Parent-reported subjective complaints in children using antiepileptic drugs: what do they mean?

Epilepsy & Behavior Epilepsy & Behavior 3 (2002) 322–329 www.academicpress.com

Parent-reported subjective complaints in children using antiepileptic drugs: what do they mean? Johannes A. Carpay,a,* Jan Vermeulen,b Hans Stroink,c Oebele F. Brouwer,d A.C. Boudewyn Peters,e Albert P. Aldenkamp,f Cees A. van Donselaar,c and Willem F.M. Artsa,c a

Department of Child Neurology, Westeinde Hospital and Juliana ChildrenÕs Hospital, The Hague, The Netherlands b Department of Psychology, ‘‘Meer en Bosch’’ Epilepsy Center, Heemstede, The Netherlands c Department of Neurology, University Hospital Dijkzigt and Sophia ChildrenÕs Hospital, Rotterdam, The Netherlands d Department of Neurology, Leiden University Medical Center, Leiden, The Netherlands e Department of Child Neurology, University Hospital and Wilhelmina ChildrenÕs Hospital, Utrecht, The Netherlands f Department of Behavioral Sciences, ‘‘Kempenhaeghe’’ Epilepsy Center, Heeze, The Netherlands Received 4 April 2002; received in revised form 17 July 2002; accepted 17 July 2002

Abstract We used a parent-completed 20-item ‘‘side effect scale’’ quantifying complaints that parents perceive to be caused by antiepileptic drugs (AEDs) in 108 children with active epilepsy. We studied the associations between parent-reported complaints, severity of seizures, and restrictions due to epilepsy, and clinical data including number and AED load. In 85% of the children at least one complaint was reported, in less than 20% complaints were perceived as a substantial problem. In a multivariate analysis, there was no significant relationship between the ‘‘side effect scale’’ score and AED load, or the number of AEDs. However, complaints were associated with parent-reported frequency and severity of seizures. We conclude that the adverse effects of seizures or parental concern about the severity and intractability of seizures in their children may have influenced the reported complaints. Ó 2002 Elsevier Science (USA). All rights reserved. Keywords: Antiepileptic drugs; Side effects; Epilepsy; Parents; Children; Quality of life scale

1. Introduction Surveys in The Netherlands and the United States have shown that more than 80% of all children with epilepsy in these countries are treated with antiepileptic drugs (AEDs) [1,2]. In clinical trials of AEDs in children, subjective complaints, such as fatigue and somnolence, are commonly reported and considered as side effects [3]. Subjective complaints are probably relatively rare when childhood epilepsy is in remission [4], but they might be more prevalent when seizures are drug resistant, because in such cases high dosages or multiple AEDs are used. The use of high dosages and multiple AEDs is generally * Corrresponding author. Present address: Department of Neurology, Hospital Gooi-Noord, P.O. Box 900, 1250 CA, Laren, The Netherlands. Fax: +3135-5391792. E-mail address: [email protected] (J.A. Carpay).

believed to increase the prevalence and severity of side effects. However, it is not always clear if subjective complaints, despite being attributed to the use of AEDs, really are caused by the AEDs or reflect something else, such as adverse effects of seizures or concern about the epilepsy itself. Complaints attributed to AEDs may influence clinical decisions about AED dosage or combining AEDs and therefore it is important to understand what they mean. We have previously described a method for a standardized quantification of the prevalence and severity of subjective complaints in children taking AEDs attributed to the medication by their parents, using the Hague Side Effects Scale (HASES) [5]. HASES comprises 20 subjective complaints that were common in a pilot population of children using AEDs. The final content of the scale was based on a psychometric analysis from the pilot sample. Items were included based on parental

1525-5050/02/$ - see front matter Ó 2002 Elsevier Science (USA). All rights reserved. PII: S 1 5 2 5 - 5 0 5 0 ( 0 2 ) 0 0 0 4 7 - 1

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suggestions during in-depth interviews about side effects, item–total correlations in a pilot version of the scale, and internal consistency of the scale, rather than items based on cliniciansÕ perceptions or on side effects reported in the literature. It is therefore possible that certain complaints, which parents perceive to be AEDrelated, are in fact related to other causes, such as ongoing seizures. HASES was reliable in terms of internal consistency (CrohnbachÕs a ¼ 0:88) and retest stability (Pearson correlation after 14 days ¼ 0.91). We report the prevalence and severity of subjective side effects as measured using HASES in children taking AEDs, and the relationship between HASES score and clinical data. We excluded children with epilepsy in remission, because it has been reported that in these children subjective complaints are limited [4]. We hypothesized that, in a context of ongoing seizures despite treatment, complaints, although attributed by the parents to their childrensÕ AEDs, could be an expression of clinical factors other than AED toxicity.

