Sleep habits and disturbances in Malaysian children with epilepsy

80..84 doi:10.1111/j.1440-1754.2009.01642.x ORIGINAL ARTICLE Sleep habits and disturbances in Malaysian children with epilepsy Lai Choo Ong, Wai Wai Yang, Sau Wei Wong, Feizel alsiddiq and Yi Soon Khu Department of Paediatrics, Universiti Kebangsaan Malaysia Medical Centre, Jalan Yaacob Latif, Kuala Lumpur, Malaysiajpc_1642 Aims: To compare sleep habits and disturbances between Malaysian children with epilepsy and their siblings (age range 4 18 years) and to determine the factors associated with greater sleep disturbance. Methods: The Sleep Disturbance Scale for Children (SDSC) questionnaire was completed by the primary caregiver for 92 epileptic children (mean age 11.1 years, 50 male, 42 females) and their healthy siblings (mean age 11.1 years, 47 males, 45 females). Details of sleep arrangements and illness severity were obtained. Multiple regression analysis was used to determine factors associated with high Total SDSC scores in epileptic patients. Results: Compared with their siblings, epileptic children had significantly higher total SDSC score (difference between means 8.7, 95% confidence interval (CI) 6.4 11.1) and subscale scores in disorders of initiating and maintaining sleep (3.9, 95% CI 2.8 5.2), sleep wake transition disorders (2.1, 95% CI 1.3 2.9), sleep-disordered breathing (0.7, 95% CI 0.3 1.1) and disorders of excessive sleepiness (1.5, 95% CI 0.6 2.4). Epileptic children had a higher prevalence of co-sleeping (73.7% vs 31.5%) and on more nights per week (difference between means 3, 95% CI 2.0 3.9) than their siblings. Higher Epilepsy Illness Severity scores were associated with higher total SDSC scores (P = 0.02). Conclusion: Co-sleeping was highly prevalent in children with epilepsy, who also had more sleep disturbances (especially problems with initiating and maintaining sleep and sleep wake transition disorders) than their siblings. Epilepsy severity contributed to the sleep disturbances. Evaluation of sleep problems should form part of the comprehensive care of children with severe epilepsy. Key words: child; epilepsy; sleep disturbance. Sleep disorders, although common in the general population, 1,2 are said to be more prevalent and serious in children with epilepsy. 3 9 The interrelationship between sleep and epilepsy is complex. 10 Sleep may activate clinical seizures as well as interictal epileptiform discharges. Hence, obtaining a sleep recording is now a standard part of the routine electroencephalogram. The sleep state also alters the morphology of epileptiform discharges in certain childhood epilepsy syndromes. Seizure occurrences in some epilepsy syndromes are linked to specific periods of the sleep wake cycle. The occurrence of nocturnal seizures, especially those of frontal lobe origin, is most frequent in nonrapid eye movement (NREM) sleep. In turn, nocturnal seizures disrupt sleep continuity, resulting in nocturnal arousals and daytime sleepiness. Therapy with certain antiepileptic drugs Key Points 1 Children with epilepsy have a higher prevalence of co-sleeping and more sleep disturbances than their healthy siblings. 2 The most common areas of sleep disturbances are in initiating and maintaining sleep and sleep wake transition disorders. 3 The severity of the epileptic disorder contributed to the sleep disturbances. Correspondence: Prof. Lai Choo Ong, Department of Paediatrics, Universiti Kebangsaan Malaysia Medical Centre, Jalan Yaacob Latif, 56000 Kuala Lumpur, Malaysia. Fax: +603 91737827; email: onglc@ppukm.ukm.my Accepted for publication 19 June 2009. (AEDs) can alter sleep architecture and influence daytime alertness. 11 Associated co-morbidities like physical disability, 5 mental retardation 6 and behavioural disorders 3 5,8,9 may contribute to disturbed sleep. There may also be a link between disordered sleep, seizure disorders and psychosocial functioning. Many children with recent onset epilepsy changed to less independent sleeping arrangements. 12 The child and family may experience more anxiety about nocturnal seizures, resulting in interrupted sleep. 