SLEEP DISORDER AND EPILEPSY IN CHILDREN. WITH TUBEROUS SCLEROSIS: A QUESTIONNAIRE-BASED STUDV

The clinical and physiological sleep disorders of children with a learning disability have been reviewed recently by Stores (1992). Recurrent themes in clinical reports are that such disorders (mainly sleeplessness) are common, severe and persistent, and that often very little effective help is provided to parents in spite of the serious adverse effects on family life and functioning. . Other important issues, unresolved in the literature because of the limited research in this area, include the relative contri- butions of biological and psychosocial factors in the development and main- tenance of sleep disorders in these children, and the relationships between sleep disruption and daytime learning and behaviour.

Tuberous sclerosis (TS) is a dominantly inherited disorder associated with learning disability and epilepsy. There is also a high prevalence of autism and other behaviour problems (Hunt and Shepherd 1993). Little research has been done on the issues associated with sleep disorders in children with TS. In a recent postal survey of 300 people with TS, carers reported problems with settling in 60 per cent and night-waking in 62 per cent (Hunt 1993). Preliminary findings on neuropsychological aspects of this con- dition have implicated sleep disturbance and epilepsy in the genesis of the common

behavioural problems of such children (Jambaque ef at. 1991). The present study was undertaken with the intention of (1) obtaining a precise clinical description of sleep problems in a group of children with TS, for comparison with non-disabled children and others with learning disability of various aetiologies; and (2) exploring the associations between different psychological, social and bio- logical factors and sleep disturbance within the TS group, in order to assess their relative possible contributions to sleep problems.

Subjects Forty children with '1's were idcntified through membership of the Tuberous Sclerosis Association of Great Britain to include both sexes between the ages of two and 15 years. There were 22 boys, and the sample included 25 children with severe, three with moderate and six with mild learning disabilities; the remaining six were considered intellectually normal. The sample represents 5 per cent of the estimated total population of children with TS in the UK in this age-range.

Two groups of non-disabled children were used for comparisons: (1) the siblings of the TS children, nine boys and 13 girls aged three to 17 years, who had no neurological or psychiatric problems, and (2) 37 children attending mainstream

schools in the local community whose sleep problems had been assessed as part of a separate study comparing sleep disturbance in children with epilepsy and in healthy children. Each of these 37 children were matched for gender and age with a child in the TS group. The three youngest preschool children were not matched with non-disabled controls, as preschool children were not included in the epilepsy study.

To assess the sleep problems in TS in relation to other causes of learning disability, a further comparison group was included, comprising children with severe learning disability whose sleep problems were described by Quine and Pahl (1989) in the follow-up part of their longitudinal studies of such children. Their total samples of 178 children included 109 boys and 69 girls, 12 of whom were in residential accommodation so that sleep data were only available for 166. In addition, since i t was a follow-up study, the group was older than the TS group (40 per cent of the sample were over 16 years old).

Method Sleep disturbance This was assessed by means of a specially developed semistructured interview based on items in a sleep questionnaire for parents developed by Simonds and Parraga (1982) for their prevalence study of sleep disorders of children in a general population. The questionnaire covers the main categories described in the International Classification of Sleep Disorders (1990). The authors reported satisfactory test-retest reliability and high return rates when the questionnaire was used in a postal survey. For the present study, enquiries concerning settling and night-waking problems were extended because these aspects were con- sidered particularly relevant for children with learning disabilities. The enquiries took the form of an interview in the child’s home, to ensure complete responses and clarification of points where necessary. As the information obtained this way was shown to correspond very closely to diary information compiled prospectively in nine cases, the interview was considered a valid method of enquiry.

For the present study, emphasis was placed on the following four sleep problems: difficulties settling the child to sleep, night-waking, parents having to get up to attend to the child, and parental sleep loss. A Sleep Index score (Quine 1991) was calculated for each child by summing the three-point scores (0 to 2) for the severity and frequency of occurrence of each of these problems, as assessed by parents over the previous six- month period (range 0 to 8).

Behaviour The Developmentally Delayed Children’s Behaviour Checklist (DDCSC) (Einfeld and Tonge 1991) was used because it has been constructed specifically to include the most prevalent behaviours observed in children with a learning disability. The 98 items are rated on a three-point scale by carers, and a total behaviour problem score can be calculated as a measure of overall behavioural disturbance. This total score has been validated for various levels of learning disability, and the cut- off scores indicating the need for psychiatric intervention established. In addition, the following subscales have been derived: disruptive, self-absorbed, language disturbed, anxious, ‘autistic related’ and antisocial. Norms are available for the prevalence of individual behaviours, subscale scores and the total behaviour problem score.