2. Methods 2.1. Design Children were consecutively recruited from the child neurology departments of three university hospitals, a pediatric hospital, and a general hospital. Eight child neurologists provided patients. Children with epilepsy were eligible when they were aged 4–16 years, were treated with at least one AED, and had not been seizurefree for more than 1 year. The neurologists selected children whose parents had sufficient written Dutch language skills to be able to complete a questionnaire. Most eligible children of first-generation immigrant parents were thus excluded. The ethical committees of the participating centers approved the study protocol. 2.2. Parental scales The items addressed in HASES are listed in Table 1. All questions in the scale refer to complaints attributed to the AED medication as recalled and perceived by the parents, in the previous 3 months. Each item includes the following four response categories: (1) no problem; (2) a mild problem; (3) moderately serious problem; (4) very serious problem. A simple scoring system was used, ranging from 1 point (no problem) to 4 points (very serious problem) for each item. For children with severe concomitant impairments, it was possible that parents indicated that certain complaints could be not applicable or could not be assessed. For example, when a child is unable to walk because of cerebral palsy, an AED cannot cause a ‘‘disturbance of walking.’’ We have

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Table 1 Items addressed in the Hague side effects scale and responses by parents of 108 children using antiepileptic drugs Item

Number (%) of 108 children reported to have a mild to very serious problem

1. Drowsiness/sleepiness 2. Dizziness 3. Uncertainty when walking 4. Falling 5. Sickness 6. Difficulty with defecation 7. Diarrhea 8. Shaking, trembling 9. Speech difficulties 10. Double or blurred vision 11. Headache 12. Fatigue 13. Loss of appetite 14. Depression 15. Hyperactivity 16. Temper tantrums, aggression 17. Slowness 18. Poorer school results 19. Decreased concentration 20. Behavioral disturbance

47 16 13 10 19 18 11 16 14 9 40 55 28 15 32 37 49 39 51 25

(44%) (15%) (12%) (9%) (18%) (17%) (10%) (15%) (13%) (8%) (37%) (51%) (26%) (14%) (30%) (34%) (45%) (36%) (47%) (23%)

computed the HASES score based on the average score of applicable items in such cases when up to five items were considered ‘‘not applicable.’’ When more than five items were considered ‘‘not applicable,’’ we excluded the case. The least severe HASES score possible is 20 (indicating that none of the complaints listed are perceived to be a problem), the most severe score is 80 (all complaints are very serious problems). Furthermore, parents were asked to complete scales addressing Seizure Severity (HASS, a 13-item scale, CrohnbachÕs a ¼ 0:85, retest Pearson correlation ¼ 0.93) [5,6] and Restrictions due to epilepsy (HARCES, a 10-item scale, CrohnbachÕs a ¼ 0:89, retest Pearson correlation ¼ 0.93) [7]. Seizure Severity scores range from 13 to 53 and Restrictions scores from 10 to 40, high scores reflecting more severe problems. The contents of HASS and HARCES are given in the Appendix A. We repeated the parental HASES assessment after 1 year. To avoid investigator bias, parents completed the questions at home. Parents were not instructed on how to interpret the meaning of items or response categories. Parents did not receive any instructions as to informing their clinician of their responses on the scales and the treating neurologist was not informed of the results on any of the parental scales. 2.3. Clinical data The medical records of all patients were reviewed for information about the following variables: age, sex, classification [8] and duration of epilepsy, name(s) and dosage(s) of AED(s), presence of mental retardation,