3 Poor-quality sleep in children with epilepsy, whether the result of nocturnal seizures or sleep anxiety, is associated with daytime inattentiveness 3,4,7 9 and has been reported to affect the quality of life. 5 The extent of sleep disturbances among epileptic children in a multicultural society like Malaysia has not been investigated. Given that sleep behaviours and arrangements in normal school-aged children differ across cultures and socioeconomic status, 2 a cross-sectional, case-control study was carried out to compare the type of sleep disturbances affecting epileptic children and their siblings and to determine factors associated with sleep disturbances. Methods Participants All children with epilepsy aged 4 18 years attending the Paediatric Neurology clinic in the Universiti Kebangsaan Malaysia 80

LC Ong et al. Sleep and epileptic Malaysian children Medical Centre from July 2007 to June 2008 were identified. Inclusion criteria included (i) children with a normal sibling in the same age range (non-disabled, no chronic illness that could interfere with sleep, e.g. asthma requiring medication, cardiac failure); (ii) neither child nor sibling on medication to promote sleep; (iii) written informed consent from a parent or caregiver who was able to complete the self-administered sleep questionnaire; and (iv) duration of epilepsy more than 1 year. Ethical approval was obtained from the institutional research and ethics committee. Assessments The Sleep Disturbance Scale for Children (SDSC) questionnaire 1 contains 26 questions rated on a Likert scale (from 1 (never) to 5 (always)) on how often each item occurred in the last 6 months. It is clustered into six subscales of sleep disturbances: (i) difficulty in initiating and maintaining sleep factor insomnia (DIMS); (ii) sleep breathing disorders (SBDs); (iii) disorders of arousal/nightmares (DAs); (iv) sleep wake transition disorders (SWTDs); (v) disorders of excessive somnolence (DOESs); and (vi) sleep hyperhydrosis. It also provides a total SDSC score (range: 26 130), with higher scores indicating greater sleep problems. The SDSC was chosen, as it had been validated. Age and sex showed no significant effect on the sleep scores in the normative sample. Raw scores can be converted to T-scores, and a T-score of >70 (2 standard deviation above the mean) is considered pathological. Permission was obtained to do a formal translation. Two versions, one in Mandarin and another in Malay language, were developed by translation and backtranslation. In the pilot test, the Mandarin version yielded a Cronbach s alpha of 0.801, while the Malay language version had a Cronbach s alpha of 0.861. Thus, the translations were of good reliability and were used in the study. Respondents answered the questionnaire using the translated version they felt most proficient in. Reliability analysis showed that Cronbach s alpha was 0.76 in the subjects and 0.74 in their siblings. This indicates a good level of internal consistency among the 26 items for both groups considered. Clinic charts and direct interview were used to obtain medical and social information of the patient and family. Co-sleeping was investigated by asking the parents the number of nights per week the child slept in the same room (room sharing) or on the same bed/mattress (bed sharing) with a caregiver. The presence and type of cerebral palsy were recorded, and the gross motor functioning level was based on the Gross Motor Function Classification System. 13 These ranged from level I (mildest) to the most debilitating level V. Seizures were considered nocturnal if more than 75% of their seizures occurred during sleep. Patients were considered to have a learning disability if they required extra help in school and their developmental quotient (DQ) was 80, and to have mental retardation if they had a DQ <80 and problems with social adaptive skills. Seizure severity was determined by using the Epilepsy Illness Severity Score (EISS). 14 This is a summative score based on seizure type and frequency, number of AEDs and observed side effects, with scores ranging from 2 (least severe) to 9 (most severe). The epilepsy syndrome was graded by using the Epilepsy Syndrome Severity Scores Child (ESSS-C). 