Factors associated with behavioral problems in children with idiopathic epilepsy

Epilepsy Research (2012) 100, 104—112

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Factors associated with behavioral problems in children with idiopathic epilepsy Vaios Dafoulis a, Efrosini Kalyva b,∗ a b

School of Medicine, Aristotle University of Thessaloniki, Greece City College, International Faculty of the University of Sheffield, 24 Proxenou Koromila Street, 546 22 Thessaloniki, Greece

Received 7 August 2011; received in revised form 25 January 2012; accepted 27 January 2012 Available online 19 February 2012

KEYWORDS Idiopathic epilepsy; Psychopathology; Pediatric; Parent proxy-reports; Behavioral problems; Predictors

Summary The present study examined whether the perceived behavioral problems of children with idiopathic epilepsy differed from those of healthy controls according to parent proxy-reports and which factors are associated with these problems. The parents of 106 children with idiopathic epilepsy and 305 healthy controls aged 6—9 years old completed the Vanderbilt ADHD Diagnostic Parent Rating Scale and the Strengths and Difficulties Questionnaire. The 106 children with idiopathic epilepsy were also interviewed using the K-SADS-PL. The parents of children with idiopathic epilepsy reported more hyperactivity, emotional and conduct problems than the parents of healthy controls, as well as less prosocial behavior. Parents detected no differences in peer problems, inattention, oppositional/defiant disorder, and anxiety/depression. Age of onset of epilepsy (later), the number of administered antiepileptic drugs (polytherapy), and gender (male) predicted behavioral problems in children with idiopathic epilepsy. The frequency of seizures was associated with behavioral problems, while age was not. Finally, children with benign focal epilepsy were rated by their parents as having less behavioral problems than children with generalized epilepsy. © 2012 Elsevier B.V. All rights reserved.

Epilepsy constitutes the most common serious neurological disorder in children with an estimated prevalence of .03—2.2% worldwide (Pellock et al., 2008). Epilepsy can have a pervasive and enduring behavioral effect on children (Austin et al., 2001; Dunn et al., 1997). The high rates of psychopathology in adults with epilepsy may be traced back to behavioral difficulties that appear in early childhood and

∗ Corresponding author. Tel.: +30 2310269095; fax: +30 2310269095. E-mail addresses: [email protected] (V. Dafoulis), [email protected] (E. Kalyva).

persist well into adolescence and adulthood (Perini et al., 1996). The investigation of behavioral aspects in childhood epilepsy is important, since behavior is a key aspect in determining the child’s progress to independence (Besag, 2004). Children with epilepsy exhibit more symptoms of psychopathology, such as suicidal ideation, depressive symptoms, anxiety, and conduct disorder symptoms, than nonepileptic peers (Barry et al., 2008; Chen et al., 2010; Dunn and Austin, 2004; Ettinger et al., 1998; Mensah et al., 2007; Rantanen et al., 2009; Titlic et al., 2009) or siblings (Austin et al., 2001, 2002). Social withdrawal, conduct problems, and aggression are also common among this population

0920-1211/$ — see front matter © 2012 Elsevier B.V. All rights reserved. doi:10.1016/j.eplepsyres.2012.01.014