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and body weight. Parents were asked to report their childÕs seizure frequency (in the last year and last month) or the duration of remission from seizures. Compliance was not formally assessed by a prospective protocol of serum drug level tests, but the clinician was asked if he or she had reasons to believe that compliance was poor, yes or no. Because children were using many different AEDs or combinations of AEDs, we computed a standardized dosage ratio to be able to make comparisons in terms of AED load [9]. For each AED we computed the average daily dosages of the study group in milligrams per kilogram (mono- and polytherapy), and for each child we calculated per AED the ratio of the prescribed daily dosage and the groupÕs average daily dosage for that AED. When a child was taking more than one AED, prescribed/average daily dosage ratios for each AED were added. For example, when a child used 10 mg/kg valproate, we computed an AED load based on the average daily maintenance dosage of valproate of 10/23.8 ¼ 0.42. When that child also used 15.7 mg/kg carbamazepine, we computed 15.7/15.7 ¼ 1 for carbamazepine plus 0.42 for valproate ¼ 1.42 for total AED load.

Table 2 Demographic and clinical variables of 108 children using antiepileptic drugs Mean (SD) age Sex Mean (SD) duration of epilepsy Seizure-free in previous 3 months

10.1 (3.3) years 56 (52%) boys 4.8 (3.7) years 25 (23%)

Epilepsy classification Localization-related Idiopathic with age-related onset Symptomatic Generalized Idiopathic with age-related onset Generalized idiopathic or symptomatic Unclassified

24 (22%) 18 (17%) 7 (7%)

Number of AEDs per patient 1 2 3 4 Mental retardation

68 (63%) 27 (25%) 12 (11%) 1 (1%) 39 (37%)

13 (12%) 46 (43%)

3. Results

12 other cases, fewer than 5 items were left open and these were scored based on the average score of other items. Demographic and clinical characteristics of the remaining 108 children are listed in Table 2. Symptomatic epilepsies dominated the epilepsy classification. More than one-third of the children were mildly to moderately mentally retarded. Only 25 children (23%) had been seizure-free in the previous 3 months. Two children were judged to be noncompliant with the prescribed AED regimen. These children were not excluded. The distribution of AEDs and dosages is outlined in Table 3. Valproate and carbamazepine were the most frequently used AEDs; valproate dosages ranged from 4.2 to 43.5 mg/kg and carbamazepine dosages ranged from 5.3 to 28.6 mg/kg. In 40 children polytherapy was used with up to four AEDs. AED load was lower for children on monotherapy (median ¼ 0.96) as compared with children on polytherapy (median ¼ 2.53, P < 0:0001). The distribution of AED load is given in Table 4. Mono- and polytherapy groups were comparable with respect to age and gender. Duration of epilepsy was longer in the children on polytherapy (median 7.0 years) than in those on monotherapy (median ¼ 2.3 years, P < 0:0001).

3.1. Subjects and clinical data

3.2. Complaints and relationship with clinical data

One hundred and seventeen children were eligible for the study; 115 parents completed and returned the questionnaire. The mother completed the questionnaire in 52, the father in 6, both parents in 54, and other primary caretakers in 3 cases. We excluded 7 children because their parents considered more than 10 items of the HASES ‘‘not applicable;’’ these were children with severe encephalopathies and multiple impairments. In

Complaints attributed by parents to the AEDs were reported in 92 children (85%). Items obtained affirmative responses from 8% (double or blurred vision) to 51% (fatigue) (Table 1). Fig. 1 shows the range and skewed distribution of scores of the 108 children taking AEDs. The median HASES score was 26. A cluster analysis of HASES scores identified two subgroups: one centering on a HASES score of 24.8 (88 children) and

2.4. Analysis For the analysis of correlations between clinical data and scores on HASES, SpearmanÕs rank correlation coefficient rs was used. The Mann–Whitney U and Kruskal–Wallis tests were used to examine group differences. We performed a cluster analysis of the HASES and of the three parental scales (HASES, Seizure Severity, and Restrictions), to detect possible specific distributions of the HASES score. By means of stepwise multiple linear regression we analyzed the influence on the HASES score of the following clinical factors: number of seizures in last year and last month, duration of epilepsy, Seizure Severity, AED load, number of AEDs used, and severity of Restrictions due to epilepsy. Because multiple correlations and comparisons were calculated, significance at P values near 0.05 has to be interpreted with caution.

