0 44.0–84.0 59.0 45.0–90.0

55.0 45.0–90.0 55.0 47.0–70.0 62.0 47.0–90.0 57.0 47.0–89.0 62.0 45.0–87.0 53.0 45.0–90.0 60.0 45.0–90.0 59.0 51.0–76.0 63.0 45.0–90.0 60.0 49.0–88.0 55.0 45.0–86.0 52.0 43.0–82.0 51.0 45.0–90.0

−2.223 .026 0.41

p

Effect size

−2.169 .030 0.40 −1.335 .182 0.24 −1.854 .064 0.34 −1.609 .108 0.29 −2.140 .032 0.39 −2.170 .030 0.40 −1.169 .242 0.21 −0.982 .326 0.18 −1.649 .099 0.30 −0.297 .766 0.05

−0.035 .972 0.01 −1.363 .173 0.25 −1.279 .201 0.23 −1.535 .125 0.28 −1.960 .050 0.36 −1.734 .083 0.32 −0.848 .396 0.15 −1.434 .152 0.26 −0.849 .396 0.16 −0.981 .327 0.18 −0.489 .624 0.09 −0.236 .814 0.04

CPRS-R = Conners' Parent Rating Scales — Revised, Conners, 1997, CTRS-R = Conners' Teacher Rating Scales — Revised, Conners, 1997, CGI = Conners' Global Index. a Wilcoxon signed-rank test.

Please cite this article as: K. Rantanen, E. Vierikko, K. Eriksson, et al., Neuropsychological group rehabilitation on neurobehavioral comorbidities in children with epilepsy, Epilepsy & Behavior, https://doi.org/10.1016/j.yebeh.2019.06.030

K. Rantanen et al. / Epilepsy & Behavior xxx (xxxx) xxx

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Please cite this article as: K. Rantanen, E. Vierikko, K. Eriksson, et al., Neuropsychological group rehabilitation on neurobehavioral comorbidities in children with epilepsy, Epilepsy & Behavior, https://doi.org/10.1016/j.yebeh.2019.06.030