15 In the ESSS-C, scores were awarded for all 36 of the International League Against Epilepsy identified epilepsy syndromes, with scores ranging from 2 for benign epilepsies to 7 for symptomatic partial epilepsies and 10 for malignant epilepsy syndromes. Statistical analysis For a 10-point difference in mean total SDSC score between patients and their siblings to be demonstrated, a sample size of 70 each was required to achieve a power of 0.8 and an alpha of 0.05. All data were processed and analysed by using SPSS (version 15.0 for Windows, SPSS Inc., Chicago, IL, USA). Univariate analysis was performed by using student t-test for continuous variables and chi-square test for categorical variables (Fisher exact test for cell values, <5). Within the epilepsy group, multiple regression analysis was used to determine factors related to higher total SDSC scores. A P-value of <0.05 was considered statistically significant. Results There were 121 patients during the study period; 21 did not have siblings that met the inclusion criteria, 8 did not complete the questionnaires. Hence, 92 data sets were available for analysis. No significant age or sex difference existed between patients (mean age, 11.1; SD 3.85 years; 50 male, 42 females) and their healthy siblings (mean age, 11.1; SD 3.59 years; 47 males, 45 females). The ethnic background was 40 (43.5%) Malay, 40 (43.5%) Chinese and 12 (13.0%) Indian. Sixty-three (68.5%) main caregivers were mothers. Table 1 shows the characteristics of the children with epilepsy. Many had severe epilepsy; 48 (52.2%) had a high EISS severity score of >5, 57 (56.5%) had symptomatic partial epilepsy and 34 (36.9%) were on more than one AED. About half of them also had cerebral palsy and/or mental retardation. Table 2 shows the differences in the various sleep parameters, total SDSC score and subscale scores among the epileptic children compared with their siblings. Children with epilepsy had significantly higher mean scores for total SDSC, DIMS, sleep breathing disorder (SDB), SWTD and DOES. There was also a significantly higher proportion of epileptic children whose sleep latency exceeded 30 min, were cosleeping (sharing a room or bed with a caregiver) and with T scores >70 for Total SDSC, DIMS and SWTD. There was no difference in the total sleep time between the two groups. For the children with epilepsy, multiple regression analysis was performed to explore the effect of EISS scores, ESSS-C scores, cognitive status, patient sex, age, nocturnal seizure, Gross Motor Function Classification System level, number of room-sharing and bed-sharing days per week on the total SDSC score (Table 3). The only significant factor was the EISS score, which contributed to 14.7% variance in the equation. Discussion The results of this study add to the growing body of evidence that children with epilepsy experience significant sleep disturbances, irrespective of their cultural background. 3 9 The nearestaged normal siblings were used as controls to reduce bias due to 81

Sleep and epileptic Malaysian children LC Ong et al. Table 1 Medical characteristics of the epileptic patients n = 92 (%) Level of cognitive function Normal 14 (15.2) Learning disability 26 (28.3) Mental retardation 52 (56.5) Physical handicap Cerebral palsy 39 (42.4) GFMCS level I and II 64 (69.5) III 1 (1.1) IV and V 27 (29.4) Visual loss 14 (15.2) Seizure characteristics Age of onset, years, mean (SD) 3.6 (2.9) Duration of epilepsy, years, mean (SD) 7.6 (4.5) Predominantly nocturnal seizures 18 (19.6) EISS score, mean (SD) 6 (1.8) ESSC score, mean (SD) 6.7 (1.79) Number of AEDs, mean (SD) 1.4 (0.66) None 3 (3.3) 1 55 (59.8) 2 28 (30.4) 3 or more 6 (6.5) Figures in parentheses indicate percentages unless indicated otherwise. AEDs, antiepileptic drugs; EISS, Epilepsy Illness Severity Score; ESSS-C, Epilepsy Syndrome Severity Score Child; GFMCS, Gross Motor Function Classification System; SD, standard deviation. Table 2 Differences in sleep parameters and SDSC scores between epileptic children (n = 92) and siblings (n = 92) Epileptic children Sibling P-value Total sleep time, hours, mean (SD) 7.7 (1.34) 7.9 (1.03) 0.229 Sleep latency >30 min, n (%) 30 (32.6) 7 (7.6) <0.001 Room sharing, n (%) 68 (73.9) 29 (31.5) <0.001 Days per week, mean (SD) 5.1 (3.09) 2.1 (3.23) <0.001 Bed sharing, n (%) 37 (40.2) 10 (10.9) <0.001 Days per