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Table 3 Number of children taking an AED, average daily maintenance dosage (ADD), and range of dosages (N ¼ 108)a AED

Monotherapy

Valproate Carbamazepine Phenytoin Ethosuximide Clobazam Clonazepam Nitrazepam Vigabatrin Phenobarbital Oxcarbazepine a

Mono- and polytherapy

N

ADD (mg/kg)

Range (mg/kg)

N

ADD (mg/kg)

Range (mg/kg)

22 27 5 4 0 0 0 3 2 5

21.5 13.0 6.1 23.2

8.0–39.0 5.3–27.3 3.5–8.0 20.0–27.8

46 49 13 8 7 2 2 20 3 8

23.8 (10.0) 15.7 (5.9) 6.5 (1.8) 21.2 (3.3) 0.52 (0.5) 0.05 (0.03) 0.58 (0.14) 42.2 (12.9) 6.8 (6.3) 33.3 (12.0)

4.2–43.5 5.3–28.6 3.5–9.2 17.4–27.8 0.18–1.9 0.02–0.08 0.44–0.72 22.7–75.0 2.0–13.9 11.8–48.7

(9.5) (4.8) (1.7) (3.4)

50.7 (21.9) 9.2 (6.7) 33.5 (14.6)

32.6–75.0 4.4–13.9 11.8–48.7

ADDs are means (SD). Note. Forty children were on polytherapy. Rescue medication is not included.

Table 4 Distribution of number of children over AED load (prescribed daily dosage/average daily dosage of all AEDs for each child in the study) and relation with number of AEDsa AED load

All (N ¼ 108)

Monotherapy (N ¼ 68)

Polytherapy (N ¼ 40)

0.01–0.33 0.34–0.66 0.67–1.00 1.01–1.33 1.34–1.66 1.67–2.00 2.01–2.33 2.34–2.66 2.67–3.00 3.01–3.33 3.34–3.66 3.67–4.00 4.01–4.33 4.34–4.66 >5.00

0 16 25 18 9 10 5 8 6 5 4 0 0 1 1

0 15 24 17 8 3 1 0 0 0 0 0 0 0 0

0 1 1 0 1 7 4 8 6 5 4 0 0 1 1

a

AED load is the sum of the mg/kg dosage of each AED used by a child, divided by the mean daily dosage of each AED used in the study. Example: An AED load of 1 means that a child either takes one AED in a dosage equal to the average dosage of that AED in the study group, or two AEDs both in a dosage equal to half the average dosage of each AED in the study group.

one on a score of 41.9 (20 children); all 108 cases were included. A cluster analysis of all three parental scales identified two clusters: Cluster 1 (33 children: HASES ¼ 36, Seizure Severity ¼ 36, and Restrictions ¼ 21) and cluster 2 (52 children: HASES ¼ 24, Seizure Severity ¼ 26, and Restrictions ¼ 16); 23 cases were not included. Thus, only a minority reported severe complaints, and high scores on the HASES were often associated with high scores on both other parental scales, addressing severity of seizures and restrictions. We found no difference in HASES score between children with normal intelligence and those with mental retardation (P ¼ 0:95) or between boys and girls (P ¼ 0:82). No significant correlation between AED load, number of AEDs used and duration of epilepsy was found (Table 5). We found significant correlations between HASES score and number of AEDs, frequency and severity of seizures, and restrictions due to epilepsy (Table 5). The stepwise multiple linear regression analyzing the influence on HASES score of various clinical factors seemed to confirm our hypothesis that complaints, although attributed by the parents to their childrensÕ

Table 5 Correlation of score on the HASES with clinical variables in univariate analysis and stepwise multiple linear regression ðN ¼ 108Þa

rs

P

Multiple regression P

0.12 0.23 0.18 0.30 0.34 0.25 0.23

0.21 0.16 0.07 0.005 <0.001 0.01 0.02

0.60 0.11 0.33 <0.001 0.23 0.27 <0.001

Univariate

Fig. 1. Distribution of score frequencies on the Hague side effects scale in 108 children. Score range: 20 (least severe score, parents perceive none of the listed complaints to be a problem) to 80 (most severe score possible, all 20 complaints listed are very serious problems).