For this study, scores were also made of those individual behaviours that fulfilled DSM-III-R criteria for pervasive develop- mental disorder (PDD), i.e. impairment of social interaction and communication skills, and a restricted range of repetitive activities and obsessive preoccupations.

Parental stress Sleep disorders in children with learning disability were one of the most important factors associated with family stress in the study of Quine and Pahl (1989). Parental factors are also likely to be related to the development or maintenance of children’s sleep problems, insofar as they affect the extent to which good sleep habits are acquired and the effectiveness with which sleep problems are dealt with when they develop. The Malaise Inventory (Rutter et al. 1970) was used as an established

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of children were severe learning disability. However, a direct comparison could not be made because not all the children in the TS group had severe learning difficulties, and 40 per cent of those in the other study were over 16 ycars old.

As well as the sleep behaviours included in the Sleep Index, 12 of the TS group were reported on the Simonds and Parraga ( I 982) questionnaire to have restless sleep every night, compared with seven of their siblings and two of the control children.

Associations within the TS group between biological or psychosocial factors and sleep disturbance

GENERAL BEHAVIOUR The mean Total Behaviour Problem Scores on the DDCBC O f 54-72 (SD 23- 15) for the children with TS was significantly higher than thc mean score of 6 - 2 (SD 2.95) for their siblings ( ~ , = 6 1 . 6 , p < 0.001). The DDCBC has been validated for children with learning disabilities only, and was used for the siblings’ behaviour only for comparison of behaviour within families. The mean for the 25 children with severe learning difficulties was 61 -32 (sn 21 -OO), and this score is within the range of DDCBC scores for children rated by child psychiatrists as psychiatric cases.

Within the TS group, there was a significant positive correlation between the Sleep Index and Total Behaviour Problem scores (Pearson correlation co- efficient = 0.4931, p<O.O1, two-tailed).

PERVASIVE DEVELOPMENTAL DISORDER Twenty-five of the children with TS were considered to have PDD (according to the criteria described earlicr). Their mean Sleep Index score was 4.84 (SD 3*2), compared with a mean of 4 . 8 (SD 2.8) for the remaining children in the group without PDD. This difference was not significant ( t = 0.22, df38, two-tailed test).

PARENTAL STRESS The mean parental score on the Malaise Inventory in the TS group was 5 .12 (SD 4*32), with six mothers scoring 5 or 6 (considered to indicate abnormal stress levels) and 12 scoring 7 or more (con-

TABLE I .

SIrep Index scores for children with TS and comparison Rroups

Group IV Sleep lndes

Meon (SD)

Children with TS 40 4 . 9 ( 3 . 1 ) Siblings aged 2 2 yrs 22 0.59. (1-02)

matched controls 37 0.41t (0.68)

children with learning disability (Quine 1991) 178 2.8 ( 2 . 5 s )

Age- and gender-

Mixed group of

*Group I/group 2, t - 6 . 3 1 , d f 6 0 , p<O*OOI. tGroup I/group 3, f 24.00. d j 7 5 , p<O.OOI. tGroup I/group 4, 1 , - 1.54, d/39,165. p<O.OS.

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0 1 2 3 4 -

5 6 7 8 S!cep Index sco’e

Fig. I . Sleep 1ndr.v scores for groups with conrrolled and uncontrolled seizures.

sidered ‘critical’ stress levels). Sleep Index and Malaise Inventory scores were not significantly related (Pearson correlation coefficient = 0.2367).

FAMI1.Y PROBLEMS The mean score on the Problem Inventory of the parents of the children with TS was 35.6 (SD 7-4), compared with 1 9 s . 6 (SD 9.8) in Quine’s group of parents with children whose learning disability was of varied aetiology ( F , = 1.75, p<0 .05) .

EPILEPSY Children with TS were divided into those with current seizures (N = 29) and those whose seizures had remitted for at least six months or who had no past history of seizures (N = 11). The mean Sleep Index score of the former group was 6.24 (SD 2-44), and significantly higher than the mean, 1 -45 (SD 1 - 5 ) , for the latter group (t=5*94, df 38, p<O.OOl). Figure 1

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Sleep Index score

Fig. 2. Sleep Index scores occording to obsence or presence o j leorning disability.

shows the strong association between current epilepsy and sleep disturbance. Data reported by parents on the modified sleep questionnaire and analysed for Sleep Index criteria showed 59 per cent of children with serious settling problems and 72 per cent with severe night-waking problems in the group with current seizures. In comparison, these problems were shown by 18 and 0 per cent, respectively, of the children with con- trolled epilepsy. From the information given by parents, there was no difference in the type of epilepsy or the treatment regime of the two groups.