week, mean (SD) 2.6 (3.35) 0.2 (1.25) <0.001 DIMS, mean (SD) 15.0 (4.97) 11.0 (2.92) <0.001 Score >70, n (%) 29 (31.5) 4 (4.3) <0.001 SBD, mean (SD) 4.3 (1.83) 3.6 (1.05) 0.002 Score >70, n (%) 10 (10.9) 3 (3.3) 0.081 DA, mean (SD) 3.5 (0.94) 3.4 (0.70) 0.435 Score >70, n (%) 3 (3.3) 3 (3.3) 1.000 SWTD, mean (SD) 10.1 (3.17) 8.0 (2.03) <0.001 Score >70, n (%) 12 (13.0) 2 (2.20) 0.010 DOES, mean (SD) 8.9 (3.37) 7.4 (2.75) 0.001 Score >70, n (%) 15 (16.3) 7 (7.6) 0.069 SHY, mean (SD) 2.6 (3.35) 2.4 (0.96) 0.613 Score >70, n (%) 2 (2.2) 2 (2.2) 1.000 Total SDSC score, mean (SD) 44.5 (9.57) 35.8 (6.20) <0.001 Score >70, n (%) 27 (29.3) 4 (4.3) <0.001 A score of >70 indicates >2 SD above the normative mean. DA, disorders of arousal; DIMS, disorders of initiating and maintaining sleep; DOES, disorders of excessive somnolence; SBD, sleep breathing disorders; SD, standard deviation; SDSC, Sleep Disturbance Scale for Children; SHY, sleep hyperhydrosis; SWTD, sleep wake transition disorders. differences in ethno-cultural outlook, parenting styles and sleep environment. The mean scores and variance (total and subscales) of the children in the control group in this study were comparable to the SDSC s original normative population, suggesting that there is little difference in parental perception of sleep disturbances among the two populations. The use of summative scores (EISS and ESSS-C) provided a better profile of the child s epilepsy than individual variables used in other studies and enabled us to run the regression analysis with fewer statistical comparisons. Approximately one-third of our patients with epilepsy had prolonged sleep latency and high DIMS scores. Problems with initiating (bedtime difficulties, increased sleep latency) and maintaining sleep (sleep fragmentation) have been reported in other questionnaire-based studies. 3 8 There are several possible reasons for the high DIMS scores in this study. Parents may be more lax with limit setting in a child with epilepsy, especially in our study population, where half had multiple disabilities. Many children in this study had chronic severe epilepsy, with the majority co-sleeping with a caregiver. Children with seizures have been noted to change to less independent sleeping arrangements, largely because of parental concern over seizure occurrence. 12 This arrangement (particularly bed sharing) can itself cause poor sleep and anxiety. 2 Furthermore, sudden unexplained death in epilepsy is more common in sleep, 16 and anxieties about seizures may prevent both child and parent from getting a good night s sleep. 3 Studies using objective measures like polysomnography (PSG) have demonstrated altered sleep architecture like sleep fragmentation and decreased REM sleep with longer REM latency in epileptic children. 9,17,18 Our study reported no difference in total sleep time between the epileptic patients and their siblings, as with other studies based on questionnaire 4 and PSG. 18 Conversely, Nunes et al. 17 reported significantly shorter total sleep times in their patients with refractory epilepsy. The mean total sleep time in this study was 7.7 h, less than that reported (9 10 h) by two questionnaire-based studies. 4,8 Two PSG-based studies on epileptic children reported total sleep times that were either equivalent to 18 or less 17 than our study. These conflicting results are probably because of differences in population characteristics and measurement methods. Both SWTD and DA are classified as parasomnias. Some questionnaire-based studies 4 8 have reported an increased incidence of parasomnias in epileptic children. It has been hypothesised that epileptiform discharges interfere with the arousal mechanism, thereby facilitating the occurrence of true parasomnias. 4,19 Our study reported a significant difference in SWTD but no difference in DA scores between the epileptic children and children in the control group. This apparent contradiction may be a result of the limitations of using a questionnaire-based instrument to differentiate between SWTD and DA, Another 82