AED load (PDD/ADD) Number of AEDs Duration of epilepsy Seizure severity Restrictions Number of seizures last year Number of seizures last month a

rs , Spearman correlation coefficient; PDD, prescribed daily dosage; ADD, average daily dosage of an antiepileptic drug in the study group (in mg/kg).

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AEDs, could be an expression of clinical factors other than AED toxicity. A contribution to our regression model on HASES score (adjusted R2 ¼ 0:22) was found for Seizure Severity (b ¼ 0:40) and number of seizures in the last month (b ¼ 0:43) (Table 5). Excluded from the model were number of seizures in the last year, AED load, number of AEDs, and Restrictions (Table 5). The correlation between the repeated HASES score after 1 year and the first score was high (rs ¼ 0:54, P < 0:0001).

4. Discussion In our sample of children with many drug-resistant cases, parents reported subjective complaints attributed to the AEDs in more than 80% of their children. However, in less than 20% of our sample were high scores on the HASES found, indicating that only a minority of the parents attributed severe complaints to the AEDs used in their children. After 1 year, a repeated HASES score was highly correlated with the first, indicating persistence of complaints despite expert neurological care, albeit blind for the results on the HASES. We realize that in this cross-sectional study the clinician has probably adjusted the prescribed medication to an individual childÕs tolerance, and therefore associations between AED load and side effects may have been minimized. Our study setting does reflect long-term clinical care by an expert child neurologist, and not the initial treatment phase of new-onset and benign childhood epilepsy, when often tolerance develops for many subjective side effects. Major clinical side effects, such as idiosyncratic reactions, have been dealt with in this phase and have therefore not been addressed in this study. Using a fixed dosage treatment protocol would probably have demonstrated an association between AED load and side effects, but may have resulted in less than the best possible treatment results for each individual child. In studies using a traditional approach toward assessing side effects, the percentage of children taking AEDs reported by clinicians to have side effects ranged between 50 and 75%. In about 10% only, side effects were considered intolerable [3,10–12]. Such subjective complaints as drowsiness/sleepiness, fatigue, and decreased concentration are commonly reported side effects, even when new-onset epilepsy, in most cases responding to first-line therapy, is being studied [3]. Although we developed HASES as a scale for quantifying subjective side effects from AEDs from the parentsÕ point of view, we considered the possibility that what parents report as side effects may be influenced by other factors. We sought to improve our understanding of the subjective complaints reported as side effects by the parents by examining their association with various clinical data.

4.1. AED load and complaints Most children in our sample had severe epilepsy in terms of resistance to AEDs. It is possible that the prevalence and severity of side effects correlate with the extent to which seizures are drug-resistant: drug resistance may lead to high-dose monotherapy ‘‘pushed to toxicity’’ or the use of a combination of AEDs. Thus, we examined if the HASES score was associated with the number and dosages of AEDs. First, we found that number of AEDs was not associated with a higher HASES score. However, a controlled study in adults showed that polytherapy may not produce more side effects than monotherapy when equal AED loads are used [13]. It is possible that not the number of AEDs but their (cumulative) dosages are associated with the severity of side effects: high-dose monotherapy regimens may be as toxic as combinations of several AEDs in a low dosage. For this reason the relation between total AED load and HASES score was studied. However, we did not find a relationship between AED load and HASES score. AED load as used in this analysis is not a well-established concept, and no generally accepted rules exist as to how it should be quantified. We feel it is a useful concept to facilitate comparisons between subjects using different AEDs and mono- and polytherapy regimens. Average daily dosages of each AED were in agreement with usual guidelines for children [14], and we have therefore not used an external standard, such as the Defined Daily Dosages proposed by the World Health Organization as used in a study in adults [9,13]. Theoretically, it is possible that the average loads for some AEDs in our study were toxic, but it seems valid to explore the difference between once or twice the average dosage (relatively low vs relatively high dosage). We applied no correction for interactions between AEDs when computing AED load in polytherapy, because the magnitude of this possible confounding factor is difficult to estimate, and average daily dosages were not very different for mono- and polytherapy. We were not able to compare our data with serum drug levels because, for most children, recent values using a standardized protocol were not available. We found no evidence for a substantial improvement of tolerance to side effects as addressed in HASES. A repeat HASES after 1 year was highly correlated with the first HASES score, indicating that parentsÕ perceptions about side effects were consistent even after 1 year of clinic visits with the opportunity to bring their view to the attention of the neurologist and to adjust treatment. Many children in our sample were mentally retarded or had other impairments. In seven children of our original sample, parents considered a large number of items (like ‘‘dizziness’’ or ‘‘speech difficulties’’) not applicable because of concomitant impairments. We have