Behavioral problems in idiopathic epilepsy (Fang and Chen, 2007; McDermott et al., 1995; Titus et al., 2008). Investigators have documented the association between psychopathology and pediatric epilepsy for more than 30 years (Ott et al., 2003) and many studies have hypothesized that the development of psychopathology in children with epilepsy is due to cognitive impairment (e.g., Carreno et al., 2008), which is usually associated with poor seizure control (Funakoshi et al., 1988), that is in turn linked to psychopathology in children (Hermann et al., 1988; Stanicolo and Galetti, 1994). The majority of studies in childhood epilepsy report that 21—60% of patients have mood disorders (Davies et al., 2003; Johnson et al., 2004; Kanner, 2009; Pellock, 2004; Plioplys, 2004; Williams et al., 2003). This discrepancy in percentages is due to a number of reasons, such as different assessment procedures and diagnostic criteria, informants, age groups, recruitment sources, and sample sizes (Caplan et al., 2005). However, it cannot be disputed that children with epilepsy have an increased risk of up to 6 times to develop psychiatric disturbances in comparison to healthy controls (Ott et al., 2003). There is actually evidence that the prevalence of behavioral disorders is higher in children with epilepsy than other chronic illnesses, such as diabetes or cardiac disease (Hoare and Mann, 1994; McDermott et al., 1995). The identification of behavioral problems in children 6 months before the first officially registered seizure indicates that psychopathology may be associated with epilepsy (Ott et al., 2003). A lot of studies have demonstrated that children with epilepsy face behavioral problems (Ekinci et al., 2009; Ettinger et al., 1998) on both dimensional and categorical measures (Dunn et al., 2009) using a variety of instruments (Ott et al., 2001). Most studies have looked at the behavioral problems of children with epilepsy using rating scales (e.g., Dunn et al., 2003; Liu et al., 2011; Loutfi et al., 2011; Sherman et al., 2007, 2010), while others used also structured and standardized interviews (e.g., Benn et al., 2010; Gonzalez-Heydrich et al., 2007). There is also evidence that young children with epilepsy have significantly increased rates of attention—deficit—hyperactivity disorder (ADHD) (Dunn et al., 2003; Hermann et al., 2007; Jones et al., 2007), which may vary from 8 to 77% according to the sample studied and the criteria used (Dunn et al., 2003). The inattentive type seems to be more prevalent in children with epilepsy and it may precede the onset of seizures in most cases — indicating thus possible common underlying neurodevelopmental abnormalities (Reilly, 2011; Waltz, 2010). The notion that the psychiatric symptoms exhibited by children with epilepsy are a manifestation of seizures or a potential side-effect of antiepileptic drugs might explain why they do not receive adequate psychiatric assessment and treatment (Dunn et al., 1999; Dunn and Austin, 1999). However, there is no doubt that when psychiatric symptoms are unrecognized and left untreated, they can cause worsened quality of life and decreased well-being (Beyenburg et al., 2005; Miller et al., 2003; Naess et al., 2007; Plioplys et al., 2007). Therefore, it is important to identify the possible manifestation of behavioral problems using a variety of measures and to explore which factors are more likely to exacerbate these behavioral problems.

105 The first aim of this study is to compare behavioral problems of children with idiopathic epilepsy and children without chronic disease, since the goal for the former is to achieve normality (Yu et al., 2008). It is hypothesized that children with idiopathic epilepsy will have significantly higher rates of behavioral problems than healthy children according to parental reports. The behavioral problems exhibited by children with idiopathic epilepsy will be assessed also through clinical interviews with them in order to validate the data from the parent-proxy reports. The second aim of the study is to identify the factors that predict behavioral problems in children with idiopathic epilepsy. It is hypothesized that age, gender, age of onset of epilepsy, frequency of seizure, type of epilepsy and number of antiepileptic drugs will predict the severity of behavioral problems in children with idiopathic epilepsy.

Methods Participants The study included 106 idiopathic epilepsy patients aged 6—9 years old (61 boys and 45 girls) and their parents, who were recruited from 3 pediatric neurology clinics (1st and 4th from AXEPA hospital and Papageorgiou hospital), the Psycho-Pedagogical Center of the Psychiatric Hospital of Thessaloniki) and 2 private practices in the wider area of Northern Greece. Out of the 106 children with idiopathic epilepsy, 12 were recruited from the 2 private practices and the remaining 94 from the public clinics. All the patients were diagnosed with idiopathic epilepsy from pediatric neurologists. To be included in the study, the patients had to have clinically certified epileptic seizures that lasted for at least 6 months; EEG evidence for epileptic activity; no history of craniocerebral contusion, cerebral surgery, old or recent infection or trauma of the CNS, neurodegenerative disorders, cerebral palsy, spastic hemoplegia, ischemic encephalopathy, meningoencephalitis, pervasive developmental disorder or mental retardation. Mental retardation was defined as IQ less than 70 according to Wechsler Intelligence Scale for Children (WISC-3, 1991) (WISC has been standardized into Greek using a very large sample of schoolchildren aged between 6 and 17 by Georgas et al. (1998)). The clinicians identified the children with epilepsy who had normal IQ, since the researchers did not have access to the actual WISC scores due to legal restrictions. Therefore, the diagnosis of idiopathic epilepsy was based on clinical history and EEG findings, as defined by the International Classification of Epilepsy (WHO, 1993). Forty-five patients (42.46%) had benign focal epilepsy and the remaining 61 (57.5%) had generalized epilepsy (with 14 having childhood absence epilepsy). No patients with frontal lobe epilepsy were identified for inclusion in the study. The characteristics of the children with idiopathic epilepsy are presented below. In terms of the age of the onset of epilepsy, 49.1% had seizures for 1 year, 26.4% for 2 years, 17% for 3 years, 4.7% for 4 years and 2.8% for 5 years. For 30% of the patients the seizures started at 6 years old, for 32% at 7 years old and for 38% at 8 years old. Regarding the frequency of their seizures, 6.6% had seizures once a day to once a week, 34.9% once a week to once a month,