LC Ong et al. Sleep and epileptic Malaysian children Table 3 Multiple regression analysis of factors associated with high Sleep Disturbance Scale for Children scores Factor B coefficient (standard error) 95% confidence interval P-value Level of cognitive function 1.3 (1.92) -2.5 to 5.13 0.493 Predominantly nocturnal seizures 0.024 (2.58) -5.2 to 5.12 0.992 Gross Motor Function Classification System level 0.5 (0.80) -1.15 to 2.05 0.576 Male sex 0.29 (1.99) -4.26 to 3.67 0.883 Age 0.1 (0.28) -0.49 to 0.65 0.779 Visual loss 2.9 (3.27) -3.5 to 9.49 0.266 Room sharing days per week -0.5 (0.42) -1.34 to 0.32 0.225 Bed sharing days per week 0.2 (0.34) -0.52 to 0.85 0.636 Epilepsy Illness Severity score 1.7 (0.62) 0.50 to 2.99 0.006 Epilepsy Syndrome Severity score 2.9 (3.27) -2.63 to 0.05 0.366 Designated a score of normal = 0, learning disability = 1, mental retardation = 2; absent = 0, present = 1; female = 0, male = 1. possibility is that some of the reported events were actually frontal nocturnal seizures that exhibit behaviours that mimic parasomnias. 10,20 An overnight video-psg with more elaborate electroencephalogram monitoring may help differentiate between epileptic and nonepileptic paroxysmal events, although there is a lack of interobserver reliability for brief arousal episodes. 19 The higher DOES scores obtained in this study are in keeping with studies showing that excessive daytime somnolence is more common in epileptic children. 4 9 However, the prevalence of excessive daytime sleepiness in this study was only 16%, in contrast to that in the study of Maganti et al. 7 and Becker et al., 9 who reported a prevalence rate of 63 and 75%, respectively. The differences may be partly explained by the different population characteristics (both studies excluded children with mental retardation) or sleep questionnaire used. Excessive daytime sleepiness may be the effect of the fragmented sleep described earlier, types of AEDs used (especially those on polytherapy or AEDs with sedative effects) or underlying obstructive sleep apnoea. Excessive daytime sleepiness in children has been associated with daytime inattentiveness and behavioural problems, 3 5,7 9 an aspect that was not covered in this study. Although our children with epilepsy had higher SBD scores, the proportion with high scores was small (11%) and not statistically different from those in the control. Other crosssectional studies based on questionnaires 7,8 or PSG 9,18 have documented much higher prevalence (14 80%) of obstructive sleep apnoea with significant sleep disruption in children with epilepsy. Sleep disruption and deprivation in turn exacerbate seizures, setting up a vicious cycle. The improvement of seizure control in adults and children with epilepsy following treatment of obstructive sleep apnoea, as reported by Malow et al., 21 justifies further confirmatory studies utilising PSG in children with high SBD scores. The only factor associated with higher total SDSC scores was the EISS score, confirming the relationship between seizure severity and sleep disturbances. 3 6,8 Unlike others, sleep disturbances in this study were not associated with age, 4,8 level of physical disability or cognitive dysfunction, 5,6 nocturnal seizures 6,14 or aetiology. 5,6,8 A study on normal school-aged children 2 found an association between co-sleeping and higher sleep scores. This was not seen in our epileptic patients, suggesting that the high prevalence of co-sleeping might be a result of parental anxiety over seizures rather than over sleep disturbances. There were several limitations in this study. The availability of English and translated versions of the SDSC was necessary in our multicultural society but has not been normed for the local population. Different questionnaires were used in other studies, so a direct comparison of the subscales scores was not possible. Our study population consisted of more severely affected patients from an urban area. Hence, the results cannot be generalised to the community or directly compared to studies with a narrower age range, 4,5,7 9 more homogenous epilepsy group 4,17,18 or excluded children with neurocognitve comorbidities. 