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chosen to exclude these cases, because we focused on detecting a broad range of problems as perceived by parents. Computing their scores based on only a few applicable items seemed inappropriate. For example, when in a severely mentally and physically handicapped child parents reported ‘‘diarrhea’’ and ‘‘loss of appetite’’ as problems and most other items as ‘‘not applicable,’’ a computed score based on the average score of these items would suggest a plethora of other problems that have no relationship with the complaint reported, and would not appropriately reflect the parental perspective. HASES probably is not a useful scale in such cases. Summarizing our data, a causal relationship between the reported prevalence and severity of side effects and the use of AEDs could not be established. However, we did find a relationship between frequency and severity of recent seizures and score on the HASES. Therefore, we hypothesize that parental reports of subjective complaints that they perceive as side effects may point to the adverse effects of seizures or to concern about the intractability and severity of seizures. When complaints are considered as such, our findings are in concordance with previous studies showing that the major factor contributing to subjective well-being or quality of life in epilepsy is probably remission from seizures [15,16]. In a study of children who had been seizure-free for at least 1 year, subjective complaints in the cognitive domain, as reported by children and their parents, were assessed before and after discontinuation of the AEDs [4]. Overall, in their seizure-free population such complaints were limited. When reports made by children were compared with those of matched controls, no difference was found and only ‘‘tiredness’’ improved after discontinuation. Parents, however, reported significant improvement in all areas related to ‘‘alertness and activation’’ after discontinuation of AEDs. The authors have explained the difference between childrenÕs and parentsÕ reports by suggesting that the children had insufficient insight into their disabilities. In this study, we have not assessed the childrenÕs reports of medicationrelated complaints, but a previous study found no substantial difference between childrenÕs and parentsÕ reports of complaints using an American English version of HASES [17]. We have developed HASES, essentially a standardized assessment of subjective complaints, to improve our tools for comparing treatment strategies and monitoring a childÕs treatment. Others have designed similar instruments, such as SEALS [18] and the ABNAS neurotoxicity scale [19]. Our findings that HASES does not simply measure side effects may suggest it is not useful and the scale should be revised. However, we feel a more fruitful approach would be to control for factors like seizure frequency and severity, before drawing conclusions with respect to such complaints as fatigue and

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somnolence. When a child is treated with AEDs, clinicians, parents, and children may all worry about possible side effects of medication. In clinical practice, HASES seems useful as an easily administered tool to quantify parentsÕ perceptions regarding side effects in a standardized way. It is important for the clinician to know these perceptions, and when complaints are substantial, they should be thoroughly discussed with the parents. We found no indication that complaints tend to disappear after 1 year of expert clinical care. Clinicians, however, should not without careful consideration of possible other causes conclude that such complaints are indeed caused by the AEDs. At least in a chronic treatment setting such as in this study, the complaints may reflect the adverse influence of seizures or parental worries about seizures rather than the adverse influence of antiepileptic medication.

Acknowledgments These investigations were supported by the Dutch National Epilepsy Fund, Project A 108. The authors are indebted to the following child neurologists for providing patients and clinical information: C.E. CatsmanBerrevoets, L.A.E.M. Laan, O. van Nieuwenhuizen, and R.J.H.M. Gooskens.

Appendix A A.1. The Hague Seizure Severity Scale for children with epilepsy. Questions relate to your childÕs condition in the past 3 months 1. How often do you notice a decrease of consciousness during a seizure in your child? a. always b. usually c. sometimes d. never 2. How long does such a decrease of consciousness last? (from time of onset to time of normal consciousness) a. very long b. long c. short d. very short e. does not apply, there is no decrease of consciousness 3. How severe have the seizures been overall? a. very severe b. fairly severe c. not very severe d. not at all severe 4. Are there any muscle jerks or cramps in the arms or legs during an attack?