Additional in formation There were 25 children with severe and three with moderate learning difficulties. 12 children were attending mainstream school, although six of them needed extra help. In the group of 29 children with uncontrolled seizures, 24 attended special schools. Seven of the children attending mainstream schools had Sleep Index scores of 4 or above, indicating severe sleep problems, with the five children in this group with uncontrolled epilepsy having Sleep Index scores of between 6 and 8. Figure 2 shows the clear association between sleep disturbance and degree of learning disability.

There are other physical conditions that can contribute to persistent sleep problems, but they were not present in most of the children. Conditions associated with TS included hemiplegia in 11 children, though in only one case was it serious enough to require turning during the night, tachycardia associated with a cardiac rhabdomyoma in one child, and

polycystic kidneys in three. Another three children, one of whom has since died, were diagnosed as having enlarging brain tumours as opposed to the normal calcified lesions associated with TS. These three children had uncontrolled epilepsy and high Sleep Index scores. Of the common diseases of childhood, eight children had eczema, nine had recurrent catarrh or bronchitis and nine had recurrent ear infections; but these prob- lems disturbed sleep only occasionally.

Discussion The present findings suggest that settling and night-waking problems which cause serious disruption of parents' sleep are very common in children with TS and much more common than in their siblings, in children in the general population and even in other groups of learning-disabled children. Of the factors that might be linked with such sleep problems, current epilepsy and general daytime behavioural disturbance show a strong association compared with pervasive developmental disorder, parental stress and other family problems, which were not . significantly associated. We also observed very high rates of disturbed behaviour in the TS group compared with their siblings, and very high rates of stress in the parents of children with TS. In addition, there was the incidental but important finding that, on the basis of descriptions provided by parents, distinction between the epileptic and non-epileptic nature of some of their children's attacks was unclear in 34 per cent of cases.

The high rate of sleep problems in this group is in keeping with that found by Hunt (1993) in a postal survey of 300 cases of TS, 73 per cent of whom were under 15 years of age. Two-thirds of this group were found to have some kind of sleep disturbance-mainly problems of settling to sleep, night-waking and early waking. In the limited research relevant to the question of how sleep disturbance arises or is maintained in such patients, Curatolo et al. (1991) associated autism and hyperkinetic behaviour with pre- dominantly frontal and posterior tubers in severely retarded children with TS. These tubers were also associated with focal EEG spikes and slow waves,

and with frequent and intractable complex partial seizures which could be followed by secondarily generalised convulsions. Clearly the relationships between sleep, organic factors and behavioural disturbance are likely to be complex in TS, but the present findings suggest that a central role might be played by epilepsy which, especially in its severe forms, can disrupt sleep physiology in a variety of ways (Stores 1992). These iinclude possible disturbance of basic sleep mechanisms by seizure activity and some anti-epileptic drugs.

The association between sleep disturb- ance and a high level of general daytime behaviour problems is in agreement with the previous findings of Clements er a/. (1986), in their study of children with severe intellectual impairment. This Consistent association in such children contrasts with the finding in normal children that generally sleep disturbance is not predictive of behaviour problems. Sometimes parents, exhausted by their child’s difficult daytime behaviour , cause settling difficulties by trying to put him or her to bed too early. This sequence of events did not account for the sleeping difficulties of the TS group, whose recorded times of being put to bed were generally usual for each child’s age and showed no consistent association with the sleep problems. I t is somewhat surprising that there was no association with psychosocial factors, but the explanation might partly be in very high rates of disturbed behaviour in the children with TS and similarly high rates of parental stress and family problems in this group. Such high levels of behavioural and psychiatric disturbance are an established feature of TS (Hunt and Shepherd 1993). This is particularly true for the children with TS and severe learning disabilities, in comparison with Quine’s group of children with learning disabilities from other causes.

An obvious question concerns the direction of such relationships, as psycho- social disturbance can be both an effect and a cause of chronic sleep problems. This difficult issue could be addressed by means of careful longitudinal studies, or intervention studies aimed at either the sleep disorder or the psychosocial

disturbance, to assess the effects of improvement in one on the other. That apart, the very high levels of stress and family dysfunction are important issues in their own right and have a bearing on the service needs of such families.

This was essentially an exploratory study, but the findings seem sufficiently instructive to justify more refined attempts to elucidate the nature, extent and causes of sleep disruption in children with TS which (as with other groups of learning-disabled children) is a serious complication to the lives of the children and their carers. Apart from the need for more extensive study of a more representative group of children with TS, including at least 50 per cent with normal intelligence, refinements are needed- especially in the assessment of the children’s sleep disturbance and their epilepsy. In addition to the clinical information provided by asking the parents about sleep disturbance, as in the present study, objective assessment of sleep patterns would be valuable to determine the full extent of the children’s sleep loss and disruption. This is now possible by means of actometry (Sadeh et al. 1991) or home sleep-recording systems, which could provide more de- tailed physiological information (McCall et al. 1989), including the effects of seizure activity on sleep structure.