4,6 9 Parental bias in reporting is inherent in questionnaire-based studies, even when siblings are used as controls. Sleep diaries and objective assessment tools like actigraphy and overnight PSG could help verify these sleep disturbances. The EISS contributed only 15% of the variance in the regression equation, suggesting that other factors associated with sleep disturbances were not identified in this study. The relationship between sleep disturbances and behaviour and the impact on the child and family was also not explored. Conclusion Children with epilepsy had a higher prevalence of co-sleeping and more sleep disturbances (especially problems with initiating and maintaining sleep and SWTDs) than their siblings. Seizure severity partly contributed to the sleep disturbances. Evaluation of sleep problems should form part of the comprehensive care of children with severe epilepsy. Future local research needs to explore the impact of sleep disturbances on behaviour and psychosocial functioning of the child and family. References 1 Bruni O, Ottaviano S, Guidetti V et al. Sleep Disturbance Scale for Children (SDSC). Construction and validation of an instrument to evaluate sleep disturbances in childhood and adolescence. J. Sleep Res. 1996; 5: 251 61. 83

Sleep and epileptic Malaysian children LC Ong et al. 2 Li S, Jin X, Yan C, Wu S, Jiang F, Shen X. Bed- and room-sharing in Chinese school-aged children: prevalence and association with sleep behaviors. Sleep Med. 2008; 9: 555 63. 3 Stores G, Wiggs L, Campling G. Sleep disorders and their relationship to psychological disturbance in children with epilepsy. Child Care Health Dev. 1998; 24: 5 19. 4 Cortesi F, Giannotti F, Ottaviano S. Sleep problems and daytime behaviour in childhood idiopathic epilepsy. Epilepsia 1999; 40: 1557 67. 5 Wirrel E, Blackman M, Barlow K, Mah J, Hamiwka L. Sleep disturbances in children with epilepsy compared with their nearest-aged siblings. Dev. Med. Child Neurol. 2005; 47: 754 9. 6 Batista BHB, Nunes ML. Evaluation of sleep habits in children with epilepsy. Epilepsy Behav. 2007; 11: 60 4. 7 Maganti R, Hausman N, Koehn M, Sandok E, Glurich I, Mukesh BN. Excessive daytime sleepiness and sleep complaints among children with epilepsy. Epilepsy Behav. 2006; 8: 272 7. 8 Byars AW, Byars KC, Johnson CS et al. The relationship between sleep problems and neuropsychological functioning in children with first recognized seizures. Epilepsy Behav. 2008; 13: 607 13. 9 Becker DA, Fennell EB, Carney PR. Daytime behaviour and sleep disturbance in childhood epilepsy. Epilepsy Behav. 2004; 5: 708 15. 10 Kotagal P, Yardi N. The relationship between sleep and epilepsy. Semin. Pediatr. Neurol. 2008; 15: 42 9. 11 Legros B, Bazil CW. Effects of antiepileptic drugs on sleep architecture: a pilot study. Sleep Med. 2003; 4: 51 5. 12 Williams J, Lange B, Sharp G et al. Altered sleeping arrangements in pediatric patients with epilepsy. Clin. Pediatr. 2000; 39: 635 42. 13 Palisano R, Rosenbaum P, Walter S, Russell D, Wood E, Galuppi B. Development and reliability of a system to classify gross motor function in children with cerebral palsy. Dev. Med. Child Neurol. 1997; 39: 214 23. 14 Austin JK, Dunn DW, Huster GA. Childhood epilepsy and asthma: changes in behaviour problems related to gender and change in condition severity. Epilepsia 2000; 41: 615 23. 15 Dunn DW, Buelow JM, Austin JK, Shinnar S, Perkins SM. Development of syndrome severity scores for pediatric epilepsy. Epilepsia 2004; 45: 661 6. 16 Opeskin K, Berkovic SF. Risk factors for sudden unexpected death in epilepsy: a controlled prospective study based on coroners cases. Seizure 2003; 12: 456 64. 17 Nunes ML, Ferri A. Arzimanoglou A, Curzi L, Appel CC, Da Costa JC. Sleep organization with partial refractory epilepsy. J. Child Neurol. 2003; 18: 763 6. 18 Maganti S, Sheth RD, Gidal BE, Hermann BP. Sleep architecture in children with idiopathic generalized epilepsy. Epilepsia 2005; 46: 104 9. 19 Zaiwalla Z, Stores G. Sleep and arousal disorders in children with epilepsy. Electroencephalogr. Clin. Neurol. 1989; 72: 107. 20 Vignatelli L, Bisulli F, Provini F et al. Interobserver reliability of video recording in the diagnosis of nocturnal frontal seizures. Epilepsia 2007; 48: 1506 11. 21 Malow BA, Weatherwax KJ, Chervin RD, Hoban TF, Marzee ML, Binns MC. Identification and treatment of obstructive sleep apnea in adults and children with epilepsy: a prospective pilot study. Sleep Med. 2003; 4: 509 15. 84