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5.

6.

7.

8.

9.

10.

11.

12.

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a. always b. usually c. sometimes d. never How long do the jerks or cramps last during an attack? a. very long b. long c. short d. very short e. does not apply, there are no jerks or cramps How noticeable are the symptoms of an attack? a. very noticeable, everyone will notice an attack b. fairly noticeable, most people will notice an attack c. not very noticeable, most people will not notice d. not at all noticeable, you have to be very alert to notice an attack During or after an attack, how often does your child seem confused? a. always b. usually c. sometimes d. never During an attack, how often does your child wet him/herself? a. always b. usually c. sometimes d. never (or unknown) During an attack, how often does your child bite his/ her tongue? a. always b. usually c. sometimes d. never How often does your child become injured during an attack (other than biting the tongue)? a. always b. usually c. sometimes d. never After the attack has finished, is your child sleepy? (including sleepiness caused by the use of rescue medication like Diazepam) a. always b. usually c. sometimes d. never After an attack, does your child complain of sickness, headache, and/or pain in the muscles? a. always b. usually c. sometimes d. never (or unknown, my child would not be able to complain about that)

13. After an attack, how long does it take, until your child can resume to normal activity? a. very long b. long c. short d. very short or direct after an attack Scoring: 4 points (or 5 in case of items 2 and 5) for least favorable alternative (a) to 1 point for most favorable alternative (d). Scale ranges from 13 (least severe seizures) to 54 (most severe seizures). A.2. The Hague restrictions in childhood epilepsy scale The following questions are about the restrictions placed on your child because of the epilepsy. If, for example, your child can ride a bicycle, but is not allowed to because of the chance of a seizure, we call it a restriction resulting from the epilepsy. If your child cannot ride a bike because of some other reason (e.g., being too small or having a handicap), it does not count as such. 1. How much extra supervision is needed in your childÕs daily activities? a. a lot b. some c. a little d. none 2. Does your child require special precautions in daily activities? (like wearing a helmet) a. always b. usually c. sometimes d. never 3. Does the epilepsy influence the freedom of your child in playing in the house? a. a lot b. some c. a little d. not at all 4. Does the epilepsy influence the freedom of your child in playing outside the house/in the street? a. a lot b. some c. a little d. not at all 5. Does the epilepsy influence the freedom of your child in going swimming? a. a lot b. some c. a little d. not at all 6. Does the epilepsy influence the freedom of your child in sporting activities (excluding swimming)? a. a lot b. some

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c. a little d. not at all 7. Does the epilepsy influence the freedom of your child in traffic (like riding a bicycle)? a. a lot b. some c. a little d. not at all 8. Does the epilepsy influence the freedom of your child in staying elsewhere for the night? a. a lot b. some c. a little d. not at all 9. Does the epilepsy influence the freedom of your child in going to parties? a. a lot b. some c. a little d. not at all 10. Does the epilepsy influence the freedom of your child in participating in PE? a. a lot b. some c. a little d. not at all Scoring: 4 points for least favorable alternative (a) to 1 point for most favorable alternative (d). Scale ranges from 10 (least severe restrictions) to 40 (most severe restrictions). References [1] Carpay JA, Arts WFM, et al. Epilepsy in childhood: an audit of clinical practice. Arch Neurol 1998;55:668–73. [2] Berg AT, Levy SR, Testa FM, Shinnar S. Treatment of newly diagnosed pediatric epilepsy: a community-based study. Arch Pediatr Adolesc Med 1999;153:1267–71. [3] Verity CM, Hosking G, Easter DJ. The paediatric EPITEG collaborative group: a multicentre comparative trial of sodium valproate and carbamazepine in paediatric epilepsy. Dev Med Child Neurol 1995;37:97–108. [4] Aldenkamp AP, Alpherts WC, Sandstedt P, et al. Antiepileptic drug-related cognitive complaints in seizure-free children with

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