106 55.7% once a month to once a year and 2.8% less than once a year. Almost 3/4 of the patients (78.3%) were administered only one antiepileptic drug, while the remaining 21.7% was administered 2 or more antiepileptic drugs. There was a history of febrile seizures in 8% of the patients, a family history of epileptic seizures in 13% of the patients, and a family history of mood disorders in 8% of the patients. In terms of other potentially stressful psychological events, 10% of the patients went through parental divorce, 7% had a new sibling in the family and 5% moved houses or changed schools. The parents of 305 nonepileptic control participants (1457 boys and 158 girls) were recruited from twenty public schools from the areas that the children with epilepsy came from and they were identified by the principals and the teachers according to their academic records. Since the researchers were not allowed access to the actual WISC scores of children with epilepsy, the two groups were matched in terms of their school reports. The control sample was part of another study conducted by the researchers. Both principals and teachers were not aware of the study’s aims and hypotheses until after it was completed. Children who have manifested signs of neurologic, psychiatric, language, or hearing disorders were excluded from the study. The two groups were matched for age (2 = .52, df = 2, p = .771) and gender (2 = 2.75, df = 1, p = .114). It should be stressed that none of the children who participated in this study were previously diagnosed with behavioral problems.

Measures The Vanderbilt ADHD Diagnostic Parent Rating Scale — VADPRS Parents of children with epilepsy and healthy controls completed the VADPRS (Vanderbilt ADHD Diagnostic Parent Rating Scale — Wolraich et al., 2003), which has been translated and standardized into Greek by Papageorgiou and Dafoulis (2005). The scale measures inattention, hyperactivity/impulsivity, oppositional-defiant disorders, conduct disorders, and anxiety/depression according to DSM-IV (APA, 2000). The items are rated on a 4-point Likert scale, where 0 = never, 1 = seldom, 2 = often, 3 = very often. Behaviors are counted if they are scored 2 (often) or 3 (very often). Cronbach ˛ for the whole scale is .95 and it is considered to be very high. Moreover, test—retest reliability that was calculated with the parents of 62 children with epilepsy who completed again the questionnaire after 5—6 months was also very satisfactory (.94); the mean score the first time was 15.18 (SD = 13.75), while the mean score the second time was 16.16 (SD = 13.94). Related-samples t-test analysis showed that the difference between those two scores was not statistically significant (t(61) = −1.63, p = .107), a fact which testifies to the reliability of the scale. Strengths and Difficulties Questionnaire — SDQ Parents of children with and without epilepsy completed also the Strengths and Difficulties Questionnaire (SDQ — Goodman, 1997), which was translated and standardized into Greek by Bibou-Nakou et al. (2002). SDQ is a brief screening measure that includes parent version for children aged 3—16 years and contains 25 items. This instrument