Similarly, it would be advantageous to have specially compiled and detailed information about the seizures and epilepsy syndromes suffered by the children with TS. This would require standardiscd evaluation of clinical and EEG characteristics as well as other information, especially the occurrence of seizures and seizure discharge during wakefulness and sleep. As in any other study based on clinical reports and conventional EEG recordings, the present account is likely to underestimate the amount of epileptic activity in this group of children. In addition to the improve- ments this would bring to the study of the role of epilepsy in sleep disruption, it would also reduce the diagnostic uncertainties concerning some of the attacks in one-third of the present sample (i.e. whether they were epileptic or not), and the risk of prescribing inappropriate

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anti-epileptic drugs. A further refinement would be a between TS Britain for financial support to A.H.

children and children with epilepsy, or with pervasive developmental disorder, of - equivalent intellectual level in an attempt Gregory Stores, M.A., M.D, , F.R,C,P., to identify possible sleep disturbances F.R.C.Psych., Clinical Reader; specific to ‘rs. University Seciion of Child and Adolescent

Psychiatry, Park Hospital for Children, Old Road, Accepted for pliblrca/ion 22nd June 1992. Headington, Oxford OX3 7LQ.

and the Tuberous Sclerosis Association of Great

Authors’ Appoinlments *Ann Hunt, B.A., Research Officer;

A ckno wledgemenrs W e thank the parents who provided the information Correspondence to first aitthor

SUMMARY Sleep disorders were investigated in 40 children with tuberous sclerosis (TS) and compared wi th those found in non-disabled children and those reported in a mixed group with learning disabilities. Significantly higher levels of deep disturbance were found in the TS group compared with both other groups. Within the TS group, current epilepsy and a high level of daytime behavioural disturbance were significantly associated with sleep disturbance. but pervasive developmental delay and high parental stress levels were not. Detailed study of the relationship between seirure aciivity and sleep disturbance in tuberous sclerosis is needed.

RESUME Troubles du sontnteil el epitilepsie chei les en fants presentant une sclkrose tubereuse: une elude sur questiotinaire Les troubles du sornmeil furent recherches chez 40 enfants presentani une sclerose tubereuse, et ils furent cornparks aux troubles presentes par des enfants sans incapacite et les troubles rapportes dans u n groupe melange presentant des difticultcs d’apprentissage. Un niveau significativernent plus eleve de troubles du sornrneil fut note dans le groupe TS par comparaison avec les autres groupes. Dans le groupe TS. une cornitialite active et un taux eleve de troubles cornportementaux durant le jour etaient significativernent associes aux troubles du somrneil rnais u n retard general de developpernent et un niveau de stress eleve chez les parents ne I’etaient pas. C‘ne analyse detaillee de la relation entre I’aciivite critique et Ies troubles du sornmeil dans la sclerose tubereuse est tres souhaitable.

ZUSAMMENFASSUNG Schlajstorirtigetr irnd Epilepsie bri Kindern ntil rirberoser Hirnsklerose: eine Fragebogenutttersuchung Es wurden die Schlafstorungen bei 40 Kindern rnit tuberoser Hirnsklerose (TS) untersucht und mit denen von gesunden Kindern und denen von einer gernischten Gruppe von Kindern rnit Lernschwierigkeiten verglichen. I n der TS Gruppe wurden signifikant haufiger Schlafstorungen gefunden als in den beiden anderen Gruppen. Epilepsie und ausgepragte Verhaltensstorungen waren in der TS gruppe signifikant rn i t Schlafstorungen verbunden, auffallige Entwicklungsverzogerungen und hochgradiger Stress dcr Eltern jedoch nicht. Es sind genaue Untersuchungen uber das Verhaltnis von Krarnpfaktivitat und Schlafstorungen bei der tuberosen Hirnsklerose erforderlich.

RESUMES Alteraciones del sitetfo y epilepsia en niiios con esclerosis tuberosa. Estudio basado en un cuestioriario Se investigaron las alteraciones del sueilo en 40 niilos con esclerosis tuberosa (ET) y se compararon con 10s hallados en nirlos no incapacitados y con 10s citados en un grupo rnixto con alteraciones del aprendizaje. Se hallaron significativamente niveles mas altos de alteraciones del suefio en el grupo con ET, en comparacion con 10s otros dos grupos. En el grupo ET una epilepsia habitual y un alto nivel de alteraciones del cornportarniento durante el dia iban asociados significativarnente con alteraciones del sueilo, pero no el retraso en el desarrollo ni 10s niveles altos de estress en 10s padres. Es necesario u n estudio detallado de la relacion entre las convulsiones y las alteraciones del sueno en la esclerosis tuberosa.

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