V. Dafoulis, E. Kalyva produces scores for hyperactivity, emotional problems, conduct problems, peer problems, and prosocial behavior. Each subscale consists of five items that are rated on a 3-point Likert scale, where 0 = not at all, 1 = a little/sometimes, and 2 = very much/all of the time. Cronbach ˛ for the whole scale is .94 and it is considered to be very high. Moreover, test—retest reliability that was calculated with the parents of 62 children with epilepsy who completed again the questionnaire after 5—6 months was also very satisfactory (.92); the mean score the first time was 8.77 (SD = 5.96), while the mean score the second time was 8.34 (SD = 6.20). Related-samples t-test analysis showed that the difference between those two scores was not statistically significant (t(61) = −1.41, p = .165), a fact which testifies to the reliability of the scale. Since there are no instruments that have been developed specifically to assess behavioral difficulties in children with epilepsy (Krishnamoorthy, 2006), widely used behavioral rating scales were employed. The high prevalence of ADHD in association with other psychiatric comorbidities in children with epilepsy justifies the use of behavioral rating scales as screening tests (Loutfi et al., 2011). However, in order to collect more reliable data for the behavioral problems of children with idiopathic epilepsy, additional clinical interviews were conducted. K-SADS-PL K-SADS-PL (Kiddie-SADS-Lifetime Version) is a diagnostic interview for children and adolescents aged 6—18 years old, which was designed to record present and past episodes of psychopathology. The K-SADS-PL, which was adapted from the K-SADS-P (Present Episode Version), was developed by Kaufman et al. (1996). It has been standardized into Greek by Korpa et al. (2002). K-SADS-PL was administered simultaneously by one psychiatrist and one psychologist who were trained to use it and the interrater agreement (i.e. number of agreements divided by number of agreements and disagreements) was 97.8%. In the case of disagreement a third experience psychiatrist with no knowledge of the research aims was asked to review the diagnosis. He also doublechecked a random selection of diagnoses in order to ensure the diagnostic reliability. The two raters conducted: an unstructured introductory interview; a diagnostic screening interview; the supplement completion checklist; the appropriate diagnostic supplements; and the Children’s Global Assessment Scale (C-GAS) ratings. Most items of the K-SADSPL are scored using a 0—3 point rating scale. Scores of 0 indicate no information is available; scores of 1 suggest the symptom is not present; scores of 2 indicate subthreshold levels of symptomatology, and scores of 3 represent threshold criteria. The remaining items are rated on a 0—2 point rating scale on which 0 implies no information; 1 implies the symptom is not present; and 2 implies the symptom is present. The interview was administered only to children with epilepsy and their parents were not present at this stage.

Procedure The approval of the appropriate ethics committees to conduct the study and to have access to the sample was

Behavioral problems in idiopathic epilepsy Table 1

Means and standard deviations of VADPRS according to parents of children with and without epilepsy.

Inattention Hyperactivity/impulsivity Oppositional/defiant disorder Conduct disorders Anxiety/depression Total score *

107

Healthy controls M (SD)

Children with epilepsy M (SD)

Total M (SD)

F

4.26 3.58 2.30 1.05 2.34 3.24

4.20 3.43 2.21 1.58 1.55 12.98

4.25 3.54 2.27 1.18 2.13 13.18

.01 .08 .04 4.48* 2.57 .03

(4.17) (3.47) (1.81) (1.03) (1.81) (13.16)

(4.10) (3.35) (1.60) (1.34) (1.24) (12.17)

(4.18) (3.34) (1.75) (1.11) (2.08) (13.09)

p < .05.

obtained. Then, the researchers approached parents of children with idiopathic epilepsy, who fulfilled the eligibility criteria, in various settings that cover approximately half of mainland Greece. Out of the 130 who were approached initially, 106 (81%) returned both questionnaires completed. The non-respondents offered lack of time and interest as a reason for non-participation. Their age ranged from 28 to 37 years old, they were mainly mothers (since they are usually the ones to bring the child to the doctor) and of middle socio-economic status (average family income); however it was not possible to assess differences in detail. The questionnaires were completed in the presence of the researchers and were assigned a code, so that the participants could be identified for the second phase of the retest. Once all the children with idiopathic epilepsy were identified and interviewed, the researchers contacted schools in the area and identified 3 children of similar age, gender and academic level according to their school report for each child with epilepsy. Out of the 318 parents of healthy children who were approached initially, 305 (96%) parents responded. All the parents were advised on where they could go if they felt that their children faced some behavioral problems. Informed consents were obtained from the parents of the children in the two groups. Half the parents completed first the SDQ and then the VADRPS, while the other half completed first the VADRPS and then the SDQ, in order to avoid the order effect. Then, the children with idiopathic epilepsy were approached by the researchers and provided their oral assent to participate in the study. It was explained to them that they could refrain at any time if they felt uncomfortable. It should be stressed that the researcher who conducted the K-SADS-PL was blind to the results of the parent rating scales, in an attempt to ensure impartiality during the assessment process. Post hoc power analysis showed that the sample of children with epilepsy that was used was adequate to run linear regression analysis. The power analysis for the specific study is .84 (a number greater than .70 is considered satisfactory, Faul et al., 2007). Univariate between-subjects ANOVA were conducted to explore differences in behavioral problems between children with idiopathic epilepsy and healthy controls according to parental reports. Linear regression analyses were run to identify the factors that predict behavioral problems in children with idiopathic epilepsy.

Results Children with and without epilepsy Reported effects of idiopathic epilepsy on VADPRS Univariate between-subjects ANOVAs showed that the effect of idiopathic epilepsy is statistically significant only for the conduct disorders subscale of the VADPRS (F(1,399) = 4.48, p (one-tailed) = .017, 2 = .011). Parents of children with idiopathic epilepsy report that their children exhibit more conduct problems than parents of healthy controls, as can be shown in Table 1. Epilepsy had no significant effect on the inattention subscale (F(1,399) = .01, p (one-tailed) = .906, 2 = .000), on hyperactivity/impulsivity subscale (F(1,399) = .08, p (one-tailed) = .770, 2 = .000), on the oppositional/defiant disorder subscale (F(1,399) = .04, p (one-tailed) = .836, 2 = .000), on the anxiety/depression subscale (F(1,399) = 2.57, p (one-tailed) = .110, 2 = .006), and on the total scale (F(1,399) = .03, p (one-tailed) = .868, 2 = .000). Reported effects of idiopathic epilepsy on SDQ Univariate between-subjects ANOVAs showed that the effect of idiopathic epilepsy is statistically significant for the hyperactivity subscale of the SDQ (F(1,399) = 4.46, p (onetailed) = .017, 2 = .011), the emotional problems subscale (F(1 , 399) = 2.82, p (one-tailed) = .046, 2 = .007), the prosocial behavior subscale (F(1,399) = 18.84, p (one-tailed) = .000, 2 = .044), as well as the total SDQ scale (F(1,399) = 3.18, p (one-tailed) = .038, 2 = .008). Children with idiopathic epilepsy have more symptoms of hyperactivity, emotional problems and behavioral problems in comparison to healthy controls according to their parents, while they also have lower prosocial behavior as can be seen in Table 2. Epilepsy had no significant effect on the conduct problems subscale (F(1,399) = .82, p (one-tailed) = .365, 2 = .002) and the peer problems subscale (F(1,399) = .07, p (one-tailed) = .797, 2 = .000).

Children with idiopathic epilepsy Age, gender, age of onset of epilepsy, frequency of seizures, type of epilepsy, number of antiepileptic drugs and SDQ A regression analysis was carried out with SDQ scores as the outcome variable and age, gender, age of onset of epilepsy,

108

V. Dafoulis, E. Kalyva

Table 2

Means and standard deviations of SDQ according to parents of children with and without epilepsy.

Hyperactivity Emotional problems Conduct problems Peer problems Total score Prosocial behavior *

Healthy controls M (SD)

Children with epilepsy M (SD)

Total M (SD)

F

2.54 1.95 1.51 1.19 7.24 9.40

3.10 2.29 1.67 1.24 8.25 8.71

2.96 2.20 1.63 1.20 7.99 8.89

4.46* 2.82* .82 .07 3.18* 18.84*

(2.34) (1.66) (1.50) (1.18) (5.66) (.96)

(2.38) (1.79) (1.59) (1.22) (4.83) (1.53)

(2.38) (1.76) (1.59) (1.16) (5.07) (1.44)

p < .05.

Table 3

Means, standard deviations and intercorrelations among the study variables.

Variables

M

SD

1

2

3

4

5

6

1. 2. 3. 4. 5. 6. 7.

2.01 1.42 1.05 1.46 2.44 1.22 7.24

.79 .50 .21* .64 .50 .41 5.66

1.00 −.06 .02 .05 −.03 .20* .11

1.00 1.00 −.02 .04 −.08 −.21*

.31 .12 .33* .53*

1.00 .13 .23* .28*

1.00 .29* .29*

1.00 .52*

Age Gender** Onset 1.86 Frequency Type*** Drugs SDQ

7

1.00

*

p < .05. Boys were rated as having more behavioral problems according to SDQ than girls (t(104) = 2.18, p = .032). *** Children with benign focal epilepsy were rated as having less behavioral problems according to SDQ than children with generalized epilepsy (t(104) = 9.51, p = .003). **

frequency of seizures, type of epilepsy, and number of antiepileptic drugs as predictive variables. These six predictors accounted for almost half of the variance in SDQ scores (R2 = .47). Age of onset of epilepsy (ˇ = .40, p = .000), the number of antiepileptic drugs (ˇ = .32, p = .000), and gender (ˇ = −.22, p = .008) demonstrated significant associations with SDQ scores. The frequency of seizures was associated with SDQ (r(106) = .28, p = .002), while age was not (r(106) = .12, p = .120). Finally, patients with benign focal epilepsy were rated by their parents as having less behavioral problems according to SDQ than patients with generalized epilepsy (t(104) = 9.51, p = .003). Intercorrelations between the variables are presented in Table 3.

Age, gender, age of onset of epilepsy, frequency of seizures, type of epilepsy, number of antiepileptic drugs and VADPRS A regression analysis was carried out with VADPRS scores as the outcome variable and age, gender, age of onset of epilepsy, frequency of seizures, type of epilepsy, and number of antiepileptic drugs as predictive variables. These six predictors accounted for almost one third of the variance in VADPRS scores (R2 = .34). The number of antiepileptic drugs (ˇ = .31, p = .001), gender (ˇ = −.28, p = .001), and age of onset of epilepsy (ˇ = .26, p = .006) demonstrated significant associations with VADPRS scores. The frequency of seizures was associated with VADPRS (r(106) = .22, p = .012), while age was not (r(106) = .09, p = .179). Finally, patients with benign focal epilepsy were rated by their parents as having

less behavioral problems according to VADPRS than patients with generalized epilepsy (t(104) = 3.89, p = .026). Intercorrelations between the variables are presented in Table 4.

K-SADS-PL The administration of K-SADS-PL revealed diagnosis of psychopathology in 27 out of the 106 children with idiopathic epilepsy (25.5%). Actually, almost half of these children (13) had more than one disorders: ten children (77%) have been diagnosed with two comorbid disorders and three children (23%) have been diagnosed with three comorbid disorders (see Table 5). It is worth mentioning that almost all children with idiopathic epilepsy who have generalized anxiety disorder, psychogenic bulimia, attention—deficit hyperactivity disorder, and conduct disorder have signs of at least one comorbid disorder. The findings from the clinical diagnostic interview are confirmed by the ratings scales of SDQ and VADPRS for the mood disorders in 4 children, as well as the remaining psychological disorders. Three out of the four children with mood disorders were girls with benign focal epilepsy. The comorbidity consisted of psychogenic bulimia in two cases, separation anxiety disorder in two cases, generalized anxiety disorder in two cases, attention deficit/hyperactivity disorder in two cases and conduct disorder in one case. Although psychogenic bulimia is rare in pubertal children, the diagnosis was done according to K-DSADS, although the authors cannot rule out that it could have been a side-effect of the antiepileptic drug that they were using for more than a year. In the case of a girl, there was

Behavioral problems in idiopathic epilepsy Table 4

109

Means, standard deviations and intercorrelations among the study variables.

Variables

M

SD

1

2

3

4

5

6

1. 2. 3. 4. 5. 6. 7.

2.01 1.42 1.05 1.46 2.44 1.22 12.98

.79 .50 .21* .64 .50 .41 11.17

1.00 −.06 .02 .05 −.04 .20* .09

1.00 1.00 −.02 .04 −.08 −.29*

.31 .12 .33* .37*

1.00 .13 .23* .22*

1.00 .30* .19*

1.00 .45*

Age Gender** Onset 1.86 Frequency Type*** Drugs VADPRS

7

1.00

*

p < .05. Boys were rated as having more behavioral problems according to VADPRS than girls (t(104) = 3.11, p = .002). *** Children with benign focal epilepsy were rated as having less behavioral problems according to VADPRS than children with generalized epilepsy (t(104) = 3.89, p = .026). **

Table 5 Percentage of psychological disorders in children with idiopathic epilepsy according to K-SADS-PL. Disorder

%

Major depression Separation anxiety Generalized anxiety Agoraphobia/special phobia Obsessive—compulsive disorder Enuresis Psychogenic bulimia ADHD Conduct disorder

3.77 3.77 4.72 2.83 2.83 7.55 2.83 6.6 7.55

comorbid major depression diagnosed by K-SADS-PL, SDQ, and VADPRS. Her parents went through a difficult divorce period one year before the diagnosis that coincided with the appearance of epileptic seizures and might have exacerbated the depressive symptomatology. Finally, 8 out of the 13 children who were diagnosed with comorbidity have benign focal epilepsy, as well as the 3 children with triple comorbidity according to K-SADS-PL.

Discussion The hypothesis that children with idiopathic epilepsy would have significantly higher rates of behavioral problems than healthy peers was confirmed from parental reports that were obtained from both rating scales; however, an interesting finding was that the statistically significant differences in behavioral problems that were identified by the parents varied according to the scale that was completed. For example, although parents of children with idiopathic epilepsy reported more conduct disorders than parents of healthy controls according to VADPRS, this difference did not emerge in the conduct problems subscale of the SDQ. Tse et al. (2007), Rantanen et al. (2009), and Bender et al. (2008) used also more than one scale to explore behavioral problems and noted some discrepancies between or within informants. This is definitely worth exploring further, since both rating scales in this study have been widely used, are standardized into Greek, and had good Cronbach ˛ and test—retest reliability. This also means that clinicians

and researchers should be aware that using different ratings scales may yield different results — especially since they have not been designed specifically for children with epilepsy (Krishnamoorthy, 2006). It is known that proxy-reports have certain limitations since parents may misinterpret some phenomena that are related to epilepsy and rate them as abnormal behaviors, increasing thus the prevalence of behavioral problems of children with epilepsy (Dantzer et al., 2003; Dunn et al., 1999; Oostrom et al., 2001). However, since the same parents provided the ratings for both scales at the same time and in counterbalanced order, it is unlikely that they might have been influenced by the above-mentioned factor. It is possible that the wording of the questions and the ‘‘symptoms’’ that each scale included resulted in different ratings. These differences in scores could reflect different conceptualization and evaluation of affective disorders for each scale (Bender et al., 2008). Parents were 4 times more likely than teachers to rate children with epilepsy as having clinically elevated ADHD symptoms, with agreement between them being higher for more severe symptoms (Sherman et al., 2010). In any case, it should be highlighted that the results of rating scales should be interpreted with caution, especially if the choice of a particular scale might affect the nature of the results. It is essential to use more specialized scales to measure certain aspects of behavioral problems more accurately and use as many sources as possible. Keeping these points in mind, it was found that children with idiopathic epilepsy had according to their parents more hyperactivity and emotional problems than healthy controls, as was found also in other studies comparing children with epilepsy and healthy controls on specific DSM-IV Axis I disorders. The risk for the former is primarily concentrated in ADHD (26.4% vs 10.0%), depressive disorders (22.6% vs 4.0%), and anxiety disorders (35.8% vs 22%) (Jones et al., 2007). Although usually there are no differences between children with epilepsy and healthy peers in psychotic or conduct disorders (Jones et al., 2007), in this study parents of children with idiopathic epilepsy rated them as presenting more conduct problems than the parents of healthy children according to one of the two scales. Moreover, the higher incidences of reported depressive/anxiety symptoms and peer problems in children with epilepsy were not confirmed in the present study. The lack of peer problems could be attributed

110 to the fact that children aged 6—9 are more likely to inform their peers about their condition (Serdari et al., 2009) and feel less stigmatized by them (Westbrook et al., 1992). The higher prevalence of the inattentive type of ADHD in children with epilepsy (Reilly, 2011; Waltz, 2010) in comparison to healthy controls was not confirmed in the present study, maybe due to the nature of the scales that were used. It is quite alarming that despite the demonstrated psychopathology, none of the children with idiopathic epilepsy who participated in this study was previously diagnosed with comorbidity, as this was one of the inclusion criteria. This shows that children with epilepsy have a higher prevalence of internalizing disorders that can go undetected and untreated (Fastenau et al., 2008). Austin et al. (2001) found that children with epilepsy with previously unrecognized seizures were already at risk of behavioral problems by the time of the first recognized seizure. Since there are serious concerns about the ability to identify underlying psychopathology in epilepsy, parents and professionals should be aware of the mental health needs of children with epilepsy and try to address them effectively before they escalate (Ott et al., 2003). The strengths of this study are: (a) the big sample size of children with idiopathic epilepsy that was recruited from a variety of settings; (b) the young age of the sample, since screening for behavior problems early in the course of the seizure disorders is essential (Tse et al., 2007); (c) it is the first study that examined test—retest reliability to look at the stability of perceived behavioral problems; (d) two different behavioral rating scales were used, providing some important insights in combination with clinical assessments; (e) the healthy control group was recruited from the same area as the sample with epilepsy and no normative data was used for comparison purposes (Ettinger et al., 1998; Oguz et al., 2002); and (f) the factors that predict the severity of psychopathology in children with idiopathic epilepsy were identified, thus giving more insight into potential prevention and intervention programs. The main limitation of this study that warrants further attention is that IQ was not taken into account in the present study, but the use of school records is a measure of the children’s intellectual abilities. It should also be stressed that the findings can be generalized to children with idiopathic epilepsy and not to the general population of children with epilepsy — and especially those with more benign forms of epilepsy. Another interesting finding is that gender, age of onset of epileptic seizures and number of antiepileptic drugs administered, affect the severity of behavioral problems in children with idiopathic epilepsy. More specifically, boys, children with later onset of epileptic seizures and children using more than one antiepileptic drug had higher levels of behavioral symptoms as rated by their parents on both scales. The variance that is explained by these factors is very satisfactory for the SDQ (47%) and quite satisfactory for the VADPRS (34%). Seizure frequency was associated with the level of behavioral problems, while there was no association between age and severity of behavioral problems according to both rating scales (it should be noted that almost half of the participants were screened during their first year of illness, which means that they were of younger age). Antiepileptic drug treatment (monotherapy vs polytherapy), age of onset of epilepsy and seizure frequency

V. Dafoulis, E. Kalyva were related to the severity of behavioral, cognitive, and linguistic comorbidity in children with epilepsy according to Caplan et al. (2008) and Freilinger et al. (2006). No other study so far has associated gender with behavioral problems in children with idiopathic epilepsy, but gender has been associated with behavioral problems in the general population — with boys being more susceptible than girls — and with the perceived quality of life of children with diabetes — with boys reporting better quality of life than girls (Kalyva et al., 2011). The type of epilepsy is associated with psychopathology in this study, as in the study of Kleen et al. (2010) who concluded that it affects the level of cognitive and behavioral comorbidities in children with epilepsy. However, in the present investigation the findings differed according to the measures used. Parents rated children with focal epilepsy as having less behavioral problems according to both scales than parents of children with generalized epilepsy. Clinical assessment, however, revealed that children with focal epilepsy were more likely to be diagnosed with comorbidity than their peers with generalized epilepsy. The latter finding is supported also by Thome-Souza et al. (2004) who found that depression and ADHD are significantly more frequent in children with focal than generalized epilepsy. Since comorbidity is linked to lower quality of life, being able to identify who is more at risk for developing psychopathology could inform not only intervention, but also prevention programs.

Acknowledgements This paper is part of a doctoral thesis. We would like to thank all the participants, the clinical settings, and the following professors: George Karpinis, Fotios Fotiou, Gregoris Abatzoglou, Ioannis Mylonas, Ioannis Tsikoulas, Anna Karlovasitou-Koniari, and Nikolaos Zilikis.

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